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DOPAMINE: DESCRIPTION
Dopamine is a catecholamine found in neurons of both the central
and peripheral nervous system. It is a monoamine and is a precursor
of adrenaline and noradrenaline. It is formed from the
decarboxylation from DOPA
Dopamine is a neurotransmitter that is has a central and
peripheral control and it contains one amino group
Naturally formed by the body It is formed by decarboxylation of
L-DOPA
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DOPAMINE: PHARMACOKINETICS
Dopamine in the form of dopamine hydrochloride is usually
administered by intravenous infusion
Onset of action occurs within five minutes of intravenous
administration and with its plasma half-life of about two minutes,
the duration of action is less than ten minutes.
Dopamine as a medication is administered via intravenous
infusion
In less than minutes, the action of dopamine takes effect
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Phenobarbital intoxication can usually be treated by supportive
measures and administration of large amounts of fluid and diuretics
to promote renal excretion of the drug.
Treatment of massive phenobarbital overdose is possible with
dopamine diuresis
DOPAMINE: PHARMACOKINETICS
Extremely large doses of phenobarbital may produce hypertension
with resulting reduction in renal blood flow. Dopamine is known to
increase renal blood flow, making it a logical therapeutic agent
for patients intoxicated with phenobarbital.
Treatment of massive phenobarbital overdose is possible with
dopamine diuresis or increased production of urine.
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DOPAMINE MECHANISMS IN INCREASING URINE OUTPUT
Dopamine has been used in the management of phenobarbital
poisoning through direct renal vasodilation, increased cardiac
output, and increased renal perfusion pressure
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Stimulation of receptors by the dopamine is dose-dependent
Low-dose. Intermediate dose, and heavy dosse
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Activation of -1 receptors in the heart
DOPAMINE
The heart has both 1and 2adrenoceptors, although the predominant
receptor type in number and function is 1. These receptors
primarily bind norepinephrine that is released from sympathetic
adrenergic nerves. Additionally, they bind norepinephrine and
epinephrine that circulate in the blood.
Beta-adrenoceptors are coupled toGs-proteins, which activate
adenylyl cyclase to formcAMPfrom ATP. Increased cAMP activates a
cAMP-dependent protein kinase (PK-A) that phosphorylates L-type
calcium channels, which causes increased calcium entry into the
cells. Increased calcium entry during action potentials leads to
enhanced release of calcium by the sarcoplasmic reticulum in the
heart; these actions increase inotropy (contractility). Gs-protein
activation also increases heart rate by opening ion channels
responsible forpacemaker currentsin the sinoatrial node. PK-A
phosphorylates sites on the sarcoplasmic reticulum, which enhances
the release of calcium through the ryanodine receptors
(ryanodine-sensitive, calcium-release channels) associated with the
sarcoplasmic reticulum. This provides more calcium for binding
thetroponin-C, which enhances inotropy. Finally, PK-A can
phosphorylate myosin light chains, which may also contribute to the
positive inotropic effect of beta-adrenoceptor stimulation. In
summary, the cardiac effects of a -agonist are increased heart
rate, contractility, conduction velocity, and relaxation rate.
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Activation of DA-1 receptors in the kidney
Dopamine (dopamine hydrochloride) is metabolized in
theliver,kidney, and plasma by MAO (monoamine oxidase)
andcatechol-O-methyltransferaseto the inactive compounds
homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic sacid.
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ReceptorResult of Receptor ActivationContribution to
Therapeutic EffectDA1The renal vasodilation will improve renal
blood flow and increase GFR.This will increase urine output and
decrease fluid retention and edema.beta1Produces a positive
inotropic effect.Increase in cardiac output. This is beneficial in
CHF.alpha1and alpha2Vasoconstriction is not a desired effect.This
will counteract the beneficial effects on renal blood flow. In
addition, increases in TPR will negatively affect cardiac
output.
