Caffeine and Related Nonprescription Sympathomimetics

Caffeine and Related Nonprescription Sympathomimetics
There are three methylxanthine alkaloids: theobromine, theophylline, and caffeine. Cocoa and chocolate contain theobromine and some caffeine. Tea contain caffeine and some theophylline. Coffee and many cola-flavored beverages are rich sources of caffeine.
Theophylline and caffeine are used in drug therapy. Methylxanthines stimulate the CNS, induce diuresis, relax smooth muscle ( bronchial muscle), and stimulate cardiac functions. Caffeine also augment the analgesic properties of salicylates and is contained in many analgesic products.
Nonprescription sympathomimetics such as ephedrine, phenylpropanolamine, and phenylephrine have been abused for their stimulant effects and are commonly found in cold preparations
Pharmacokinetics:
In adults Caffeine is metabolized to theophylline by the cytochrome P-450 enzyme system with approximately 1 % excreted unchanged in the urine. However, in neonates approximately 85 % of a dose is excreted unchanged in the urine. Decreased elimination and a prolonged half-life may increase caffeine toxicity in neonates and premature infants. The metabolism of a child approaches that of an adult at the approximate age of 8 months.
Phenylpropanolamine is a weak base that is readily absorbed in the small intestine. Maximum concentrations occur approximately 1.5 hours after ingestion. High per cent of a given dose of phenylpropanolamine will be excreted unchanged in the urine. Approximately 8–20 per cent of a dose of ephedrine undergoes N-demethylation to phenylpropanolamine. Phenylephrine has a bioavailability of 38 per cent. most of a given dose is excreted unchanged in the urine.
Pathaphysiology
Caffeine has many effects in the body:
(1) Adenosine receptor antagonism.
(2) Phosphodiesterase inhibition.
(3) Enhanced intracellular calcium levels.
Adenosine receptor antagonism leads to vasoconstriction, hypertension, tremor, and agitation. These effects are frequently seen in caffeine overdose. These effects are the reverse of those seen with adenosine agonist activity, such as arterial vasodilation, inhibition of catecholamine release, and slowing of cardiac pacemaker cells.
Caffeine inhibits phosphodiesterases, causing increased levels of cyclic AMP, which results in increased levels of catecholamines. Muscle contractility is enhanced through increased intracellular calcium levels. Stimulation of gastric acid and intestinal secretions and lowering of lower esophageal sphincter tone by caffeine commonly result in diarrhea and abdominal cramping.
Clinical presentation of caffeine toxicity
• Acute Toxicity
• Chronic Toxicity
LABORATORY STUDIES
Treatment