Corneal microdeposits are found in almost all individuals (over 90%) who have been taking amiodarone for more than six months, particularly at doses higher than 400 mg/day. These deposits generally do not cause any symptoms, although approximately 10% of patients may experience a perception of a ‘bluish halo’ around objects they see.

Amiodarone can also have other effects on the eye, but these are much less common, occurring in only 1-2% of patients. These effects include optic neuropathy, nonarteritic anterior ischemic optic neuropathy (N-AION), optic disc swelling, and visual field defects.

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.

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.

Paracetamol levels should be measured 4 hours after ingestion. If the patient arrives at the emergency department more than 4 hours after ingestion, the levels can be taken immediately. However, if the patient has not reached the 4-hour mark yet, the measurement should be postponed until they reach that time.

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.

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

Paracetamol overdose is the most common overdose in the U.K. and is also the leading cause of acute liver failure. The liver damage occurs due to a metabolite of paracetamol called N-acetyl-p-benzoquinoneimine (NAPQI), which depletes the liver’s glutathione stores and directly harms liver cells. Severe liver damage and even death can result from an overdose of more than 12 g or > 150 mg/kg body weight.

The clinical manifestations of paracetamol overdose can be divided into four stages:

Stage 1 (0-24 hours): Patients may not show any symptoms, but common signs include nausea, vomiting, and abdominal discomfort.

Stage 2 (24-48 hours): Right upper quadrant pain and tenderness develop, along with the possibility of hypoglycemia and reduced consciousness.

Stage 3 (48-96 hours): Hepatic failure begins, characterized by jaundice, coagulopathy, and encephalopathy. Loin pain, haematuria, and proteinuria may indicate early renal failure.

Stage 4 (> 96 hours): Hepatic failure worsens progressively, leading to cerebral edema, disseminated intravascular coagulation (DIC), and ultimately death.

The earliest and most sensitive indicator of liver damage is a prolonged INR, which starts to rise approximately 24 hours after the overdose. Liver function tests (LFTs) typically remain normal until 18 hours after the overdose. However, AST and ALT levels then sharply increase and can exceed 10,000 units/L by 72-96 hours. Bilirubin levels rise more slowly and peak around 5 days.

The primary treatment for paracetamol overdose is acetylcysteine. Acetylcysteine is a highly effective antidote, but its efficacy diminishes rapidly if administered more than 8 hours after a significant ingestion. Ingestions exceeding 75 mg/kg are considered significant.

Acetylcysteine should be given based on a 4-hour level or administered empirically if the presentation occurs more than 8 hours after a significant overdose. If the overdose is staggered or the timing is uncertain, empirical treatment is also recommended. The treatment regimen is as follows:

– First dose: 150 mg/kg in 200 mL 5% glucose over 1 hour
– Second dose 50 mg/kg in 500 mL 5% glucose over 4 hours
– Third dose 100 mg/kg in 1000 mL 5% glucose over 16 hours

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.

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.

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

First-generation antipsychotics, also known as conventional or typical antipsychotics, are powerful blockers of the dopamine D2 receptor. However, each drug in this category has different effects on other receptors, such as serotonin type 2 (5-HT2), alpha1, histaminic, and muscarinic receptors.

These first-generation antipsychotics are known to have a high incidence of extrapyramidal side effects, which include rigidity, bradykinesia, dystonias, tremor, akathisia, tardive dyskinesia, and neuroleptic malignant syndrome (NMS). NMS is a rare and life-threatening reaction to neuroleptic medications, characterized by fever, muscle stiffness, changes in mental state, and dysfunction of the autonomic nervous system. NMS typically occurs shortly after starting or increasing the dose of neuroleptic treatment.

On the other hand, second-generation antipsychotics, also referred to as novel or atypical antipsychotics, are dopamine D2 antagonists, except for aripiprazole. These medications are associated with lower rates of extrapyramidal side effects and NMS compared to the first-generation antipsychotics. However, they have higher rates of metabolic side effects and weight gain.

It is important to note that serotonin syndrome shares similar features with NMS but can be distinguished by the causative agent, most commonly the serotonin-specific reuptake inhibitors.

The primary treatment for paracetamol overdose is acetylcysteine. Acetylcysteine is an extremely effective antidote, but its effectiveness decreases quickly if administered more than a few hours after a significant ingestion. Ingestions that exceed 75 mg/kg are considered to be significant.

For patients who decline treatment, methionine is a helpful alternative. It is taken orally in a dosage of 2.5 g every 4 hours, with a total dose of 10 g.

Ipratropium bromide commonly leads to dry mouth as a side effect. Additionally, it may result in constipation, cough, sudden bronchospasm, headache, nausea, and palpitations. In patients with prostatic hyperplasia and bladder outflow obstruction, it can cause urinary retention. Furthermore, susceptible individuals may experience acute closed-angle glaucoma as a result of using this medication.

Corneal microdeposits are found in almost all individuals (over 90%) who have been taking amiodarone for more than six months, particularly at doses higher than 400 mg/day. These deposits generally do not cause any symptoms, although approximately 10% of patients may experience a perception of a ‘bluish halo’ around objects they see.

Amiodarone can also have other effects on the eye, but these are much less common, occurring in only 1-2% of patients. These effects include optic neuropathy, nonarteritic anterior ischemic optic neuropathy (N-AION), optic disc swelling, and visual field defects.

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.

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.

Intralipid is a lipid emulsion that is commonly used as a source of nutrition in parenteral nutrition. However, it has also been found to be effective in treating local anesthetic toxicity. When administered intravenously, Intralipid acts as a lipid sink, meaning it can bind to the local anesthetic agent and remove it from the affected tissues, thereby reversing the toxic effects.

In cases of cardiac arrest related to local anesthetic toxicity, Intralipid can be administered as a bolus followed by an infusion. The recommended dose is typically 1.5 mL/kg bolus over 1 minute, followed by an infusion of 0.25 mL/kg/minute for 10 minutes. This can be repeated if necessary.

It is important to note that while Intralipid has shown promising results in treating local anesthetic toxicity, it should not replace standard ALS protocols. Basic life support (BLS) measures, such as cardiopulmonary resuscitation (CPR), should still be initiated immediately, and advanced cardiac life support (ACLS) protocols should be followed.

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.

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..

During the first trimester of pregnancy, the use of trimethoprim is linked to an increased risk of neural tube defects because it antagonizes folate. If it is not possible to use an alternative antibiotic, it is recommended that pregnant women taking trimethoprim also take high-dose folic acid. However, the use of trimethoprim in the second and third trimesters of pregnancy is considered safe.

Below 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 trimesters, they can cause hypoperfusion, renal failure, and the oligohydramnios sequence.

Aminoglycosides (e.g. gentamicin): They can cause ototoxicity and deafness.

Aspirin: High doses 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 significant risks.

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

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

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

Chloramphenicol: It can cause grey baby syndrome.

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

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

Heparin: It can cause maternal bleeding and thrombocytopenia.

Isoniazid: It can lead to maternal liver damage and neuropathy and seizures in the neonate.

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.

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.

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.

Digoxin toxicity can be triggered by hypokalaemia, a condition characterized by low levels of potassium in the body. This occurs because digoxin competes with potassium for binding sites, and when potassium levels are low, there is less competition for digoxin to bind to these sites. Additionally, other factors such as hypomagnesaemia, hypercalcaemia, hypernatraemia, and acidosis can also contribute to digoxin toxicity.

Further Reading:

Digoxin is a medication used for rate control in atrial fibrillation and for improving symptoms in heart failure. It works by decreasing conduction through the atrioventricular node and increasing the force of cardiac muscle contraction. However, digoxin toxicity can occur, and plasma concentration alone does not determine if a patient has developed toxicity. Symptoms of digoxin toxicity include feeling generally unwell, lethargy, nausea and vomiting, anorexia, confusion, yellow-green vision, arrhythmias, and gynaecomastia.

ECG changes seen in digoxin toxicity include downsloping ST depression with a characteristic Salvador Dali sagging appearance, flattened, inverted, or biphasic T waves, shortened QT interval, mild PR interval prolongation, and prominent U waves. There are several precipitating factors for digoxin toxicity, including hypokalaemia, increasing age, renal failure, myocardial ischaemia, electrolyte imbalances, hypoalbuminaemia, hypothermia, hypothyroidism, and certain medications such as amiodarone, quinidine, verapamil, and diltiazem.

Management of digoxin toxicity involves the use of digoxin specific antibody fragments, also known as Digibind or digifab. Arrhythmias should be treated, and electrolyte disturbances should be corrected with close monitoring of potassium levels. It is important to note that digoxin toxicity can be precipitated by hypokalaemia, and toxicity can then lead to hyperkalaemia.

Postural tremor is frequently seen as a neurological side effect in individuals taking sodium valproate. Additionally, a resting tremor may also manifest. It has been observed that around 25% of patients who begin sodium valproate therapy develop a tremor within the first year. Other potential side effects of sodium valproate include gastric irritation, nausea and vomiting, involuntary movements, temporary hair loss, weight gain in females, and impaired liver function.

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.

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. Its mechanism of action involves inhibiting the Na/K ATPase in cardiac myocytes, which leads to an increase in intracellular sodium concentration. This, in turn, indirectly increases the availability of intracellular calcium through Na/Ca exchange.

The rise in intracellular calcium levels caused by digoxin results in a positive inotropic effect, meaning it strengthens the force of heart contractions, and a negative chronotropic effect, meaning it slows down the heart rate.

Therapeutic plasma levels of digoxin typically range between 1.0-1.5 nmol/l. However, higher concentrations may be necessary, and the specific value can vary between different laboratories. It is important to note that the risk of toxicity significantly increases when digoxin levels exceed 2 nmol/l.

Signs and symptoms of digoxin toxicity include nausea, vomiting, diarrhea, abdominal pain, confusion, tachyarrhythmias or bradyarrhythmias, xanthopsia (yellow-green vision), and hyperkalemia (an early sign of significant toxicity).

Several factors can potentially contribute to digoxin toxicity. These include being elderly, having renal failure, experiencing myocardial ischemia, having hypokalemia, hypomagnesemia, hypercalcemia, hypernatremia, acidosis, or hypothyroidism.

Additionally, there are several drugs that can increase the risk of digoxin toxicity. These include spironolactone, amiodarone, quinidine, verapamil, diltiazem, and drugs that cause hypokalemia, such as thiazide and loop diuretics.

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.

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.

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.

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.

Excessive intake of lithium is linked to the development of low anion gap acidosis. In cases of lithium overdose, a common outcome is the occurrence of low anion gap acidosis.

Further Reading:

Arterial blood gases (ABG) are an important diagnostic tool used to assess a patient’s acid-base status and respiratory function. When obtaining an ABG sample, it is crucial to prioritize safety measures to minimize the risk of infection and harm to the patient. This includes performing hand hygiene before and after the procedure, wearing gloves and protective equipment, disinfecting the puncture site with alcohol, using safety needles when available, and properly disposing of equipment in sharps bins and contaminated waste bins.

To reduce the risk of harm to the patient, it is important to test for co-lateral circulation using the modified Allen test for radial artery puncture. Additionally, it is essential to inquire about any occlusive vascular conditions or anticoagulation therapy that may affect the procedure. The puncture site should be checked for signs of infection, injury, or previous surgery. After the test, pressure should be applied to the puncture site or the patient should be advised to apply pressure for at least 5 minutes to prevent bleeding.

Interpreting ABG results requires a systematic approach. The core set of results obtained from a blood gas analyser includes the partial pressures of oxygen and carbon dioxide, pH, bicarbonate concentration, and base excess. These values are used to assess the patient’s acid-base status.

The pH value indicates whether the patient is in acidosis, alkalosis, or within the normal range. A pH less than 7.35 indicates acidosis, while a pH greater than 7.45 indicates alkalosis.

The respiratory system is assessed by looking at the partial pressure of carbon dioxide (pCO2). An elevated pCO2 contributes to acidosis, while a low pCO2 contributes to alkalosis.

The metabolic aspect is assessed by looking at the bicarbonate (HCO3-) level and the base excess. A high bicarbonate concentration and base excess indicate alkalosis, while a low bicarbonate concentration and base excess indicate acidosis.

Analyzing the pCO2 and base excess values can help determine the primary disturbance and whether compensation is occurring. For example, a respiratory acidosis (elevated pCO2) may be accompanied by metabolic alkalosis (elevated base excess) as a compensatory response.

The anion gap is another important parameter that can help determine the cause of acidosis. It is calculated by subtracting the sum of chloride and bicarbonate from the sum of sodium and potassium.