Lec 7 OTC caffeine, theophylline and antihistamine.pdf

OTC drug toxicity caffeine, theophylline and antihistamine Dr. Mohammed Fareed Caffeine, theophylline, and theobromine are xanthine derivatives . The compounds contain the purine nucleus and are naturally occurring xanthine derivatives. Both caffeine and theophylline are distributed throughout the t...

OTC drug toxicity caffeine, theophylline and antihistamine Dr. Mohammed Fareed Caffeine, theophylline, and theobromine are xanthine derivatives . The compounds contain the purine nucleus and are naturally occurring xanthine derivatives. Both caffeine and theophylline are distributed throughout the tea leaves. Proposed Mechanism of Toxicity of Methylxanthines (a) Increased calcium release from intracellular sites (b) Accumulation of cyclic nucleotides, especially cyclic AMP (cAMP) (c) Adenosine receptor blockade. Toxicity probably results from more than one mechanism. Direct stimulation of the chemoreceptor trigger zone appears to cause the nausea and vomiting. TOXICOKINETICS OF XANTHINES Xanthine derivatives are well absorbed orally, reaching peak distribution within two hours. The compounds are metabolized by the liver to methylxanthine and methyluric acid derivatives. The drugs are eliminated by the kidney with a half-life of 3 to 15 h in nonsmokers (4 to 5 h in adult smokers). 1 CAFFEINE Because of ubiquitous occurrence, caffeine is distributed throughout coffee, tea, chocolate, and cola beverages, with coffee beans and tea leaves containing equivalent amounts of the stimulant (up to 2%). Brewed coffee show off the highest amounts of caffeine (up to 100 mg). Instant and decaffeinated coffees contain less (up to 75 and 5 mg, respectively). CAFFIENE SIGNS AND SYMPTOMS OF TOXICITY Adverse effects are observed with doses around 1 g, but acute toxic doses appear to be between 5 and 10 g either intravenously or orally. These doses can produce effects on the CNS, including restlessness, excitement, and insomnia that can progress to delirium. Patients may see flashes of light and hear ringing and other noises. Muscles become tense and spastic. Cardiovascular effects may include tachycardia, ventricular fibrillation, and cardiopulmonary arrest. As toxicity progresses, convulsions, coma, and death . Treatment (Acute Toxicity): 1. GI Decontamination: Activated charcoal, cathartic. 2 2. CVS: - Supraventricular tachycardia: Beta-adrenergic antagonists like esmolol or calcium channel blockers. - Ventricular tachycardia/fibrillation: Cardioversion, or the use of lignocaine. 3. CNS: Benzodiazepines like midazolam or barbiturates can be given for convulsions or agitation. IV glucose may help, especially in children. 4. Anti-emetics such as metoclopramide for persistent vomiting. - Antiulcer regimens may be required in some cases, H2 antagonists or hydrogen pump inhibitors 5. Potentially lethal ingestions with life-threatening complications (cardiac arrhythmias, severe CNS toxicity) can be managed by charcoal haemoperfusion THEOPHYLLINE SIGNS AND SYMPTOMS OF TOXICITY Theophylline shares similar properties with caffeine, although its toxicity is more acute and more common; chronic toxicity, however, is unlikely. Therapeutic blood levels are strictly regulated at 10 to 20 microgram/ml, but vary depending on interactions with other drugs, inaccurate dosing, accidental or intentional overdose ingestion. Nausea related with oral tablets. 3 Most theophylline preparations are available as controlled-release dosage forms. Acute Toxicity 1. CNS: Convulsions, hypothermia, ataxia, visual hallucinations. Coma is uncommon. 2. CVS: Cardiac arrhythmias. 3. Metabolic: Hypokalaemia, hyperglycaemia, hypercalcaemia, and metabolic acidosis. Theophylline toxicity treatment 1. Decontamination: a. Gastric lavage (unless there are contraindications such as convulsions). b. Activated charcoal , However vomiting must be controlled. 2. Stabilization: monitor vital signs, serum potassium, enzymes and serum theophylline levels. 3. Symptomatic measure: a. Treat vomiting with metoclopramide (10 mg) b. Hypotension refractory to fluids and vasopressors such as dopamine, may respond to alpha-adrenergic drugs such as levarterenol. 4 c. Supraventricular tachycardia and multifocal atrial tachycardia respond to propranolol and verapamil respectively. d. Convulsions often do not respond to conventional measures, and administration of intravenous thiopentone may be necessary. e. Correction of hypokalaemia may necessitate the use of potassium chloride (5–10 mEq/hour). f. Hyperthermia and rhabdomyolysis can be treated with dantrolene . Hydration and maintenance of high urine output are essential. 4. Special measures: a. Haemoperfusion is effective in theophylline overdose, and is the elimination procedure of choice. Indications include intractable convulsions, persistent hypotension, uncontrollable arrhythmias, and serum theophylline levels greater than 60 to 80 mcg/ml. TOLERANCE AND WITHDRAWAL Caffeine withdrawal is associated with chronic use and is demonstrated abruptly within 12 to 24 h after the last dose. Initial symptoms, including headache, anxiety, fatigue, and craving behavior, last for about one week. There is demonstrated tolerance to the diuretic action and the insomnia produced with theophylline, but no tolerance develops to the CNS stimulation or bronchodilation. 5 ANTIHISTAMINES TOXICITY Signs of toxicity: Tremors, excitable auditory and visual hallucinations. Usual anticholinergic symptoms; dry mouth and dry, hot skin. Cardiac : Heart palpitations Treatment: Activated charcoal and magnesium sulfate used. 6