Sympathomimetic drugs (Direct-acting)

1. Sympathomimetic drugs (Direct-acting)
Directly binds to and stimulate adrenergic receptors.
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Used for cardiovascular, respiratory, and other conditions
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Effect mechanism; α, β or dopamine receptors are categorized by affinity.
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They act on sympathetic nervous system and get body in “Fight or flight” mode
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Adrenoceptors;
These are α, β, or dopamine receptors.
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types; Alpha1, Alpha2, Beta1, Beta2, Beta3, D1 and D2
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These receptors are also G protein bound.
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The only prototype that works against both α and β is Epinephrine
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These medications have no effect on D1/D2 receptors
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α Very high doses and β High doses can act on its receptors.
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Alpha agonists;
alpha 1; phenylephrine, epinephrine, norepinephrine,.
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α1 – Gq protein coupled.
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activates phospholipase C and releases IP3 and DAG from the membrane lipids.
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IP3 acts on intracellular receptors to cause Ca release from intracellular stores
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Receptor activation causes vascular smooth muscle contraction especially in skin, splanchnic (abdominal cavity
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organs).
This increases vascular resistance, and MAP (mean arterial pressure).
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In response body develops reflexive bradycardia.
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Eye: Phenylephrine (selective α agonist) causes mydriasis and decrease aqueous humor production (α2
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receptors)
GI: Both, smooth muscle and neurons of GI tract have α and β receptors, which cause relaxation (lowered
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peristalsis, no time for digestion when in fight/flight mode)
Tıssue; most vascular smooth muscle > action; contracts increase vascular resistance
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Tıssue; pupillary dilator muscle > action; contracts mydriasis
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Tıssue; pilomotor smooth muscle > action; contracts erects hair
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Tıssue; bladder trigone > action; contraction
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Tıssue; liver > action; stimulates
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alpha 2; clonidine, epinephrine, norepinephrine, oxymetazoline.
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α2 – Gi protein coupled.
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Inhibits adenylyl cyclase and reduces intracellular cAMP
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α2 – Receptor activation causes vasoconstriction when administered intravenously or topically (nasal spray),
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but when given orally they accumulate in the CNS and reduce sympathetic outflow
clonidine, cause vasoconstriction at the site of injection, and lower the blood pressure
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GI: Both, smooth muscle and neurons of GI tract have α and β receptors, which cause relaxation (lowered
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peristalsis, no time for digestion when in fight/flight mode)
Tıssue; adrenergic and cholinergic nerve terminals > action; inhibits transmitter release.
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Tıssue; platelets > action; stimulates aggregation
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Tıssue; some vascular smooth muscle > action; contracts
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Tıssue; adipocytes > actions; inhibits lipolysis
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Tıssue; pancreatic B cells > actions; inhibits insulin release
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Alpha Nonselective; norepinephrine
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Beta agonists
Beta 1; Dobutamine, Epinephrine, Norepinephrine, Isoproterenol,
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Gs protein coupled. Increase intracellular cAMP
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2. GI: Both, smooth muscle and neurons of GI tract have α and β receptors, which cause relaxation (lowered
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peristalsis, no time for digestion when in fight/flight mode)
Tıssue; heart > actions; stimulates rate and force
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Tıssue; juxtaglomerular cells of kidney > action; stimulates renin releases
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Beta 2; albuterol, epinephrine, isoproterenol, salmetertol
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Gs protein coupled. Increase intracellular cAMP
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cause reduction in arteriolar tone in the skeletal muscle and reduce peripheral vascular resistance and MAP
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Bronchi: Strong relaxation of bronchial smooth muscle (β2 agonists isoproterenol and albuterol), therefore
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these agents can be used to reverse bronchospasm
GI: Both, smooth muscle and neurons of GI tract have α and β receptors, which cause relaxation (lowered
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peristalsis, no time for digestion when in fight/flight mode)
Tıssue; airways, uterine, and vascular smooth muscle > action; relaxes
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Tıssue; liver > action; stimulates glycogenolysis
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Tıssue; pancreatic B cells > action; stimulates insulin releases
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Tıssue; somatic motor neuron (voluntary muscle) > action; causes tremor
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Tıssue; heart > actions; stimulates rate and force
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Beta 3
Gs protein coupled. Increase intracellular cAMP
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Tıssue: Adipocytes > action; stimulates lipolysis
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Beta Nonselective; isoproterenol
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Dopamine 1;
Gs protein coupled.
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Receptor activation causes vasodilation in the splanchnic and renal vasculature.
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Increase cAMP in neurons and vascular smooth muscle. Vessel dilatation
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Tıssue; Renal and other splanchnic blood vessels > action; dilates decrease resistance
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Dopamine 2;
Gi protein coupled. Inhibits adenylyl cyclase and reduces intracellular cAMP
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Tıssue; nerve terminals > actions; inhibits adenylyl cyclase
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Mechanisms of action
For example, amphetamines, tyramine, and cocaine can inhibit neurotransmitter reuptake from the synaptic cleft
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These neurotransmitters are metabolized by catechol-O-methyltransferase and monoamine oxidase.
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monoamine oxidase inhibitors increase the amount of stored catecholamines.
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Pharmacokinetics
Catecholamines are administered parenterally because they have no effect when given orally.
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They have short duration of action and no significant CNS penetration
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Phenylisopropylamines are orally active;
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The effects of Phenyl Isopropylamines last much longer than catecholamines do. (At CNS)
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Tyramine, is not a phenylisopropylamine, is rapidly metabolized by MAO and therefore is not active orally.
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