The recommended dose of adrenaline is 7 mg per kilogram of body weight, with a maximum limit of 500 mg.

Local anaesthetics, such as lidocaine, bupivacaine, and prilocaine, are commonly used in the emergency department for topical or local infiltration to establish a field block. Lidocaine is often the first choice for field block prior to central line insertion. These anaesthetics work by blocking sodium channels, preventing the propagation of action potentials.

However, local anaesthetics can enter the systemic circulation and cause toxic side effects if administered in high doses. Clinicians must be aware of the signs and symptoms of local anaesthetic systemic toxicity (LAST) and know how to respond. Early signs of LAST include numbness around the mouth or tongue, metallic taste, dizziness, visual and auditory disturbances, disorientation, and drowsiness. If not addressed, LAST can progress to more severe symptoms such as seizures, coma, respiratory depression, and cardiovascular dysfunction.

The management of LAST is largely supportive. Immediate steps include stopping the administration of local anaesthetic, calling for help, providing 100% oxygen and securing the airway, establishing IV access, and controlling seizures with benzodiazepines or other medications. Cardiovascular status should be continuously assessed, and conventional therapies may be used to treat hypotension or arrhythmias. Intravenous lipid emulsion (intralipid) may also be considered as a treatment option.

If the patient goes into cardiac arrest, CPR should be initiated following ALS arrest algorithms, but lidocaine should not be used as an anti-arrhythmic therapy. Prolonged resuscitation may be necessary, and intravenous lipid emulsion should be administered. After the acute episode, the patient should be transferred to a clinical area with appropriate equipment and staff for further monitoring and care.

It is important to report cases of local anaesthetic toxicity to the appropriate authorities, such as the National Patient Safety Agency in the UK or the Irish Medicines Board in the Republic of Ireland. Additionally, regular clinical review should be conducted to exclude pancreatitis, as intravenous lipid emulsion can interfere with amylase or lipase assays.

Isoniazid has the potential to induce acute hepatitis, but it is not considered a known cause of cholestatic jaundice. On the other hand, there are several drugs that have been identified as culprits for cholestatic jaundice. These include nitrofurantoin, erythromycin, cephalosporins, verapamil, NSAIDs, ACE inhibitors, tricyclic antidepressants, phenytoin, azathioprine, carbamazepine, oral contraceptive pills, diazepam, ketoconazole, and tamoxifen. It is important to be aware of these medications and their potential side effects in order to ensure patient safety.

Paracetamol poisoning occurs when the liver is unable to metabolize paracetamol properly, leading to the production of a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI). Normally, NAPQI is conjugated by glutathione into a non-toxic form. However, during an overdose, the liver’s conjugation systems become overwhelmed, resulting in increased production of NAPQI and depletion of glutathione stores. This leads to the formation of covalent bonds between NAPQI and cell proteins, causing cell death in the liver and kidneys.

Symptoms of paracetamol poisoning may not appear for the first 24 hours or may include abdominal symptoms such as nausea and vomiting. After 24 hours, hepatic necrosis may develop, leading to elevated liver enzymes, right upper quadrant pain, and jaundice. Other complications can include encephalopathy, oliguria, hypoglycemia, renal failure, and lactic acidosis.

The management of paracetamol overdose depends on the timing and amount of ingestion. Activated charcoal may be given if the patient presents within 1 hour of ingesting a significant amount of paracetamol. N-acetylcysteine (NAC) is used to increase hepatic glutathione production and is given to patients who meet specific criteria. Blood tests are taken to assess paracetamol levels, liver function, and other parameters. Referral to a medical or liver unit may be necessary, and psychiatric follow-up should be considered for deliberate overdoses.

In cases of staggered ingestion, all patients should be treated with NAC without delay. Blood tests are also taken, and if certain criteria are met, NAC can be discontinued. Adverse reactions to NAC are common and may include anaphylactoid reactions, rash, hypotension, and nausea. Treatment for adverse reactions involves medications such as chlorpheniramine and salbutamol, and the infusion may be stopped if necessary.

The prognosis for paracetamol poisoning can be poor, especially in cases of severe liver injury. Fulminant liver failure may occur, and liver transplant may be necessary. Poor prognostic indicators include low arterial pH, prolonged prothrombin time, high plasma creatinine, and hepatic encephalopathy.

Amiodarone is a medication that can have numerous harmful side effects, making it crucial to conduct a comprehensive clinical assessment before starting treatment with it. Some of the side effects associated with amiodarone include corneal microdeposits, photosensitivity, nausea, sleep disturbance, hyperthyroidism, hypothyroidism, acute hepatitis and jaundice, peripheral neuropathy, lung fibrosis, QT prolongation, and optic neuritis (although this is very rare). If optic neuritis occurs, immediate discontinuation of amiodarone is necessary to prevent the risk of blindness.

The majority of patients taking amiodarone experience corneal microdeposits, but these typically resolve after treatment is stopped and rarely affect vision. Amiodarone has a chemical structure similar to thyroxine and can bind to the nuclear thyroid receptor, leading to both hypothyroidism and hyperthyroidism. However, hypothyroidism is more commonly observed, affecting around 5-10% of patients.

Phenytoin is a potent anti-epileptic drug that is no longer recommended as the initial treatment for generalized or partial epilepsy due to its toxic effects. Users often experience common symptoms such as ataxia, nystagmus, diplopia, tremor, and dysarthria. Additionally, other side effects may include depression, decreased cognitive abilities, coarse facial features, acne, gum enlargement, polyneuropathy, and blood disorders.

Warfarin has been found to elevate the likelihood of bleeding events when taken in conjunction with NSAIDs like ibuprofen. Consequently, it is advisable to refrain from co-prescribing warfarin with ibuprofen. For more information on this topic, please refer to the BNF section on warfarin interactions.

Gentamicin is an antibiotic belonging to the aminoglycoside class. It works by binding to the 30S subunit of the ribosome in bacteria, thereby preventing the binding of aminoacyl-tRNA and ultimately inhibiting the initiation of protein synthesis.

The two most significant side effects associated with gentamicin are hearing loss and reversible nephrotoxicity. These side effects are directly related to the dosage of the medication and are more commonly observed in elderly individuals.

Hearing loss occurs due to damage to the vestibular apparatus located in the inner ear. On the other hand, nephrotoxicity is caused by the inhibition of protein synthesis in renal cells. This inhibition leads to necrosis of the cells in the proximal convoluted tubule and results in a condition known as acute tubular necrosis.

In summary, gentamicin mechanism of action and side effects, such as hearing loss and reversible nephrotoxicity, are closely linked to its interaction with the bacterial ribosome and its impact on protein synthesis. These effects are particularly prevalent in the elderly population.

Anticholinergic drugs work by blocking the effects of acetylcholine, a neurotransmitter, in both the central and peripheral nervous systems. These drugs are commonly used in clinical practice and include antihistamines, typical and atypical antipsychotics, anticonvulsants, antidepressants, antispasmodics, antiemetics, antiparkinsonian agents, antimuscarinics, and certain plants. When someone ingests an anticholinergic drug, they may experience a toxidrome, which is characterized by an agitated delirium and various signs of acetylcholine receptor blockade in the central and peripheral systems.

The central effects of anticholinergic drugs result in an agitated delirium, which is marked by fluctuating mental status, confusion, restlessness, visual hallucinations, picking at objects in the air, mumbling, slurred speech, disruptive behavior, tremor, myoclonus, and in rare cases, coma or seizures. On the other hand, the peripheral effects can vary and may include dilated pupils, sinus tachycardia, dry mouth, hot and flushed skin, increased body temperature, urinary retention, and ileus.

An overdose of aspirin often leads to a combination of respiratory alkalosis and metabolic acidosis. Initially, the stimulation of the respiratory center causes hyperventilation and results in respiratory alkalosis. However, as the overdose progresses, the direct acidic effects of aspirin cause an increase in the anion gap and metabolic acidosis.

Here is a summary of common causes for different acid-base disorders:

Respiratory alkalosis can be caused by hyperventilation due to factors such as anxiety, pulmonary embolism, CNS disorders (such as stroke or encephalitis), altitude, pregnancy, and the early stages of aspirin overdose.

Respiratory acidosis can occur in individuals with chronic obstructive pulmonary disease (COPD), life-threatening asthma, pulmonary edema, sedative drug overdose (such as opioids or benzodiazepines), neuromuscular diseases, and obesity.

Metabolic alkalosis can be caused by vomiting, potassium depletion (often due to diuretic usage), Cushing’s syndrome, and Conn’s syndrome.

Metabolic acidosis with a raised anion gap can result from conditions such as lactic acidosis (caused by factors like hypoxemia, shock, sepsis, or tissue infarction), ketoacidosis (associated with diabetes, starvation, or excessive alcohol consumption), renal failure, and poisoning (including the late stages of aspirin overdose, methanol or ethylene glycol ingestion).

Metabolic acidosis with a normal anion gap can be seen in renal tubular acidosis, diarrhea, ammonium chloride ingestion, and adrenal insufficiency.

Phyllocontin Continus contains aminophylline, which is a combination of theophylline and ethylenediamine. It is a bronchodilator that is commonly used to manage COPD and asthma.

In this case, the woman is showing symptoms of theophylline toxicity, which may have been triggered by the antibiotic prescribed for her urinary tract infection. Quinolone antibiotics, like ciprofloxacin, can increase the concentration of theophyllines in the blood, leading to toxicity.

There are other medications that can also interact with theophyllines. These include macrolide antibiotics such as clarithromycin, allopurinol, antifungals like ketoconazole, and calcium-channel blockers such as amlodipine. It is important to be aware of these interactions to prevent any potential complications.

Extrapyramidal side effects refer to drug-induced movements that encompass acute dyskinesias and dystonic reactions, tardive dyskinesia, Parkinsonism, akinesia, akathisia, and neuroleptic malignant syndrome. These side effects occur due to the blockade or depletion of dopamine in the basal ganglia, leading to a lack of dopamine that often resembles idiopathic disorders of the extrapyramidal system.

The primary culprits behind extrapyramidal side effects are the first-generation antipsychotics, which act as potent antagonists of the dopamine D2 receptor. Among these antipsychotics, haloperidol and fluphenazine are the two drugs most commonly associated with extrapyramidal side effects. On the other hand, second-generation antipsychotics like olanzapine have lower rates of adverse effects on the extrapyramidal system compared to their first-generation counterparts.

While less frequently, other medications can also contribute to extrapyramidal symptoms. These include certain antidepressants, lithium, various anticonvulsants, antiemetics, and, in rare cases, oral contraceptive agents.

Hyperpyrexia and hypoglycemia are more frequently observed in children than in adults due to salicylate poisoning. Both adults and children may experience common clinical manifestations such as nausea, vomiting, tinnitus, deafness, sweating, dehydration, hyperventilation, and cutaneous flushing. However, it is important to note that xanthopsia is associated with digoxin toxicity, not salicylate poisoning.

Thiazide diuretics, a commonly prescribed medication, can lead to two main electrolyte imbalances in patients. One of these is hyponatremia, which occurs in around 13.7% of individuals taking thiazide diuretics. The other is hypokalemia, which is observed in approximately 8.5% of patients on this medication. These electrolyte disturbances are frequently encountered in primary care settings. For more information on this topic, please refer to the article titled Thiazide diuretic prescription and electrolyte abnormalities in primary care.

The use of NSAIDs during the third trimester of pregnancy is associated with several risks. These risks include delayed onset of labor, premature closure of the fetal ductus arteriosus, and fetal kernicterus, which is a condition characterized by bilirubin-induced brain dysfunction. Additionally, there is a slight increase in the risk of first-trimester abortion if NSAIDs are used early in pregnancy.

Below is a list outlining the most commonly encountered drugs that have adverse effects during pregnancy:

Drug: ACE inhibitors (e.g. ramipril)
Adverse effects: If given in the second and third trimester, ACE inhibitors can cause hypoperfusion, renal failure, and the oligohydramnios sequence.

Drug: Aminoglycosides (e.g. gentamicin)
Adverse effects: Aminoglycosides can cause ototoxicity, leading to deafness in the fetus.

Drug: Aspirin
Adverse effects: High doses of aspirin can cause first-trimester abortions, delayed onset of labor, premature closure of the fetal ductus arteriosus, and fetal kernicterus. However, low doses (e.g. 75 mg) have no significant associated risk.

Drug: Benzodiazepines (e.g. diazepam)
Adverse effects: When given late in pregnancy, benzodiazepines can cause respiratory depression and a neonatal withdrawal syndrome.

Drug: Calcium-channel blockers
Adverse effects: If given in the first trimester, calcium-channel blockers can cause phalangeal abnormalities. If given in the second and third trimester, they can cause fetal growth retardation.

In order to achieve satisfactory bronchodilation, most individuals require a plasma theophylline concentration of 10-20 mg/litre (55-110 micromol/litre). However, it is possible for a lower concentration to still be effective. Adverse effects can occur within the range of 10-20 mg/litre, and their frequency and severity increase when concentrations exceed 20 mg/litre.

To measure plasma theophylline concentration, a blood sample should be taken five days after starting oral treatment and at least three days after any dose adjustment. For modified-release preparations, the blood sample should typically be taken 4-6 hours after an oral dose (specific sampling times may vary, so it is advisable to consult local guidelines). If aminophylline is administered intravenously, a blood sample should be taken 4-6 hours after initiating treatment.

Digoxin is a medication used to treat atrial fibrillation and flutter as well as congestive cardiac failure. It belongs to a class of drugs called cardiac glycosides. Digoxin works by inhibiting the Na/K ATPase pump in the cardiac myocytes, which are the cells of the heart. This inhibition leads to an increase in the concentration of sodium inside the cells and indirectly increases the availability of calcium through the Na/Ca exchange mechanism. The rise in intracellular calcium levels results in a positive inotropic effect, meaning it strengthens the force of the heart’s contractions, and a negative chronotropic effect, meaning it slows down the heart rate.

However, it’s important to note that digoxin can cause toxicity, which is characterized by high levels of potassium in the blood, known as hyperkalemia. Normally, the Na/K ATPase pump helps maintain the balance of sodium and potassium by allowing sodium to leave the cells and potassium to enter. When digoxin blocks this pump, it disrupts this balance and leads to higher levels of potassium in the bloodstream.

Interestingly, the risk of developing digoxin toxicity is higher in individuals with low levels of potassium, known as hypokalemia. This is because digoxin binds to the ATPase pump at the same site as potassium. When potassium levels are low, digoxin can more easily bind to the ATPase pump and exert its inhibitory effects.

In summary, digoxin is a cardiac glycoside that is used to treat certain heart conditions. It works by inhibiting the Na/K ATPase pump, leading to increased intracellular calcium levels and resulting in a positive inotropic effect and negative chronotropic effect. However, digoxin can also cause toxicity, leading to high levels of potassium in the blood. The risk of toxicity is higher in individuals with low potassium levels.

Potentially, there can be a serious condition called hypokalaemia, which is characterized by low levels of potassium in the body. This condition should be taken seriously, especially in cases of severe asthma, as it can be made worse by certain medications like theophyllines (such as aminophylline and Uniphyllin Continus), corticosteroids, and low oxygen levels. Additionally, the use of thiazide and loop diuretics can also worsen hypokalaemia. Therefore, it is important to regularly monitor the levels of potassium in the blood of individuals with severe asthma.

It is worth noting that spironolactone, a type of diuretic, is known as a potassium-sparing medication. This means that it does not typically contribute to hypokalaemia.

There are various specific remedies available for different types of poisons and overdoses. The following list provides an outline of some of these antidotes:

Poison: Benzodiazepines
Antidote: Flumazenil

Poison: Beta-blockers
Antidotes: Atropine, Glucagon, Insulin

Poison: Carbon monoxide
Antidote: Oxygen

Poison: Cyanide
Antidotes: Hydroxocobalamin, Sodium nitrite, Sodium thiosulphate

Poison: Ethylene glycol
Antidotes: Ethanol, Fomepizole

Poison: Heparin
Antidote: Protamine sulphate

Poison: Iron salts
Antidote: Desferrioxamine

Poison: Isoniazid
Antidote: Pyridoxine

Poison: Methanol
Antidotes: Ethanol, Fomepizole

Poison: Opioids
Antidote: Naloxone

Poison: Organophosphates
Antidotes: Atropine, Pralidoxime

Poison: Paracetamol
Antidotes: Acetylcysteine, Methionine

Poison: Sulphonylureas
Antidotes: Glucose, Octreotide

Poison: Thallium
Antidote: Prussian blue

Poison: Warfarin
Antidote: Vitamin K, Fresh frozen plasma (FFP)

By utilizing these specific antidotes, medical professionals can effectively counteract the harmful effects of various poisons and overdoses.

There is an increased risk of neural tube defects in women with epilepsy who take carbamazepine during pregnancy, ranging from 2 to 10 times higher. Additionally, there is a risk of haemorrhagic disease of the newborn associated with this medication. It is crucial to have discussions about epilepsy treatments with women of childbearing age during the planning stages so that they can start early supplementation of folic acid.

Below is a list outlining the most commonly encountered drugs that have adverse effects during pregnancy:

ACE inhibitors (e.g. ramipril): If given in the second and third trimester, these medications can cause hypoperfusion, renal failure, and the oligohydramnios sequence.

Aminoglycosides (e.g. gentamicin): These drugs can lead to ototoxicity and deafness in the fetus.

Aspirin: High doses of aspirin can cause first-trimester abortions, delayed onset labor, premature closure of the fetal ductus arteriosus, and fetal kernicterus. However, low doses (e.g. 75 mg) do not pose significant risks.

Benzodiazepines (e.g. diazepam): When given late in pregnancy, these medications can result in respiratory depression and a neonatal withdrawal syndrome.

Calcium-channel blockers: If given in the first trimester, these drugs can cause phalangeal abnormalities. If given in the second and third trimesters, they can lead to fetal growth retardation.

Carbamazepine: This medication is associated with haemorrhagic disease of the newborn and neural tube defects.

Chloramphenicol: Use of this drug can cause grey baby syndrome in newborns.

Corticosteroids: If given in the first trimester, corticosteroids may cause orofacial clefts in the fetus.

Danazol: When administered in the first trimester, danazol can cause masculinization of the female fetuses genitals.

Finasteride: Pregnant women should avoid handling finasteride tablets. Crushed or broken tablets can be absorbed through the skin and affect male sex organ development in the fetus.

Haloperidol: If given in the first trimester, haloperidol may cause limb malformations. In the third trimester, there is an increased risk of extrapyramidal symptoms in the neonate.

Heparin: Use of heparin during pregnancy is associated with an acceptable bleeding rate and a low rate of thrombotic recurrence in the mother.

Extrapyramidal side effects are most commonly seen with the piperazine phenothiazines (fluphenazine, prochlorperazine, and trifluoperazine) and butyrophenones (benperidol and haloperidol). Among these, haloperidol is the most frequently implicated antipsychotic drug.

Tardive dyskinesia, which involves involuntary rhythmic movements of the tongue, face, and jaw, typically occurs after prolonged treatment or high doses. It is the most severe manifestation of extrapyramidal symptoms, as it may become irreversible even after discontinuing the causative medication, and treatment options are generally ineffective.

Dystonia, characterized by abnormal movements of the face and body, is more commonly observed in children and young adults and tends to appear after only a few doses. Acute dystonia can be managed with intravenous administration of procyclidine (5 mg) or benzatropine (2 mg) as a bolus.

Akathisia refers to an unpleasant sensation of restlessness, while akinesia refers to an inability to initiate movement.

In individuals with renal impairment, there is an increased sensitivity of the brain to antipsychotic drugs, necessitating the use of reduced doses.

Elderly patients with dementia-related psychosis who are treated with haloperidol face an elevated risk of mortality. This is believed to be due to an increased likelihood of cardiovascular events and infections such as pneumonia.

Contraindications for the use of antipsychotic drugs include reduced consciousness or coma, central nervous system depression, and the presence of phaeochromocytoma.

The following list provides a summary of common causes for different acid-base disorders.

Respiratory alkalosis can be caused by hyperventilation, such as during periods of anxiety. It can also be a result of conditions like pulmonary embolism, CNS disorders (such as stroke or encephalitis), altitude, pregnancy, or the early stages of aspirin overdose.

Respiratory acidosis is often associated with chronic obstructive pulmonary disease (COPD) or life-threatening asthma. It can also occur due to pulmonary edema, sedative drug overdose (such as opiates or benzodiazepines), neuromuscular disease, obesity, or other respiratory conditions.

Metabolic alkalosis can be caused by vomiting, potassium depletion (often due to diuretic usage), Cushing’s syndrome, or Conn’s syndrome.

Metabolic acidosis with a raised anion gap can occur due to lactic acidosis (such as in cases of hypoxemia, shock, sepsis, or infarction) or ketoacidosis (such as in diabetes, starvation, or alcohol excess). It can also be a result of renal failure or poisoning (such as in late stages of aspirin overdose, methanol or ethylene glycol ingestion).

Metabolic acidosis with a normal anion gap can be caused by conditions like renal tubular acidosis, diarrhea, ammonium chloride ingestion, or adrenal insufficiency.

When furosemide and gentamicin are prescribed together, there is a higher chance of experiencing ototoxicity and deafness. It is recommended to avoid co-prescribing these medications. For more information, you can refer to the BNF section on furosemide interactions.

Flumazenil is a specific antagonist for benzodiazepines that can be beneficial in certain situations. It acts quickly, taking less than 1 minute to take effect, but its effects are short-lived and only last for less than 1 hour. The recommended dosage is 200 μg every 1-2 minutes, with a maximum dose of 3mg per hour.

It is important to avoid using Flumazenil if the patient is dependent on benzodiazepines or is taking tricyclic antidepressants. This is because it can trigger a withdrawal syndrome in these individuals, potentially leading to seizures or cardiac arrest.

Ciprofloxacin is known to inhibit the activity of cytochrome P450 enzymes, which can lead to increased levels of theophylline in the blood. Therefore, it is recommended to avoid prescribing ciprofloxacin and theophylline together. For more information on the interactions between these two medications, you can refer to the relevant section on theophylline interactions in the British National Formulary (BNF).

The classification of severity in salicylate overdose can sometimes be confused by mixing up the ingested dose and the measured plasma salicylate level. To clarify, when using the blood salicylate level, moderate toxicity is indicated by a level of 350-700 mg/L, while severe toxicity is indicated by a level exceeding 700 mg/L.

Further Reading:

Salicylate poisoning, particularly from aspirin overdose, is a common cause of poisoning in the UK. One important concept to understand is that salicylate overdose leads to a combination of respiratory alkalosis and metabolic acidosis. Initially, the overdose stimulates the respiratory center, leading to hyperventilation and respiratory alkalosis. However, as the effects of salicylate on lactic acid production, breakdown into acidic metabolites, and acute renal injury occur, it can result in high anion gap metabolic acidosis.

The clinical features of salicylate poisoning include hyperventilation, tinnitus, lethargy, sweating, pyrexia (fever), nausea/vomiting, hyperglycemia and hypoglycemia, seizures, and coma.

When investigating salicylate poisoning, it is important to measure salicylate levels in the blood. The sample should be taken at least 2 hours after ingestion for symptomatic patients or 4 hours for asymptomatic patients. The measurement should be repeated every 2-3 hours until the levels start to decrease. Other investigations include arterial blood gas analysis, electrolyte levels (U&Es), complete blood count (FBC), coagulation studies (raised INR/PTR), urinary pH, and blood glucose levels.

To manage salicylate poisoning, an ABC approach should be followed to ensure a patent airway and adequate ventilation. Activated charcoal can be administered if the patient presents within 1 hour of ingestion. Oral or intravenous fluids should be given to optimize intravascular volume. Hypokalemia and hypoglycemia should be corrected. Urinary alkalinization with intravenous sodium bicarbonate can enhance the elimination of aspirin in the urine. In severe cases, hemodialysis may be necessary.

Urinary alkalinization involves targeting a urinary pH of 7.5-8.5 and checking it hourly. It is important to monitor for hypokalemia as alkalinization can cause potassium to shift from plasma into cells. Potassium levels should be checked every 1-2 hours.

In cases where the salicylate concentration is high (above 500 mg/L in adults or 350 mg/L in children), sodium bicarbonate can be administered intravenously. Hemodialysis is the treatment of choice for severe poisoning and may be indicated in cases of high salicylate levels, resistant metabolic acidosis, acute kidney injury, pulmonary edema, seizures and coma..

An overdose of Amitriptyline, a tricyclic antidepressant, leads to a toxic effect known as anticholinergic toxidrome. This occurs when the muscarinic acetylcholine receptors are blocked, causing the characteristic signs and symptoms associated with this condition.

Further Reading:

Tricyclic antidepressant (TCA) overdose is a common occurrence in emergency departments, with drugs like amitriptyline and dosulepin being particularly dangerous. TCAs work by inhibiting the reuptake of norepinephrine and serotonin in the central nervous system. In cases of toxicity, TCAs block various receptors, including alpha-adrenergic, histaminic, muscarinic, and serotonin receptors. This can lead to symptoms such as hypotension, altered mental state, signs of anticholinergic toxicity, and serotonin receptor effects.

TCAs primarily cause cardiac toxicity by blocking sodium and potassium channels. This can result in a slowing of the action potential, prolongation of the QRS complex, and bradycardia. However, the blockade of muscarinic receptors also leads to tachycardia in TCA overdose. QT prolongation and Torsades de Pointes can occur due to potassium channel blockade. TCAs can also have a toxic effect on the myocardium, causing decreased cardiac contractility and hypotension.

Early symptoms of TCA overdose are related to their anticholinergic properties and may include dry mouth, pyrexia, dilated pupils, agitation, sinus tachycardia, blurred vision, flushed skin, tremor, and confusion. Severe poisoning can lead to arrhythmias, seizures, metabolic acidosis, and coma. ECG changes commonly seen in TCA overdose include sinus tachycardia, widening of the QRS complex, prolongation of the QT interval, and an R/S ratio >0.7 in lead aVR.

Management of TCA overdose involves ensuring a patent airway, administering activated charcoal if ingestion occurred within 1 hour and the airway is intact, and considering gastric lavage for life-threatening cases within 1 hour of ingestion. Serial ECGs and blood gas analysis are important for monitoring. Intravenous fluids and correction of hypoxia are the first-line therapies. IV sodium bicarbonate is used to treat haemodynamic instability caused by TCA overdose, and benzodiazepines are the treatment of choice for seizure control. Other treatments that may be considered include glucagon, magnesium sulfate, and intravenous lipid emulsion.

There are certain things to avoid in TCA overdose, such as anti-arrhythmics like quinidine and flecainide, as they can prolonged depolarization.

The therapeutic range for carbamazepine is between 4 and 10 mg/L. This range indicates the optimal concentration of the medication in the bloodstream for it to be effective in treating certain conditions. It is important for healthcare professionals to monitor the levels of carbamazepine in a patient’s blood to ensure they are within this range. If the levels are too low, the medication may not be effective, while levels that are too high can lead to potential side effects. By maintaining carbamazepine levels within the therapeutic range, healthcare providers can maximize the benefits of the medication while minimizing any potential risks.

St. John’s wort can reduce the effectiveness of warfarin, an anticoagulant medication. Therefore, it is important for patients who are taking warfarin to be aware that they should avoid using St. John’s wort as a supplement. For more information on this interaction, you can refer to the BNF section on warfarin interactions.

In cases of anaphylaxis, it is important to administer non-sedating antihistamines after adrenaline administration and initial resuscitation. Previous guidelines recommended the use of chlorpheniramine and hydrocortisone as third line treatments, but the 2021 guidelines have removed this recommendation. Corticosteroids are no longer advised. Instead, it is now recommended to use non-sedating antihistamines such as cetirizine, loratadine, and fexofenadine, as alternatives to the sedating antihistamine chlorpheniramine. The top priority treatments for anaphylaxis are adrenaline, oxygen, and fluids. The Resuscitation Council advises that administration of non-sedating antihistamines should occur after the initial resuscitation.

Further Reading:

Anaphylaxis is a severe and life-threatening hypersensitivity reaction that can have sudden onset and progression. It is characterized by skin or mucosal changes and can lead to life-threatening airway, breathing, or circulatory problems. Anaphylaxis can be allergic or non-allergic in nature.

In allergic anaphylaxis, there is an immediate hypersensitivity reaction where an antigen stimulates the production of IgE antibodies. These antibodies bind to mast cells and basophils. Upon re-exposure to the antigen, the IgE-covered cells release histamine and other inflammatory mediators, causing smooth muscle contraction and vasodilation.

Non-allergic anaphylaxis occurs when mast cells degrade due to a non-immune mediator. The clinical outcome is the same as in allergic anaphylaxis.

The management of anaphylaxis is the same regardless of the cause. Adrenaline is the most important drug and should be administered as soon as possible. The recommended doses for adrenaline vary based on age. Other treatments include high flow oxygen and an IV fluid challenge. Corticosteroids and chlorpheniramine are no longer recommended, while non-sedating antihistamines may be considered as third-line treatment after initial stabilization of airway, breathing, and circulation.

Common causes of anaphylaxis include food (such as nuts, which is the most common cause in children), drugs, and venom (such as wasp stings). Sometimes it can be challenging to determine if a patient had a true episode of anaphylaxis. In such cases, serum tryptase levels may be measured, as they remain elevated for up to 12 hours following an acute episode of anaphylaxis.

The Resuscitation Council (UK) provides guidelines for the management of anaphylaxis, including a visual algorithm that outlines the recommended steps for treatment.
https://www.resus.org.uk/sites/default/files/2021-05/Emergency%20Treatment%20of%20Anaphylaxis%20May%202021_0.pdf

An overdose of Amitriptyline can lead to the development of an anticholinergic toxidrome. This toxidrome is characterized by various symptoms, which can be remembered using the phrase ‘mad as a hatter, hot as hell, red as a beat, dry as a bone, and blind as a bat’. Some of these symptoms include a dry mouth and an elevated body temperature.

Further Reading:

Tricyclic antidepressant (TCA) overdose is a common occurrence in emergency departments, with drugs like amitriptyline and dosulepin being particularly dangerous. TCAs work by inhibiting the reuptake of norepinephrine and serotonin in the central nervous system. In cases of toxicity, TCAs block various receptors, including alpha-adrenergic, histaminic, muscarinic, and serotonin receptors. This can lead to symptoms such as hypotension, altered mental state, signs of anticholinergic toxicity, and serotonin receptor effects.

TCAs primarily cause cardiac toxicity by blocking sodium and potassium channels. This can result in a slowing of the action potential, prolongation of the QRS complex, and bradycardia. However, the blockade of muscarinic receptors also leads to tachycardia in TCA overdose. QT prolongation and Torsades de Pointes can occur due to potassium channel blockade. TCAs can also have a toxic effect on the myocardium, causing decreased cardiac contractility and hypotension.

Early symptoms of TCA overdose are related to their anticholinergic properties and may include dry mouth, pyrexia, dilated pupils, agitation, sinus tachycardia, blurred vision, flushed skin, tremor, and confusion. Severe poisoning can lead to arrhythmias, seizures, metabolic acidosis, and coma. ECG changes commonly seen in TCA overdose include sinus tachycardia, widening of the QRS complex, prolongation of the QT interval, and an R/S ratio >0.7 in lead aVR.

Management of TCA overdose involves ensuring a patent airway, administering activated charcoal if ingestion occurred within 1 hour and the airway is intact, and considering gastric lavage for life-threatening cases within 1 hour of ingestion. Serial ECGs and blood gas analysis are important for monitoring. Intravenous fluids and correction of hypoxia are the first-line therapies. IV sodium bicarbonate is used to treat haemodynamic instability caused by TCA overdose, and benzodiazepines are the treatment of choice for seizure control. Other treatments that may be considered include glucagon, magnesium sulfate, and intravenous lipid emulsion.

There are certain things to avoid in TCA overdose, such as anti-arrhythmics like quinidine and flecainide, as they can prolonged depolarization.

Sodium bicarbonate is recommended as a treatment for TCA overdose according to the latest guidelines from RCEM and NPIS in 2021. Previous editions also suggested using glucagon if IV fluids and sodium bicarbonate were ineffective in treating the overdose.

Further Reading:

Tricyclic antidepressant (TCA) overdose is a common occurrence in emergency departments, with drugs like amitriptyline and dosulepin being particularly dangerous. TCAs work by inhibiting the reuptake of norepinephrine and serotonin in the central nervous system. In cases of toxicity, TCAs block various receptors, including alpha-adrenergic, histaminic, muscarinic, and serotonin receptors. This can lead to symptoms such as hypotension, altered mental state, signs of anticholinergic toxicity, and serotonin receptor effects.

TCAs primarily cause cardiac toxicity by blocking sodium and potassium channels. This can result in a slowing of the action potential, prolongation of the QRS complex, and bradycardia. However, the blockade of muscarinic receptors also leads to tachycardia in TCA overdose. QT prolongation and Torsades de Pointes can occur due to potassium channel blockade. TCAs can also have a toxic effect on the myocardium, causing decreased cardiac contractility and hypotension.

Early symptoms of TCA overdose are related to their anticholinergic properties and may include dry mouth, pyrexia, dilated pupils, agitation, sinus tachycardia, blurred vision, flushed skin, tremor, and confusion. Severe poisoning can lead to arrhythmias, seizures, metabolic acidosis, and coma. ECG changes commonly seen in TCA overdose include sinus tachycardia, widening of the QRS complex, prolongation of the QT interval, and an R/S ratio >0.7 in lead aVR.

Management of TCA overdose involves ensuring a patent airway, administering activated charcoal if ingestion occurred within 1 hour and the airway is intact, and considering gastric lavage for life-threatening cases within 1 hour of ingestion. Serial ECGs and blood gas analysis are important for monitoring. Intravenous fluids and correction of hypoxia are the first-line therapies. IV sodium bicarbonate is used to treat haemodynamic instability caused by TCA overdose, and benzodiazepines are the treatment of choice for seizure control. Other treatments that may be considered include glucagon, magnesium sulfate, and intravenous lipid emulsion.

There are certain things to avoid in TCA overdose, such as anti-arrhythmics like quinidine and flecainide, as they can prolonged depolarization.

N-acetylcysteine (NAC) enhances the production of glutathione, a substance that helps in the detoxification process. Specifically, NAC aids in the conjugation of NAPQI, a harmful metabolite of paracetamol, with glutathione, thereby neutralizing its toxicity.

Further Reading:

Paracetamol poisoning occurs when the liver is unable to metabolize paracetamol properly, leading to the production of a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI). Normally, NAPQI is conjugated by glutathione into a non-toxic form. However, during an overdose, the liver’s conjugation systems become overwhelmed, resulting in increased production of NAPQI and depletion of glutathione stores. This leads to the formation of covalent bonds between NAPQI and cell proteins, causing cell death in the liver and kidneys.

Symptoms of paracetamol poisoning may not appear for the first 24 hours or may include abdominal symptoms such as nausea and vomiting. After 24 hours, hepatic necrosis may develop, leading to elevated liver enzymes, right upper quadrant pain, and jaundice. Other complications can include encephalopathy, oliguria, hypoglycemia, renal failure, and lactic acidosis.

The management of paracetamol overdose depends on the timing and amount of ingestion. Activated charcoal may be given if the patient presents within 1 hour of ingesting a significant amount of paracetamol. N-acetylcysteine (NAC) is used to increase hepatic glutathione production and is given to patients who meet specific criteria. Blood tests are taken to assess paracetamol levels, liver function, and other parameters. Referral to a medical or liver unit may be necessary, and psychiatric follow-up should be considered for deliberate overdoses.

In cases of staggered ingestion, all patients should be treated with NAC without delay. Blood tests are also taken, and if certain criteria are met, NAC can be discontinued. Adverse reactions to NAC are common and may include anaphylactoid reactions, rash, hypotension, and nausea. Treatment for adverse reactions involves medications such as chlorpheniramine and salbutamol, and the infusion may be stopped if necessary.

The prognosis for paracetamol poisoning can be poor, especially in cases of severe liver injury. Fulminant liver failure may occur, and liver transplant may be necessary. Poor prognostic indicators include low arterial pH, prolonged prothrombin time, high plasma creatinine, and hepatic encephalopathy.

Spironolactone is a medication used to treat conditions such as congestive cardiac failure, hypertension, hepatic cirrhosis with ascites and edema, and Conn’s syndrome. It functions as a competitive aldosterone receptor antagonist, primarily working in the distal convoluted tubule. In this area, it hinders the reabsorption of sodium ions and enhances the reabsorption of potassium ions. Spironolactone is commonly known as a potassium-sparing diuretic.

The main side effect of spironolactone is hyperkalemia, particularly when renal impairment is present. In severe cases, hyperkalemia can be life-threatening. Additionally, there is a notable occurrence of gastrointestinal disturbances, with nausea and vomiting being the most common. Women may experience menstrual disturbances, while men may develop gynecomastia, both of which are attributed to the antiandrogenic effects of spironolactone.

Amiodarone has a chemical structure that is similar to thyroxine and has the ability to bind to the nuclear thyroid receptor. This medication has the potential to cause both hypothyroidism and hyperthyroidism, although hypothyroidism is more commonly observed, affecting around 5-10% of patients.

There are several side effects associated with the use of amiodarone. These include the formation of microdeposits in the cornea, increased sensitivity to sunlight resulting in photosensitivity, feelings of nausea, disturbances in sleep patterns, and the development of either hyperthyroidism or hypothyroidism. In addition, there have been reported cases of acute hepatitis and jaundice, peripheral neuropathy, lung fibrosis, and QT prolongation.

It is important to be aware of these potential side effects when considering the use of amiodarone as a treatment option. Regular monitoring and close medical supervision are necessary to detect and manage any adverse reactions that may occur.

The maximum dose of adrenaline is 2 mg/kg, regardless of its concentration or addition. However, when calculating the volume requirements, the concentration of adrenaline becomes a factor.

Further Reading:

Local anaesthetics, such as lidocaine, bupivacaine, and prilocaine, are commonly used in the emergency department for topical or local infiltration to establish a field block. Lidocaine is often the first choice for field block prior to central line insertion. These anaesthetics work by blocking sodium channels, preventing the propagation of action potentials.

However, local anaesthetics can enter the systemic circulation and cause toxic side effects if administered in high doses. Clinicians must be aware of the signs and symptoms of local anaesthetic systemic toxicity (LAST) and know how to respond. Early signs of LAST include numbness around the mouth or tongue, metallic taste, dizziness, visual and auditory disturbances, disorientation, and drowsiness. If not addressed, LAST can progress to more severe symptoms such as seizures, coma, respiratory depression, and cardiovascular dysfunction.

The management of LAST is largely supportive. Immediate steps include stopping the administration of local anaesthetic, calling for help, providing 100% oxygen and securing the airway, establishing IV access, and controlling seizures with benzodiazepines or other medications. Cardiovascular status should be continuously assessed, and conventional therapies may be used to treat hypotension or arrhythmias. Intravenous lipid emulsion (intralipid) may also be considered as a treatment option.

If the patient goes into cardiac arrest, CPR should be initiated following ALS arrest algorithms, but lidocaine should not be used as an anti-arrhythmic therapy. Prolonged resuscitation may be necessary, and intravenous lipid emulsion should be administered. After the acute episode, the patient should be transferred to a clinical area with appropriate equipment and staff for further monitoring and care.

It is important to report cases of local anaesthetic toxicity to the appropriate authorities, such as the National Patient Safety Agency in the UK or the Irish Medicines Board in the Republic of Ireland. Additionally, regular clinical review should be conducted to exclude pancreatitis, as intravenous lipid emulsion can interfere with amylase or lipase assays.

Loop diuretics, like furosemide, commonly result in several electrolyte imbalances. These imbalances include hyponatremia, which is a decrease in sodium levels in the blood. Another common imbalance is hypokalemia, which refers to low levels of potassium. Additionally, loop diuretics can cause hypocalcemia, a condition characterized by low levels of calcium in the blood. Another electrolyte affected by loop diuretics is magnesium, as they can lead to hypomagnesemia, which is a deficiency of magnesium. Lastly, loop diuretics can cause hypochloremic alkalosis, which is a condition characterized by low levels of chloride in the blood and an increase in blood pH.

This patient has presented with symptoms and signs consistent with myopathy. Myopathy is characterized by muscle weakness, muscle atrophy, and reduced tone and reflexes. Hyperkalemia is a known biochemical cause for myopathy, while other metabolic causes include hypokalemia, hypercalcemia, hypomagnesemia, hyperthyroidism, hypothyroidism, diabetes mellitus, Cushing’s disease, and Conn’s syndrome. In this case, ACE inhibitors, such as ramipril, are a well-recognized cause of hyperkalemia and are likely responsible.

Commonly encountered side effects of ACE inhibitors include renal impairment, persistent dry cough, angioedema (with delayed onset), rashes, upper respiratory tract symptoms (such as a sore throat), and gastrointestinal upset.

Lithium is a commonly prescribed medication for bipolar disorder, as it helps stabilize mood. The recommended therapeutic range for lithium levels is typically between 0.4 and 0.8 mmol/l, although this range may vary depending on the laboratory. For maintenance therapy and treatment in older individuals, the lower end of the range is usually targeted. Toxic effects of lithium are typically observed when levels exceed 1.5 mmol/l. It is important to monitor lithium levels one week after starting therapy and after any dosage adjustments.

One potential side effect of lithium is the development of nephrogenic diabetes insipidus, a condition that affects the kidneys’ ability to concentrate urine. However, lithium does not cause diabetes mellitus. Another known side effect is hypothyroidism, which is a decrease in thyroid hormone production, but it does not lead to hyperthyroidism, an overactive thyroid.

Signs of lithium toxicity include nausea, vomiting, diarrhea, tremors, ataxia (loss of coordination), confusion, increased muscle tone, clonus (repetitive, involuntary muscle contractions), nephrogenic diabetes insipidus, convulsions, coma, and renal failure. It is crucial to be aware of these symptoms and seek medical attention if they occur.

Salicylate poisoning initially leads to respiratory alkalosis, followed by metabolic acidosis. Salicylates, like aspirin, stimulate the respiratory center in the medulla, causing hyperventilation and respiratory alkalosis. This is usually the first acid-base imbalance observed in salicylate poisoning. As aspirin is metabolized, it disrupts oxidative phosphorylation in the mitochondria, leading to an increase in lactate levels due to anaerobic metabolism. The accumulation of lactic acid and acidic metabolites then causes metabolic acidosis.

Further Reading:

Salicylate poisoning, particularly from aspirin overdose, is a common cause of poisoning in the UK. One important concept to understand is that salicylate overdose leads to a combination of respiratory alkalosis and metabolic acidosis. Initially, the overdose stimulates the respiratory center, leading to hyperventilation and respiratory alkalosis. However, as the effects of salicylate on lactic acid production, breakdown into acidic metabolites, and acute renal injury occur, it can result in high anion gap metabolic acidosis.

The clinical features of salicylate poisoning include hyperventilation, tinnitus, lethargy, sweating, pyrexia (fever), nausea/vomiting, hyperglycemia and hypoglycemia, seizures, and coma.

When investigating salicylate poisoning, it is important to measure salicylate levels in the blood. The sample should be taken at least 2 hours after ingestion for symptomatic patients or 4 hours for asymptomatic patients. The measurement should be repeated every 2-3 hours until the levels start to decrease. Other investigations include arterial blood gas analysis, electrolyte levels (U&Es), complete blood count (FBC), coagulation studies (raised INR/PTR), urinary pH, and blood glucose levels.

To manage salicylate poisoning, an ABC approach should be followed to ensure a patent airway and adequate ventilation. Activated charcoal can be administered if the patient presents within 1 hour of ingestion. Oral or intravenous fluids should be given to optimize intravascular volume. Hypokalemia and hypoglycemia should be corrected. Urinary alkalinization with intravenous sodium bicarbonate can enhance the elimination of aspirin in the urine. In severe cases, hemodialysis may be necessary.

Urinary alkalinization involves targeting a urinary pH of 7.5-8.5 and checking it hourly. It is important to monitor for hypokalemia as alkalinization can cause potassium to shift from plasma into cells. Potassium levels should be checked every 1-2 hours.

In cases where the salicylate concentration is high (above 500 mg/L in adults or 350 mg/L in children), sodium bicarbonate can be administered intravenously. Hemodialysis is the treatment of choice for severe poisoning and may be indicated in cases of high salicylate levels, resistant metabolic acidosis, acute kidney injury, pulmonary edema, seizures and coma.

Moderate to severe cyanide poisoning typically leads to a condition called high anion gap metabolic acidosis, characterized by elevated levels of lactate (>10 mmol/L). Cyanide toxicity can occur from inhaling smoke produced by burning materials such as plastics, wools, silk, and other natural and synthetic polymers, which can release hydrogen cyanide (HCN). Symptoms of cyanide poisoning include headaches, nausea, decreased consciousness or loss of consciousness, and seizures. Measuring cyanide levels is not immediately helpful in managing a patient suspected of cyanide toxicity. Cyanide binds to the ferric (Fe3+) ion of cytochrome oxidase, causing a condition known as histotoxic hypoxia and resulting in lactic acidosis. The presence of a high lactate level (>10) and a classic high anion gap metabolic acidosis should raise suspicion of cyanide poisoning in a clinician.

Further Reading:

Burn injuries can be classified based on their type (degree, partial thickness or full thickness), extent as a percentage of total body surface area (TBSA), and severity (minor, moderate, major/severe). Severe burns are defined as a >10% TBSA in a child and >15% TBSA in an adult.

When assessing a burn, it is important to consider airway injury, carbon monoxide poisoning, type of burn, extent of burn, special considerations, and fluid status. Special considerations may include head and neck burns, circumferential burns, thorax burns, electrical burns, hand burns, and burns to the genitalia.

Airway management is a priority in burn injuries. Inhalation of hot particles can cause damage to the respiratory epithelium and lead to airway compromise. Signs of inhalation injury include visible burns or erythema to the face, soot around the nostrils and mouth, burnt/singed nasal hairs, hoarse voice, wheeze or stridor, swollen tissues in the mouth or nostrils, and tachypnea and tachycardia. Supplemental oxygen should be provided, and endotracheal intubation may be necessary if there is airway obstruction or impending obstruction.

The initial management of a patient with burn injuries involves conserving body heat, covering burns with clean or sterile coverings, establishing IV access, providing pain relief, initiating fluid resuscitation, measuring urinary output with a catheter, maintaining nil by mouth status, closely monitoring vital signs and urine output, monitoring the airway, preparing for surgery if necessary, and administering medications.

Burns can be classified based on the depth of injury, ranging from simple erythema to full thickness burns that penetrate into subcutaneous tissue. The extent of a burn can be estimated using methods such as the rule of nines or the Lund and Browder chart, which takes into account age-specific body proportions.

Fluid management is crucial in burn injuries due to significant fluid losses. Evaporative fluid loss from burnt skin and increased permeability of blood vessels can lead to reduced intravascular volume and tissue perfusion. Fluid resuscitation should be aggressive in severe burns, while burns <15% in adults and <10% in children may not require immediate fluid resuscitation. The Parkland formula can be used to calculate the intravenous fluid requirements for someone with a significant burn injury.

Activated charcoal should be administered in cases of salicylate overdose if the patient arrives at the medical facility within one hour of ingestion and the amount ingested is greater than 125 mg per kilogram of body weight.

Further Reading:

Salicylate poisoning, particularly from aspirin overdose, is a common cause of poisoning in the UK. One important concept to understand is that salicylate overdose leads to a combination of respiratory alkalosis and metabolic acidosis. Initially, the overdose stimulates the respiratory center, leading to hyperventilation and respiratory alkalosis. However, as the effects of salicylate on lactic acid production, breakdown into acidic metabolites, and acute renal injury occur, it can result in high anion gap metabolic acidosis.

The clinical features of salicylate poisoning include hyperventilation, tinnitus, lethargy, sweating, pyrexia (fever), nausea/vomiting, hyperglycemia and hypoglycemia, seizures, and coma.

When investigating salicylate poisoning, it is important to measure salicylate levels in the blood. The sample should be taken at least 2 hours after ingestion for symptomatic patients or 4 hours for asymptomatic patients. The measurement should be repeated every 2-3 hours until the levels start to decrease. Other investigations include arterial blood gas analysis, electrolyte levels (U&Es), complete blood count (FBC), coagulation studies (raised INR/PTR), urinary pH, and blood glucose levels.

To manage salicylate poisoning, an ABC approach should be followed to ensure a patent airway and adequate ventilation. Activated charcoal can be administered if the patient presents within 1 hour of ingestion. Oral or intravenous fluids should be given to optimize intravascular volume. Hypokalemia and hypoglycemia should be corrected. Urinary alkalinization with intravenous sodium bicarbonate can enhance the elimination of aspirin in the urine. In severe cases, hemodialysis may be necessary.

Urinary alkalinization involves targeting a urinary pH of 7.5-8.5 and checking it hourly. It is important to monitor for hypokalemia as alkalinization can cause potassium to shift from plasma into cells. Potassium levels should be checked every 1-2 hours.

In cases where the salicylate concentration is high (above 500 mg/L in adults or 350 mg/L in children), sodium bicarbonate can be administered intravenously. Hemodialysis is the treatment of choice for severe poisoning and may be indicated in cases of high salicylate levels, resistant metabolic acidosis, acute kidney injury, pulmonary edema, seizures and coma..

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by the presence of low sodium levels and low osmolality due to the inappropriate and continuous release or action of the hormone, despite normal or increased blood volume. This leads to a decreased ability to excrete water.
There are several factors that can cause SIADH, with carbamazepine being a well-known example. These causes can be grouped into different categories. One category is CNS damage, which includes conditions like meningitis and subarachnoid hemorrhage. Another category is malignancy, with small-cell lung cancer being a common cause. Certain drugs, such as carbamazepine, SSRIs, amitriptyline, and morphine, can also trigger SIADH. Infections, such as pneumonia, lung abscess, and brain abscess, are another potential cause. Lastly, endocrine disorders like hypothyroidism can contribute to the development of SIADH.

An elevated pH (normal range 7.34-7.45) suggests alkalosis. A low pCO2 (normal range 4.4-6.0 Kpa) indicates that the respiratory system is causing the alkalosis. The metabolic system, on the other hand, is not contributing to either alkalosis or acidosis as both the bicarbonate and base excess levels are within the normal ranges.

Further Reading:

Salicylate poisoning, particularly from aspirin overdose, is a common cause of poisoning in the UK. One important concept to understand is that salicylate overdose leads to a combination of respiratory alkalosis and metabolic acidosis. Initially, the overdose stimulates the respiratory center, leading to hyperventilation and respiratory alkalosis. However, as the effects of salicylate on lactic acid production, breakdown into acidic metabolites, and acute renal injury occur, it can result in high anion gap metabolic acidosis.

The clinical features of salicylate poisoning include hyperventilation, tinnitus, lethargy, sweating, pyrexia (fever), nausea/vomiting, hyperglycemia and hypoglycemia, seizures, and coma.

When investigating salicylate poisoning, it is important to measure salicylate levels in the blood. The sample should be taken at least 2 hours after ingestion for symptomatic patients or 4 hours for asymptomatic patients. The measurement should be repeated every 2-3 hours until the levels start to decrease. Other investigations include arterial blood gas analysis, electrolyte levels (U&Es), complete blood count (FBC), coagulation studies (raised INR/PTR), urinary pH, and blood glucose levels.

To manage salicylate poisoning, an ABC approach should be followed to ensure a patent airway and adequate ventilation. Activated charcoal can be administered if the patient presents within 1 hour of ingestion. Oral or intravenous fluids should be given to optimize intravascular volume. Hypokalemia and hypoglycemia should be corrected. Urinary alkalinization with intravenous sodium bicarbonate can enhance the elimination of aspirin in the urine. In severe cases, hemodialysis may be necessary.

Urinary alkalinization involves targeting a urinary pH of 7.5-8.5 and checking it hourly. It is important to monitor for hypokalemia as alkalinization can cause potassium to shift from plasma into cells. Potassium levels should be checked every 1-2 hours.

In cases where the salicylate concentration is high (above 500 mg/L in adults or 350 mg/L in children), sodium bicarbonate can be administered intravenously. Hemodialysis is the treatment of choice for severe poisoning and may be indicated in cases of high salicylate levels, resistant metabolic acidosis, acute kidney injury, pulmonary edema, seizures and coma.

Glucagon is the preferred initial treatment for beta-blocker poisoning when there are symptoms of slow heart rate and low blood pressure.

Further Reading:

Poisoning in the emergency department is often caused by accidental or intentional overdose of prescribed drugs. Supportive treatment is the primary approach for managing most poisonings. This includes ensuring a clear airway, proper ventilation, maintaining normal fluid levels, temperature, and blood sugar levels, correcting any abnormal blood chemistry, controlling seizures, and assessing and treating any injuries.

In addition to supportive treatment, clinicians may need to consider strategies for decontamination, elimination, and administration of antidotes. Decontamination involves removing poisons from the skin or gastrointestinal tract. This can be done through rinsing the skin or using methods such as activated charcoal, gastric lavage, induced emesis, or whole bowel irrigation. However, induced emesis is no longer commonly used, while gastric lavage and whole bowel irrigation are rarely used.

Elimination methods include urinary alkalinization, hemodialysis, and hemoperfusion. These techniques help remove toxins from the body.

Activated charcoal is a commonly used method for decontamination. It works by binding toxins in the gastrointestinal tract, preventing their absorption. It is most effective if given within one hour of ingestion. However, it is contraindicated in patients with an insecure airway due to the risk of aspiration. Activated charcoal can be used for many drugs, but it is ineffective for certain poisonings, including pesticides (organophosphates), hydrocarbons, strong acids and alkalis, alcohols (ethanol, methanol, ethylene glycol), iron, lithium, and solvents.

Antidotes are specific treatments for poisoning caused by certain drugs or toxins. For example, cyanide poisoning can be treated with dicobalt edetate, hydroxocobalamin, or sodium nitrite and sodium thiosulphate. Benzodiazepine poisoning can be treated with flumazanil, while opiate poisoning can be treated with naloxone. Other examples include protamine for heparin poisoning, vitamin K or fresh frozen plasma for warfarin poisoning, fomepizole or ethanol for methanol poisoning, and methylene blue for methemoglobinemia caused by benzocaine or nitrates.

There are many other antidotes available for different types of poisoning, and resources such as TOXBASE and the National Poisons Information Service (NPIS) can provide valuable advice on managing poisonings.

The clinical manifestations of theophylline toxicity are more closely associated with acute poisoning rather than chronic overexposure. The primary clinical features of theophylline toxicity include headache, dizziness, nausea and vomiting, abdominal pain, tachycardia and dysrhythmias, seizures, mild metabolic acidosis, hypokalaemia, hypomagnesaemia, hypophosphataemia, hypo- or hypercalcaemia, and hyperglycaemia. Seizures are more prevalent in cases of acute overdose compared to chronic overexposure. In contrast, chronic theophylline overdose typically presents with minimal gastrointestinal symptoms. Cardiac dysrhythmias are more frequently observed in individuals who have experienced chronic overdose rather than acute overdose.

Angiotensin-converting enzyme (ACE) inhibitors are the primary cause of drug-induced angioedema in the UK and USA, mainly due to their widespread use. The incidence of angioedema caused by ACE inhibitors ranges from 0.1 to 0.7% among recipients, with evidence suggesting a consistent and persistent risk each year. Interestingly, individuals of African descent are approximately five times more likely to experience this adverse reaction.

The most common symptoms observed in patients with ACE inhibitor-induced angioedema include swelling of the lips, tongue, or face. However, another manifestation of this condition is episodic abdominal pain caused by intestinal angioedema. Notably, urticaria (hives) and itching are absent in these cases.

The underlying mechanism of ACE inhibitor-induced angioedema appears to involve the activation of the complement system or other pro-inflammatory cytokines, such as prostaglandins and histamine. These substances trigger rapid dilation of blood vessels and the accumulation of fluid, leading to edema.

Although less frequently associated with angioedema, other medications that may cause this condition include angiotensin-receptor blockers (ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs), bupropion (e.g., Zyban and Wellbutrin), beta-lactam antibiotics, statins, and proton pump inhibitors.

Fortunately, most cases of drug-induced angioedema are mild and can be effectively managed by discontinuing the medication and prescribing oral antihistamines.

Activated charcoal is a commonly used substance for decontamination in cases of poisoning. Its main function is to adsorb the molecules of the ingested toxin onto its surface.

Activated charcoal is a chemically inert form of carbon. It is a fine black powder that has no odor or taste. It is produced by subjecting carbonaceous matter to high heat, a process known as pyrolysis, and then treating it with a zinc chloride solution to increase its concentration. This process creates a network of pores within the charcoal, giving it a large absorptive area of approximately 3,000 m2/g. This allows it to effectively inhibit the absorption of toxins by up to 50%.

The usual dose of activated charcoal is 50 grams for adults and 1 gram per kilogram of body weight for children. It can be administered orally or through a nasogastric tube. It is important to administer it within one hour of ingestion, and it may be repeated after one hour if necessary.

However, there are certain situations where activated charcoal should not be used. These include cases where the patient is unconscious or in a coma, as there is a risk of aspiration. It should also be avoided if seizures are imminent, as there is a risk of aspiration. Additionally, if there is reduced gastrointestinal motility, activated charcoal should not be used to prevent the risk of obstruction.

Activated charcoal is effective in treating overdose with certain drugs and toxins, such as aspirin, paracetamol, barbiturates, tricyclic antidepressants, digoxin, amphetamines, morphine, cocaine, and phenothiazines. However, it is ineffective in cases of overdose with iron, lithium, boric acid, cyanide, ethanol, ethylene glycol, methanol, malathion, DDT, carbamate, hydrocarbon, strong acids, or alkalis.

There are potential adverse effects associated with the use of activated charcoal. These include nausea and vomiting, diarrhea, constipation, bezoar formation (a mass of undigested material that can cause blockages), bowel obstruction, pulmonary aspiration (inhalation of charcoal into the lungs), and impaired absorption of oral medications or antidotes.

Fluoroquinolones are a rare but acknowledged cause of tendinopathy and spontaneous tendon rupture. It is estimated that tendon disorders related to fluoroquinolones occur in approximately 15 to 20 out of every 100,000 patients. These issues are most commonly observed in individuals who are over the age of 60.

The Achilles tendon is the most frequently affected, although cases involving other tendons such as the quadriceps, peroneus brevis, extensor pollicis longus, the long head of biceps brachii, and rotator cuff tendons have also been reported. The exact underlying mechanism is not fully understood, but it is believed that fluoroquinolone drugs may hinder collagen function and/or disrupt blood supply to the tendon.

There are other risk factors associated with spontaneous tendon rupture, including corticosteroid therapy, hypercholesterolemia, gout, rheumatoid arthritis, long-term dialysis, and renal transplantation.

Amlodipine is a medication that belongs to the class of calcium-channel blockers and is often prescribed for the management of high blood pressure. One of the most frequently observed side effects of calcium-channel blockers is the swelling of the ankles. Additionally, individuals taking these medications may also experience other common side effects such as nausea, flushing, dizziness, sleep disturbances, headaches, fatigue, abdominal pain, and palpitations.

Calcium-channel blocker overdose is a serious condition that should always be taken seriously as it can be potentially life-threatening. The two most dangerous types of calcium channel blockers in overdose are verapamil and diltiazem. These medications work by binding to the alpha-1 subunit of L-type calcium channels, which prevents the entry of calcium into the cells. These channels play a crucial role in the functioning of cardiac myocytes, vascular smooth muscle cells, and islet beta-cells.

Significant toxicity can occur with the ingestion of more than 10 tablets of verapamil (160 mg or 240 mg immediate or sustained-release capsules) or diltiazem (180 mg, 240 mg or 360 mg immediate or sustained-release capsules). In children, even 1-2 tablets of immediate or sustained-release verapamil or diltiazem can be harmful. Symptoms usually appear within 1-2 hours of taking standard preparations, but with slow-release versions, the onset of severe toxicity may be delayed by 12-16 hours, with peak effects occurring after 24 hours.

The main clinical manifestations of calcium-channel blocker overdose include nausea and vomiting, low blood pressure, slow heart rate and first-degree heart block, heart muscle ischemia and stroke, kidney failure, pulmonary edema, and high blood sugar levels.

When managing a patient with calcium-channel blocker overdose, certain bedside investigations are crucial. These include checking blood glucose levels, performing an electrocardiogram (ECG), and obtaining an arterial blood gas sample. Additional investigations that can provide helpful information include assessing urea and electrolyte levels, conducting a chest X-ray to check for pulmonary edema, and performing an echocardiography.

Naloxone is a specific antidote for opioid overdose. It effectively reverses respiratory depression and coma when given in sufficient dosage. The initial dose is administered intravenously at 400 micrograms, followed by 800 micrograms for up to 2 doses at 1-minute intervals if there is no response to the preceding dose. If there is still no response, the dosage is increased to 2 mg for one dose. In seriously poisoned patients, a 4 mg dose may be required. If the intravenous route is not feasible, naloxone can also be given by intramuscular injection.

Due to its shorter duration of action compared to most opioids, close monitoring and repeated injections are necessary. The frequency of doses should be based on the respiratory rate and depth of coma, with the dose generally repeated every 2-3 minutes up to a maximum of 10 mg. In cases where repeated doses are needed, naloxone can be administered through a continuous infusion, which should be adjusted according to the vital signs. Initially, the infusion rate can be set at 60% of the initial resuscitative IV dose per hour.

It is important to note that in opioid addicts, the administration of naloxone may trigger a withdrawal syndrome characterized by symptoms such as abdominal cramps, nausea, and diarrhea. However, these symptoms typically subside within 2 hours.

The key components of first aid for snake bites in the UK involve immobilizing the patient and the affected limb, as well as administering paracetamol for pain relief. When it comes to venomous snake bites, it is important to immobilize the limb using a splint or sling, but not to use a tourniquet or pressure bandage for adder bites. In certain areas, such as NSW, Australia, where venomous snakes can cause rapidly progressing and life-threatening paralysis, pressure bandage immobilization is recommended. However, this is not the case in the UK. Anti-venom is not always necessary for adder bites, and its administration should be based on a thorough assessment of the patient’s condition and the presence of appropriate indications. Paracetamol is the preferred choice for pain relief in UK snake bites, as aspirin and ibuprofen can worsen bleeding tendencies that may result from adder bites. Similarly, heparin should be avoided for the same reason.

Further Reading:

Snake bites in the UK are primarily caused by the adder, which is the only venomous snake species native to the country. While most adder bites result in minor symptoms such as pain, swelling, and inflammation, there have been cases of life-threatening illness and fatalities. Additionally, there are instances where venomous snakes that are kept legally or illegally also cause bites in the UK.

Adder bites typically occur from early spring to late autumn, with the hand being the most common site of the bite. Symptoms can be local or systemic, with local symptoms including sharp pain, tingling or numbness, and swelling that spreads proximally. Systemic symptoms may include spreading pain, tenderness, inflammation, regional lymph node enlargement, and bruising. In severe cases, anaphylaxis can occur, leading to symptoms such as nausea, vomiting, abdominal pain, diarrhea, and shock.

It is important for clinicians to be aware of the potential complications and complications associated with adder bites. These can include acute renal failure, pulmonary and cerebral edema, acute gastric dilatation, paralytic ileus, acute pancreatitis, and coma and seizures. Anaphylaxis symptoms can appear within minutes or be delayed for hours, and hypotension is a critical sign to monitor.

Initial investigations for adder bites include blood tests, ECG, and vital sign monitoring. Further investigations such as chest X-ray may be necessary based on clinical signs. Blood tests may reveal abnormalities such as leukocytosis, raised hematocrit, anemia, thrombocytopenia, and abnormal clotting profile. ECG changes may include tachyarrhythmias, bradyarrhythmias, atrial fibrillation, and ST segment changes.

First aid measures at the scene include immobilizing the patient and the bitten limb, avoiding aspirin and ibuprofen, and cleaning the wound site in the hospital. Tetanus prophylaxis should be considered. In cases of anaphylaxis, prompt administration of IM adrenaline is necessary. In the hospital, rapid assessment and appropriate resuscitation with intravenous fluids are required.

Antivenom may be indicated in cases of hypotension, systemic envenoming, ECG abnormalities, peripheral neutrophil leucocytosis, elevated serum creatine kinase or metabolic acidosis, and extensive or rapidly spreading local swelling. Zagreb antivenom is commonly used in the UK, with an initial dose of 8 mL.

Tetracycline antibiotics, such as tetracycline and doxycycline, have the potential to cause staining on permanent teeth while they are still forming beneath the gum line. This staining occurs when the drug becomes calcified within the tooth during its development. It is important to note that children are vulnerable to tetracycline-related tooth staining until approximately the age of 8. Additionally, pregnant women should avoid taking tetracycline as it can affect the development of teeth in the unborn child.

The drugs that have the highest association with the development of drug-induced lupus are procainamide and hydralazine. While some of the other medications mentioned in this question have also been reported to cause drug-induced lupus, the strength of their association is much weaker.

Sodium bicarbonate is used to treat severe TCA toxicity by reducing the risk of seizures and arrhythmia. The goal is to increase the serum pH to a range of 7.45 to 7.55 through alkalinisation.

Further Reading:

Tricyclic antidepressant (TCA) overdose is a common occurrence in emergency departments, with drugs like amitriptyline and dosulepin being particularly dangerous. TCAs work by inhibiting the reuptake of norepinephrine and serotonin in the central nervous system. In cases of toxicity, TCAs block various receptors, including alpha-adrenergic, histaminic, muscarinic, and serotonin receptors. This can lead to symptoms such as hypotension, altered mental state, signs of anticholinergic toxicity, and serotonin receptor effects.

TCAs primarily cause cardiac toxicity by blocking sodium and potassium channels. This can result in a slowing of the action potential, prolongation of the QRS complex, and bradycardia. However, the blockade of muscarinic receptors also leads to tachycardia in TCA overdose. QT prolongation and Torsades de Pointes can occur due to potassium channel blockade. TCAs can also have a toxic effect on the myocardium, causing decreased cardiac contractility and hypotension.

Early symptoms of TCA overdose are related to their anticholinergic properties and may include dry mouth, pyrexia, dilated pupils, agitation, sinus tachycardia, blurred vision, flushed skin, tremor, and confusion. Severe poisoning can lead to arrhythmias, seizures, metabolic acidosis, and coma. ECG changes commonly seen in TCA overdose include sinus tachycardia, widening of the QRS complex, prolongation of the QT interval, and an R/S ratio >0.7 in lead aVR.

Management of TCA overdose involves ensuring a patent airway, administering activated charcoal if ingestion occurred within 1 hour and the airway is intact, and considering gastric lavage for life-threatening cases within 1 hour of ingestion. Serial ECGs and blood gas analysis are important for monitoring. Intravenous fluids and correction of hypoxia are the first-line therapies. IV sodium bicarbonate is used to treat haemodynamic instability caused by TCA overdose, and benzodiazepines are the treatment of choice for seizure control. Other treatments that may be considered include glucagon, magnesium sulfate, and intravenous lipid emulsion.

There are certain things to avoid in TCA overdose, such as anti-arrhythmics like quinidine and flecainide, as they can prolonged depolarization.

Theophylline, a medication commonly used to treat respiratory conditions, can be affected by certain drugs, either increasing or decreasing its plasma concentration and half-life. Drugs that can increase the plasma concentration of theophylline include calcium channel blockers like verapamil, cimetidine, fluconazole, macrolides such as erythromycin, methotrexate, and quinolones like ciprofloxacin. On the other hand, drugs like carbamazepine, phenobarbitol, phenytoin (and fosphenytoin), rifampicin, and St. John’s wort can decrease the plasma concentration of theophylline. It is important to be aware of these interactions when prescribing or taking theophylline to ensure its effectiveness and avoid potential side effects.

There is an increased risk of neural tube defects in women with epilepsy who take carbamazepine during pregnancy, ranging from 2 to 10 times higher. Additionally, there is a risk of haemorrhagic disease of the newborn associated with this medication. It is crucial to have discussions about epilepsy treatments with women of childbearing age during the planning stages so that they can start early supplementation of folic acid.

Below is a list outlining the most commonly encountered drugs that have adverse effects during pregnancy:

ACE inhibitors (e.g. ramipril): If given in the second and third trimester, these medications can cause hypoperfusion, renal failure, and the oligohydramnios sequence.

Aminoglycosides (e.g. gentamicin): These drugs can lead to ototoxicity and deafness in the fetus.

Aspirin: High doses of aspirin can cause first-trimester abortions, delayed onset labor, premature closure of the fetal ductus arteriosus, and fetal kernicterus. However, low doses (e.g. 75 mg) do not pose significant risks.

Benzodiazepines (e.g. diazepam): When given late in pregnancy, these medications can result in respiratory depression and a neonatal withdrawal syndrome.

Calcium-channel blockers: If given in the first trimester, these drugs can cause phalangeal abnormalities. If given in the second and third trimesters, they can lead to fetal growth retardation.

Carbamazepine: This medication is associated with haemorrhagic disease of the newborn and neural tube defects.

Chloramphenicol: Use of this drug can cause grey baby syndrome in newborns.

Corticosteroids: If given in the first trimester, corticosteroids may cause orofacial clefts in the fetus.

Danazol: When administered in the first trimester, danazol can cause masculinization of the female fetuses genitals.

Finasteride: Pregnant women should avoid handling finasteride tablets. Crushed or broken tablets can be absorbed through the skin and affect male sex organ development in the fetus.

Haloperidol: If given in the first trimester, haloperidol may cause limb malformations. In the third trimester, there is an increased risk of extrapyramidal symptoms in the neonate.

Heparin: Use of heparin during pregnancy is associated with an acceptable bleeding rate and a low rate of thrombotic recurrence in the mother.

Calcium-channel blocker overdose is a serious condition that can be life-threatening. The most dangerous types of calcium channel blockers in overdose are verapamil and diltiazem. These medications work by binding to the alpha-1 subunit of L-type calcium channels, which prevents the entry of calcium into cells. These channels are important for the functioning of cardiac myocytes, vascular smooth muscle cells, and islet beta-cells.

When managing a patient with calcium-channel blocker overdose, it is crucial to follow the standard ABC approach for resuscitation. If there is a risk of life-threatening toxicity, early intubation and ventilation should be considered. Invasive blood pressure monitoring is also necessary if hypotension and shock are developing.

The specific treatments for calcium-channel blocker overdose primarily focus on supporting the cardiovascular system. These treatments include:

1. Fluid resuscitation: Administer up to 20 mL/kg of crystalloid solution.

2. Calcium administration: This can temporarily increase blood pressure and heart rate. Options include 10% calcium gluconate (60 mL IV) or 10% calcium chloride (20 mL IV) via central venous access. Repeat boluses can be given up to three times, and a calcium infusion may be necessary to maintain serum calcium levels above 2.0 mEq/L.

3. Atropine: Consider administering 0.6 mg every 2 minutes, up to a total of 1.8 mg. However, atropine is often ineffective in these cases.

4. High dose insulin – euglycemic therapy (HIET): The use of HIET in managing cardiovascular toxicity has evolved. It used to be a last-resort measure, but early administration is now increasingly recommended. This involves giving a bolus of short-acting insulin (1 U/kg) and 50 mL of 50% glucose IV (unless there is marked hyperglycemia). Therapy should be continued with a short-acting insulin/dextrose infusion. Glucose levels should be monitored frequently, and potassium should be replaced if levels drop below 2.5 mmol/L.

5. Vasoactive infusions: Catecholamines such as dopamine, adrenaline, and/or noradrenaline can be titrated to achieve the desired inotropic and chronotropic effects.

6. Sodium bicarbonate: Consider using sodium bicarbonate in cases where a severe metabolic acidosis develops.

Aminoglycosides have the ability to pass through the placenta and can lead to damage to the 8th cranial nerve in the fetus, resulting in permanent bilateral deafness.

ACE inhibitors, such as ramipril, can cause hypoperfusion, renal failure, and the oligohydramnios sequence if given in the 2nd and 3rd trimesters.

Aminoglycosides, like gentamicin, can cause ototoxicity and deafness in the fetus.

High doses of aspirin can lead to 1st trimester abortions, delayed onset labor, premature closure of the fetal ductus arteriosus, and fetal kernicterus. However, low doses (e.g. 75 mg) do not pose significant risks.

Benzodiazepines, including diazepam, when administered late in pregnancy, can result in respiratory depression and a neonatal withdrawal syndrome.

Calcium-channel blockers, if given in the 1st trimester, can cause phalangeal abnormalities. If given in the 2nd and 3rd trimesters, they can lead to fetal growth retardation.

Carbamazepine can cause hemorrhagic disease of the newborn and neural tube defects.

Chloramphenicol is associated with grey baby syndrome.

Corticosteroids, if given in the 1st trimester, may cause orofacial clefts.

Danazol, if given in the 1st trimester, can cause masculinization of the female fetuses genitals.

Finasteride should not be handled by pregnant women as crushed or broken tablets can be absorbed through the skin and affect male sex organ development.

Haloperidol, if given in the 1st trimester, may cause limb malformations. If given in the 3rd trimester, there is an increased risk of extrapyramidal symptoms in the neonate.

Heparin can lead to maternal bleeding and thrombocytopenia.

Isoniazid can cause maternal liver damage and neuropathy and seizures in the neonate.

Isotretinoin carries a high risk of teratogenicity, including multiple congenital malformations, spontaneous abortion, and intellectual disability.

Lithium, if given in the 1st trimester, poses a risk of fetal cardiac malformations.

Theophylline is a medication used to treat severe asthma. It is a bronchodilator that comes in modified-release forms, which can maintain therapeutic levels in the blood for 12 hours. Theophylline works by inhibiting phosphodiesterase and blocking the breakdown of cyclic AMP. It also competes with adenosine on A1 and A2 receptors.

Achieving the right dose of theophylline can be challenging because there is a narrow range between therapeutic and toxic levels. The half-life of theophylline can be influenced by various factors, further complicating dosage adjustments. It is recommended to aim for serum levels of 10-20 mg/l six to eight hours after the last dose.

Unlike many other medications, the specific brand of theophylline can significantly impact its effects. Therefore, it is important to prescribe theophylline by both its brand name and generic name.

Several factors can increase the half-life of theophylline, including heart failure, cirrhosis, viral infections, and certain drugs. Conversely, smoking, heavy drinking, and certain medications can decrease the half-life of theophylline.

There are several drugs that can either increase or decrease the plasma concentration of theophylline. Calcium channel blockers, cimetidine, fluconazole, macrolides, methotrexate, and quinolones can increase the concentration. On the other hand, carbamazepine, phenobarbitol, phenytoin, rifampicin, and St. John’s wort can decrease the concentration.

The clinical symptoms of theophylline toxicity are more closely associated with acute overdose rather than chronic overexposure. Common symptoms include headache, dizziness, nausea, vomiting, abdominal pain, rapid heartbeat, dysrhythmias, seizures, mild metabolic acidosis, low potassium, low magnesium, low phosphates, abnormal calcium levels, and high blood sugar.

Seizures are more prevalent in acute overdose cases, while chronic overdose typically presents with minimal gastrointestinal symptoms. Cardiac dysrhythmias are more common in chronic overdose situations compared to acute overdose.

Tinnitus is often seen as an early indication of salicylate toxicity, which occurs when there is an excessive use of salicylate. Another common symptom is feeling nauseous and/or vomiting. In the initial stages of a salicylate overdose, individuals may experience respiratory alkalosis, which is caused by the direct stimulation of the respiratory centers in the medulla by salicylate. This leads to hyperventilation and the elimination of carbon dioxide, resulting in alkalosis. As the body metabolizes salicylate, a metabolic acidosis may develop.

Further Reading:

Salicylate poisoning, particularly from aspirin overdose, is a common cause of poisoning in the UK. One important concept to understand is that salicylate overdose leads to a combination of respiratory alkalosis and metabolic acidosis. Initially, the overdose stimulates the respiratory center, leading to hyperventilation and respiratory alkalosis. However, as the effects of salicylate on lactic acid production, breakdown into acidic metabolites, and acute renal injury occur, it can result in high anion gap metabolic acidosis.

The clinical features of salicylate poisoning include hyperventilation, tinnitus, lethargy, sweating, pyrexia (fever), nausea/vomiting, hyperglycemia and hypoglycemia, seizures, and coma.

When investigating salicylate poisoning, it is important to measure salicylate levels in the blood. The sample should be taken at least 2 hours after ingestion for symptomatic patients or 4 hours for asymptomatic patients. The measurement should be repeated every 2-3 hours until the levels start to decrease. Other investigations include arterial blood gas analysis, electrolyte levels (U&Es), complete blood count (FBC), coagulation studies (raised INR/PTR), urinary pH, and blood glucose levels.

To manage salicylate poisoning, an ABC approach should be followed to ensure a patent airway and adequate ventilation. Activated charcoal can be administered if the patient presents within 1 hour of ingestion. Oral or intravenous fluids should be given to optimize intravascular volume. Hypokalemia and hypoglycemia should be corrected. Urinary alkalinization with intravenous sodium bicarbonate can enhance the elimination of aspirin in the urine. In severe cases, hemodialysis may be necessary.

Urinary alkalinization involves targeting a urinary pH of 7.5-8.5 and checking it hourly. It is important to monitor for hypokalemia as alkalinization can cause potassium to shift from plasma into cells. Potassium levels should be checked every 1-2 hours.

In cases where the salicylate concentration is high (above 500 mg/L in adults or 350 mg/L in children), sodium bicarbonate can be administered intravenously. Hemodialysis is the treatment of choice for severe poisoning and may be indicated in cases of high salicylate levels, resistant metabolic acidosis, acute kidney injury, pulmonary edema, seizures and coma.

Digoxin-specific antibody (DigiFab) is an antidote used to counteract digoxin overdose. It is a purified and sterile preparation of digoxin-immune ovine Fab immunoglobulin fragments. These fragments are derived from healthy sheep that have been immunized with a digoxin derivative called digoxin-dicarboxymethoxylamine (DDMA). DDMA is a digoxin analogue that contains the essential cyclopentanoperhydrophenanthrene: lactone ring moiety coupled to keyhole limpet hemocyanin (KLH).

DigiFab has a higher affinity for digoxin compared to the affinity of digoxin for its sodium pump receptor, which is believed to be the receptor responsible for its therapeutic and toxic effects. When administered to a patient who has overdosed on digoxin, DigiFab binds to digoxin molecules, reducing the levels of free digoxin in the body. This shift in equilibrium away from binding to the receptors helps to reduce the cardiotoxic effects of digoxin. The Fab-digoxin complexes are then eliminated from the body through the kidney and reticuloendothelial system.

The indications for using DigiFab in cases of acute and chronic digoxin toxicity are summarized below:

Acute digoxin toxicity:
– Cardiac arrest
– Life-threatening arrhythmia
– Potassium level >5 mmol/l
– Ingestion of >10 mg of digoxin (in adults)
– Ingestion of >4 mg of digoxin (in children)
– Digoxin level >12 ng/ml

Chronic digoxin toxicity:
– Cardiac arrest
– Life-threatening arrhythmia
– Significant gastrointestinal symptoms
– Symptoms of digoxin toxicity in the presence of renal failure

Activated charcoal prevents the absorption of poisons by absorbing them onto its surface through weak electrostatic forces.

Further Reading:

Poisoning in the emergency department is often caused by accidental or intentional overdose of prescribed drugs. Supportive treatment is the primary approach for managing most poisonings. This includes ensuring a clear airway, proper ventilation, maintaining normal fluid levels, temperature, and blood sugar levels, correcting any abnormal blood chemistry, controlling seizures, and assessing and treating any injuries.

In addition to supportive treatment, clinicians may need to consider strategies for decontamination, elimination, and administration of antidotes. Decontamination involves removing poisons from the skin or gastrointestinal tract. This can be done through rinsing the skin or using methods such as activated charcoal, gastric lavage, induced emesis, or whole bowel irrigation. However, induced emesis is no longer commonly used, while gastric lavage and whole bowel irrigation are rarely used.

Elimination methods include urinary alkalinization, hemodialysis, and hemoperfusion. These techniques help remove toxins from the body.

Activated charcoal is a commonly used method for decontamination. It works by binding toxins in the gastrointestinal tract, preventing their absorption. It is most effective if given within one hour of ingestion. However, it is contraindicated in patients with an insecure airway due to the risk of aspiration. Activated charcoal can be used for many drugs, but it is ineffective for certain poisonings, including pesticides (organophosphates), hydrocarbons, strong acids and alkalis, alcohols (ethanol, methanol, ethylene glycol), iron, lithium, and solvents.

Antidotes are specific treatments for poisoning caused by certain drugs or toxins. For example, cyanide poisoning can be treated with dicobalt edetate, hydroxocobalamin, or sodium nitrite and sodium thiosulphate. Benzodiazepine poisoning can be treated with flumazanil, while opiate poisoning can be treated with naloxone. Other examples include protamine for heparin poisoning, vitamin K or fresh frozen plasma for warfarin poisoning, fomepizole or ethanol for methanol poisoning, and methylene blue for methemoglobinemia caused by benzocaine or nitrates.

There are many other antidotes available for different types of poisoning, and resources such as TOXBASE and the National Poisons Information Service (NPIS) can provide valuable advice on managing poisonings.

Lithium toxicity presents with various symptoms, including nausea and vomiting, diarrhea, tremor, ataxia, confusion, increased muscle tone, clonus, nephrogenic diabetes insipidus, convulsions, coma, and renal failure. One notable symptom associated with digoxin toxicity is xanthopsia.

Statins, although generally safe and well-tolerated, can cause myopathy and myotoxicity. This range of muscle-related side effects can vary from mild muscle pain to the most severe case of rhabdomyolysis, which can lead to kidney failure, blood clotting issues, and even death.

The different levels of myotoxicity associated with statins are as follows:
– Myalgia: muscle symptoms without an increase in creatine kinase (CK) levels.
– Asymptomatic myopathy: elevated CK levels without muscle symptoms.
– Myositis: muscle symptoms with CK levels elevated less than 10 times the upper limit of normal.
– Rhabdomyolysis: muscle symptoms with CK levels elevated more than 10 times the upper limit of normal, potentially leading to myoglobinuria (presence of myoglobin in urine) and renal failure.

Most statins are broken down by the cytochrome P450 enzyme system. When taken with drugs that strongly inhibit this system, the concentration of statins in the blood can significantly increase. This, in turn, raises the risk of myopathy. A well-known example of this is the combination of statins with macrolide antibiotics like erythromycin and clarithromycin. Co-prescribing these drugs with statins has been linked to a higher risk of myopathy, hospitalization due to rhabdomyolysis, acute kidney injury, and increased mortality rates.

Salicylate poisoning is a fairly common form of poisoning that can lead to organ damage and death if not treated promptly. The symptoms of salicylate poisoning include nausea, vomiting, ringing in the ears, hearing loss, excessive sweating, dehydration, rapid breathing, flushed skin, and high fever in children. In severe cases, convulsions, swelling of the brain, coma, kidney failure, fluid in the lungs, and unstable heart function can occur.

The treatment for salicylate poisoning involves stabilizing the patient’s airway, breathing, and circulation as needed, preventing further absorption of the poison, enhancing its elimination from the body, correcting any metabolic abnormalities, and providing supportive care. Unfortunately, there is no specific antidote available for salicylates. If a large amount of salicylate has been ingested within the past hour (more than 4.5 grams in adults or more than 2 grams in children), gastric lavage (stomach pumping) and administration of activated charcoal (50 grams) are recommended to reduce absorption and increase elimination.

Medical investigations for salicylate poisoning should include measuring the level of salicylate in the blood, analyzing arterial blood gases, performing an electrocardiogram (ECG), checking blood glucose levels, assessing kidney function and electrolyte levels, and evaluating blood clotting. ECG abnormalities that may be present include widening of the QRS complex, AV block, and ventricular arrhythmias.

The severity of salicylate poisoning is determined by the level of salicylate in the blood. Mild poisoning is defined as a salicylate level below 450 mg/L, moderate poisoning is between 450-700 mg/L, and severe poisoning is above 700 mg/L. In severe cases, aggressive intravenous fluid therapy is necessary to correct dehydration, and administration of 1.26% sodium bicarbonate can help eliminate the salicylate from the body. It is important to maintain a urine pH of greater than 7.5, ideally between 8.0-8.5. However, forced alkaline diuresis is no longer recommended. Life-threatening cases may require admission to the intensive care unit, intubation and ventilation, and possibly hemodialysis.

Activated charcoal should be given to patients who have ingested paracetamol and meet two criteria: they must present within one hour of ingestion, and they must have taken a dose of paracetamol that is equal to or greater than 150 mg/kg. The recommended dose of activated charcoal is 50g, which is typically administered as 300ml. It is important to note that the dose criteria of 150 mg/kg is based on the amount of paracetamol reported by the patient, not on paracetamol levels, which should not be assessed until at least four hours after ingestion.

Further Reading:

Paracetamol poisoning occurs when the liver is unable to metabolize paracetamol properly, leading to the production of a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI). Normally, NAPQI is conjugated by glutathione into a non-toxic form. However, during an overdose, the liver’s conjugation systems become overwhelmed, resulting in increased production of NAPQI and depletion of glutathione stores. This leads to the formation of covalent bonds between NAPQI and cell proteins, causing cell death in the liver and kidneys.

Symptoms of paracetamol poisoning may not appear for the first 24 hours or may include abdominal symptoms such as nausea and vomiting. After 24 hours, hepatic necrosis may develop, leading to elevated liver enzymes, right upper quadrant pain, and jaundice. Other complications can include encephalopathy, oliguria, hypoglycemia, renal failure, and lactic acidosis.

The management of paracetamol overdose depends on the timing and amount of ingestion. Activated charcoal may be given if the patient presents within 1 hour of ingesting a significant amount of paracetamol. N-acetylcysteine (NAC) is used to increase hepatic glutathione production and is given to patients who meet specific criteria. Blood tests are taken to assess paracetamol levels, liver function, and other parameters. Referral to a medical or liver unit may be necessary, and psychiatric follow-up should be considered for deliberate overdoses.

In cases of staggered ingestion, all patients should be treated with NAC without delay. Blood tests are also taken, and if certain criteria are met, NAC can be discontinued. Adverse reactions to NAC are common and may include anaphylactoid reactions, rash, hypotension, and nausea. Treatment for adverse reactions involves medications such as chlorpheniramine and salbutamol, and the infusion may be stopped if necessary.

The prognosis for paracetamol poisoning can be poor, especially in cases of severe liver injury. Fulminant liver failure may occur, and liver transplant may be necessary. Poor prognostic indicators include low arterial pH, prolonged prothrombin time, high plasma creatinine, and hepatic encephalopathy.

Activated charcoal is a useful treatment for many drug poisonings, but it is not effective against certain types of poisonings. To remember these exceptions, you can use the mnemonic PHAILS. This stands for Pesticides (specifically organophosphates), Hydrocarbons, Acids (strong), alkalis (strong), alcohols (such as ethanol, methanol, and ethylene glycol), Iron, Lithium, and Solvents.

Further Reading:

Poisoning in the emergency department is often caused by accidental or intentional overdose of prescribed drugs. Supportive treatment is the primary approach for managing most poisonings. This includes ensuring a clear airway, proper ventilation, maintaining normal fluid levels, temperature, and blood sugar levels, correcting any abnormal blood chemistry, controlling seizures, and assessing and treating any injuries.

In addition to supportive treatment, clinicians may need to consider strategies for decontamination, elimination, and administration of antidotes. Decontamination involves removing poisons from the skin or gastrointestinal tract. This can be done through rinsing the skin or using methods such as activated charcoal, gastric lavage, induced emesis, or whole bowel irrigation. However, induced emesis is no longer commonly used, while gastric lavage and whole bowel irrigation are rarely used.

Elimination methods include urinary alkalinization, hemodialysis, and hemoperfusion. These techniques help remove toxins from the body.

Activated charcoal is a commonly used method for decontamination. It works by binding toxins in the gastrointestinal tract, preventing their absorption. It is most effective if given within one hour of ingestion. However, it is contraindicated in patients with an insecure airway due to the risk of aspiration. Activated charcoal can be used for many drugs, but it is ineffective for certain poisonings, including pesticides (organophosphates), hydrocarbons, strong acids and alkalis, alcohols (ethanol, methanol, ethylene glycol), iron, lithium, and solvents.

Antidotes are specific treatments for poisoning caused by certain drugs or toxins. For example, cyanide poisoning can be treated with dicobalt edetate, hydroxocobalamin, or sodium nitrite and sodium thiosulphate. Benzodiazepine poisoning can be treated with flumazanil, while opiate poisoning can be treated with naloxone. Other examples include protamine for heparin poisoning, vitamin K or fresh frozen plasma for warfarin poisoning, fomepizole or ethanol for methanol poisoning, and methylene blue for methemoglobinemia caused by benzocaine or nitrates.

There are many other antidotes available for different types of poisoning, and resources such as TOXBASE and the National Poisons Information Service (NPIS) can provide valuable advice on managing poisonings.

Cytochrome p450 enzyme inhibitors have the ability to enhance the effects of warfarin, leading to an increase in the International Normalized Ratio (INR). To remember the commonly encountered cytochrome p450 enzyme inhibitors, the mnemonic O DEVICES can be utilized. Each letter in the mnemonic represents a specific inhibitor: O for Omeprazole, D for Disulfiram, E for Erythromycin (as well as other macrolide antibiotics), V for Valproate (specifically sodium valproate), I for Isoniazid, C for Ciprofloxacin, E for Ethanol (when consumed acutely), and S for Sulphonamides.

Sodium valproate is considered the most high-risk anti-epileptic drug during pregnancy. A recent review found that up to 40% of children born to women who took sodium valproate while pregnant experienced some form of adverse effect. These effects include a 1.5% risk of neural tube defects and an increased risk of cardiac, craniofacial, and limb defects. Additionally, there is a significant risk of neurodevelopmental problems in childhood.

Here is a list outlining the commonly encountered drugs that have adverse effects during pregnancy:

ACE inhibitors (e.g. ramipril): If given in the second and third trimester, these drugs can cause hypoperfusion, renal failure, and the oligohydramnios sequence.

Aminoglycosides (e.g. gentamicin): These drugs can cause ototoxicity and deafness in the fetus.

Aspirin: High doses of aspirin can lead to first-trimester abortions, delayed onset labor, premature closure of the fetal ductus arteriosus, and fetal kernicterus. However, low doses (e.g. 75 mg) do not pose a significant risk.

Benzodiazepines (e.g. diazepam): When given late in pregnancy, these drugs can cause respiratory depression and a neonatal withdrawal syndrome.

Calcium-channel blockers: If given in the first trimester, these drugs can cause phalangeal abnormalities. If given in the second and third trimester, they can lead to fetal growth retardation.

Carbamazepine: This drug can cause hemorrhagic disease of the newborn and neural tube defects.

Chloramphenicol: Use of this drug can result in gray baby syndrome.

Corticosteroids: If given in the first trimester, corticosteroids may cause orofacial clefts in the fetus.

Danazol: If given in the first trimester, this drug can cause masculinization of the female fetuses genitals.

Finasteride: Pregnant women should avoid handling finasteride as crushed or broken tablets can be absorbed through the skin and affect male sex organ development.

Haloperidol: If given in the first trimester, this drug may cause limb malformations. If given in the third trimester, there is an increased risk of extrapyramidal symptoms in the neonate.

Heparin: Maternal bleeding and thrombocytopenia are potential adverse outcomes.

Theophylline is a medication used to treat severe asthma. It is a bronchodilator that comes in modified-release forms, which can maintain therapeutic levels in the blood for 12 hours. Theophylline works by inhibiting phosphodiesterase and blocking the breakdown of cyclic AMP. It also competes with adenosine on A1 and A2 receptors.

Achieving the right dose of theophylline can be challenging because there is a narrow range between therapeutic and toxic levels. The half-life of theophylline can be influenced by various factors, further complicating dosage adjustments. It is recommended to aim for serum levels of 10-20 mg/l six to eight hours after the last dose.

Unlike many other medications, the specific brand of theophylline can significantly impact its effects. Therefore, it is important to prescribe theophylline by both its brand name and generic name.

Several factors can increase the half-life of theophylline, including heart failure, cirrhosis, viral infections, and certain drugs. Conversely, smoking, heavy drinking, and certain medications can decrease the half-life of theophylline.

There are several drugs that can either increase or decrease the plasma concentration of theophylline. Calcium channel blockers, cimetidine, fluconazole, macrolides, methotrexate, and quinolones can increase the concentration. On the other hand, carbamazepine, phenobarbitol, phenytoin, rifampicin, and St. John’s wort can decrease the concentration.

The clinical symptoms of theophylline toxicity are more closely associated with acute overdose rather than chronic overexposure. Common symptoms include headache, dizziness, nausea, vomiting, abdominal pain, rapid heartbeat, dysrhythmias, seizures, mild metabolic acidosis, low potassium, low magnesium, low phosphates, abnormal calcium levels, and high blood sugar.

Seizures are more prevalent in acute overdose cases, while chronic overdose typically presents with minimal gastrointestinal symptoms. Cardiac dysrhythmias are more common in chronic overdose situations compared to acute overdose.

Urinary alkalinisation, which involves the intravenous administration of sodium bicarbonate, carries the risk of hypokalaemia. It is important to note that both alkalosis and acidosis can cause shifts in potassium levels. In the case of alkalinisation, potassium is shifted from the plasma into the cells. Therefore, it is crucial to closely monitor the patient for hypokalaemia by checking their potassium levels every 1-2 hours.

Further Reading:

Salicylate poisoning, particularly from aspirin overdose, is a common cause of poisoning in the UK. One important concept to understand is that salicylate overdose leads to a combination of respiratory alkalosis and metabolic acidosis. Initially, the overdose stimulates the respiratory center, leading to hyperventilation and respiratory alkalosis. However, as the effects of salicylate on lactic acid production, breakdown into acidic metabolites, and acute renal injury occur, it can result in high anion gap metabolic acidosis.

The clinical features of salicylate poisoning include hyperventilation, tinnitus, lethargy, sweating, pyrexia (fever), nausea/vomiting, hyperglycemia and hypoglycemia, seizures, and coma.

When investigating salicylate poisoning, it is important to measure salicylate levels in the blood. The sample should be taken at least 2 hours after ingestion for symptomatic patients or 4 hours for asymptomatic patients. The measurement should be repeated every 2-3 hours until the levels start to decrease. Other investigations include arterial blood gas analysis, electrolyte levels (U&Es), complete blood count (FBC), coagulation studies (raised INR/PTR), urinary pH, and blood glucose levels.

To manage salicylate poisoning, an ABC approach should be followed to ensure a patent airway and adequate ventilation. Activated charcoal can be administered if the patient presents within 1 hour of ingestion. Oral or intravenous fluids should be given to optimize intravascular volume. Hypokalemia and hypoglycemia should be corrected. Urinary alkalinization with intravenous sodium bicarbonate can enhance the elimination of aspirin in the urine. In severe cases, hemodialysis may be necessary.

Urinary alkalinization involves targeting a urinary pH of 7.5-8.5 and checking it hourly. It is important to monitor for hypokalemia as alkalinization can cause potassium to shift from plasma into cells. Potassium levels should be checked every 1-2 hours.

In cases where the salicylate concentration is high (above 500 mg/L in adults or 350 mg/L in children), sodium bicarbonate can be administered intravenously. Hemodialysis is the treatment of choice for severe poisoning and may be indicated in cases of high salicylate levels, resistant metabolic acidosis, acute kidney injury, pulmonary edema, seizures and coma.

Beta-blockers, like bisoprolol, and verapamil have a strong negative effect on the force of ventricular contraction. When these medications are taken together, they can significantly reduce ventricular contraction and lead to a slow heart rate, known as bradycardia. Additionally, the risk of developing AV block is increased. In certain situations, this combination can result in severe low blood pressure or even a complete absence of heart rhythm, known as asystole. Therefore, it is important to avoid using these medications together to prevent these potentially dangerous effects.

The standard drug regimen for tuberculosis is generally safe to use during pregnancy, with the exception of streptomycin which should be avoided. However, the use of isoniazid during pregnancy has been associated with potential risks such as liver damage in the mother and the possibility of neuropathy and seizures in the newborn.

Here is a list outlining some commonly encountered drugs that have adverse effects during pregnancy:

ACE inhibitors (e.g. ramipril): If taken during the second and third trimesters, these medications can lead to reduced blood flow, kidney failure, and a condition called oligohydramnios.

Aminoglycosides (e.g. gentamicin): These drugs can cause ototoxicity, resulting in hearing loss in the baby.

Aspirin: High doses of aspirin can increase the risk of first trimester abortions, delayed labor, premature closure of the fetal ductus arteriosus, and a condition called fetal kernicterus. However, low doses (e.g. 75 mg) do not pose significant risks.

Benzodiazepines (e.g. diazepam): When taken late in pregnancy, these medications can cause respiratory depression in the baby and lead to a withdrawal syndrome.

Calcium-channel blockers: If taken during the first trimester, these drugs can cause abnormalities in the fingers and toes. If taken during the second and third trimesters, they may result in fetal growth retardation.

Carbamazepine: This medication can increase the risk of hemorrhagic disease in the newborn and neural tube defects.

Chloramphenicol: Use of this drug in newborns can lead to a condition known as grey baby syndrome.

Corticosteroids: If taken during the first trimester, corticosteroids may increase the risk of orofacial clefts in the baby.

Danazol: When taken during the first trimester, this medication can cause masculinization of the female fetuses genitals.

Finasteride: Pregnant women should avoid handling crushed or broken tablets of finasteride as it can be absorbed through the skin and affect the development of male sex organs in the baby.

Haloperidol: If taken during the first trimester, this medication may increase the risk of limb malformations. If taken during the third trimester, it can lead to an increased risk of extrapyramidal symptoms in the newborn.

Heparin: Use of heparin during pregnancy is associated with an acceptable bleeding rate and a low rate of thrombotic recurrence in the mother.

Carboxyhaemoglobin (COHb) blood levels are utilized for the identification of carbon monoxide poisoning. COHb is the substance produced when carbon monoxide attaches to haemoglobin. It is important to note that carbaminohemoglobin (also known as carbaminohaemoglobin, carboxyhemoglobin, and carbohemoglobin) is the compound formed when carbon dioxide binds to hemoglobin, and should not be mistaken for COHb.

Further Reading:

Carbon monoxide (CO) is a dangerous gas that is produced by the combustion of hydrocarbon fuels and can be found in certain chemicals. It is colorless and odorless, making it difficult to detect. In England and Wales, there are approximately 60 deaths each year due to accidental CO poisoning.

When inhaled, carbon monoxide binds to haemoglobin in the blood, forming carboxyhaemoglobin (COHb). It has a higher affinity for haemoglobin than oxygen, causing a left-shift in the oxygen dissociation curve and resulting in tissue hypoxia. This means that even though there may be a normal level of oxygen in the blood, it is less readily released to the tissues.

The clinical features of carbon monoxide toxicity can vary depending on the severity of the poisoning. Mild or chronic poisoning may present with symptoms such as headache, nausea, vomiting, vertigo, confusion, and weakness. More severe poisoning can lead to intoxication, personality changes, breathlessness, pink skin and mucosae, hyperpyrexia, arrhythmias, seizures, blurred vision or blindness, deafness, extrapyramidal features, coma, or even death.

To help diagnose domestic carbon monoxide poisoning, there are four key questions that can be asked using the COMA acronym. These questions include asking about co-habitees and co-occupants in the house, whether symptoms improve outside of the house, the maintenance of boilers and cooking appliances, and the presence of a functioning CO alarm.

Typical carboxyhaemoglobin levels can vary depending on whether the individual is a smoker or non-smoker. Non-smokers typically have levels below 3%, while smokers may have levels below 10%. Symptomatic individuals usually have levels between 10-30%, and severe toxicity is indicated by levels above 30%.

When managing carbon monoxide poisoning, the first step is to administer 100% oxygen. Hyperbaric oxygen therapy may be considered for individuals with a COHb concentration of over 20% and additional risk factors such as loss of consciousness, neurological signs, myocardial ischemia or arrhythmia, or pregnancy. Other management strategies may include fluid resuscitation, sodium bicarbonate for metabolic acidosis, and mannitol for cerebral edema.

This patient exhibits clinical features that are consistent with the ingestion of a drug that blocks the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. There are several anticholinergic drugs commonly used in clinical practice. Some examples include antihistamines like promethazine and diphenhydramine, typical and atypical antipsychotics such as haloperidol and quetiapine, anticonvulsants like carbamazepine, antidepressants like tricyclic antidepressants, and antispasmodics like hyoscine butylbromide. Other sources of anticholinergic effects can come from plants like datura species and certain mushrooms.

When someone ingests an anticholinergic drug, they may experience a toxidrome, which is characterized by an agitated delirium and various signs of acetylcholine receptor blockade in both the central and peripheral nervous system. The central inhibition leads to an agitated delirium, which is marked by fluctuating mental status, confusion, restlessness, visual hallucinations, picking at objects in the air, mumbling, slurred speech, disruptive behavior, tremor, myoclonus, and in rare cases, coma and seizures. The peripheral inhibition can cause dilated pupils, sinus tachycardia, dry mouth, hot and flushed skin, increased body temperature, urinary retention, and ileus.

In summary, the ingestion of an anticholinergic drug can result in a toxidrome characterized by an agitated delirium and various signs of central and peripheral acetylcholine receptor blockade. It is important to be aware of the potential effects of these drugs and to recognize the clinical features associated with their ingestion.

To ensure prompt response in case of an adverse reaction, it is important to have adrenaline, antihistamine, and steroid readily available when administering Zagreb antivenom.

Further Reading:

Snake bites in the UK are primarily caused by the adder, which is the only venomous snake species native to the country. While most adder bites result in minor symptoms such as pain, swelling, and inflammation, there have been cases of life-threatening illness and fatalities. Additionally, there are instances where venomous snakes that are kept legally or illegally also cause bites in the UK.

Adder bites typically occur from early spring to late autumn, with the hand being the most common site of the bite. Symptoms can be local or systemic, with local symptoms including sharp pain, tingling or numbness, and swelling that spreads proximally. Systemic symptoms may include spreading pain, tenderness, inflammation, regional lymph node enlargement, and bruising. In severe cases, anaphylaxis can occur, leading to symptoms such as nausea, vomiting, abdominal pain, diarrhea, and shock.

It is important for clinicians to be aware of the potential complications and complications associated with adder bites. These can include acute renal failure, pulmonary and cerebral edema, acute gastric dilatation, paralytic ileus, acute pancreatitis, and coma and seizures. Anaphylaxis symptoms can appear within minutes or be delayed for hours, and hypotension is a critical sign to monitor.

Initial investigations for adder bites include blood tests, ECG, and vital sign monitoring. Further investigations such as chest X-ray may be necessary based on clinical signs. Blood tests may reveal abnormalities such as leukocytosis, raised hematocrit, anemia, thrombocytopenia, and abnormal clotting profile. ECG changes may include tachyarrhythmias, bradyarrhythmias, atrial fibrillation, and ST segment changes.

First aid measures at the scene include immobilizing the patient and the bitten limb, avoiding aspirin and ibuprofen, and cleaning the wound site in the hospital. Tetanus prophylaxis should be considered. In cases of anaphylaxis, prompt administration of IM adrenaline is necessary. In the hospital, rapid assessment and appropriate resuscitation with intravenous fluids are required.

Antivenom may be indicated in cases of hypotension, systemic envenoming, ECG abnormalities, peripheral neutrophil leucocytosis, elevated serum creatine kinase or metabolic acidosis, and extensive or rapidly spreading local swelling. Zagreb antivenom is commonly used in the UK, with an initial dose of 8 mL.

Calcium-channel blocker overdose is a serious condition that can be life-threatening. The most dangerous types of calcium channel blockers in overdose are verapamil and diltiazem. These medications work by binding to the alpha-1 subunit of L-type calcium channels, which prevents the entry of calcium into cells. These channels are important for the functioning of cardiac myocytes, vascular smooth muscle cells, and islet beta-cells.

When managing a patient with calcium-channel blocker overdose, it is crucial to follow the standard ABC approach for resuscitation. If there is a risk of life-threatening toxicity, early intubation and ventilation should be considered. Invasive blood pressure monitoring is also necessary if hypotension and shock are developing.

The specific treatments for calcium-channel blocker overdose primarily focus on supporting the cardiovascular system. These treatments include:

1. Fluid resuscitation: Administer up to 20 mL/kg of crystalloid solution.

2. Calcium administration: This can temporarily increase blood pressure and heart rate. Options include 10% calcium gluconate (60 mL IV) or 10% calcium chloride (20 mL IV) via central venous access. Repeat boluses can be given up to three times, and a calcium infusion may be necessary to maintain serum calcium levels above 2.0 mEq/L.

3. Atropine: Consider administering 0.6 mg every 2 minutes, up to a total of 1.8 mg. However, atropine is often ineffective in these cases.

4. High dose insulin – euglycemic therapy (HIET): The use of HIET in managing cardiovascular toxicity has evolved. It used to be a last-resort measure, but early administration is now increasingly recommended. This involves giving a bolus of short-acting insulin (1 U/kg) and 50 mL of 50% glucose IV (unless there is marked hyperglycemia). Therapy should be continued with a short-acting insulin/dextrose infusion. Glucose levels should be monitored frequently, and potassium should be replaced if levels drop below 2.5 mmol/L.

5. Vasoactive infusions: Catecholamines such as dopamine, adrenaline, and/or noradrenaline can be titrated to achieve the desired inotropic and chronotropic effects.

6. Sodium bicarbonate: Consider using sodium bicarbonate in cases where a severe metabolic acidosis develops.

The use of tetracyclines is not recommended during pregnancy as it can have harmful effects on the developing fetus. When taken during the second half of pregnancy, tetracyclines may lead to permanent yellow-grey discoloration of the teeth and enamel hypoplasia. Children affected by this may also be more prone to cavities. Additionally, tetracyclines have been associated with congenital defects, problems with bone growth, and liver toxicity in pregnant women.

Here is a list outlining the commonly encountered drugs that can have adverse effects during pregnancy:

ACE inhibitors (e.g. ramipril): If taken in the second and third trimesters, ACE inhibitors can cause reduced blood flow, kidney failure, and a condition called oligohydramnios.

Aminoglycosides (e.g. gentamicin): Aminoglycosides can cause ototoxicity, leading to hearing loss in the fetus.

Aspirin: High doses of aspirin can result in first trimester abortions, delayed labor, premature closure of the fetal ductus arteriosus, and a condition called fetal kernicterus. However, low doses (e.g. 75 mg) do not pose significant risks.

Benzodiazepines (e.g. diazepam): When taken late in pregnancy, benzodiazepines can cause respiratory depression in the newborn and a withdrawal syndrome.

Calcium-channel blockers: If taken in the first trimester, calcium-channel blockers can cause abnormalities in the fingers and toes. If taken in the second and third trimesters, they can lead to fetal growth retardation.

Carbamazepine: Carbamazepine has been associated with a condition called hemorrhagic disease of the newborn and an increased risk of neural tube defects.

Chloramphenicol: Chloramphenicol can cause a condition known as grey baby syndrome in newborns.

Corticosteroids: If taken in the first trimester, corticosteroids may increase the risk of orofacial clefts in the fetus.

Danazol: When taken in the first trimester, danazol can cause masculinization of the female fetuses genitals.

Finasteride: Pregnant women should avoid handling finasteride tablets as the drug can be absorbed through the skin and affect the development of male sex organs in the fetus.

Haloperidol: If taken during the first trimester, this medication may increase the risk of limb malformations. If taken during the third trimester, it can lead to an increased risk of extrapyramidal symptoms in the newborn.

Prolonged QRS duration is associated with an increased risk of seizures and arrhythmia. Therefore, when QRS prolongation is observed, it is recommended to consider initiating treatment with sodium bicarbonate.

Further Reading:

Tricyclic antidepressant (TCA) overdose is a common occurrence in emergency departments, with drugs like amitriptyline and dosulepin being particularly dangerous. TCAs work by inhibiting the reuptake of norepinephrine and serotonin in the central nervous system. In cases of toxicity, TCAs block various receptors, including alpha-adrenergic, histaminic, muscarinic, and serotonin receptors. This can lead to symptoms such as hypotension, altered mental state, signs of anticholinergic toxicity, and serotonin receptor effects.

TCAs primarily cause cardiac toxicity by blocking sodium and potassium channels. This can result in a slowing of the action potential, prolongation of the QRS complex, and bradycardia. However, the blockade of muscarinic receptors also leads to tachycardia in TCA overdose. QT prolongation and Torsades de Pointes can occur due to potassium channel blockade. TCAs can also have a toxic effect on the myocardium, causing decreased cardiac contractility and hypotension.

Early symptoms of TCA overdose are related to their anticholinergic properties and may include dry mouth, pyrexia, dilated pupils, agitation, sinus tachycardia, blurred vision, flushed skin, tremor, and confusion. Severe poisoning can lead to arrhythmias, seizures, metabolic acidosis, and coma. ECG changes commonly seen in TCA overdose include sinus tachycardia, widening of the QRS complex, prolongation of the QT interval, and an R/S ratio >0.7 in lead aVR.

Management of TCA overdose involves ensuring a patent airway, administering activated charcoal if ingestion occurred within 1 hour and the airway is intact, and considering gastric lavage for life-threatening cases within 1 hour of ingestion. Serial ECGs and blood gas analysis are important for monitoring. Intravenous fluids and correction of hypoxia are the first-line therapies. IV sodium bicarbonate is used to treat haemodynamic instability caused by TCA overdose, and benzodiazepines are the treatment of choice for seizure control. Other treatments that may be considered include glucagon, magnesium sulfate, and intravenous lipid emulsion.

There are certain things to avoid in TCA overdose, such as anti-arrhythmics like quinidine and flecainide, as they can prolonged depolarization.

Prolongation of the QT interval can lead to a dangerous ventricular arrhythmia called torsades de pointes, which can result in sudden cardiac death. There are several commonly used medications that are known to cause QT prolongation.

Low levels of potassium (hypokalaemia) and magnesium (hypomagnesaemia) can increase the risk of QT prolongation. For example, diuretics can interact with QT-prolonging drugs by causing hypokalaemia.

The QT interval varies with heart rate, and formulas are used to correct the QT interval for heart rate. Once corrected, it is referred to as the QTc interval. The QTc interval is typically reported on the ECG printout. A normal QTc interval is less than 440 ms.

If the QTc interval is greater than 440 ms but less than 500 ms, it is considered borderline. Although there may be some variation in the literature, a QTc interval within these values is generally considered borderline prolonged. In such cases, it is important to consider reducing the dose of QT-prolonging drugs or switching to an alternative medication that does not prolong the QT interval.

A prolonged QTc interval exceeding 500 ms is clinically significant and is likely to increase the risk of arrhythmia. Any medications that prolong the QT interval should be reviewed immediately.

Here are some commonly encountered drugs that are known to prolong the QT interval:

Antimicrobials:
– Erythromycin
– Clarithromycin
– Moxifloxacin
– Fluconazole
– Ketoconazole

Antiarrhythmics:
– Dronedarone
– Sotalol
– Quinidine
– Amiodarone
– Flecainide

Antipsychotics:
– Risperidone
– Fluphenazine
– Haloperidol
– Pimozide
– Chlorpromazine
– Quetiapine
– Clozapine

Antidepressants:
– Citalopram/escitalopram
– Amitriptyline
– Clomipramine
– Dosulepin
– Doxepin
– Imipramine
– Lofepramine

Antiemetics:
– Domperidone
– Droperidol
– Ondansetron/Granisetron

Others:
– Methadone
– Protein kinase inhibitors (e.g. sunitinib)

Atropine and pralidoxime are both considered antidotes for treating organophosphate poisoning. Organophosphates work by inhibiting acetylcholinesterase at nerve synapses. In addition to providing supportive care and administering antidotes, it is important to decontaminate patients as part of their treatment plan for organophosphate poisoning.

While both atropine and pralidoxime are recognized as antidotes, pralidoxime is not commonly used. Atropine works by competing with acetylcholine at the muscarinic receptors. On the other hand, pralidoxime helps reactivate acetylcholinesterase-organophosphate complexes that have not lost an alkyl side chain, known as non-aged complexes. However, pralidoxime is not effective against organophosphates that have already formed or rapidly form aged acetylcholinesterase complexes. The evidence regarding the effectiveness of pralidoxime is conflicting.

Further Reading:

Chemical incidents can occur as a result of leaks, spills, explosions, fires, terrorism, or the use of chemicals during wars. Industrial sites that use chemicals are required to conduct risk assessments and have accident plans in place for such incidents. Health services are responsible for decontamination, unless mass casualties are involved, and all acute health trusts must have major incident plans in place.

When responding to a chemical incident, hospitals prioritize containment of the incident and prevention of secondary contamination, triage with basic first aid, decontamination if not done at the scene, recognition and management of toxidromes (symptoms caused by exposure to specific toxins), appropriate supportive or antidotal treatment, transfer to definitive treatment, a safe end to the hospital response, and continuation of business after the event.

To obtain advice when dealing with chemical incidents, the two main bodies are Toxbase and the National Poisons Information Service. Signage on containers carrying chemicals and material safety data sheets (MSDS) accompanying chemicals also provide information on the chemical contents and their hazards.

Contamination in chemical incidents can occur in three phases: primary contamination from the initial incident, secondary contamination spread via contaminated people leaving the initial scene, and tertiary contamination spread to the environment, including becoming airborne and waterborne. The ideal personal protective equipment (PPE) for chemical incidents is an all-in-one chemical-resistant overall with integral head/visor and hands/feet worn with a mask, gloves, and boots.

Decontamination of contaminated individuals involves the removal and disposal of contaminated clothing, followed by either dry or wet decontamination. Dry decontamination is suitable for patients contaminated with non-caustic chemicals and involves blotting and rubbing exposed skin gently with dry absorbent material. Wet decontamination is suitable for patients contaminated with caustic chemicals and involves a warm water shower while cleaning the body with simple detergent.

After decontamination, the focus shifts to assessing the extent of any possible poisoning and managing it. The patient’s history should establish the chemical the patient was exposed to, the volume and concentration of the chemical, the route of exposure, any protective measures in place, and any treatment given. Most chemical poisonings require supportive care using standard resuscitation principles, while some chemicals have specific antidotes. Identifying toxidromes can be useful in guiding treatment, and specific antidotes may be administered accordingly.

The Arthus reaction is a response that occurs when antigen/antibody complexes are formed in the skin after an antigen is injected. Although rare, these reactions can happen after receiving vaccines that contain tetanus toxoid or diphtheria toxoid. They are classified as a type III hypersensitivity reaction.

Arthus reactions are characterized by pain, swelling, induration, hemorrhage, and sometimes necrosis. Typically, these symptoms appear 4-12 hours after vaccination.

Type III hypersensitivity reactions occur when insoluble antigen-antibody complexes accumulate in different tissues and are not effectively cleared by the body’s innate immune cells. This leads to an inflammatory response in the affected tissues.

Some other examples of type III hypersensitivity reactions include immune complex glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, serum sickness, and extrinsic allergic alveolitis.

Verapamil is a type of calcium-channel blocker that is commonly used to treat irregular heart rhythms and chest pain. It is important to note that verapamil should not be taken at the same time as beta-blockers like atenolol and bisoprolol. This is because when these medications are combined, they can have a negative impact on the heart’s ability to contract and the heart rate, leading to a significant drop in blood pressure, slow heart rate, impaired conduction between the upper and lower chambers of the heart, heart failure (due to decreased ability of the heart to pump effectively), and even a pause in the heart’s normal rhythm. For more information, you can refer to the section on verapamil interactions in the British National Formulary (BNF).

Lipid emulsion is known to cause pancreatitis as a common side effect. According to the AAGBI guidelines, patients who are given lipid emulsion should be closely monitored with regular clinical evaluations. This includes conducting amylase or lipase tests daily for two days after receiving the emulsion.

Further Reading:

Local anaesthetics, such as lidocaine, bupivacaine, and prilocaine, are commonly used in the emergency department for topical or local infiltration to establish a field block. Lidocaine is often the first choice for field block prior to central line insertion. These anaesthetics work by blocking sodium channels, preventing the propagation of action potentials.

However, local anaesthetics can enter the systemic circulation and cause toxic side effects if administered in high doses. Clinicians must be aware of the signs and symptoms of local anaesthetic systemic toxicity (LAST) and know how to respond. Early signs of LAST include numbness around the mouth or tongue, metallic taste, dizziness, visual and auditory disturbances, disorientation, and drowsiness. If not addressed, LAST can progress to more severe symptoms such as seizures, coma, respiratory depression, and cardiovascular dysfunction.

The management of LAST is largely supportive. Immediate steps include stopping the administration of local anaesthetic, calling for help, providing 100% oxygen and securing the airway, establishing IV access, and controlling seizures with benzodiazepines or other medications. Cardiovascular status should be continuously assessed, and conventional therapies may be used to treat hypotension or arrhythmias. Intravenous lipid emulsion (intralipid) may also be considered as a treatment option.

If the patient goes into cardiac arrest, CPR should be initiated following ALS arrest algorithms, but lidocaine should not be used as an anti-arrhythmic therapy. Prolonged resuscitation may be necessary, and intravenous lipid emulsion should be administered. After the acute episode, the patient should be transferred to a clinical area with appropriate equipment and staff for further monitoring and care.

It is important to report cases of local anaesthetic toxicity to the appropriate authorities, such as the National Patient Safety Agency in the UK or the Irish Medicines Board in the Republic of Ireland. Additionally, regular clinical review should be conducted to exclude pancreatitis, as intravenous lipid emulsion can interfere with amylase or lipase assays.

Antipsychotics and antidepressants are drugs that are known to cause QT prolongation, which is a potentially dangerous heart rhythm abnormality. Similarly, SSRIs and other antidepressants are also associated with QT prolongation. On the other hand, beta-blockers like bisoprolol are used to shorten the QT interval and are considered as a treatment option for long QT syndrome. However, it’s important to note that sotalol, although classified as a beta blocker, acts differently by blocking potassium channels. This unique mechanism of action makes sotalol a class III anti-arrhythmic agent and may result in QT interval prolongation.

Further Reading:

Long QT syndrome (LQTS) is a condition characterized by a prolonged QT interval on an electrocardiogram (ECG), which represents abnormal repolarization of the heart. LQTS can be either acquired or congenital. Congenital LQTS is typically caused by gene abnormalities that affect ion channels responsible for potassium or sodium flow in the heart. There are 15 identified genes associated with congenital LQTS, with three genes accounting for the majority of cases. Acquired LQTS can be caused by various factors such as certain medications, electrolyte imbalances, hypothermia, hypothyroidism, and bradycardia from other causes.

The normal QTc values, which represent the corrected QT interval for heart rate, are typically less than 450 ms for men and less than 460ms for women. Prolonged QTc intervals are considered to be greater than these values. It is important to be aware of drugs that can cause QT prolongation, as this can lead to potentially fatal arrhythmias. Some commonly used drugs that can cause QT prolongation include antimicrobials, antiarrhythmics, antipsychotics, antidepressants, antiemetics, and others.

Management of long QT syndrome involves addressing any underlying causes and using beta blockers. In some cases, an implantable cardiac defibrillator (ICD) may be recommended for patients who have experienced recurrent arrhythmic syncope, documented torsades de pointes, previous ventricular tachyarrhythmias or torsades de pointes, previous cardiac arrest, or persistent syncope. Permanent pacing may be used in patients with bradycardia or atrioventricular nodal block and prolonged QT. Mexiletine is a treatment option for those with LQT3. Cervicothoracic sympathetic denervation may be considered in patients with recurrent syncope despite beta-blockade or in those who are not ideal candidates for an ICD. The specific treatment options for LQTS depend on the type and severity of the condition.

Grey baby syndrome is a rare but serious side effect that can occur in neonates, especially premature babies, as a result of the build-up of the antibiotic chloramphenicol. This condition is characterized by several symptoms, including ashen grey skin color, poor feeding, vomiting, cyanosis, hypotension, hypothermia, hypotonia, cardiovascular collapse, abdominal distension, and respiratory difficulties.

During pregnancy, there are several drugs that can have adverse effects on the developing fetus. ACE inhibitors, such as ramipril, if given in the second and third trimesters, can lead to hypoperfusion, renal failure, and the oligohydramnios sequence. Aminoglycosides, like gentamicin, can cause ototoxicity and deafness. High doses of aspirin can result in first-trimester abortions, delayed onset labor, premature closure of the fetal ductus arteriosus, and fetal kernicterus. However, low doses of aspirin (e.g., 75 mg) do not pose significant risks.

Benzodiazepines, such as diazepam, when administered late in pregnancy, can cause respiratory depression and a neonatal withdrawal syndrome. Calcium-channel blockers, if given in the first trimester, may lead to phalangeal abnormalities, while their use in the second and third trimesters can result in fetal growth retardation. Carbamazepine can cause hemorrhagic disease of the newborn and neural tube defects.

Chloramphenicol, as mentioned earlier, can cause grey baby syndrome. Corticosteroids, if given in the first trimester, may cause orofacial clefts. Danazol, if administered in the first trimester, can cause masculinization of the female fetuses genitals. Pregnant women should avoid handling crushed or broken tablets of finasteride, as it can be absorbed through the skin and affect male sex organ development.

Haloperidol, if given in the first trimester, may cause limb malformations, while its use in the third trimester increases the risk of extrapyramidal symptoms in the neonate. Heparin can lead to maternal bleeding and thrombocytopenia. Isoniazid can cause maternal liver damage and neuropathy and seizures in the neonate. Isotretinoin carries a high risk of teratogenicity, including multiple congenital malformations, spontaneous abortion, and intellectual disability.

When it comes to managing seizures in cases of TCA overdose, benzodiazepines are considered the most effective treatment. Diazepam or lorazepam are commonly administered for this purpose. However, it’s important to note that lamotrigine and carbamazepine are typically used for preventing seizures rather than for immediate seizure control.

Further Reading:

Tricyclic antidepressant (TCA) overdose is a common occurrence in emergency departments, with drugs like amitriptyline and dosulepin being particularly dangerous. TCAs work by inhibiting the reuptake of norepinephrine and serotonin in the central nervous system. In cases of toxicity, TCAs block various receptors, including alpha-adrenergic, histaminic, muscarinic, and serotonin receptors. This can lead to symptoms such as hypotension, altered mental state, signs of anticholinergic toxicity, and serotonin receptor effects.

TCAs primarily cause cardiac toxicity by blocking sodium and potassium channels. This can result in a slowing of the action potential, prolongation of the QRS complex, and bradycardia. However, the blockade of muscarinic receptors also leads to tachycardia in TCA overdose. QT prolongation and Torsades de Pointes can occur due to potassium channel blockade. TCAs can also have a toxic effect on the myocardium, causing decreased cardiac contractility and hypotension.

Early symptoms of TCA overdose are related to their anticholinergic properties and may include dry mouth, pyrexia, dilated pupils, agitation, sinus tachycardia, blurred vision, flushed skin, tremor, and confusion. Severe poisoning can lead to arrhythmias, seizures, metabolic acidosis, and coma. ECG changes commonly seen in TCA overdose include sinus tachycardia, widening of the QRS complex, prolongation of the QT interval, and an R/S ratio >0.7 in lead aVR.

Management of TCA overdose involves ensuring a patent airway, administering activated charcoal if ingestion occurred within 1 hour and the airway is intact, and considering gastric lavage for life-threatening cases within 1 hour of ingestion. Serial ECGs and blood gas analysis are important for monitoring. Intravenous fluids and correction of hypoxia are the first-line therapies. IV sodium bicarbonate is used to treat haemodynamic instability caused by TCA overdose, and benzodiazepines are the treatment of choice for seizure control. Other treatments that may be considered include glucagon, magnesium sulfate, and intravenous lipid emulsion.

There are certain things to avoid in TCA overdose, such as anti-arrhythmics like quinidine and flecainide, as they can prolonged depolarization.

Clozapine is the atypical antipsychotic that is most likely to result in notable weight gain. Additionally, it is linked to the emergence of impaired glucose metabolism and metabolic syndrome.

Prolongation of the QT interval can lead to a dangerous ventricular arrhythmia called torsades de pointes, which can result in sudden cardiac death. There are several commonly used medications that are known to cause QT prolongation.

Low levels of potassium (hypokalaemia) and magnesium (hypomagnesaemia) can increase the risk of QT prolongation. For example, diuretics can interact with QT-prolonging drugs by causing hypokalaemia.

The QT interval varies with heart rate, and formulas are used to correct the QT interval for heart rate. Once corrected, it is referred to as the QTc interval. The QTc interval is typically reported on the ECG printout. A normal QTc interval is less than 440 ms.

If the QTc interval is greater than 440 ms but less than 500 ms, it is considered borderline. Although there may be some variation in the literature, a QTc interval within these values is generally considered borderline prolonged. In such cases, it is important to consider reducing the dose of QT-prolonging drugs or switching to an alternative medication that does not prolong the QT interval.

A prolonged QTc interval exceeding 500 ms is clinically significant and is likely to increase the risk of arrhythmia. Any medications that prolong the QT interval should be reviewed immediately.

Here are some commonly encountered drugs that are known to prolong the QT interval:

Antimicrobials:
– Erythromycin
– Clarithromycin
– Moxifloxacin
– Fluconazole
– Ketoconazole

Antiarrhythmics:
– Dronedarone
– Sotalol
– Quinidine
– Amiodarone
– Flecainide

Antipsychotics:
– Risperidone
– Fluphenazine
– Haloperidol
– Pimozide
– Chlorpromazine
– Quetiapine
– Clozapine

Antidepressants:
– Citalopram/escitalopram
– Amitriptyline
– Clomipramine
– Dosulepin
– Doxepin
– Imipramine
– Lofepramine

Antiemetics:
– Domperidone
– Droperidol
– Ondansetron/Granisetron

Others:
– Methadone
– Protein kinase inhibitors (e.g. sunitinib)

For asymptomatic patients, it is recommended to measure salicylate levels 4 hours after ingestion. However, if the patient is experiencing symptoms, the initial levels should be taken 2 hours after ingestion. In this case, the levels should be monitored every 2-3 hours until a decrease is observed.

Further Reading:

Salicylate poisoning, particularly from aspirin overdose, is a common cause of poisoning in the UK. One important concept to understand is that salicylate overdose leads to a combination of respiratory alkalosis and metabolic acidosis. Initially, the overdose stimulates the respiratory center, leading to hyperventilation and respiratory alkalosis. However, as the effects of salicylate on lactic acid production, breakdown into acidic metabolites, and acute renal injury occur, it can result in high anion gap metabolic acidosis.

The clinical features of salicylate poisoning include hyperventilation, tinnitus, lethargy, sweating, pyrexia (fever), nausea/vomiting, hyperglycemia and hypoglycemia, seizures, and coma.

When investigating salicylate poisoning, it is important to measure salicylate levels in the blood. The sample should be taken at least 2 hours after ingestion for symptomatic patients or 4 hours for asymptomatic patients. The measurement should be repeated every 2-3 hours until the levels start to decrease. Other investigations include arterial blood gas analysis, electrolyte levels (U&Es), complete blood count (FBC), coagulation studies (raised INR/PTR), urinary pH, and blood glucose levels.

To manage salicylate poisoning, an ABC approach should be followed to ensure a patent airway and adequate ventilation. Activated charcoal can be administered if the patient presents within 1 hour of ingestion. Oral or intravenous fluids should be given to optimize intravascular volume. Hypokalemia and hypoglycemia should be corrected. Urinary alkalinization with intravenous sodium bicarbonate can enhance the elimination of aspirin in the urine. In severe cases, hemodialysis may be necessary.

Urinary alkalinization involves targeting a urinary pH of 7.5-8.5 and checking it hourly. It is important to monitor for hypokalemia as alkalinization can cause potassium to shift from plasma into cells. Potassium levels should be checked every 1-2 hours.

In cases where the salicylate concentration is high (above 500 mg/L in adults or 350 mg/L in children), sodium bicarbonate can be administered intravenously. Hemodialysis is the treatment of choice for severe poisoning and may be indicated in cases of high salicylate levels, resistant metabolic acidosis, acute kidney injury, pulmonary edema, seizures and coma.

The therapeutic range for lithium typically falls between 0.4-0.8 mmol/l, although this range may differ depending on the laboratory. In general, the lower end of the range is the desired level for maintenance therapy and treatment in older individuals. Toxic effects are typically observed when levels exceed 1.5 mmol/l.

Theophylline, a medication commonly used to treat respiratory conditions, can be affected by certain drugs, either increasing or decreasing its plasma concentration and half-life. Drugs that can increase the plasma concentration of theophylline include calcium channel blockers like verapamil, cimetidine, fluconazole, macrolides such as erythromycin, methotrexate, and quinolones like ciprofloxacin. On the other hand, drugs like carbamazepine, phenobarbitol, phenytoin (and fosphenytoin), rifampicin, and St. John’s wort can decrease the plasma concentration of theophylline. It is important to be aware of these interactions when prescribing or taking theophylline to ensure its effectiveness and avoid potential side effects.

Patients who present with an anticholinergic toxidrome can be difficult to manage due to the agitation and disruptive behavior that is typically present. It is important to provide meticulous supportive care to address the behavioral effects of delirium and prevent complications such as dehydration, injury, and pulmonary aspiration. Often, one-to-one nursing is necessary.

The management approach for these patients is as follows:

1. Resuscitate using a standard ABC approach.
2. Administer sedation for behavioral control. Benzodiazepines, such as IV diazepam in 5 mg-10 mg increments, are the first-line therapy. The goal is to achieve a patient who is sleepy but easily roused. It is important to avoid over-sedating the patient as this can increase the risk of aspiration.
3. Prescribe intravenous fluids as patients are typically unable to eat and drink, and may be dehydrated upon presentation.
4. Insert a urinary catheter as urinary retention is often present and needs to be managed.
5. Consider physostigmine as the specific antidote for anticholinergic delirium in carefully selected cases. Physostigmine acts as a reversible acetylcholinesterase inhibitor, temporarily blocking the breakdown of acetylcholine. This enhances its effects at muscarinic and nicotinic receptors, thereby reversing the effects of the anticholinergic agents.

Physostigmine is indicated in the following situations:

1. Severe anticholinergic delirium that does not respond to benzodiazepine sedation.
2. Poisoning with a pure anticholinergic agent, such as atropine.

The dosage and administration of physostigmine are as follows:

1. Administer in a monitored setting with appropriate staff and resources to manage adverse effects.
2. Perform a 12-lead ECG before administration to rule out bradycardia, AV block, or broadening of the QRS.
3. Administer IV physostigmine 0.5-1 mg as a slow push over 5 minutes. Repeat every 10 minutes up to a maximum of 4 mg.
4. The clinical end-point of therapy is the resolution of delirium.
5. Delirium may reoccur in 1-4 hours as the effects of physostigmine wear off. In such cases, the dose may be cautiously repeated.

The clinical manifestations of theophylline toxicity are more closely associated with acute poisoning rather than chronic overexposure. The primary clinical features of theophylline toxicity include headache, dizziness, nausea and vomiting, abdominal pain, tachycardia and dysrhythmias, seizures, mild metabolic acidosis, hypokalaemia, hypomagnesaemia, hypophosphataemia, hypo- or hypercalcaemia, and hyperglycaemia. Seizures are more prevalent in cases of acute overdose compared to chronic overexposure. In contrast, chronic theophylline overdose typically presents with minimal gastrointestinal symptoms. Cardiac dysrhythmias are more frequently observed in individuals who have experienced chronic overdose rather than acute overdose.

The recommended dose of activated charcoal for adults and children aged 12 or over to prevent the absorption of poisons in the gastrointestinal tract is 50g.

Further Reading:

Paracetamol poisoning occurs when the liver is unable to metabolize paracetamol properly, leading to the production of a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI). Normally, NAPQI is conjugated by glutathione into a non-toxic form. However, during an overdose, the liver’s conjugation systems become overwhelmed, resulting in increased production of NAPQI and depletion of glutathione stores. This leads to the formation of covalent bonds between NAPQI and cell proteins, causing cell death in the liver and kidneys.

Symptoms of paracetamol poisoning may not appear for the first 24 hours or may include abdominal symptoms such as nausea and vomiting. After 24 hours, hepatic necrosis may develop, leading to elevated liver enzymes, right upper quadrant pain, and jaundice. Other complications can include encephalopathy, oliguria, hypoglycemia, renal failure, and lactic acidosis.

The management of paracetamol overdose depends on the timing and amount of ingestion. Activated charcoal may be given if the patient presents within 1 hour of ingesting a significant amount of paracetamol. N-acetylcysteine (NAC) is used to increase hepatic glutathione production and is given to patients who meet specific criteria. Blood tests are taken to assess paracetamol levels, liver function, and other parameters. Referral to a medical or liver unit may be necessary, and psychiatric follow-up should be considered for deliberate overdoses.

In cases of staggered ingestion, all patients should be treated with NAC without delay. Blood tests are also taken, and if certain criteria are met, NAC can be discontinued. Adverse reactions to NAC are common and may include anaphylactoid reactions, rash, hypotension, and nausea. Treatment for adverse reactions involves medications such as chlorpheniramine and salbutamol, and the infusion may be stopped if necessary.

The prognosis for paracetamol poisoning can be poor, especially in cases of severe liver injury. Fulminant liver failure may occur, and liver transplant may be necessary. Poor prognostic indicators include low arterial pH, prolonged prothrombin time, high plasma creatinine, and hepatic encephalopathy.

Statins, although generally safe and well-tolerated, can cause myopathy and myotoxicity. This range of muscle-related side effects can vary from mild muscle pain to the most severe case of rhabdomyolysis, which can lead to kidney failure, blood clotting issues, and even death.

The different levels of myotoxicity associated with statins are as follows:
– Myalgia: muscle symptoms without an increase in creatine kinase (CK) levels.
– Asymptomatic myopathy: elevated CK levels without muscle symptoms.
– Myositis: muscle symptoms with CK levels elevated less than 10 times the upper limit of normal.
– Rhabdomyolysis: muscle symptoms with CK levels elevated more than 10 times the upper limit of normal, potentially leading to myoglobinuria (presence of myoglobin in urine) and renal failure.

Most statins are broken down by the cytochrome P450 enzyme system. When taken with drugs that strongly inhibit this system, the concentration of statins in the blood can significantly increase. This, in turn, raises the risk of myopathy. A well-known example of this is the combination of statins with macrolide antibiotics like erythromycin and clarithromycin. Co-prescribing these drugs with statins has been linked to a higher risk of myopathy, hospitalization due to rhabdomyolysis, acute kidney injury, and increased mortality rates.

Thiazide diuretics, like bendroflumethiazide and hydrochlorothiazide, have the potential to raise levels of uric acid in the blood, which can worsen gout symptoms in individuals who are susceptible to the condition.

Other medications, such as diuretics, beta-blockers, ACE inhibitors, and non-losartan ARBs, are also linked to an increased risk of gout.

On the other hand, calcium-channel blockers like amlodipine and verapamil, as well as losartan, have been found to lower uric acid levels and are associated with a reduced risk of gout.

TCA toxicity can be identified through specific changes seen on an electrocardiogram (ECG). Sinus tachycardia, which is a faster than normal heart rate, and widening of the QRS complex are key features of TCA toxicity. These ECG changes occur due to the blocking of sodium channels and muscarinic receptors (M1) by the medication. In the case of an amitriptyline overdose, additional ECG changes may include prolongation of the QT interval, an R/S ratio greater than 0.7 in lead aVR, and the presence of ventricular arrhythmias such as torsades de pointes. The severity of the QRS prolongation on the ECG is associated with the likelihood of adverse events. A QRS duration greater than 100 ms is predictive of seizures, while a QRS duration greater than 160 ms is predictive of ventricular arrhythmias like ventricular tachycardia or torsades de pointes.

Further Reading:

Tricyclic antidepressant (TCA) overdose is a common occurrence in emergency departments, with drugs like amitriptyline and dosulepin being particularly dangerous. TCAs work by inhibiting the reuptake of norepinephrine and serotonin in the central nervous system. In cases of toxicity, TCAs block various receptors, including alpha-adrenergic, histaminic, muscarinic, and serotonin receptors. This can lead to symptoms such as hypotension, altered mental state, signs of anticholinergic toxicity, and serotonin receptor effects.

TCAs primarily cause cardiac toxicity by blocking sodium and potassium channels. This can result in a slowing of the action potential, prolongation of the QRS complex, and bradycardia. However, the blockade of muscarinic receptors also leads to tachycardia in TCA overdose. QT prolongation and Torsades de Pointes can occur due to potassium channel blockade. TCAs can also have a toxic effect on the myocardium, causing decreased cardiac contractility and hypotension.

Early symptoms of TCA overdose are related to their anticholinergic properties and may include dry mouth, pyrexia, dilated pupils, agitation, sinus tachycardia, blurred vision, flushed skin, tremor, and confusion. Severe poisoning can lead to arrhythmias, seizures, metabolic acidosis, and coma. ECG changes commonly seen in TCA overdose include sinus tachycardia, widening of the QRS complex, prolongation of the QT interval, and an R/S ratio >0.7 in lead aVR.

Management of TCA overdose involves ensuring a patent airway, administering activated charcoal if ingestion occurred within 1 hour and the airway is intact, and considering gastric lavage for life-threatening cases within 1 hour of ingestion. Serial ECGs and blood gas analysis are important for monitoring. Intravenous fluids and correction of hypoxia are the first-line therapies. IV sodium bicarbonate is used to treat haemodynamic instability caused by TCA overdose, and benzodiazepines are the treatment of choice for seizure control. Other treatments that may be considered include glucagon, magnesium sulfate, and intravenous lipid emulsion.

There are certain things to avoid in TCA overdose, such as anti-arrhythmics like quinidine and flecainide, as they can prolonged depolarization. Amiodarone should

Non-selective beta-blockers, like propranolol, can cause severe bronchospasm in individuals with asthma, particularly when taken in high doses. The current guidelines from the British Thoracic Society (BTS) recommend avoiding the use of beta-blockers in asthma patients. However, there is some evidence suggesting that the long-term use of cardioselective beta-blockers does not appear to trigger asthma attacks in individuals with mild or moderate asthma.

Beta-blockers play a crucial role in the treatment of patients who have a history of previous myocardial infarction or systolic dysfunction. In individuals with asthma and one of these diagnoses, it is unlikely that the potential benefits of beta-blockers outweigh the risks of worsening asthma symptoms.

The Royal College of Emergency Medicine (RCEM) recognizes four antidotes that can be used to treat cyanide poisoning: Hydroxycobalamin, Sodium thiosulphate, Sodium nitrite, and Dicobalt edetate. When managing cyanide toxicity, it is important to provide supportive treatment using the ABCDE approach. This includes administering supplemental high flow oxygen, providing hemodynamic support (including the use of inotropes if necessary), and administering the appropriate antidotes. In the UK, these four antidotes should be readily available in Emergency Departments according to the RCEM/NPIS guideline on antidote availability. Hydroxocobalamin followed by sodium thiosulphate is generally the preferred treatment if both options are available. Healthcare workers should be aware that patients with cyanide poisoning may expel HCN through vomit and skin, so it is crucial to use appropriate personal protective equipment when caring for these patients.

Further Reading:

Burn injuries can be classified based on their type (degree, partial thickness or full thickness), extent as a percentage of total body surface area (TBSA), and severity (minor, moderate, major/severe). Severe burns are defined as a >10% TBSA in a child and >15% TBSA in an adult.

When assessing a burn, it is important to consider airway injury, carbon monoxide poisoning, type of burn, extent of burn, special considerations, and fluid status. Special considerations may include head and neck burns, circumferential burns, thorax burns, electrical burns, hand burns, and burns to the genitalia.

Airway management is a priority in burn injuries. Inhalation of hot particles can cause damage to the respiratory epithelium and lead to airway compromise. Signs of inhalation injury include visible burns or erythema to the face, soot around the nostrils and mouth, burnt/singed nasal hairs, hoarse voice, wheeze or stridor, swollen tissues in the mouth or nostrils, and tachypnea and tachycardia. Supplemental oxygen should be provided, and endotracheal intubation may be necessary if there is airway obstruction or impending obstruction.

The initial management of a patient with burn injuries involves conserving body heat, covering burns with clean or sterile coverings, establishing IV access, providing pain relief, initiating fluid resuscitation, measuring urinary output with a catheter, maintaining nil by mouth status, closely monitoring vital signs and urine output, monitoring the airway, preparing for surgery if necessary, and administering medications.

Burns can be classified based on the depth of injury, ranging from simple erythema to full thickness burns that penetrate into subcutaneous tissue. The extent of a burn can be estimated using methods such as the rule of nines or the Lund and Browder chart, which takes into account age-specific body proportions.

Fluid management is crucial in burn injuries due to significant fluid losses. Evaporative fluid loss from burnt skin and increased permeability of blood vessels can lead to reduced intravascular volume and tissue perfusion. Fluid resuscitation should be aggressive in severe burns, while burns <15% in adults and <10% in children may not require immediate fluid resuscitation. The Parkland formula can be used to calculate the intravenous fluid requirements for someone with a significant burn injury.

In managing patients with carbon monoxide poisoning, the primary intervention is providing 100% oxygen. This is because carbon monoxide has a higher affinity for hemoglobin than oxygen, leading to decreased oxygen delivery to tissues. By administering 100% oxygen, the patient is able to displace carbon monoxide from hemoglobin and increase oxygen levels in the blood, which is crucial for the patient’s recovery.

Further Reading:

Carbon monoxide (CO) is a dangerous gas that is produced by the combustion of hydrocarbon fuels and can be found in certain chemicals. It is colorless and odorless, making it difficult to detect. In England and Wales, there are approximately 60 deaths each year due to accidental CO poisoning.

When inhaled, carbon monoxide binds to haemoglobin in the blood, forming carboxyhaemoglobin (COHb). It has a higher affinity for haemoglobin than oxygen, causing a left-shift in the oxygen dissociation curve and resulting in tissue hypoxia. This means that even though there may be a normal level of oxygen in the blood, it is less readily released to the tissues.

The clinical features of carbon monoxide toxicity can vary depending on the severity of the poisoning. Mild or chronic poisoning may present with symptoms such as headache, nausea, vomiting, vertigo, confusion, and weakness. More severe poisoning can lead to intoxication, personality changes, breathlessness, pink skin and mucosae, hyperpyrexia, arrhythmias, seizures, blurred vision or blindness, deafness, extrapyramidal features, coma, or even death.

To help diagnose domestic carbon monoxide poisoning, there are four key questions that can be asked using the COMA acronym. These questions include asking about co-habitees and co-occupants in the house, whether symptoms improve outside of the house, the maintenance of boilers and cooking appliances, and the presence of a functioning CO alarm.

Typical carboxyhaemoglobin levels can vary depending on whether the individual is a smoker or non-smoker. Non-smokers typically have levels below 3%, while smokers may have levels below 10%. Symptomatic individuals usually have levels between 10-30%, and severe toxicity is indicated by levels above 30%.

When managing carbon monoxide poisoning, the first step is to administer 100% oxygen. Hyperbaric oxygen therapy may be considered for individuals with a COHb concentration of over 20% and additional risk factors such as loss of consciousness, neurological signs, myocardial ischemia or arrhythmia, or pregnancy. Other management strategies may include fluid resuscitation, sodium bicarbonate for metabolic acidosis, and mannitol for cerebral edema.

Digoxin-specific antibody (DigiFab) is an antidote used to counteract digoxin overdose. It is a purified and sterile preparation of digoxin-immune ovine Fab immunoglobulin fragments. These fragments are derived from healthy sheep that have been immunized with a digoxin derivative called digoxin-dicarboxymethoxylamine (DDMA). DDMA is a digoxin analogue that contains the essential cyclopentanoperhydrophenanthrene: lactone ring moiety coupled to keyhole limpet hemocyanin (KLH).

DigiFab has a higher affinity for digoxin compared to the affinity of digoxin for its sodium pump receptor, which is believed to be the receptor responsible for its therapeutic and toxic effects. When administered to a patient who has overdosed on digoxin, DigiFab binds to digoxin molecules, reducing the levels of free digoxin in the body. This shift in equilibrium away from binding to the receptors helps to reduce the cardiotoxic effects of digoxin. The Fab-digoxin complexes are then eliminated from the body through the kidney and reticuloendothelial system.

The indications for using DigiFab in cases of acute and chronic digoxin toxicity are summarized below:

Acute digoxin toxicity:
– Cardiac arrest
– Life-threatening arrhythmia
– Potassium level >5 mmol/l
– Ingestion of >10 mg of digoxin (in adults)
– Ingestion of >4 mg of digoxin (in children)
– Digoxin level >12 ng/ml

Chronic digoxin toxicity:
– Cardiac arrest
– Life-threatening arrhythmia
– Significant gastrointestinal symptoms
– Symptoms of digoxin toxicity in the presence of renal failure