The most commonly observed change in the electrocardiogram (ECG) during a tricyclic antidepressant (TCA) overdose is sinus tachycardia. Additionally, other ECG changes that can be seen in TCA overdose include prolongation of the PR interval, broadening of the QRS complex, prolongation of the QT interval, and the occurrence of ventricular arrhythmias in cases of severe toxicity. The cardiotoxic effects of TCAs are caused by the blocking of sodium channels, which leads to broadening of the QRS complex, and the blocking of potassium channels, which results in prolongation of the QT interval. The severity of the QRS broadening is associated with 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.

Gynaecomastia, a condition characterized by the enlargement of breast tissue in males, can be caused by certain drugs. Some medications that have been associated with gynaecomastia include Cimetidine, Omeprazole, Spironolactone, Digoxin, Furosemide, Finasteride, and certain antipsychotics. Interestingly, Ranitidine, another medication commonly used for gastric issues, does not tend to cause gynaecomastia. In fact, studies have shown that gynaecomastia caused by Cimetidine can be resolved when it is substituted with Ranitidine.

If IV methylene blue is obtained, it is typically used to treat a specific cause. However, if there is no response to methylene blue, alternative treatments such as hyperbaric oxygen or exchange transfusion may be considered. In cases where the cause is NADH-methaemoglobinaemia reductase deficiency, ascorbic acid can be used as a potential treatment.

Further Reading:

Methaemoglobinaemia is a condition where haemoglobin is oxidised from Fe2+ to Fe3+. This process is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin, converting it back to haemoglobin. In healthy individuals, methaemoglobin levels are typically less than 1% of total haemoglobin. However, an increase in methaemoglobin can lead to tissue hypoxia as Fe3+ cannot bind oxygen effectively.

Methaemoglobinaemia can be congenital or acquired. Congenital causes include haemoglobin chain variants (HbM, HbH) and NADH methaemoglobin reductase deficiency. Acquired causes can be due to exposure to certain drugs or chemicals, such as sulphonamides, local anaesthetics (especially prilocaine), nitrates, chloroquine, dapsone, primaquine, and phenytoin. Aniline dyes are also known to cause methaemoglobinaemia.

Clinical features of methaemoglobinaemia include slate grey cyanosis (blue to grey skin coloration), chocolate blood or chocolate cyanosis (brown color of blood), dyspnoea, low SpO2 on pulse oximetry (which often does not improve with supplemental oxygen), and normal PaO2 on arterial blood gas (ABG) but low SaO2. Patients may tolerate hypoxia better than expected. Severe cases can present with acidosis, arrhythmias, seizures, and coma.

Diagnosis of methaemoglobinaemia is made by directly measuring the level of methaemoglobin using a co-oximeter, which is present in most modern blood gas analysers. Other investigations, such as a full blood count (FBC), electrocardiogram (ECG), chest X-ray (CXR), and beta-human chorionic gonadotropin (bHCG) levels (in pregnancy), may be done to assess the extent of the condition and rule out other contributing factors.

Active treatment is required if the methaemoglobin level is above 30% or if it is below 30% but the patient is symptomatic or shows evidence of tissue hypoxia. Treatment involves maintaining the airway and delivering high-flow oxygen, removing the causative agents, treating toxidromes and consider giving IV dextrose 5%.

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.

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

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.

Cytochrome p450 enzyme inducers have the ability to hinder the effects of warfarin, leading to a decrease in INR levels. To remember the commonly encountered cytochrome p450 enzyme inducers, the mnemonic PC BRASS can be utilized. Each letter in the mnemonic represents a specific inducer: P for Phenytoin, C for Carbamazepine, B for Barbiturates, R for Rifampicin, A for Alcohol (chronic ingestion), S for Sulphonylureas, and S for Smoking. These inducers can have an impact on the effectiveness of warfarin and should be taken into consideration when prescribing or using this medication.

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.

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).

Anticholinergic drugs have been found to worsen cognitive impairment in individuals with dementia. Certain commonly prescribed medications are associated with a higher anticholinergic burden, which can lead to increased cognitive decline. Examples of drugs with high anticholinergic potency include tricyclic antidepressants like amitriptyline hydrochloride, paroxetine, first-generation antihistamines such as chlorpheniramine maleate and promethazine hydrochloride, certain antipsychotics like olanzapine, clozapine, and quetiapine, urinary antispasmodics like solifenacin, oxybutynin, and tolterodine, and antimuscarinics like ipratropium, tiotropium, atropine, and cyclopentolate. However, it’s important to note that rivastigmine and memantine are recommended as first-line treatments for Alzheimer’s and DLB, while haloperidol, despite being an antipsychotic, has low anticholinergic potency.

Further Reading:

Dementia is a progressive and irreversible clinical syndrome characterized by cognitive and behavioral symptoms. These symptoms include memory loss, impaired reasoning and communication, personality changes, and reduced ability to carry out daily activities. The decline in cognition affects multiple domains of intellectual functioning and is not solely due to normal aging.

To diagnose dementia, a person must have impairment in at least two cognitive domains that significantly impact their daily activities. This impairment cannot be explained by delirium or other major psychiatric disorders. Early-onset dementia refers to dementia that develops before the age of 65.

The most common cause of dementia is Alzheimer’s disease, accounting for 50-75% of cases. Other causes include vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Less common causes include Parkinson’s disease dementia, Huntington’s disease, prion disease, and metabolic and endocrine disorders.

There are several risk factors for dementia, including age, mild cognitive impairment, genetic predisposition, excess alcohol intake, head injury, depression, learning difficulties, diabetes, obesity, hypertension, smoking, Parkinson’s disease, low social engagement, low physical activity, low educational attainment, hearing impairment, and air pollution.

Assessment of dementia involves taking a history from the patient and ideally a family member or close friend. The person’s current level of cognition and functional capabilities should be compared to their baseline level. Physical examination, blood tests, and cognitive assessment tools can also aid in the diagnosis.

Differential diagnosis for dementia includes normal age-related memory changes, mild cognitive impairment, depression, delirium, vitamin deficiencies, hypothyroidism, adverse drug effects, normal pressure hydrocephalus, and sensory deficits.

Management of dementia involves a multi-disciplinary approach that includes non-pharmacological and pharmacological measures. Non-pharmacological interventions may include driving assessment, modifiable risk factor management, and non-pharmacological therapies to promote cognition and independence. Drug treatments for dementia should be initiated by specialists and may include acetylcholinesterase inhibitors, memantine, and antipsychotics in certain cases.

In summary, dementia is a progressive and irreversible syndrome characterized by cognitive and behavioral symptoms. It has various causes and risk factors, and its management involves a multi-disciplinary approach.

Digoxin is a medication used to manage heart failure and atrial fibrillation. It works by inhibiting the Na+/K+ ATPase in the myocardium, which slows down the ventricular response and has a positive effect on the heart’s contraction. Although less commonly used nowadays, digoxin still plays a role in certain cases.

One advantage of digoxin is its long half-life, allowing for once-daily maintenance doses. However, it is important to monitor the dosage to ensure it is correct and to watch out for factors that may lead to toxicity, such as renal dysfunction and hypokalemia. Once a steady state has been achieved, regular monitoring of plasma digoxin concentrations is not necessary unless there are concerns.

In atrial fibrillation, the effectiveness of digoxin treatment is best assessed by monitoring the ventricular rate. The target range for plasma digoxin concentration is 1.0-1.5 nmol/L, although higher levels of up to 2 nmol/L may be needed in some cases. It is important to note that the plasma concentration alone cannot reliably indicate toxicity, but levels above 2 nmol/L significantly increase the risk. To manage hypokalemia, which can increase the risk of digoxin toxicity, a potassium-sparing diuretic or potassium supplementation may be prescribed.

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.

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.

Lithium is a medication used to stabilize mood and is approved for the treatment and prevention of mania, bipolar disorder, recurrent depression, and aggressive or self-harming behavior. During pregnancy and the postnatal period, it is important to monitor lithium levels more frequently. If taken during the first trimester, lithium is associated with an increased risk of fetal cardiac malformations, such as Ebstein’s anomaly. If taken during the second and third trimesters, there is a risk of various complications in the newborn, including hypotonia, lethargy, feeding problems, hypothyroidism, goiter, and nephrogenic diabetes insipidus.

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

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

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

Drug: Aspirin
Adverse effects: 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.

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

Drug: Calcium-channel blockers
Adverse effects: If taken during the first trimester, calcium-channel blockers can cause phalangeal abnormalities. If taken during the second and third trimesters, they can lead to fetal growth retardation.

If someone consumes at least 75 mg of paracetamol per kilogram of body weight within a 24-hour period, it is considered to be a significant ingestion. Ingesting more than 150 mg of paracetamol per kilogram of body weight within 24 hours poses a serious risk of harm.

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.

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.

The most frequent cause of non-allergic drug induced angioedema is ACE inhibitors. Symptoms usually appear several days to weeks after beginning the medication. It is important to note that penicillin and NSAIDs are the primary drug culprits for angioedema, but they trigger it through an IgE mediated allergic mechanism, resulting in both angioedema and urticaria. The onset of symptoms in these cases typically occurs within minutes to hours after exposure.

Further Reading:

Angioedema and urticaria are related conditions that involve swelling in different layers of tissue. Angioedema refers to swelling in the deeper layers of tissue, such as the lips and eyelids, while urticaria, also known as hives, refers to swelling in the epidermal skin layers, resulting in raised red areas of skin with itching. These conditions often coexist and may have a common underlying cause.

Angioedema can be classified into allergic and non-allergic types. Allergic angioedema is the most common type and is usually triggered by an allergic reaction, such as to certain medications like penicillins and NSAIDs. Non-allergic angioedema has multiple subtypes and can be caused by factors such as certain medications, including ACE inhibitors, or underlying conditions like hereditary angioedema (HAE) or acquired angioedema.

HAE is an autosomal dominant disease characterized by a deficiency of C1 esterase inhibitor. It typically presents in childhood and can be inherited or acquired as a result of certain disorders like lymphoma or systemic lupus erythematosus. Acquired angioedema may have similar clinical features to HAE but is caused by acquired deficiencies of C1 esterase inhibitor due to autoimmune or lymphoproliferative disorders.

The management of urticaria and allergic angioedema focuses on ensuring the airway remains open and addressing any identifiable triggers. In mild cases without airway compromise, patients may be advised that symptoms will resolve without treatment. Non-sedating antihistamines can be used for up to 6 weeks to relieve symptoms. Severe cases of urticaria may require systemic corticosteroids in addition to antihistamines. In moderate to severe attacks of allergic angioedema, intramuscular epinephrine may be considered.

The management of HAE involves treating the underlying deficiency of C1 esterase inhibitor. This can be done through the administration of C1 esterase inhibitor, bradykinin receptor antagonists, or fresh frozen plasma transfusion, which contains C1 inhibitor.

In summary, angioedema and urticaria are related conditions involving swelling in different layers of tissue. They can coexist and may have a common underlying cause. Management involves addressing triggers, using antihistamines, and in severe cases, systemic corticosteroids or other specific treatments for HAE.

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.

Haemodialysis is recommended for patients with salicylate poisoning if they meet any of the following criteria: plasma salicylate level exceeding 700 mg/L, metabolic acidosis that does not improve with treatment (plasma pH below 7.2), acute kidney injury, pulmonary edema, seizures, coma, unresolved central nervous system effects despite correcting acidosis, persistently high salicylate concentrations that do not respond to urinary alkalinisation. Severe cases of salicylate poisoning, especially in patients under 10 years old or over 70 years old, may require dialysis earlier than the listed indications.

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 utilized substance for decontamination in cases of poisoning. Its main function is to attract and bind 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. This powder is created by subjecting carbonaceous matter to high heat, a process known as pyrolysis, and then concentrating it with a solution of zinc chloride. Through this process, the activated charcoal develops a complex network of pores, providing it with a large surface area of approximately 3,000 m2/g. This extensive surface area allows it to effectively hinder the absorption of the harmful toxin by up to 50%.

The typical dosage for adults is 50 grams, while children are usually given 1 gram per kilogram of body weight. Activated charcoal can be administered orally or through a nasogastric tube. It is crucial to administer it within one hour of ingestion, and if necessary, a second dose may be repeated after one hour.

Opioid poisoning is a common occurrence in the Emergency Department. It can occur as a result of recreational drug use, such as heroin, or from prescribed opioids like morphine sulfate tablets or dihydrocodeine.

The symptoms of opioid overdose include a decreased level of consciousness or even coma, reduced respiratory rate, apnea, pinpoint pupils, low blood pressure, cyanosis, convulsions, and non-cardiogenic pulmonary edema (in cases of intravenous heroin usage). The most common cause of death from opioid overdose is respiratory depression, which typically happens within an hour of the overdose. Vomiting is also common, and there is a risk of aspiration.

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

Since naloxone has a shorter duration of action than most opioids, close monitoring and repeated injections are necessary. The dosage should be adjusted based on the respiratory rate and depth of coma. Generally, the dose is 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, with the infusion rate initially set at 60% of the initial resuscitative intravenous dose per hour.

In opioid addicts, the administration of naloxone may trigger a withdrawal syndrome, characterized by abdominal cramps, nausea, and diarrhea. However, these symptoms typically subside within 2 hours.

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.

Organophosphate poisoning is characterized by a set of symptoms known as SLUDGE (Salivation, Lacrimation, Urination, Defecation, Gastric cramps, Emesis). Additionally, individuals affected may experience pinpoint pupils, profuse sweating, tremors, and confusion. Organophosphates serve as the foundation for various weaponized nerve agents like Sarin and VX, which were infamously employed by the terrorist group Aum Shinrikyo during multiple attacks in Tokyo in the mid-1990s. While SLUDGE is a commonly used acronym to recall the clinical features, it is important to note that other symptoms such as pinpoint pupils, profuse sweating, tremors, and confusion are not included in the acronym.

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.

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.

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.

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

The use of low-dose aspirin during pregnancy is considered safe and can be used to manage recurrent miscarriage, clotting disorders, and pre-eclampsia. On the other hand, high-dose aspirin carries several risks, especially if used in the third trimester. These risks include delayed onset of labor, premature closure of the fetal ductus arteriosus, and fetal kernicterus (a condition that affects the brain due to high levels of bilirubin). Additionally, there is a slight increase in the risk of first-trimester abortion if high-dose aspirin is used early in pregnancy.

Below is a list outlining 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 (damage to the ear) and deafness.

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.

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.

Salicylate poisoning often leads to a metabolic acidosis characterized by a high anion gap. The patient in question is experiencing this type of acid-base disturbance. This particular acid-base imbalance is typically seen in cases of poisoning with substances such as glycols (ethylene and propylene), salicylates (aspirin), paracetamol, methanol, isoniazid, and paraldehyde.

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 collateral 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.