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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
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