Related Subjects:
|Drug Toxicity - clinical assessment
|Metabolic acidosis
|Aspirin or Salicylates toxicity
|Ethylene glycol toxicity
|Ethanol toxicity
|Methanol toxicity
|Ricin toxicity
|Carbon Tetrachloride Toxicity
|Renal Tubular Acidosis
|Lactic acidosis
|Iron Toxicity
|Tricyclic Antidepressant Toxicity
|Opiate Toxicity
|Carbon monoxide Toxicity
|Benzodiazepine Toxicity
|Paracetamol (Acetaminophen) toxicity
|Amphetamine toxicity
|Beta Blocker toxicity
|Calcium channel blockers toxicity
|Cannabis toxicity
|Cyanide toxicity
|Digoxin Toxicity
|Lithium Toxicity
|NSAIDS Toxicity
|Ecstasy toxicity
|Paraquat toxicity
|Quinine toxicity
|SSRI Toxicity
|Theophylline Toxicity
|Organophosphate (OP) Toxicity
|Toxin elimination by dialysis
|Drug Toxicity with Specific Antidotes
ℹ️ About
- Theophylline is a methylxanthine bronchodilator, historically used in asthma and COPD. 🌬️
- Narrow therapeutic window (therapeutic 10–20 mcg/mL) → toxicity with even modest overdoses or drug interactions.
- Mechanism:
- Phosphodiesterase inhibition → ↑cAMP → ↑β-adrenergic activity (tachycardia, arrhythmias, tremor).
- Adenosine receptor antagonism → seizures, tachyarrhythmias, GI upset.
- Catecholamine surge → metabolic disturbances (hypokalaemia, hyperglycaemia, lactic acidosis).
- Common causes of toxicity: accidental overdose, sustained-release preparations, drug interactions (e.g. macrolides, ciprofloxacin). ⚠️
Clinical Presentation 🩺
- Gastrointestinal: Early and prominent - severe nausea, persistent vomiting, abdominal pain (sometimes mistaken for gastroenteritis). 🤢
- Cardiovascular: Tachycardia, hypotension, atrial fibrillation, SVT, atrial flutter, ventricular tachycardia, ventricular fibrillation.
- Neurological: Tremor, agitation, anxiety, insomnia; seizures are common and may be refractory. ⚡
- Metabolic: Hypokalaemia, hypomagnesaemia, hypophosphataemia, hyperglycaemia, metabolic acidosis, lactic acidosis.
- Chronic toxicity: Particularly in elderly or renal impairment; may present with persistent nausea, tremor, insomnia, tachycardia rather than dramatic seizures.
Investigations 🔬
- Serum theophylline level:
- Therapeutic: 10–20 mcg/mL
- Toxicity: >20 mcg/mL
- Severe/life-threatening: >60–80 mcg/mL
- Bloods: Look for:
- Hypokalaemia (due to β-adrenergic stimulation driving K⁺ into cells).
- Hypophosphataemia, hypomagnesaemia, calcium derangements.
- Hyperglycaemia from catecholamine surge.
- Metabolic & lactic acidosis.
- ECG: Atrial fibrillation/flutter, SVT, VT, VF, sinus tachycardia. 📉
- ABG: May show metabolic acidosis or mixed picture if seizures/arrhythmias cause hypoxia.
Management 💉
- Stabilise ABCs: Secure airway if seizures or repeated vomiting; oxygen & IV access; continuous cardiac monitoring.
- Seizures: Benzodiazepines (IV diazepam or lorazepam). Refractory seizures may need barbiturates or propofol. ❌ Avoid phenytoin (ineffective, pro-arrhythmic).
- Electrolytes: Correct hypokalaemia, Mg²⁺, phosphate; monitor closely (rebound hypokalaemia common).
- GI decontamination:
- Multi-dose activated charcoal (MDAC): Enhances clearance via gut secretion (enterohepatic recycling).
- Whole-bowel irrigation (WBI) if large sustained-release ingestion.
- Gastric lavage only if intubated & within 1h of ingestion.
- Arrhythmias:
- β-blockers (e.g. propranolol, esmolol) for severe tachyarrhythmias - but caution in asthma/COPD. 🫁
- Lidocaine sometimes used for ventricular arrhythmias. ❌ Avoid adenosine (blocked by theophylline).
- Haemodialysis: Effective for severe toxicity (levels >100 mcg/mL, seizures, arrhythmias, shock, or failure of MDAC). Removes drug rapidly despite protein binding.
- Supportive: Antiemetics (ondansetron), IV fluids, cooling if hyperthermia.
Prognosis 📉
- Mortality up to 10% in severe overdoses; seizures and ventricular arrhythmias are main causes of death.
- Chronic toxicity in elderly can mimic other illnesses; recognition is key to prevent fatal escalation.
- Rapid institution of MDAC and correction of electrolytes improves outcomes significantly.
Clinical Pearls ✨
- 🚑 Clues to diagnosis: Refractory vomiting + tremor + unexplained arrhythmia = think theophylline.
- ⚡ Unique feature: MDAC speeds elimination due to enterohepatic circulation.
- ❌ Adenosine is ineffective in SVT due to receptor antagonism - use β-blockers instead.
- 💡 Hypokalaemia may persist despite replacement until theophylline cleared - keep repeating levels.
- 📚 Common exam trap: differentiating acute vs chronic toxicity - chronic toxicity may occur at “therapeutic” levels, especially in elderly or with drug interactions.
