aDrugs commonly causing poisonings

Essentials

  • For general principles of identifying and treating poisoning, see (Treatment of poisoning).
  • Benzodiazepines are the most common group of drugs that cause poisonings.
Table 1. Features of poisoning caused by certain groups of psychopharmaceuticals (antidepressants, antipsychotics, lithium)
SSRIs, SNRIs and other new generation antidepressants Tricyclic antidepressants Antipsychotics Lithium
Severe poisoning caused by an SSRI or other new generation antidepressant alone is rare. Poisoning is rare but exceptionally severe. Tolerance may be low if the patient is unaccustomed to antipsychotics. People who have not previously used lithium may tolerate even high doses, and people using lithium may show symptoms of poisoning at even only slight overdose
Active ingredients belonging to the group Fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram
Venlafaxine, mirtazapine, reboxetine		 Nortriptyline, amitriptyline, clomipramine, trimipramine, doxepin Chlorpromazine, levomepromazine, promazine, chlorprothixene, thioridazine, haloperidol, perphenazine
Olanzapine, risperidone, quetiapine, clozapine		 Lithium
Mechanism of action Inhibition of reuptake of serotonin (in some cases noradrenaline or dopamine) Inhibition of reuptake of serotonin, noradrenaline and dopamine in nerve cells + sodium channel blockade Dopamine receptor blockade, in some cases also effects such as serotonin, muscarine or histamine receptor blockade Exact mechanism of action not known
Clinical picture
  • GI symptoms: nausea, vomiting
  • CNS symptoms: vertigo, restlessness, ataxia, tremor, mild sedation, rarely deep unconsciousness or convulsions
  • Hyponatraemia
  • Venlafaxine may also cause anticholinergic symptoms or QT interval prolongation
  • Serotonin syndrome possible
  • Anticholinergic symptoms (urinary retention, paralytic ileus, dry mouth, visual disturbances, mydriasis)
  • Sedation, confusion, ataxia
  • Treatment-resistant convulsions
  • Respiratory depression, respiratory distress
  • Haemodynamic failure
  • Widened QRS complex, ventricular tachycardia
  • Anticholinergic symptoms
  • CNS symptoms: agitation, confusion, extrapyramidal symptoms, impaired consciousness, convulsions
  • Disturbed temperature regulation
  • Hypotension, arrhythmia; QT interval prolongation; torsades de pointes with a delay of as long as 15 h for some agents
  • In long-term use, neuroleptic malignant syndrome is possible
  • GI symptoms: nausea, vomiting, diarrhoea
  • CNS symptoms: restlessness, confusion, tremor, ataxia, muscle weakness and stiffness, impaired consciousness, convulsions
  • Respiratory depression
  • Arrhythmia, hypotension
Treatment
  • Wide QRS: consider sodium bicarbonate (Nabic*).
  • Beware of agents prolonging the QT interval (such as ondansetron, amiodarone)!
  • Intubation anaesthesia at an early stage; medicinal charcoal
  • Anticholinergic effects: medicinal charcoal may be useful for a longer time.
  • Wide QRS, arrhythmia: Nabic*
  • Recurrent VT: lidocaine
  • The anticholinergic effect slows down absorption; therefore medicinal charcoal may be useful for a longer time.
  • Avoid agents prolonging the QT interval (such as ondansetron, amiodarone)!
  • Torsades de pointes: magnesium
  • Wide QRS: consider Nabic*
  • Not bound to medicinal charcoal.
  • Elimination can be accelerated by dialysis.
  • Treatment guided by lithium levels, which do not correlate directly with the severity of poisoning; symptoms are one of the factors determining the need for treatment and monitoring.
* Sodium bicarbonate (NaHCO3)

Benzodiazepines

  • Symptoms
    • Sedative syndrome (see table (Treatment of poisoning))
    • Hypotension may occur; it is mainly mild and associated with mixed poisoning.
    • Respiratory depression is possible; however, in most cases it is caused by a blocked airway in an unconscious person.
  • Preparations used as sleep medication are more dangerous than the less sedative ones.
  • Long-term users tolerate clearly higher doses; on the other hand, there is a risk of even severe withdrawal symptoms if use is suddenly interrupted.
  • Other pharmaceutical agents lowering the level of consciousness and alcohol potentiate the toxic effects; alcohol concentrations must be assessed with a breathalyser.

Antidepressants

  • Tricyclic antidepressants are clearly most dangerous, SSRIs are the safest, and venlafaxine and mirtazapine are between these two groups. See table T1.
  • Prolonged QTc-time is associated with drug poisonings caused by antidepressants, especially tricyclics. In the case of SSRIs, there are suggestions that citalopram may be more toxic in this respect.
  • Serotonin syndrome (see table (Treatment of poisoning)) is a possible adverse effect of all antidepressants, particularly SSRI drugs.

Tricyclic antidepressants

  • Doses exceeding 1 g are dangerous.
  • Anticholinergic effects are significant. They delay gastric emptying, and thus the effect of medicinal charcoal lasts longer (recommended when less than 12 hours have elapsed from drug ingestion). On the other hand, in rare cases, severe symptoms have been reported even several days after drug ingestion.
  • Typical symptoms of severe intoxication
    • CNS symptoms: impaired consciousness, convulsions
    • Cardiac symptoms: conduction disturbances (AV conduction, branch blocks) and arrhythmias (both atrial and ventricular brady- and tachycardias)
    • Wide QRS complex, > 0.12 sec, on ECG is a warning sign.

SSRIs

  • Usually cause only mild intoxications.
    • CNS symptoms (agitation, restlessness, confusion, muscle rigidity, convulsions)
    • Symptoms of the autonomic nervous system (tachycardia, sweating, flushes, mydriasis)
    • Some drugs have been found to cause cardiac conduction disorders (widening of the QRS complex, prolongation of QT interval) when used in high doses.
  • Serotonin syndrome (see table (Treatment of poisoning)) may occur, usually as a result of concomitant use of other drugs or herbal medicinal products containing Saint-John's wort (hypericum).
  • Symptoms suggesting serotonin syndrome
    • Hyperthermia
    • Muscle jerks (myoclonus)
    • Irreversible symptoms develop eventually: convulsions, hyperthermia, increased intracranial pressure, death.

Antipsychotics

  • High-dose antipsychotics (levomepromazine, chlorpromazine, etc.) have been considered more dangerous than low-dose drugs (e.g. haloperidol). See T1
    • Cardiorespiratory depression is more severe.
    • The elimination half-life of many antipsychotics is long and anticholinergic effects are common: therefore, sufficiently long follow-up is needed and administration of medicinalcharcoal is necessary even in the later stages of poisoning.
  • Symptoms
    • Anticholinergic syndrome (see table (Treatment of poisoning))
    • Frequently hypotension and tachycardia
    • Arrhythmias, particularly rapid ones
    • Extrapyramidal symptoms (particularly with low-dose antipsychotics)
    • Unconsciousness, convulsions, respiratory depression

Opioids

  • These drugs are abused, and oral and transdermal preparations are also injected.
  • Remember combination preparations (in particular codeine + paracetamol) and treat intoxication caused by all components
  • There is typically an opioid syndrome that is aggravated by other sedative drugs or alcohol.
    • impaired consciousness
    • pinhole pupils
    • respiratory depression (bradypnoea and cyanosis)
  • Tramadol causes atypical symptoms (convulsions, nausea, seldom respiratory depression).
  • In addition, some opioids cause cardiac conduction disorders (prolonged QT interval), some a risk of serotonin syndrome in association with mixed poisoning involving antidepressants.
Table 2. Features of poisoning caused by certain groups of drugs (analgesics, antirheumatics, antiepileptics, iron, antidiabetics)
Drug group Features associated with poisoning Treatment
Paracetamol
  • One of the most common causes of severe drug poisoning either alone or as one causative agent in mixed poisoning. N.B.! Combination products (with codeine, for instance) – risk of paracetamol poisoning even if its dose in the combination is low.
  • Toxic dose 150 mg/kg. In a person weighing 70 kg, for example, > 10 g/24 h or > 6 g for at least 2 days.
  • Poisoning may occur at lower doses if there is abundant alcohol consumption, use of drugs affecting liver metabolism, hepatic or renal failure, fatty liver
  • Toxicity is associated with NAPQI, a hepatotoxic metabolite eliminated by glutathione.
  • The patient may remain asymptomatic for a long time. Life-threatening liver damage will develop in 3–5 days.
  • Initial treatment: medicinal charcoal, symptomatic treatment
  • Antidote (given in hospital): For severe poisoning, N-acetylcysteine should be started as soon as possible.
Aspirin
Other NSAIDs
  • Untreated aspirin poisoning may be fatal; should be kept in mind as a differential diagnostic alternative in case of mixed poisoning or disturbed consciousness of unknown cause.
  • Toxic dose of aspirin: for children, 150 mg/kg, for adults, > 6.5 g. Advanced age and renal failure are predisposing factors.
  • Metabolic acidosis, impaired consciousness, convulsions and haemodynamic failure are signs of poor prognosis.
  • Poisoning with other NSAIDs is less dangerous.
  • Initial treatment: medicinal charcoal; avoid hyperventilation, maintain pH at > 7.3, sodium bicarbonate (Nabic*), as necessary
  • In hospital, measurement of blood concentration; in case of severe poisoning, dialysis and intensive care
Antiepileptic drugs
Phenytoin, carbamazepine, valproic acid, lamotrigine, lacosamide, topiramate, levetiracetam, pregabalin, gabapentin
  • The toxic dose and clinical symptoms depend on the substance; furthermore, there is very little information available about the toxicity of new drugs. Do not hesitate to contact a specialized poison information center.
  • Many of the products are depot products with slow absorption and delayed onset of symptoms.
  • CNS symptoms: sedation, coordination and balance problems, muscle jerks (myoclonia), convulsions
  • Respiratory depression, arrhythmia, conduction defects
  • Bone marrow and liver damage possible as late symptoms in many patients
  • Initial treatment: medicinal charcoal, symptomatic treatment
  • In hospital, treatment guided by blood concentrations. Rarely dialysis.
Methotrexate
  • Single doses below 200 mg rarely cause severe poisoning but recurrent taking of even low doses (such as 25 mg/day) may do so.
  • The patient may be completely asymptomatic at first.
  • GI symptoms, fever, rash. Development of liver and kidney damage and bone marrow depression (neutropenic sepsis), CNS symptoms: headache, visual disturbances, confusion
  • Fatal poisoning is possible if, for instance, a dose meant to be taken once a week has accidentally been taken every day.
  • Initial treatment: medicinal charcoal, symptomatic treatment
  • In hospital, measurement of blood concentrations, folic acid, as necessary, calcium folinate as an antidote, alkalization of urine to speed up elimination, granulocyte growth factor, as necessary
Iron
  • Prescription and over-the-counter products. In addition to actual iron products, many vitamin products and herbal medicinal products contain iron.
  • In overdose, iron may have local, even caustic, effects on the gastrointestinal tract.
  • As systemic symptoms, metabolic acidosis and damage to several organs will follow.
  • Toxic dose: more than 60 mg/kg, moderately severe to severe poisoning, less than 40 mg/kg, usually no more than mild poisoning. The dose should be assessed as the amount of elemental iron (Fe) in the product, not of iron salts.
  • Initially, there are typically local GI irritation symptoms: severe vomiting, gastric pain, diarrhoea. After absorption, haemodynamic failure, acidosis, GI bleeding, unconsciousness and liver damage may develop.
  • Initial treatment: symptomatic treatment. Medicinal charcoal will not bind iron.
  • In hospital, intestinal lavage; consider endoscopic/surgical removal in severe cases; chest X-ray may show iron tablets. Gastric lavage is of no use. Deferoxamine can be used as an antidote.
Oral antidiabetics
  • Metformin may cause severe lactic acidosis but not hypoglycaemia in monotherapy.
  • Sulphonylureas may cause hypoglycaemia continuing for several days.
  • Hypokalaemia, hypomagnesaemia and hypophosphataemia are also common.
  • Initial treatment: medicinal charcoal, sugary food p.o., glucose infusion, as necessary, and Nabic* as first aid for acidosis, as necessary
  • In hospital, sufficiently long follow-up, need for glucose infusion for as long as several days
Insulin
  • The effect of rapid-acting insulins starts within a few minutes, that of long-acting insulins within 1–2 hours.
  • Treatment may be necessary for several days, for ultra-long acting insulins (glargine, detemir, degludec) for up to 3 days.
  • Also hypokalaemia, hypomagnesaemia and hypophosphataemia
  • Initial treatment: sugary food orally, glucose infusion, as necessary
  • In hospital, sufficiently long follow-up, need for glucose infusion for as long as several days
* Sodium bicarbonate (NaHCO3)

Other analgesics

  • The most harmful substances are over-the-counter aspirin and paracetamol (see T2)
  • Because of the large amount of drug in the tablets the dose of medicinal charcoal often needs to be increased.
  • Paracetamol poisoning is asymptomatic at first but its treatment should be started rapidly (see (Paracetamol poisoning)).

Aspirin (Acetylsalicylic acid)

  • For children, doses > 150 mg/kg and for adults doses > 6 g are dangerous.
  • Symptoms
    • GI symptoms (nausea, vomiting, diarrhoea, abdominal pain)
    • CNS symptoms (tinnitus, convulsions, unconsciousness)
    • Severe acidosis and hyperventilation
    • Haemodynamic failure

Other non-steroidal anti-inflammatory drugs

  • Usually cause only mild poisonings
  • Mainly GI symptoms
  • Severe symptoms (convulsions, renal failure, coagulation disturbances) are rare.

Pregabalin

  • A widely used analgesic that is also much misused, also intravenously
  • The most common symptoms of poisoning are nystagmus and decreased level of consciousness.

Cardiac drugs

  • Poisonings are rare considering the wide use of these drugs. However, they are invariably severe (see T3).
  • Drugs affecting the pumping ability and electrical activation of the heart cause the most severe poisonings while less severe poisonings are caused by drugs with only vasodilating activity.
Table 3. Features of poisoning due to cardiovascular drugs
Drug group Features associated with poisoning
ACE inhibitors and ARBs
  • Rarely cause significant haemodynamic failure in monotherapy.
  • Hyperkalaemia and renal failure are possible.
Diuretics
  • Rarely cause significant haemodynamic failure in monotherapy.
  • Disturbed fluid or electrolyte balance is possible.
Nitrates
  • Erythema, pulsating headache, palpitations, vertigo, hypotension, nausea, vomiting
  • Severe haemodynamic failure is possible with high doses; methemoglobinaemia may occur, as well.
Beta-blockers and calcium-channel blockers
  • Life-threatening poisoning possible, particularly if both have been taken
  • Poisoning may be difficult to treat and of long duration.
    • Hypotension due to impaired pumping ability, cardiac arrhythmia and conduction defects, in some patients vasodilation (amlodipine); bronchospasm and hypoglycaemia possible with beta-blockers
  • In addition to vasoactive agents, consider glucagon, insulin-glucose infusion, calcium gluconate
  • In very severe cases of poisoning, ECMO after due consideration
Other antiarrhythmic drugs
  • With sodium and potassium channel blockers, life-threatening poisoning is possible; the effect depends not only on dose but also on the mechanism of action.
  • Sodium channel blockade: e.g. flecainide
  • Potassium channel blockade: e.g. amiodarone, dronedarone, sotalol
  • Many retard/depot products
    • Symptoms may appear with delay, and telemetry/therapy may be required for several days.
  • Sodium bicarbonate can be used as an antidote for sodium channel blockade, lidocaine for the treatment of refractory ventricular fibrillation (beware of amiodarone).
Digoxin and other cardiac glycosides (e.g. foxglove/digitalis products)
  • Renal failure predisposes to toxicity. In elderly people, for example, toxicity is possible even at therapeutic doses if another condition develops that has negative effects on the body, such as infection + dehydration.
  • Many pharmaceutical agents increase digoxin concentrations.
  • Clinical picture: GI symptoms, hyperkalaemia (in chronic cases, hypokalaemia), all kinds of cardiac symptoms: brady-/tachyarrhythmia, all AV blocks, headache, drowsiness, confusion
  • Treat brady- and tachyarrhythmias according to general principles
  • In case of severe poisoning, use specific antidote
Chloroquine, hydroxychloroquine
  • As little as one tablet may be dangerous for a child.
  • In addition to other symptoms of poisoning, marked negative inotropic effect, i.e. reduced cardiac pumping. In addition, hyperkalaemia, widening of the QRS complex and severe ventricular arrhythmias, prolonged QT interval.
N.B!
  • Many antidepressants, antipsychotics and antiepileptics have some sodium and/or potassium channel blocking effect, and poisoning with such drugs may therefore also have severe ECG effects (widening of QRS complex, prolongation of QT interval) and cause life-threatening arrhythmia.

Beta-blockers

  • May rapidly (in as little as 30 min.) cause poorly manageable circulatory shock (see T3).
  • Symptoms
    • Bradycardia and hypotension, which may be provoked rapidly by, for example, vomiting.
    • Convulsions
    • Pulmonary oedema of non-cardiac origin
    • Bronchus obstruction in asthmatic patients
    • Hypoglycaemia

Calcium channel blockers

  • Cause symptoms resembling beta-blocker poisoning, but with a slower effect (see T3).
  • Doses that are double the therapeutic dose may allready cause circulatory symptoms. With long-acting preparations the symptom onset may be after several hours.

Digoxin

  • Most poisonings are accidents and result from the narrow therapeutic range (see T3).
  • Predisposing factors
    • Renal failure (age!)
    • Hypokalaemia, hypercalcaemia
    • Acidosis and hypoxia (poor tissue circulation is thus an independent risk factor!).
  • Symptoms are variable
    • Impaired general condition and confusion
    • CNS symptoms: disturbances of colour vision, headache, weakness, unconsciousness, convulsions
    • Various arrhythmias, particularly bradycardia and conduction disturbances but atrial or ventricular tachyarrhythmias are also possible.

Antiepileptic drugs

  • In particular the older drugs phenytoin, carbamazepine and valproic acid cause similar symptoms.
    • GI symptoms (abdominal pain, nausea, vomiting)
    • CNS symptoms: loss of consciousness, convulsions
    • Circulatory and respiratory depression is possible.
  • Blood concentrations can be measured and they affect the treatment decisions.

Chloroquine

  • Doses of only a few grams cause rapidly developing circulatory and respiratory depression (see T3). In children less than one year of age, a single tablet may be life threatening.

References

1. Vieweg WV, Wood MA. Tricyclic antidepressants, QT interval prolongation, and torsade de pointes. Psychosomatics 2004 Sep-Oct;45(5):371-7.  [PMID:15345781]
2. Kelly CA, Dhaun N, Laing WJ, Strachan FE, Good AM, Bateman DN. Comparative toxicity of citalopram and the newer antidepressants after overdose. J Toxicol Clin Toxicol 2004;42(1):67-71.  [PMID:15083939]
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