Cardiovascular medications

Cardiovascular medications
?-blockers
These have negative inotropic and chronotropic effects. Some have additional properties that may increase toxicity, such as blockade of sodium channels (e.g. propranolol) or potassium channels (e.g. sotalol).
Clinical features
The major features of toxicity are bradycardia and hypotension. Heart block, pulmonary oedema and cardiogenic shock occur in severe poisoning. Beta-blockers with sodium channel-blocking effects may cause seizures, confusion and coma, while sotalol may be associated with repolarisation abnormalities (including QTc prolongation) and torsades de pointes
Management
Intravenous fluids may reverse hypotension but care is required to avoid pulmonary oedema. Bradycardia and hypotension may respond to high doses of atropine (up to 3 mg in an adult). The adrenoceptor agonist isoproterenol (isoprenaline) may also be effective but high doses are often needed. Glucagon (5-10 mg over 10 mins, then 1-5 mg/hr by infusion), is now more commonly used.
Calcium channel blockers
Calcium channel blockers are highly toxic in overdose via blockade of L-type calcium channels. Dihydropyridines such as nifedipine or amlodipine affect vascular smooth muscle in particular, resulting in vasodilatation. Rate-limiting calcium channel blockers such as diltiazem and verapamil have direct cardiac effects, resulting in bradycardia and reduced myocardial contractility.
Clinical features
Hypotension is associated with vasodilatation and myocardial depression. Bradycardias and heart block may also occur, especially with verapamil and diltiazem. Non-cardiac effects include gastrointestinal disturbances, confusion, metabolic acidosis, hyperglycaemia and hyperkalaemia.
Management
Hypotension should be corrected with intravenous fluids, taking care to avoid pulmonary oedema. Persistent hypotension may respond to intravenous calcium gluconate (10 mg i.v. over 5 mins, repeated as required). Isoproterenol and glucagon may also be useful. Successful use of intravenous insulin with glucose (10-20% dextrose with insulin at 0.5-1.0 U/kg/hr), so-called hyperinsulinaemia euglycaemic therapy , has been reported in patients unresponsive to other strategies. Cardiac pacing may be needed for severe unresponsive bradycardias or heart block.
Cardiac glycosides
Poisoning with digoxin is usually accidental, arising from prescription of an excessive dose, impairment of renal function or drug interactions. Clinical features
Characteristic cardiac effects of toxicity are tachyarrhythmias (either atrial or ventricular) and bradycardias, with or without atrioventricular block. Ventricular bigeminy is common and atrial tachycardia with evidence of atrioventricular block is highly suggestive of the diagnosis. Severe poisoning is associated with hyperkalaemia. Non-cardiac features include confusion, headache, nausea, vomiting, diarrhoea and (rarely) altered colour vision.
Management
Activated charcoal is commonly administered to patients presenting early after ingestion of an acute overdose. Urea, electrolytes and creatinine should be measured, a 12-lead ECG performed and cardiac monitoring instituted. Hypoxia, hypokalaemia (sometimes associated with concurrent diuretic use), hypomagnesaemia and acidosis increase the risk of arrhythmias and should be corrected. Significant bradycardias may respond to atropine, although temporary pacing is sometimes needed. Ventricular arrhythmias may respond to intravenous magnesium. If available, digoxin-specific antibody fragments should be administered when there are severe ventricular arrhythmias or unresponsive bradycardias.
Antimalarials
Chloroquine
Chloroquine is highly toxic; doses of 5 g or more of chloroquine base are likely to be fatal in an adult.
Clinical features
Features of toxicity occur within 1 hour of ingestion and include nausea, vomiting, agitation, drowsiness, hypokalaemia, acidosis, headaches and blurred vision. Coma, convulsions and hypotension may occur in severe poisoning. ECG changes indicating conduction and repolarisation delay (prolonged QRS and QTc intervals) occur and are associated with ventricular tachycardia (including torsades de pointes), ventricular fibrillation and sudden death.
Management
Activated charcoal should be given to all patients presenting within 1 hour of ingestion of chloroquine in amounts greater than 15 mg/kg. The cardiac rhythm should be monitored and dysrhythmias managed. The arterial pH should be corrected, but hypokalaemia is thought to have a protective effect and should not be corrected in the first 8 hours after poisoning. High-dose diazepam (2 mg/kg body weight i.v. over 30 mins) has been suggested as having a protective effect, especially if given in the early stages of severe chloroquine poisoning, but evidence is limited as yet. Respiratory support may be required.


Quinine
Quinine salts are widely used for treating malaria and leg cramps. Deaths have been reported with as little as 1.5 g in an adult and 900 mg in a child.
Clinical features
Features of toxicity include nausea, vomiting, tremor, tinnitus and deafness. Hypotension, haemolysis, renal failure, ataxia, convulsions and coma are features of serious poisoning. Conduction and repolarisation delay results in prolonged QRS and QTc intervals on the ECG, and ventricular tachycardia (including torsades de pointes), ventricular fibrillation and sudden death may occur. Quinine-induced retinal vasoconstriction and retinal photoreceptor cell toxicity may result in blurred vision and impaired colour perception. This usually develops a few hours after overdose and progresses to constriction of the visual field, scotoma and complete blindness associated with pupillary dilatation and unresponsiveness to light. Fundoscopy may show retinal artery spasm, disc pallor and retinal oedema. Although visual loss can be permanent, some degree of recovery often occurs over several weeks.
Management
Multiple-dose activated charcoal should be commenced in patients who have taken quinine in amounts greater than 15 mg/kg. Gastric lavage may also be considered if patients have presented within 1 hour. All patients should have a 12-lead ECG and cardiac monitoring, and their urea, electrolytes and glucose checked. Dysrhythmias, hypotension, seizures and coma should be managed
There are no effective treatments for the visual effects of quinine. Stellate ganglion block and retrobulbar or intravenous injections of vasodilators such as nitrates were previously used but are ineffective, as are haemodialysis and haemoperfusion.
Iron
The toxicity of iron preparations is related to their elemental iron content.
Clinical features
Early clinical features include gastrointestinal disturbance with the passage of grey or black stools. Haematemesis or rectal bleeding may occur. Hyperglycaemia and leucocytosis suggest significant toxicity. Drowsiness, convulsions, coma, metabolic acidosis and cardiovascular collapse may occur in severe poisoning.
Early symptoms may improve or even resolve within 6-12 hours, but hepatocellular necrosis may develop 12-24 hours after overdose and occasionally this progresses to hepatic failure. Gastrointestinal strictures are late complications of iron poisoning.
Management
Gastric lavage may be considered in patients presenting within 1 hour of overdose. Activated charcoal is ineffective since iron is not bound. Serum iron concentration should be measured. The antidote desferrioxamine chelates iron and should be administered immediately in patients with severe features, without waiting for serum iron concentrations to be available. Symptomatic patients with high serum iron concentrations (e.g. > 5 mg/L) should also receive desferrioxamine. Desferrioxamine may cause hypotension, allergic reactions and occasionally pulmonary oedema. Otherwise treatment is supportive and directed at complications.
Antipsychotic drugs
Antipsychotic drugs are often prescribed for patients at high risk of self-harm or suicide, and are commonly encountered in overdose.
Clinical features
Drowsiness, tachycardia and hypotension are frequently found. Anticholinergic features and acute dystonias (e.g. oculogyric crisis, torticollis and trismus) may occur after overdose with typical antipsychotics such as haloperidol or chlorpromazine. QT interval prolongation and torsades de pointes may occur with some antipsychotics. Convulsions may occur.
Management
Activated charcoal may be of benefit if given sufficiently early. Cardiac monitoring should be undertaken for at least 6 hours. Management is largely supportive, with treatment directed at complications
Antidiabetic agents
Antidiabetic agents commonly causing toxicity in overdose include the sulphonylureas (e.g. chlorpropamide, glibenclamide, gliclazide, glipizide and tolbutamide), biguanides (metformin and phenformin) and insulins.
Clinical features
Sulphonylureas and parenteral insulin cause hypoglycaemia when taken in overdose, although insulin is non-toxic if ingested. The duration of hypoglycaemia depends on the half-life or release characteristics of the preparation and may be prolonged over several days with long-acting agents such as chlorpropamide, insulin zinc suspension or insulin glargine.
Features of hypoglycaemia include nausea, agitation, sweating, aggression and behavioural disturbances, confusion, tachycardia, hypothermia, drowsiness, coma or convulsions. Permanent neurological damage can occur if the hypoglycaemia is prolonged.
Metformin is uncommonly associated with hypoglycaemia. Its major toxic effect in overdose is lactic acidosis, which can be associated with a high mortality, and is particularly common in older patients and those with renal or hepatic impairment, or when ethanol is co-ingested. Other features of metformin overdose are nausea and vomiting, diarrhoea, abdominal pain, drowsiness, coma, hypotension and cardiovascular collapse.
Management
Activated charcoal should be considered for all patients who present within 1 hour of ingestion of a substantial overdose of an oral hypoglycaemic agent. Venous blood glucose, urea and electrolytes should be measured and tests repeated regularly. Hypoglycaemia should be corrected using oral or intravenous glucose (50 mL of 50% dextrose); an infusion of 10-20% dextrose may be required to prevent recurrence. Intramuscular glucagon can be used as an alternative, especially if intravenous access is unavailable. Failure to regain consciousness within a few minutes of normalisation of the blood glucose can indicate that a central nervous system (CNS) depressant has also been ingested, the hypoglycaemia has been prolonged, or there is another cause for the coma (e.g. cerebral haemorrhage or oedema).
Arterial blood gases should be taken after metformin overdose to assess the extent of acidosis. If present, plasma lactate should be measured and acidosis should be corrected with intravenous sodium bicarbonate (e.g. 250 mL 1.26% solution or 50 mL 8.4% solution, repeated as necessary). In severe cases haemodialysis or haemodiafiltration is used.