Sympathomimetic drugs directly bind to and stimulate adrenergic receptors like alpha, beta, and dopamine receptors. They act on the sympathetic nervous system to activate the body's fight or flight response. The main types are alpha and beta agonists which exert their effects through G-protein coupled receptors and can cause effects like vasoconstriction, increased heart rate, bronchodilation, and more. These drugs are typically administered parenterally due to their short duration of action and lack of oral effectiveness.

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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