Toxicology – Isoniazid (INH) Toxicity
Source
Isoniazid (INH) is a first-line antitubercular medication used to treat both latent and active tuberculosis. It is structurally related to pyridoxine (vitamin B6).
Typical Presentation
Acute overdose classically presents with severe, refractory seizures and metabolic acidosis. Children are particularly vulnerable, and toxicity may occur rapidly after ingestion. Chronic use is associated with liver injury and neurological complications.
Clinical Features
Acute Toxicity
Symptoms may begin within 30 minutes of ingestion and include:

• Refractory seizures
• Altered mental status or coma
• Vomiting
• Slurred speech
• Hyperreflexia or hyporeflexia
• Tachycardia
• Oliguria

Laboratory findings often reveal:

• High anion gap metabolic acidosis
• Elevated lactate levels

Chronic Toxicity
Long-term exposure may cause:

• Elevated liver enzymes and hepatitis
• Hepatocellular necrosis
• Peripheral neuropathy
• Optic neuritis
• Vitamin B6 deficiency
• Autoimmune manifestations (e.g., anemia, arthritis, eosinophilia)

Mechanism of Action
INH interferes with pyridoxine (vitamin B6) metabolism, impairing pyridoxine-dependent enzymatic pathways. This leads to depletion of GABA and excess glutamate activity, predisposing patients to seizures.
Management
Treatment focuses on seizure control, airway stabilization, and reversal of vitamin B6 depletion:

• Benzodiazepines, propofol, or barbiturates for seizures
• Sodium bicarbonate for severe acidosis
• Supportive airway and hemodynamic management

The specific antidote is pyridoxine (vitamin B6):

• Ideally given gram-for-gram equal to the amount of INH ingested
• If the dose is unknown, an initial 5 g IV dose is recommended and may be repeated if seizures continue

For chronic toxicity, daily pyridoxine supplementation may improve neurological symptoms.
Key Points

• Consider INH poisoning in patients with seizures unresponsive to standard anticonvulsants.
• Refractory seizures plus metabolic acidosis is highly suggestive.
• Pyridoxine is the definitive antidote.
• Chronic therapy may cause neuropathy and hepatotoxicity.

​91. Toxicology – Colchicine Toxicity
Source
Colchicine is a medication commonly prescribed for gout, pericarditis, and familial Mediterranean fever. It is derived from the autumn crocus plant (Colchicum autumnale) and has a narrow therapeutic index.
Typical Presentation
Patients usually present after an overdose with severe gastrointestinal symptoms that may initially resemble infectious gastroenteritis. Toxicity can rapidly progress to multiorgan failure over the following days.
Clinical Features
Colchicine poisoning classically progresses through three stages:

• Phase 1 (within hours): Severe nausea, vomiting, diarrhea, abdominal pain, dehydration, tachycardia, hypotension, and early kidney injury.
• Phase 2 (days later): Multisystem toxicity develops, including bone marrow suppression, low white blood cell counts, kidney and liver failure, rhabdomyolysis, pulmonary edema, ARDS, cardiovascular collapse, and pancytopenia.
• Phase 3 (recovery phase): Survivors may later develop hair loss (alopecia) and ascending peripheral neuropathy.

Mechanism of Action
Colchicine disrupts microtubule formation and inhibits mitosis, impairing rapidly dividing cells such as those in the gastrointestinal tract and bone marrow.
Management
Treatment is primarily supportive and includes:

• Aggressive IV fluid resuscitation
• Airway and hemodynamic support
• Antiemetics for severe GI symptoms
• Activated charcoal to reduce enterohepatic recirculation

Granulocyte colony-stimulating factor (G-CSF) may help in severe leukopenia. Hemodialysis is ineffective because colchicine is poorly removed by dialysis.
Key Points

• Early symptoms may mimic viral gastroenteritis.
• Toxicity can progress rapidly to fatal multiorgan failure.
• Bone marrow suppression is a major complication.
• Dialysis is not useful in colchicine overdose.

Toxicology – Hyperkalemia (Elevated Potassium Levels)

Source
Elevated potassium levels can result from potassium supplements, kidney failure (especially in dialysis patients), and certain medications such as ACE inhibitors, NSAIDs, and potassium-sparing diuretics. It may also occur due to cellular breakdown in conditions like rhabdomyolysis, hemolysis, or tumor lysis syndrome.

Typical Presentation
Patients may present with vague symptoms such as weakness or fatigue, but serious cases often involve cardiac abnormalities detected on ECG, especially in those with impaired kidney function.

Clinical Features
Symptoms are often nonspecific and may include:

• Generalized weakness and malaise
• Slow heart rate (bradycardia)
• Cardiac arrhythmias

ECG changes are key and may progress in severity:

• Peaked T waves
• Prolonged PR interval
• Flattened or absent P waves
• Widened QRS complex
• “Sine wave” pattern leading to cardiac arrest
• 
  

Mechanism of Action
High extracellular potassium alters the electrical gradient across cardiac cells, making them more excitable and prone to dangerous arrhythmias.

Management
Treatment is urgent and involves three main strategies:

1. Stabilize the heart
   • IV calcium (calcium gluconate or calcium chloride) to protect cardiac membranes
2. Shift potassium into cells
   • Insulin with glucose
   • β-agonists (e.g., high-dose nebulized albuterol)
   • Sodium bicarbonate (in cases of acidosis)
3. Remove potassium from the body
   • Dialysis (most effective in severe cases)
   • Potassium-binding resins (e.g., sodium polystyrene sulfonate)
   • 
     

Key Points

• ECG monitoring is essential in suspected hyperkalemia.
• Calcium does not lower potassium—it stabilizes the heart.
• Severe hyperkalemia is a medical emergency due to risk of fatal arrhythmias.
• Kidney function plays a major role in potassium regulation.

Toxicology – Lithium Toxicity
Source
Lithium carbonate is commonly prescribed for bipolar disorder. It is also used in industrial settings, including fireworks production.

Typical Presentation
Toxicity may occur from acute overdose, chronic accumulation, or a combination of both. Patients on long-term therapy are especially at risk if kidney function declines or if interacting medications are introduced.

Clinical Features
Lithium toxicity presents in three main patterns:

• Acute toxicity: Predominantly gastrointestinal symptoms such as nausea, vomiting, diarrhea, and dizziness. Kidney injury and mild cardiac changes (e.g., QT prolongation) may occur.
• Chronic toxicity: Mainly neurological symptoms including tremor, weakness, hyperreflexia, involuntary movements, poor coordination, confusion, and altered consciousness, which can progress to coma.
• Acute-on-chronic toxicity: A combination of both GI and neurological symptoms, often more severe.

Mechanism of Action
Lithium affects multiple intracellular pathways, including inhibition of signaling systems and neurotransmitter modulation. It is eliminated almost entirely by the kidneys, making renal function a key factor in toxicity.

Management
Treatment is supportive and focuses on enhancing elimination:

• IV fluids to improve kidney perfusion and promote excretion
• Whole bowel irrigation for sustained-release ingestion
• Hemodialysis for severe cases (e.g., high lithium levels, neurological symptoms, or kidney impairment)
• ​

Key Points

• Toxicity risk increases with dehydration, kidney dysfunction, and certain medications (e.g., NSAIDs, ACE inhibitors).
• Neurological symptoms are more prominent in chronic toxicity.
• Lithium levels may rise again after dialysis, requiring repeated treatments.
• Activated charcoal is not effective for lithium overdose.
• Therapeutic levels are typically 0.6–1.2 mEq/L.

Toxicology – Methylxanthine Toxicity (Caffeine, Theophylline, Theobromine)

Source
Methylxanthines include compounds such as caffeine, theophylline (used in respiratory diseases), and theobromine (found in chocolate). These substances are present in beverages, medications, and certain foods.

Typical Presentation
Toxicity often results from overdose—intentional or accidental—and can present with both gastrointestinal and cardiovascular symptoms. Severe cases may rapidly progress to life-threatening complications.

Clinical Features
Early symptoms commonly include headache, nausea, vomiting (often persistent), abdominal discomfort, and diarrhea. As toxicity worsens, patients may develop:

• Rapid heart rate and breathing
• Low blood pressure with wide pulse pressure
• Tremors, agitation, and restlessness
• Seizures, including status epilepticus
• Cardiac arrhythmias (ranging from sinus tachycardia to ventricular fibrillation)

Laboratory abnormalities may include metabolic acidosis, elevated lactate, low potassium levels, and high blood glucose.

Mechanism of Action
Methylxanthines exert multiple effects:

• Block adenosine receptors (removing inhibitory CNS effects)
• Stimulate β-adrenergic activity, increasing heart rate and blood pressure
• Inhibit phosphodiesterase, leading to increased cAMP and intracellular calcium

These combined actions result in heightened stimulation of the nervous and cardiovascular systems.

Management
Treatment is primarily supportive and may include:

• IV fluids and vasopressors (e.g., norepinephrine or phenylephrine) for hypotension
• Benzodiazepines for seizures
• Management of arrhythmias (often with calcium channel blockers)
• Activated charcoal to reduce absorption
• Whole bowel irrigation for sustained-release ingestions

Hemodialysis may be required in severe cases, particularly with high drug levels or complications such as refractory seizures, hypotension, or serious arrhythmias.

Key Points

• Severe toxicity can cause persistent vomiting, seizures, and dangerous arrhythmias.
• Theobromine is especially toxic to animals (e.g., dogs, rabbits).
• Dialysis is considered in life-threatening cases.
• Multidose activated charcoal may enhance elimination.​

Toxicology – Digitalis (Digoxin) Toxicity

Source
Digoxin is a cardiac medication used to manage conditions like atrial fibrillation and heart failure. Similar cardiac glycosides are naturally found in plants such as foxglove, oleander, and milkweed, as well as in certain toads (e.g., Bufo species).

Typical Presentation
Patients—often elderly with underlying heart disease—may present with gastrointestinal complaints, abnormal heart rhythms, and visual disturbances. Toxicity can occur from acute overdose or chronic accumulation.

Clinical Features

• Acute toxicity: Symptoms usually appear several hours after ingestion and include nausea, vomiting, elevated potassium levels, and dangerous cardiac arrhythmias.
• Chronic toxicity: More subtle and varied, including fatigue, confusion, weakness, gastrointestinal upset, and visual changes (e.g., blurred vision, yellow-tinted vision or “xanthopsia”).

Cardiac effects are prominent and may include slow heart rate (bradycardia), heart block, atrial or ventricular arrhythmias, and even cardiac arrest.

Mechanism of Action
Digoxin works by inhibiting the sodium–potassium ATPase pump, which increases intracellular calcium and enhances cardiac contractility. It also increases vagal tone, slowing conduction through the heart. However, these same effects predispose to abnormal heart rhythms in overdose.
​
Management
Treatment focuses on stabilizing the patient and addressing arrhythmias:

• Supportive care with cardiac monitoring
• Atropine for symptomatic bradycardia
• Correction of electrolyte imbalances (especially potassium and magnesium)
• Activated charcoal if ingestion is recent
• Digoxin-specific antibody fragments (Digoxin immune Fab) for severe toxicity (e.g., life-threatening arrhythmias, high potassium, or hemodynamic instability)

Advanced measures such as pacing or antiarrhythmics may be required.
Key Points

• Toxicity can be acute or chronic, with different clinical patterns.
• Visual disturbances are a classic clue.
• Hyperkalemia in acute toxicity is a poor prognostic sign.
• Digoxin levels should be interpreted carefully, especially early after ingestion.
• Antibody therapy is the definitive treatment in severe cases.​

 Toxicology – Strychnine Poisoning

Source
Strychnine is a naturally occurring toxin derived from the seeds of the Strychnos nux-vomica tree. It is commonly used in rodenticides and pest control products and may also be found as an adulterant in illicit drugs.

Typical Presentation
Exposure typically follows ingestion or inhalation. Patients often present with sudden onset of severe muscle spasms and convulsions, sometimes after accidental or intentional ingestion of poison products.

Clinical Features
Early signs include anxiety, increased salivation, and dilated pupils. Rapidly, painful muscle spasms begin in the face and neck—manifesting as grimacing (risus sardonicus) and jaw stiffness (trismus)—then spread to the entire body.
Patients develop intense, prolonged muscle contractions (tetany), often with a characteristic arching posture (opisthotonus). Unlike typical seizures, patients may remain conscious and aware during these episodes. Severe complications include:

• Rhabdomyolysis
• Hyperthermia
• Metabolic (lactic) acidosis
• Respiratory failure due to sustained muscle contraction

Mechanism of Action
Strychnine blocks the inhibitory neurotransmitter glycine in the central nervous system, particularly at the spinal cord level. Without glycine’s inhibitory effect, motor neurons become overactive, leading to uncontrolled muscle contractions and spasms.

Management
Treatment is supportive and focused on controlling muscle activity and protecting the airway:

• Benzodiazepines and barbiturates for seizure and spasm control
• Early intubation with sedation and use of nondepolarizing paralytics (e.g., rocuronium, vecuronium)
• IV fluids for rhabdomyolysis
• Active cooling for hyperthermia

Key Points

• Patients may remain conscious during severe spasms (“conscious seizures”).
• Avoid succinylcholine, as it can worsen muscle contractions.
• Respiratory failure is a major cause of death.
• Rapid, aggressive supportive care is critical.​

Toxicology – Ethylene Glycol (Antifreeze Poisoning)

Source
Ethylene glycol is commonly found in antifreeze and hydraulic brake fluids. Its sweet taste increases the risk of accidental ingestion, especially in children and animals.

Typical Presentation
Patients often present hours after ingestion with progressive symptoms that evolve in stages, beginning with neurological and gastrointestinal complaints and later affecting the heart, lungs, and kidneys.

Clinical Features
Ethylene glycol toxicity typically progresses through three stages:

• Stage I (30 min–12 hrs): Early symptoms resemble alcohol intoxication, including confusion, dizziness, slurred speech, nausea, vomiting, and abdominal pain.
• Stage II (12–36 hrs): Cardiopulmonary effects develop, including rapid heart rate, elevated blood pressure, rapid breathing, and severe metabolic acidosis. Low calcium levels may cause muscle spasms, tetany, and decreased reflexes. Serious complications include brain swelling, lung injury, and cardiovascular collapse.
• Stage III (24–72 hrs): Kidney injury becomes prominent, with decreased urine output, blood or protein in urine, electrolyte disturbances, and possible kidney failure.

Mechanism of Action
Ethylene glycol itself is not highly toxic, but it is metabolized into harmful compounds such as glycolic acid and oxalic acid. Glycolic acid causes severe metabolic acidosis and cellular damage, while oxalic acid binds calcium to form crystals that deposit in the kidneys, leading to renal failure.

Management
Treatment focuses on preventing toxic metabolite formation and enhancing elimination:

• Fomepizole is the preferred antidote; it blocks alcohol dehydrogenase.
• Ethanol may be used if fomepizole is unavailable.
• Hemodialysis is indicated in severe cases to remove toxins and correct acidosis.
• Thiamine and pyridoxine help shift metabolism toward less harmful pathways.

Key Points

• Sweet taste increases risk of accidental ingestion.
• Severe metabolic acidosis is a hallmark finding.
• Calcium oxalate crystals may be seen in urine.
• Kidney failure is a major late complication.
• Early treatment is critical to prevent irreversible damage.​

Toxicology – Isopropyl Alcohol (Isopropanol) Toxicity


Source
Isopropyl alcohol is commonly found in products such as rubbing alcohol, disinfectants, cleaning solutions, deicers, solvents, and certain fuel additives.


Typical Presentation
Patients often present with signs of significant intoxication, sometimes mistaken for ethanol ingestion. A distinguishing clue may be a fruity or acetone-like odor on the breath.


Clinical Features
This produces a hypnosedative toxidrome, often more intense than ethanol. Symptoms include slurred speech, impaired coordination, unsteady gait, nystagmus, confusion, and disinhibition. Severe cases may progress to hypotension, hypothermia, coma, and respiratory arrest.


Gastrointestinal irritation is prominent, with abdominal pain and possible hemorrhagic gastritis or esophagitis. Laboratory findings may show:

• Increased osmolal gap

• Presence of ketones (without significant acidosis)

• Nongap metabolic acidosis

• Falsely elevated creatinine

Mechanism of Action
Isopropanol acts as a central nervous system depressant via GABA receptor activity. It is metabolized by alcohol dehydrogenase into acetone, which is less toxic and responsible for the characteristic fruity odor.


Management
Treatment is primarily supportive:

• Airway protection and monitoring

• Intravenous fluids for hypotension

• Vasopressors if needed

Hemodialysis may be considered in severe cases, particularly when there is persistent coma or refractory hypotension. Unlike other toxic alcohols, antidotes such as fomepizole are not used because the metabolite (acetone) is not highly toxic.


Key Points

• More potent intoxicant than ethanol.

• Causes ketosis without significant anion gap acidosis.

• Fruity breath odor is due to acetone formation.

• Management is usually supportive, with dialysis reserved for severe toxicity.