| Indication |
For management of fatigue, orthostatic hypotension, and for the short term treatment of apnea of prematurity in infants. |
| Pharmacodynamics |
Caffeine, a naturally occurring xanthine derivative like
theobromine and the bronchodilator theophylline, is used as a CNS
stimulant, mild diuretic, and respiratory stimulant (in neonates with
apnea of prematurity). Often combined with analgesics or with ergot
alkaloids, caffeine is used to treat migraine and other headache types.
Over the counter, caffeine is available to treat drowsiness or mild
water-weight gain. |
| Mechanism of action |
Caffeine stimulates medullary, vagal, vasomotor, and respiratory
centers, promoting bradycardia, vasoconstriction, and increased
respiratory rate. This action was previously believed to be due
primarily to increased intracellular cyclic 3′,5′-adenosine
monophosphate (cyclic AMP) following inhibition of phosphodiesterase,
the enzyme that degrades cyclic AMP. It is now thought that xanthines
such as caffeine act as antagonists at adenosine-receptors within the
plasma membrane of virtually every cell. As adenosine acts as an
autocoid, inhibiting the release of neurotransmitters from presynaptic
sites but augmenting the actions of norepinephrine or angiotensin,
antagonism of adenosine receptors promotes neurotransmitter release.
This explains the stimulatory effects of caffeine. Blockade of the
adenosine A1 receptor in the heart leads to the accelerated, pronounced
"pounding" of the heart upon caffeine intake. |
| Absorption |
Readily absorbed after oral or parenteral administration. The peak
plasma level for caffeine range from 6-10mg/L and the mean time to
reach peak concentration ranged from 30 minutes to 2 hours. |
| Volume of distribution |
- 0.8 to 0.9 L/kg [infants]
- 0.6 L/kg [adults]
|
| Protein binding |
Low (25 to 36%). |
| Metabolism |
Hepatic cytochrome P450 1A2 (CYP 1A2) is involved in caffeine
biotransformation. About 80% of a dose of caffeine is metabolized to
paraxanthine (1,7-dimethylxanthine), 10% to theobromine
(3,7-dimethylxanthine), and 4% to theophylline (1,3-dimethylxanthine). |
| Route of elimination |
In young infants, the elimination of caffeine is much slower than that in adults due to immature hepatic and/or renal function. |
| Half life |
3 to 7 hours in adults, 65 to 130 hours in neonates |
| Clearance |
Not Available |
| Toxicity |
LD50=127 mg/kg (orally in mice) |
