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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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