Pharmacological rationale for the clinical use of caffeine

Abstract

Caffeine is widely consumed in beverages to obtain mild CNS stimulant effects. Long term use produces tolerance to some of the pharmacological effects. Withdrawal of caffeine, even from moderate intake levels, can produce symptoms such as headache, fatigue and anxiety. Caffeine is used therapeutically in combination with ergotamine for migraine headaches and in combination with nonsteroidal anti-inflammatory drugs in analgesic formulations. Caffeine alone is used as a somnolytic, to treat various headache conditions, respiratory depression in neonates, postprandial hypotension and obesity, and to enhance seizure duration in electroconvulsive therapy. In some headache and in pain paradigms, caffeine may produce direct adjuvant analgesic properties, while in other headache conditions (perioperative, postdural puncture) caffeine may be effective by alleviating a manifestation of caffeine withdrawal. Other uses, such as to promote wakefulness, for respiratory stimulation and seizure prolongation, rely on central stimulant properties of caffeine. Effects of caffeine on the vasculature may contribute to the relief of some headaches and in postprandial hypotension. Blockade of methylxanthine-sensitive adenosine receptors is the currently accepted mechanism of action of caffeine.