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ADRENERGICADRENERGIC ANTAGONITS ANTAGONITS

SAMUEL AGUAZIM ( MD)

Organization of ClassOrganization of Class

The effect of the SNS can be blocked either by decreasing sympathetic outflow from the brain, suppressing release of NE from terminals or by blocking postsynaptic receptors.

Adrenergic antagonists reduce the effectiveness of sympathetic nerve stimulation and effects of exogenously applied agonists, such as Isoproterenol.

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What are adrenergic What are adrenergic antagonistsantagonists

They are drugs that bind to adrenergic receptors but do not initiate the usual intracellular response

They are divided into 2 main subdivisions1. alpha blockers2. beta blockers In this chapter we will discuss alpha 2 agonist because

it reduce sympathetic nerve activity and are used to treat hypertension

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ADRENERGIC BLOCKERSADRENERGIC BLOCKERSALPHA BLOCKERS

Alpha 1 Blockers Nonselective Alpha

BlockersDoxazosin Phenoxybenzamine Prazosin PhentolamineTerazosin Most alpha antagonists allow vasodilatation and thus,

decrease blood pressure( remember a-receptor activation results in vasoconstriction)

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DRUGS AFFECTING NEUROTRANSMITTER UPTAKE OR RELEASE

CocaineGuanethidineReserpine

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PhenoxybenzaminePhenoxybenzamine

Blocks alpha 1 and 2, irreversible blockade MOSTLY Noncompetitive inhibitor Actions - prevents Vaso-Constriction, induces a reflex

tachycardia Epinephrine reversal Therapeutic uses :

– Opposing catecholamines --pheochromocytoma– Causes vasodilation – Benign prostatic hypertrophy– Spinal cord injuries

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SE:Postural hypotensionSexual dysfunction ( inhibit ejaculation)TachycardiaContraindicated in ↓ coronary perfusion.

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PhentolaminePhentolamine

Alpha 1 and 2 blockerCompetitive inhibitorDuration of action lessUses & SE – mostly same as Phenoxybenzamine.

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Alpha 1 specific blockersAlpha 1 specific blockersPrazosinTerazosinDoxazosin – long actingBlockade of alpha 1 adrenergic receptors on

vascular smooth muscle inhibits constriction of arterioles and veins. This results in decreased peripheral vascular resistance and lower blood pressure.

Blockade in bladder ( relaxation and decreased resistance to urine flow)

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Actions ----- Dose ---- Uses -----

Side effects ----

CVS Avoid high doses HTN and prevention

of urinary retention in patients who have benign prostatic hypertrophy

Orthostatic hypotension

Nasal stuffiness Fatigue Sexual dysfunction

(less)

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BETA BLOCKERSNon Selective Beta 1 selective

Blockers BlockersPropranolol Metoprolol Timolol AtenololNadolol Esmolol Acebutolol Betaxolol Labetalol - Both Alpha and Beta Blocker Beta 1receptors found in the heart and their activation

leads to an increase in HR and contractility . Beta 2 receptor are found in SM of the respiratory tract,

the uterus and blood vessels. Their activation leads to relaxation of SM

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Non selective beta antagonistsNon selective beta antagonists

PropranololTimololNadolol

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PropranololPropranolol

CVS – HR ↓ , CO ↓PERIPHERAL VESSELS – NO ALPHA ACTIONBRONCHI - ↑ CONTRACTIONSODIUM LEVELS - ↑GLYCOGENOLYSIS -↓ GLUCAGON - ↓BLOCKS DRUGS – Isoproterenol , & β actions of epinephrine

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USESUSES

HTN ---- decreases COANGINA---decreases oxygen demandMI---- protects myocardiumGLAUCOMA-- TimololMIGRAINEHYPERTHYROIDISM– blunts

sympathetic stimulation

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SIDE EFFECTSSIDE EFFECTS

BRONCHOCONSTRICTIONCONTRAINDICATION –ASTHMA, COPDARRHYTHMIAS – gradual reduction in doseSEXUAL IMPAIREMENT

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NON SELECTIVE BETA NON SELECTIVE BETA ANTAGONISTSANTAGONISTS

TIMOLOLNADOLOL → very long duration of action

Considered more potent than propranolol.

Same effects and SE as propranolol.

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SELECTIVE BETA 1 SELECTIVE BETA 1 ANTAGONISTS (Cardioselective)ANTAGONISTS (Cardioselective)

ATENOLOLMETOPROLOLESMOLOL

USES – HTN,ANGINACAN BE USED IN COPD, Diabetics

CASES

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ANTAGONISTS AND ANTAGONISTS AND PARTIAL AGONISTSPARTIAL AGONISTS

PINDOLOLACEBUTOLOLThey very mildly stimulate both beta 1 and

beta 2 adrenergic receptors.

USES : HTN with moderate bradycardia

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ALPHA AND BETA ALPHA AND BETA BLOCKERBLOCKER

LABETALOL( non-selective)

Peripheral vasodilation -- ↓ B.PNo vasoconstrictive effectUSES : OLD AGE HTN, congestive heart

failureSE: Orthostatic hypotension and dizziness.

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NT AFFECTING DRUGSNT AFFECTING DRUGSRESERPINEIt blocks Norepinephrine transport from

CYTOPLASM TO STORAGE VESICLE

USES -- ↓B.P. ↓ H.R

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NT AFFECTING DRUGSNT AFFECTING DRUGSGUANETHIDINE

–BLOCKS RELEASE OF stored NE IN VESICLE TO MEMBRANE

USES—gradual lowering of B.P and H.R. in hypertensives

SE: orthostatic hypotension and sexual dysfunction

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NT AFFECTING DRUGSNT AFFECTING DRUGS

COCAINE Block Na-K ATPaseREUPTAKE DECREASED (NE)USES ----local anesthetic???

General use of beta blockersGeneral use of beta blockers

Angina, hypertension, post MI ( ALL DRUGS)ANTIARRTHYMICS( CLASS 2

PROPRANOL,ACETABUTOLOL,ESMOLOL,)GLAUCOMA: TIMOLOLMIGRAINE, THYROTOXICOSIS,

PERFORMANCE ANXIETY, ESSENTIAL TREMOL: PROPRANOLOL

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COMBINED ALPHA 1 AND BETA BLOCKING ACTIVITY

LABETALOL AND CARVEDILOR: USED IN CONGESTIVE HEART FAILURE

POTASSIUM CHANNEL BLOACKADE AND BETA BLOCKING ACTIVITIY

SOTALOL: USED IN ANTIARRTHYMIC (CLASS 3)

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