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Sympathetic

Drugs Overview
SYMPATHOMIMETIC CATHECOLAMINES
Direct acting norEP
o Alpha-1 selective agonist - Primary transmitter of CNS
Phenylephrine - Most of sympathetic postganglionic fiber
Methoxanine Ep
Midrodrine - Major hormone of the adrenal medulla
Oxymetazolene Dopamine
Xylomethazolene - predominant transmitter of the extrapyramidal system
o Alpha-2 selective agonist
Clonidine SYNTHESIS, STORAGE & RELEASE OF CATHECOLAMINES
Apraclonidine
Methyldoopa
o Non-selective (alpha and beta)
Epinephrine
Norepinephrine
Ephedrine (mixed)
Phenylpropanolamine
o Beta-1 selective agonist
Dobutamine
o Beta 2 selective
Ritoridine
Albuterol, bitoleterol, procaterol , fenoletrol,
metaproterenol
Terbutaline
o Non-selective beta
Isoproterenol
o Dopamine receptor agonist:
Dopamine, fenoldopam
Indirect-acting
o Amphetamine-like
Amphetamine
Tyramine (cheese)
Phenmetrazine
o Cathecolamine uptake inhibitors
TCA
Coccaine Tyrosine is the precursor compound
Duloxetine Tyrosine hydroxylase is the RLE
Sibutramine Stored in vesicles though VMAT
o MAO inhibitor Release:
Depolarization opening of VG calcium channels
SYMPATHOLYTICS increase IC calcium fusion of VAMP and SNAP
Alpha-1selective antagonist release of norEP
o Prazosin NET (NorEp transporter)
o Terasozin Reuptake of norEP into the cytoplasm
o Doxasozin Drugs affecting synthesis, storage and release of
o Phenoxybenzamine (irreversible) catecholamine
Alpha-2 selective antagonist Metyrosine
o Yohimbine Blocks tyrosine hydroxylase
o Tolazoline Reserpine
Non-selective alpha antagonist Blocks VMAT
o phentolamine Bretylium & Guanethidine
Non-selective alpha and beta antagonist Blocks release
o Labetalol Coccaine & TCA
o Carvedilol Blocks NET
Beta-1 selective antagonist Amphetamine, tyramine, ephedrine
o Metoprolol, acebutolol, atenelol, betaxolol, esmolol Competes for NET
Beta-2 selective
o Butoxamine REGULATION OF NOREPINEPHRINE
Non-selective beta antagonist Reuptake into nerve terminals
o Propanolol, sotalol, nadolol, pindolol, timolol Alpha-2 receptors (autoreceptor)
Dopamine receptor antagonist Stimulation by norEP will cause inhibition of its release
o Chlopromazine Up & down regulation
o haloperidol Dilution by Diffusion out of the Junctional Cleft and Uptake at
Extraneuronal sites
SNS vs PsNS ENT: E>NE>dopamine
OCT1: D=E>norEP
OCT2: D>NE>E
Metabolic transformation
MAO
COMT

ADRNERGIC RECEPTORS
G-protein coupled
Gs: stimulatory G protein of
adenylyl cyclase inc cyclic
AMP
Gi and Go: the inhibitory G
proteins of adenylyl cyclase
Gq and G11: G proteins
coupling receptors to
phospholipase C
Non-selective drugs have greater contraindications

Alpha-1 SPECIFIC DRUGS


VASOCONSTRICTION Epinephrine is the drug of choice for anaphylaxis
Effects Phenoxybenzamine is an irreversible alpha 1 antagonist; action
- Increase in ABP persist even after its clearance
- Mydriasis, dec IOP Methydopa may have extrapyramidal symptoms as its adverse
- Erects hair effects
- Prostate and bladder base contraction
- (+) Inotropic
Alpha-2 receptors
Blocks release of norEP
Localized effect: vasoconstriction
Central effect:
- Inhibits platelet aggregation
- Inhibit lipolysis
- Inhibits renin secretion
- Inhibit insulin release
Beta1
Effects:
- Heart:
chrono, ino, dromo
- Blood vessels
vasodilatation
- Juxtaglomerular apparatus
increase secretion of renin
Beta 2
Effects:
- Vasodilataion
- Bronchodilation
- Uterus relaxation
- Hypokalemia
- Promotes gluconeogenesis
- Activates glycogenolysis
Dopamine Receptors
D1:
Effects:
- Dilates renal blood vessels
- Dilates coronary, splanchnic & other resistance
vessels
Target receptor for emergency hypertension
D2
Effects:
- Modulates or inhibits NTA release

PHARMACOLOGIC MODIFICATIONS
Substitution of OH on Benzene Rings
Greater activity on alpha and beta receptors
- Epinephrine > phenyleprine
Less degradation by COMT
Alkyl substitution of amino group
Greater beta-receptor activity
NorEp<ep<isoproterinol
Methyl substitution on the Alpha Carbon
Less degradation by MAO
Indirect acting drugs
Eg. ephedrine, amphetamine
OH group on Beta carbon
Direct acting

SOME GENERALIZATIONS
Alpha vs Beta receptors
Beta receptors
- More sensitive
Alpha receptors
- More potent receptors

Ep vs. NorEp
Epinephrine:
- Alpha1 = alpha2
- Beta1 = beta2
Norepinephrine:
- Alpha 1 = alpha 2
- Beta 1 > beta2
NOTE: NorEP has greater vasoconstricting effect; Ep has greater
diabetogenic effect

Alpha receptors
Ep> norEp > isoproterenol
Beta receptors
Isoproterenol> ep> norEp