Flashcards in Adrenergic Pharmacology Deck (68)
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Synthesis and Storage of Dopamine (DA), norepinephrine (NE, and epinephrine
Tyrosine transported from plasma into nerve cell via Na+ dependent carrier. Oxidation to DOPA by tyrosine hydroxylase (rate limiting step). DOPA decarboxylated to form DA. DA transported into synaptic vesicles for protection via amine transporter system. DA hydroxylated to norepinephrine by dopamine B-hydroxylase within vesicle. NE is transported back to cytoplasm and methylated to epinephrine in adrenal medulla and stored in chromaffin cells.
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Release of NE
Action potential triggers calcium influx, causing release of vesicles through exocytosis
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Binding to Receptor
Postsynaptic (alpha and beta that work w/ g protein secondary messenger system) receptor activated by binding of NE --> intracellular response via 2nd messenger
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Drugs that affect synthesis/uptake/release
Alpha methyltyrosine, reserpine, tyramine. guanethidine, amphetimine, cocaine, imipramine, fluoxetine, tricyclic antidepressents, phenelzine, selegiline
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Alpha-methyltyrosine
Inhibits tyrosine hydroxylase
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Reserpine
Blocks VMAT, transport of bioamines from cytoplasm into vesicles.
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Tyramine
Dietary amines usually metabolized by MAO in GI and liver. In pt with MAO inhibitors tyramine is absorbed, large amounts cause displacement of vesicular NE and non vesicular release resulting in HTN crisis.
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Guanethidine
Displaces NE in storage vesicles, leading to gradual depletion of NE
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Amphetamine
Displaces endogenous NE, blocks reuptake by NET and DAT
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Cocaine
Potent inhibitor of NET, eliminated catecholamine transport
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Imipramine, fluoxetine
Inhibitors of NET
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Tricyclic antidepressents
Blocks Na+/K+ ATPase, blocks NET, prevents uptake of epinephrine and NE and increases DOA
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Phenelzine
Inhibits MAO-A, increasing NE and 5-HT serotonin content. Inhibits metabolism of NE and seratonin
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Selegiline
Inhibits MAO, increasing DA.
Low doses for tx of Parkinson Disease
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Adrenergic Receptors
Alpha and beta based on affinity to adrenergic agonists
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Alpha affinity
Epinephrine binds the best, then NE, and lastly isoproteranol
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Beta affinity
Isoproteranol > epinephrine > norepinephrine
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Activity of Agonists- Alpha 1
Vasoconstriction
Increases PVR, BP, mydriasis, and increased closure of the sphincter of bladder
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Activity of Agonists- Alpha 2
Central feedback receptor
Inhibit NE release (auto receptors) resulting in lowered BP, inhibit insulin release
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Activity of Agonists- Beta 1
Primary receptor located in the heart
Tachycardia, increased myocardial contractility, resulting in increased cardiac output, increased release of renin (controls BP), and increased lipolysis
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Activity of Agonists- Beta 2
Primarily located in the vasculature and lungs
Vasodilation, decreased PVR, decreased DBP, bronchodilation, increased muscle and liver glycogenolysis, increased glucagon release, relax uterine smooth muscle.
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Desensitization of receptors
Make receptors unavailable for interaction through sequestion. Down regulate receptors, and unable to couple G-proteins.
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Symapthyomimetic
Adrenergic drug which acts directl on adrenergic receptors activating them. Aka adrenergic agonists.
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Endogenous catecholamines
Epinephrine, NE, and DA
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Characteristics of adrenergic agonists- catecholamines
OH group in the 3,4 position of the benzene ring
Rapid inactivation because of enzymes scattered through various tissues
OH groups prevent penetration to the CNS
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Characteristics of adrenergic agonists- non-catecholamines
Lack catechol OH group, have linger half lives and have higher lipid affinity- CH3
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Characteristics of adrenergic agonists- substitution on amine nitrogen
Increase affinity for Beta-receptors
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Adrenergic agonist- direct effect
Epinephrine, NE, albuterol, pirbuterol, terbutaline, dobutamine, dopamine, isoproteranol, phenylephrine, clonidine, salmeterol, and formoterol
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Adrenergic agonist- indirect
Amphetimine and tyramine
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