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Antidepressants
Tricyclic antidepressants
Overdose with tricyclic antidepressants (TCAs) carries a high morbidity
and mortality because of their sodium channel-blocking, anticholinergic
and α-adrenoceptor-blocking effects.
Clinical features
Anticholinergic effects are common . Severe complications include
convulsions, coma and arrhythmias (ventricular tachycardia, ventricular
fibrillation and, less commonly, heart block). Hypotension results from
inappropriate vasodilatation or impaired myocardial contractility.
Serious complications appear more common with dosulepin and
amitriptyline.
Management
Activated charcoal should be administered if the patient presents
within 1 hour. A 12-lead ECG should be taken and continuous cardiac
monitoring maintained for at least 6 hours. Prolongation of the QRS
interval (especially if > 0.16 secs) indicates severe sodium channel
blockade and a high risk of arrhythmia. QT interval prolongation may
also occur. Arterial blood gases should be measured in suspected
severe poisoning. In patients with arrhythmias, significant QRS or QT
prolongation or acidosis, intravenous sodium bicarbonate (50 mL of
8.4% solution) should be administered and repeated to correct pH.
The correction of the acidosis and the sodium loading that results may
bring about rapid improvement in ECG features and arrhythmias.
Hypoxia and electrolyte abnormalities should also be corrected. Anti-
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arrhythmic drugs should only be given on specialist advice. Prolonged
seizures should be treated initially with intravenous benzodiazepines.
SSRI
Lithium
Antidiabetic agents
Overdose is uncommon but toxic effects can be severe.
Clinical features
Sulphonylureas, meglitinides (e.g. nateglinide, repaglinide) and
parenteral insulin cause hypoglycaemia when taken in overdose,
although insulin is non-toxic if ingested by mouth. 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 glibenclamide, insulin zinc suspension or insulin glargine.
Features of hypoglycaemia include nausea, agitation, sweating,
aggression, delirium, tachycardia, hypothermia, drowsiness,
convulsions and coma. Permanent neurological damage can occur if
hypoglycaemia is prolonged. Hypoglycaemia can be diagnosed using
bedside glucose strips but venous blood should also be sent for
laboratory confirmation. Metformin is uncommonly associated with
hypoglycaemia. Its major toxic effect is lactic acidosis, which can have a
high mortality, and is particularly common in older patients and those
with renal or hepatic impairment, or when ethanol has been co-
ingested. Other features of metformin overdose are nausea, vomiting,
diarrhoea, abdominal pain, drowsiness, coma, hypotension and
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cardiovascular collapse. There is limited experience of overdose
involving thiazolidinediones (e.g. pioglitazone) and dipeptidyl peptidase
4 (DPP-4) inhibitors (e.g. sitagliptin) but significant hypoglycaemia is
unlikely.
Management
Activated charcoal should be considered for recent substantial
overdose. Venous blood glucose and urea and electrolytes should be
measured and measurement 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 of
coma (e.g. cerebral haemorrhage or oedema).
Cardiovascular medications
Although not common, cardiovascular drug overdose is important
because features of toxicity are often severe.
Beta-blockers
Major features of toxicity are bradycardia and hypotension; heart
block, pulmonary oedema and cardiogenic shock occur in severe
poisoning. Those with additional sodium channel-blocking effects (e.g.
propranolol, acebutolol, carvedilol) may cause seizures, delirium and
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coma, while sotalol, which also blocks potassium channels, may cause
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) or an infusion of isoproterenol.
Glucagon (5–10 mg over 10 mins, then 1–5 mg/hr by infusion)
counteracts β-blockade by stimulating intracellular cyclic
adenosine monophosphate (cAMP) production and is now more
commonly used.
In severe cases, ‘hyperinsulinaemia euglycaemic therapy’ has
been used, as described under calcium channel blockers below.
The efficacy of lipid emulsion therapy in severe poisoning with
lipid-soluble β-blockers, such as propranolol, carvedilol and
oxprenolol, is uncertain.
Calcium channel blockers
Dihydropyridines (e.g. nifedipine, amlodipine) cause vasodilatation,
whereas diltiazem and verapamil have predominantly cardiac
effects, including bradycardia and reduced myocardial contractility.
Clinical features
Hypotension due to vasodilatation or myocardial depression is
common and bradycardias and heart block may also occur,
especially with verapamil and diltiazem. Gastrointestinal
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disturbances, delirium, metabolic acidosis, hyperglycaemia and
hyperkalaemia may also be present.
Management
Hypotension should be corrected with intravenous fluids,
taking care to avoid pulmonary oedema.
Persistent hypotension may respond to intravenous calcium
gluconate (10 mg IV 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 initially at 0.5–2.0 U/kg/ hr, increasing to
5–10 U/kg/hr according to clinical response), so-called
‘hyperinsulinaemia euglycaemic therapy’, has been reported
in patients unresponsive to other strategies. The mechanism
of action remains to be fully elucidated, but in states of shock
myocardial metabolism switches from use of free fatty acids
to glucose. Calcium channel blocker poisoning is also
associated with hypoinsulinaemia and insulin resistance,
impeding glucose uptake by myocytes. High doses of insulin
inhibit lipolysis and increase glucose uptake and the efficiency
of glucose utilisation.
Cardiac pacing may be needed for severe unresponsive
bradycardias or heart block.
Lipid emulsion therapy has also been used in severe
poisoning with apparent benefit, although evidence is largely
anecdotal.
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Digoxin and oleander
Poisoning with digoxin is usually accidental, arising from prescription of
an excessive dose, impairment of renal function or drug interactions. In
South Asia, deliberate self-poisoning with yellow oleander, containing
cardiac glycosides, is common.
Clinical features
Cardiac effects include 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 often associated with hyperkalaemia. Non-cardiac features
include delirium, headache, nausea, vomiting, diarrhoea and (rarely)
altered colour vision. Digoxin poisoning can be confirmed by elevated
plasma concentration.
Management
Activated charcoal is commonly administered to patients
presenting soon after acute ingestion, although evidence of
benefit is lacking.
Urea, electrolytes and creatinine should be measured.
a 12-lead ECG performed and cardiac monitoring instituted.
Hypoxia, hypokalaemia (sometimes caused by 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.
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If available, digoxin-specific antibody fragments should be
administered when there are severe refractory ventricular
arrhythmias or bradycardias. These are effective for both digoxin
and yellow oleander poisoning.
Iron
antipsychotics