A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Caffeine - Sodium Benzoate Pharmacology, Pharmacokinetics, Studies, Metabolism - Caffeine and Sodium Benzoate
Caffeine - Sodium Benzoate Pharmacology, Pharmacokinetics, Studies, Metabolism - Caffeine and Sodium Benzoate
CLINICAL PHARMACOLOGY
Caffeine is pharmacologically similar to the other xanthine
drugs, such as theobromine
and theophylline; however, these three agents differ in the intensity
of their actions on various structures. Caffeine’s CNS
and skeletal muscle effects
are greater than those of other xanthines. In
all other areas, theophylline
has greater activity
than caffeine, although some studies report
that caffeine has greater
diuretic effect
than theobromine. The increased levels of intracellular
cyclic-AMP mediate most
of caffeine’s pharmacologic actions. Caffeine competitively inhibits
phosphodiesterase, the enzyme
that degrades cyclic
3’- 5’ adenosine monophosphate.
Caffeine stimulates all levels of the CNS. Caffeine’s cortical
effects are milder and of shorter duration
than those of amphetamines. In
slightly larger doses, caffeine
stimulates medullary vagal,
vasomotor and respiratory
centers, promoting bradycardia,
vasoconstriction, and increased respiratory
rate.
Caffeine produces a positive
inotropic effect
on the myocardium
and a positive chronotropic
effect at the sinoatrial
node, causing transient increases in heart
rate, force of contraction,
cardiac output
and heart work. In doses
greater than 250 mg, the centrally mediated vagal
effects of caffeine
may be masked by increased
sinus rates, tachycardia,
extrasystoles, or other major ventricular
arrhythmias may result.
Caffeine constricts cerebral vasculature. In
contrast, the drug directly
dilates peripheral
blood vessels, decreasing
peripheral vascular
resistance. The effect
of this decrease in peripheral
vascular resistance
(and possibly that of vagal
cardiac stimulation)
on blood pressure
is offset by increased cardiac output
(and possibly stimulation
of the medullary vasomotor
area). The overall effect
of caffeine on heart
rate and blood
pressure depends on
whether CNS or peripheral
effects predominate. Therapeutic doses of caffeine increase blood
pressure only slightly.
Caffeine stimulates voluntary
skeletal muscle,
increasing the force of contraction
and decreasing muscular
fatigue. The drug also
stimulates gastric acid
secretion from parietal
cells. Caffeine increases renal
blood flow and glomerular
filtration rate
and decreases proximal
tubular reabsorption
of sodium and water,
resulting in mild diuresis.
Caffeine stimulates glycogenolysis
and lipolysis, but increase in blood glucose and in plasma
lipids are insignificant in normal
patients. Tolerance may develop to the diuretic,
cardiovascular,
and CNS effects of caffeine.
PHARMACOKINETICS
Caffeine is rapidly distributed throughout the body
tissues, readily crossing the placenta
and blood-brain barrier. Approximately 17% of the drug is bound
to plasma proteins. Caffeine
has approximately a half-life [T ½] of 3-4 hours in adults.
In adults, the drug
is rapidly metabolized in the liver
to 1-methyluric acid, 1-methylxanthine
and 7-methylxanthine. Caffeine and its metabolites are excreted
primarily by the kidneys.
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