Toxicology – Cyanide Poisoning

Source

Cyanide exposure can occur during smoke inhalation from structural fires, especially when materials such as wool, silk, plastics, insulation, or rubber burn. It may also be encountered in certain industrial settings, some foods or plant products, and rarely from prolonged nitroprusside therapy.

Typical Presentation

A patient exposed to heavy smoke or an occupational cyanide source may rapidly develop confusion, shortness of breath, chest discomfort, seizures, or cardiovascular collapse. Cyanide toxicity should be considered in severe smoke inhalation with unexplained lactic acidosis or sudden hemodynamic deterioration.

Clinical Features

Possible findings include:

• Headache
• Nausea and vomiting
• Altered mental status
• Dilated pupils
• Rapid breathing
• Tachycardia
• Early hypertension
• Later hypotension and respiratory depression
• Chest pain
• Seizures
• Cardiovascular collapse

Laboratory abnormalities may show:

• Severe lactic acidosis
• High anion gap metabolic acidosis
• Unusually high venous oxygen content because tissues cannot effectively extract oxygen

Mechanism of Action

Cyanide inhibits cytochrome c oxidase in the mitochondrial electron transport chain. This blocks aerobic cellular respiration, preventing tissues from using oxygen despite adequate oxygen delivery and causing rapid anaerobic metabolism and lactate accumulation.

Management

Treatment requires immediate supportive care:

• High-flow oxygen and airway support
• Cardiac and hemodynamic monitoring
• Aggressive management of seizures and shock
• Hydroxocobalamin is a preferred antidotal therapy because it binds cyanide to form a less toxic compound that can be eliminated
• Sodium thiosulfate may also be used to enhance conversion of cyanide to thiocyanate

Nitrite-based antidotes induce methemoglobinemia and are generally less desirable when carbon monoxide exposure is also suspected, as commonly occurs in fire victims.

Key Points

• Think of cyanide toxicity in patients with severe smoke inhalation plus cardiovascular collapse or marked lactic acidosis.
• Cyanide prevents cells from using oxygen rather than preventing oxygen from reaching the blood.
• Hydroxocobalamin is a major antidote used in suspected cyanide poisoning.
• A markedly elevated lactate level can serve as an important indirect clue.

Toxicology – Antipsychotic Toxicity

Source

Antipsychotic medications are used to treat conditions such as schizophrenia, psychosis, severe agitation, and bipolar disorder. They include first-generation agents such as haloperidol and second-generation agents such as risperidone, olanzapine, quetiapine, clozapine, and aripiprazole.

Typical Presentation

A patient with excessive antipsychotic exposure may present with drowsiness, confusion, tachycardia, and hypotension. Severe toxicity can progress to respiratory depression, seizures, coma, or cardiac conduction abnormalities.

Clinical Features

Possible findings include:

• Sedation or agitation
• Ataxia
• Confusion
• Seizures
• Coma
• Respiratory depression
• Orthostatic hypotension

Some agents may also produce anticholinergic findings, including:

• Dilated pupils
• Dry skin and mucous membranes
• Tachycardia
• Urinary retention
• Reduced bowel sounds
• Agitation

ECG abnormalities may include:

• QRS widening
• QT prolongation
• Cardiac dysrhythmias in severe cases

Mechanism of Action

Most antipsychotics block dopamine D2 receptors to varying degrees. First-generation drugs generally produce stronger D2 blockade and therefore more extrapyramidal adverse effects. Many second-generation agents also affect serotonin receptors. Additional blockade of α1-adrenergic, histamine, and muscarinic receptors contributes to hypotension, sedation, and anticholinergic effects.

Management

Treatment is primarily supportive:

• Airway and respiratory support when necessary
• Continuous ECG and cardiac monitoring
• IV fluids for hypotension
• Vasopressors may be required for persistent hypotension
• Treat significant QRS widening or QT-related dysrhythmias according to toxicology and resuscitation guidance
• Benzodiazepines may be used for seizures or severe agitation

Key Points

• Antipsychotics can cause extrapyramidal symptoms, dystonia, neuroleptic malignant syndrome, anticholinergic effects, and orthostatic hypotension.
• Clozapine is associated with agranulocytosis.
• Seizures are uncommon overall but are more strongly associated with clozapine.
• Cardiac monitoring is important because some agents can prolong the QT interval or impair conduction.

Toxicology – Phenytoin & Fosphenytoin Toxicity

Source

Phenytoin is an anticonvulsant used for seizure control. Fosphenytoin is a water-soluble prodrug of phenytoin that is commonly used intravenously because it is better tolerated.

Typical Presentation

A patient taking phenytoin may present with unsteady gait, slurred speech, lethargy, and altered mental status. Neurological findings usually become more pronounced as the serum concentration rises.

Clinical Features

Acute toxicity is dominated by neurological symptoms, including:

• Nystagmus
• Nausea and vomiting
• Ataxia and poor coordination
• Slurred speech
• Lethargy
• Extrapyramidal movements
• Altered mental status
• Coma in severe cases

IV phenytoin can also cause:

• Hypotension
• Ventricular dysrhythmias
• Cardiovascular collapse

Chronic therapy may be associated with:

• Gingival hyperplasia
• Coarsening of facial features
• Chronic ataxia
• Liver injury

Mechanism of Action

Phenytoin inhibits voltage-gated sodium channels in neurons, reducing repetitive neuronal firing. Excessive concentrations produce predominantly cerebellar and CNS dysfunction.

Management

Treatment is mainly supportive:

• Airway and respiratory support when necessary
• Neurological monitoring
• Cardiac monitoring after IV phenytoin toxicity
• Activated charcoal may be considered in appropriate recent oral exposures
• Manage hypotension, dysrhythmias, or other complications supportively

There is no specific antidote for phenytoin toxicity.

Key Points

• Nystagmus, ataxia, and slurred speech are classic findings of phenytoin toxicity.
• Neurological toxicity generally worsens as drug levels rise.
• IV phenytoin formulations can cause significant cardiovascular toxicity.
• Fosphenytoin is generally safer for IV administration because it does not contain the propylene glycol vehicle used in traditional IV phenytoin.
• IV phenytoin may cause severe local tissue injury, sometimes referred to as purple glove syndrome.

Toxicology – Carbamazepine Toxicity

Source

Carbamazepine is an anticonvulsant used for seizure disorders, trigeminal neuralgia, neuropathic pain, and bipolar disorder.

Typical Presentation

A patient, often after accidental or intentional ingestion, may develop marked drowsiness, unsteady gait, slurred speech, and altered mental status. Severe poisoning can progress to seizures, respiratory depression, coma, and cardiac conduction abnormalities.

Clinical Features

Possible findings include:

• Sedation and confusion
• Ataxia
• Dysarthria
• Nystagmus
• Anticholinergic features
• Respiratory depression
• Seizures
• Coma

ECG abnormalities may include:

• QRS widening
• QT prolongation
• Cardiac dysrhythmias in severe toxicity

Mechanism of Action

Carbamazepine blocks voltage-gated sodium channels, accounting for both its therapeutic anticonvulsant activity and many of its toxic effects. It is structurally related to tricyclic antidepressants and also has anticholinergic and sedating properties.

Management

Treatment is primarily supportive:

• Airway and respiratory support when needed
• Continuous cardiac monitoring and serial ECGs
• Benzodiazepines for seizures
• Sodium bicarbonate for clinically significant sodium-channel blockade with QRS widening
• Serial carbamazepine concentrations may be useful because absorption can be delayed and levels may continue to rise
• Multiple-dose activated charcoal may enhance elimination in selected significant poisonings
• Hemodialysis or hemoperfusion may be considered in severe or refractory toxicity with specialist guidance

Key Points

• Although carbamazepine treats seizures, overdose can itself cause seizures.
• Ataxia, nystagmus, sedation, and anticholinergic findings are common neurological clues.
• Sodium-channel blockade can produce dangerous cardiac conduction abnormalities.
• Chronic carbamazepine therapy may be associated with hyponatremia.

Toxicology – Monoamine Oxidase Inhibitor (MAOI) Toxicity

Source

Monoamine oxidase inhibitors are antidepressants now used mainly for atypical or treatment-resistant depression. Certain MAO-inhibiting drugs are also used in Parkinson disease.

Typical Presentation

A patient taking an MAOI may present with severe agitation, hypertension, sweating, tachycardia, and altered mental status. In overdose, symptoms can be significantly delayed and may later progress from a hyperadrenergic state to profound hypotension and cardiovascular collapse.

Clinical Features

MAOI toxicity can appear in several forms:

• Hyperadrenergic crisis: Headache, flushing, diaphoresis, dilated pupils, tachycardia, severe hypertension, and agitation. This may occur after consumption of high-tyramine foods while taking an MAOI.
• Acute overdose: Similar hyperadrenergic findings plus hyperthermia, vomiting, diarrhea, psychosis, myoclonus, seizures, and marked altered mental status. Severe cases may progress to coma, hypotension, and cardiovascular collapse.
• Serotonin syndrome: May occur when MAOIs are combined with other serotonergic medications and is characterized by altered mental status, autonomic instability, and neuromuscular hyperactivity.

Symptoms after overdose may not appear for many hours and can persist for several days.

Mechanism of Action

MAOIs inhibit monoamine oxidase, the enzyme responsible for breaking down serotonin, norepinephrine, and dopamine. This causes accumulation of these neurotransmitters and excessive adrenergic and serotonergic activity.

Management

Treatment is primarily supportive:

• Airway and respiratory support when necessary
• Continuous cardiac and blood pressure monitoring
• Benzodiazepines for agitation and seizures
• Rapid cooling for significant hyperthermia
• Short-acting IV antihypertensive therapy may be required for severe hypertension
• IV fluids and vasopressors may be necessary if cardiovascular collapse develops
• Gastrointestinal decontamination may be considered in appropriate recent exposures

Because toxicity can be delayed, significant MAOI overdoses generally require prolonged monitored observation.

Key Points

• MAOI overdose can have a markedly delayed onset.
• Early toxicity often produces a hyperadrenergic state with hypertension and agitation.
• Severe poisoning may later progress to hypotension, coma, and cardiovascular collapse.
• Combining MAOIs with serotonergic drugs can precipitate serotonin syndrome.

Toxicology – Tricyclic Antidepressant (TCA) Toxicity

Source

Tricyclic antidepressants were once widely used for depression but are now also prescribed for conditions such as neuropathic pain, migraine prevention, OCD, and nocturnal enuresis. Examples include amitriptyline, clomipramine, desipramine, doxepin, imipramine, and nortriptyline.

Typical Presentation

A patient with TCA overdose may present with altered mental status, anticholinergic findings, seizures, hypotension, or ECG abnormalities, especially a widened QRS complex.

Clinical Features

Toxicity commonly affects the nervous and cardiovascular systems.

Anticholinergic findings:

• Dilated pupils
• Dry skin and mucous membranes
• Flushing
• Hyperthermia
• Tachycardia
• Urinary retention
• Confusion

Other important findings include:

• Sedation progressing to coma
• Seizures
• Orthostatic hypotension
• Cardiac arrhythmias

ECG abnormalities may include:

• Sinus tachycardia
• PR prolongation
• QRS widening
• QT prolongation
• Potentially fatal ventricular dysrhythmias

Mechanism of Action

TCAs have several pharmacologic actions, including:

• Anticholinergic activity
• Antihistamine effects
• α-adrenergic blockade
• Inhibition of serotonin and norepinephrine reuptake

Their most dangerous cardiac effect results from voltage-gated sodium channel blockade, which slows cardiac conduction and widens the QRS. Potassium-channel effects may also contribute to QT prolongation.

Management

Treatment requires rapid supportive care:

• Airway and respiratory support as needed
• Continuous cardiac monitoring and serial ECGs
• Benzodiazepines for seizures
• IV fluids for hypotension
• Sodium bicarbonate is the key therapy when significant QRS widening, ventricular dysrhythmias, or persistent hypotension is present
• Vasopressor support, typically norepinephrine, may be required if hypotension persists
• IV lipid emulsion may be considered in severe refractory toxicity with specialist guidance

Key Points

• QRS widening is an important marker of severe TCA toxicity.
• Increasing QRS duration is associated with a greater risk of seizures and ventricular arrhythmias.
• Cyclobenzaprine is structurally similar to TCAs and may produce a similar overdose pattern.
• Some TCAs, particularly desipramine, may produce prominent cardiotoxicity even without obvious anticholinergic findings.

 Toxicology – Bupropion Toxicity

Source

Bupropion is a prescription medication used primarily as an antidepressant and as an aid for smoking cessation. It is available in immediate-release and extended-release formulations.

Typical Presentation

A patient with excessive bupropion exposure may initially develop agitation and tachycardia before suddenly experiencing a generalized seizure. Extended-release formulations are particularly important because serious neurological and cardiovascular effects may be delayed.

Clinical Features

Possible manifestations include:

• Agitation and restlessness
• Sinus tachycardia
• Hypertension
• Nausea and vomiting
• Lethargy or altered mental status
• Orthostatic hypotension
• Seizures, which are a major feature of toxicity
• QRS widening
• QTc prolongation
• Cardiovascular instability in severe poisoning

Seizure risk increases with greater exposure, although seizures have occasionally been reported during therapeutic use.

Mechanism of Action

Bupropion primarily inhibits the reuptake of dopamine and norepinephrine, increasing their activity within the CNS. Its effects on dopamine are particularly prominent. The medication undergoes hepatic metabolism and has active metabolites that may contribute to prolonged toxicity.

Management

Treatment is primarily supportive:

• Maintain and protect the airway when necessary
• Continuous cardiac and neurological monitoring
• Benzodiazepines are first-line treatment for seizures
• Manage status epilepticus aggressively if it develops
• Monitor ECG for QRS and QT abnormalities
• Gastrointestinal decontamination may be considered in selected significant exposures
• Severe cardiovascular toxicity may require advanced toxicology-directed supportive therapies

Extended-release overdoses generally require prolonged observation because seizures and cardiovascular complications can occur after a substantial delay.

Key Points

• Seizures are a hallmark of bupropion toxicity.
• Extended-release preparations can produce delayed seizures.
• ECG abnormalities may include QRS widening and QTc prolongation.
• Severe poisoning can progress from agitation and tachycardia to seizures, altered consciousness, and cardiovascular collapse.

Toxicology – Selective Serotonin Reuptake Inhibitor (SSRI) Toxicity

Source

SSRIs are widely used to treat depression, anxiety disorders, and several other psychiatric conditions. Common agents include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

Typical Presentation

Most isolated SSRI overdoses cause only mild symptoms. Patients may present with nausea, vomiting, drowsiness, agitation, or changes in heart rate. More serious toxicity can occur with large exposures, certain agents, or when serotonin-enhancing drugs are combined.

Clinical Features

Possible effects include:

• Nausea and vomiting
• Tachycardia or bradycardia
• Drowsiness or agitation
• Ataxia
• Altered mental status
• Rarely, coma

Citalopram and escitalopram are particularly associated with QT prolongation and cardiac conduction abnormalities.

Severe serotonergic excess may cause serotonin syndrome, characterized by:

• Agitation or confusion
• Hyperreflexia, clonus, or muscle rigidity
• Tremor or myoclonus
• Tachycardia
• Diaphoresis
• Hyperthermia
• Nausea and vomiting
• Autonomic instability

Mechanism of Action

SSRIs inhibit serotonin reuptake, increasing serotonin concentrations and receptor stimulation within the central nervous system. Excessive serotonergic activity can produce serotonin syndrome.

Management

Treatment is primarily supportive:

• Airway and cardiorespiratory monitoring
• IV fluids when needed
• Benzodiazepines for agitation, tremor, or seizures
• Active cooling for significant hyperthermia
• Continuous ECG monitoring when cardiac toxicity is a concern
• Cyproheptadine may be considered in significant serotonin syndrome under specialist guidance

Severe serotonin syndrome may require intensive supportive care, including airway management and sedation.

Key Points

• Isolated SSRI overdoses are generally less cardiotoxic than tricyclic antidepressant or MAOI poisoning.
• Citalopram and escitalopram deserve particular attention because of their potential for QT prolongation.
• Serotonin syndrome is suggested by the combination of altered mental status, autonomic instability, and neuromuscular hyperactivity.
• Clinical observation and ECG findings help determine the appropriate duration of monitoring.

Toxicology – Imidazoline Poisoning

Source

Imidazolines are found in many over-the-counter eye drops and nasal decongestants. Examples include tetrahydrozoline, oxymetazoline, naphazoline, and xylometazoline. Clonidine is pharmacologically related to this group.

Typical Presentation

After accidental or intentional ingestion of an imidazoline-containing product, a patient may rapidly become drowsy, hypotensive, or unconscious. Severe poisoning can resemble clonidine toxicity with marked CNS and respiratory depression.

Clinical Features

Oral exposure may produce:

• Drowsiness and CNS depression
• Hypotension
• Bradycardia or other heart-rate abnormalities
• Nausea and vomiting
• Syncope
• Hypothermia
• Respiratory depression or apnea
• Seizures
• Coma

A brief period of hypertension may occur early because of peripheral vasoconstriction.

Mechanism of Action

Imidazolines stimulate α-adrenergic receptors. Their topical action produces vasoconstriction, which explains their effectiveness as decongestants. After systemic absorption, central α2-adrenergic effects reduce sympathetic activity, producing CNS depression, bradycardia, and hypotension.

Management

There is no established specific antidote, so treatment is primarily supportive:

• Maintain the airway and assist ventilation when necessary
• Monitor cardiac rhythm and blood pressure
• Give IV fluids for clinically significant hypotension
• Vasopressors may be required for persistent cardiovascular instability
• Early hypertension is usually temporary and often does not require treatment
• Gastrointestinal decontamination may be considered in selected recent exposures

Key Points

• Ingestion of topical eye or nasal decongestants can cause serious systemic poisoning.
• The clinical picture can closely resemble clonidine toxicity.
• Severe cases may cause profound CNS and respiratory depression.
• Chronic excessive use of topical nasal decongestants can cause rebound congestion (rhinitis medicamentosa).