1. THEOPHYLLINE OVERDOSE Prof. A. Walubo Department of Pharmacology

2. Case report Emergency Dept. A 22-yr-old F, 6 hrs after ingestion of 20 g of S-R theophylline Nausea, Vomiting and palpitations. PMH: Not asthmatic & never used theophylline before Lab: - K + = 2.4 mmol/l; - Theophylline s-conc.= 105 mg/L. Admitted: ICU, Intubated and mechanically ventilated Admn charcoal by NG tube: 50g x 3 + magnesium sulfate. Dev’ped => severe hypotension and convulsed: - Rx: colloids, inotropes and diazepam, respectively. 8 hrs: Theo-level had dropped to 48 mg/l. => haemoperfusion started, 6 hr later level was 24 mg/l; The following 2 days, she made a full recovery. Nephrol Dial Transplant (2005) 20: 2869

3. Pharmacological properties of theophylline Mechanism Inhibits PDE => increased cAMP. Inhibits adenosine receptors, => tachycardia & CNS stimulation. Increased catecholamines: Adrenaline & noradrenaline Neurological Agitation, tremors, hypertonicity Nausea, vomiting & hyperventilation Seizures, coma Cardiovascular +ve inotropic & chronotropic action SVT and ventricular arrhythmias Hypotension, cardiac arrest Respiratory Smooth muscle relaxation Improved ventilatory muscle power Metabolic Metabolic acidosis Respiratory alkalosis Hypokalaemia Hypophosphataemia Hypomagnesaemia Hyperglycaemia Gastrointestinal Increased acid & pepsin secretion Abdominal pain & GIT haemorrhage Renal Increased RBF Increased GFR Intensive Care Med (1990) 16:394-398

4. Clinical Categories MildModerateSevere Nausea V + toler. decont. V + not toler.decont. P 140 SBP > 120 mmHgSBP > 100 mmHgSBP < 100 mmHg No arrhythmiaAtrial or V-ectopicsSVT or V-Tachy. Agitation or hyperreflexiaSeizuresK < 3.0 mmol/LGlu > 10 mmol/L Rising Theo conc NB: Potentially significant toxicity: -all chronic overmedication, -acute ingestions of > 10 mg/kg (8 mg/kg) -acute ingestions with mod-sev. s/s

5. Criteria for admission Theophylline > 50 mg/L in acute poisoning Theophylline > 40 mg/L in chronic poisoning Theophylline > 40 mg/L in pts 60 yrs Theophylline > 40 mg/L in pts with chronic illness

6. Indications for haemodialysis/perfusion Clinically severe toxicity. Theophylline conc. > 150 mg/L. Theophylline conc. > 100 mg/L in acute ingestion. Theophylline conc. > 60 mg/L in chronic ingestion. Failure of repeated dose charcoal therapy NB: Local threshold concentrations can be chosen above which an unacceptable risk of life-threatening events exists even if the patient shows only moderate toxicity.

7. Management of severe theophylline poisoning Emergency department History and examination ECG monitoring Establish IV access, NS Blood:- Theo level + Na, K, ABG, Glu, Urea + Cr, & FBC Electrolyte therapy commence: - KCL 20 mmol/h - MgSO4 10 mmol/h - KPO4 5 mmol/h Gastric lavage Intragastric act. charcoal 50 g Intensive care unit Act charcoal 10 g hrly with 20% mannitol or other carthatic. IV-fluids: careful fluid balance Repeat Theo: 4-6 hourly. Sodium bicarbonate Antiemetic: ondanstr. + ranitidine Seizures – diazepam, then thiopentone, intubation and positive pressure ventilation Serious arrhyth - ? propranolol Severe toxicity: haemoperfusion or hemodialysis. Intensive Care Med (1990) 16:394-398

8. END