sympatholytics I alpha blockers
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Transcript of sympatholytics I alpha blockers
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Sympatholytics I
Dr. Pramod Bhalerao
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Receptor location in the body
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α1 α2Location Postjunctional on
effector organsPrejunctional on nerve ending (α2A),extrajunctional in certain blood vessels
Function subserved
Genitourinary Smooth muscle–contractionBlood vessel: VasoconstrictionHeart—arrhythmia
Inhibition of transmitter releaseBlood vessel: Vasoconstriction
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Receptor location
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α1 α2Selective agonist Phenylephrine ClonidineSelective antagonist Prazosin Yohimbine
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Adrenergic responses mediated through receptors
• Constriction of arterioles and veins → rise in BP (α1 + α2)
• Heart—little action, arrhythmia at high dose (α1)
• Contraction of radial muscles of iris → mydriasis (α1), decreased aqueous secretion.
• Bladder trigone—contraction (α1) (Urinary retention)
• Male sex organs—ejaculation (α1)
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blockers
• These drugs inhibit adrenergic responses mediated through the α adrenergic receptors without affecting those mediated through β receptors.
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Classification • I. Nonequilibrium type• (i) β-Haloalkylamines—Phenoxybenzamine.
• II. Equilibrium type (competitive)• A. Nonselective• (i) Ergot alkaloids—Ergotamine• (ii) Hydrogenated ergot alkaloids—Dihydroergotamine (DHE)• (iii) Imidazoline—Phentolamine• (iv) Miscellaneous–Chlorpromazine• B. α1 selective—Prazosin, Terazosin, Doxazosin, Alfuzosin, Tamsulosin• C. α2 selective—Yohimbine
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General effects of blockers
• Blockade of vasoconstrictor α1 (also α2) receptors reduces peripheral resistance.
• Pooling of blood in capacitance vessels → venous return and cardiac output are reduced → fall in BP.
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General effects of blockers
• Fall in BP due to blockers menifest as postural hypotension.
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General effects of blockers
• Reflex tachycardia occurs due to • Fall in mean arterial pressure• Increased release of NA due to blockade of
presynaptic α2 receptors
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General effects of blockers
• Nasal stuffiness result from blockade of α receptors in nasal blood vessels
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General effects of blockers
• Miosis result from blockade of α receptors in radial muscles of iris.
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General effects of blockers
• Tone of smooth muscle in bladder trigone, sphincter and prostate is reduced by blockade of α1 receptors (mostly of the α1A subtype) → urine flow in patients with benign hypertrophy of prostate (BHP) is improved.
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General effects of blockers
• Contractions of vas deferens and related organs which result in ejaculation are coordinated through α receptors—
• α blockers can inhibit ejaculation; this may manifest as impotence.
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Phenoxybenzamine
• Nonequilibrium (irreversible) type of α blockade.
• Uses: Pheochromocytoma,Secondary shock.
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Phentolamine
• It equally blocks α1 and α2 receptors
• Used as a quick and short acting α blocker for diagnosis and intraoperative management of pheochromocytoma and for control of hypertension due to clonidine withdrawal, cheese reaction, etc.
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Prazocin
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Prazosin
• First of the highly selective α1 blockers.
• Postural hypotension occurs in the beginning, which may cause dizziness and fainting as ‘first dose effect’.
• This can be minimized by starting with a low dose and taking it at bedtime.
• Other α blocking side effects (miosis, nasal stuffiness, inhibition of ejaculation).
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Prazosin
• Prazosin is effective orally (bioavailability ~60%).• Its plasma t½ is 2–3 hours.
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Terazosin
• Higher bioavailability (90%) and longer plasma t½ (~12 hr)
• Single daily dose.
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Doxazosin
• Long acting (t½ 18 hr).• Single daily dose.
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Tamsulosin
• Relatively uroselective α1A/ α1D blocker(α1A subtype predominate in the bladder base and prostate)
• It may be a better tolerated α1 blocker for BHP in patients who continue to suffer postural hypotension with terazosin /doxazosin.
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Uses of blockers
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Pheochromocytoma
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Pheochromocytoma
• A tumour of adrenal medullary cells.
• Excess CAs are secreted which can cause intermittent or persistent hypertension.
• Rx-Phenoxybenzamine /Phentolamine.
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Hypertension
• blockers improve lipid profile.
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Benign hypertrophy of prostate (BHP)
• The urinary obstruction caused by BHP has a • static component due to increased size of prostate. • dynamic component due to increased tone of
bladder neck/prostate smooth muscle.
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Benign hypertrophy of prostate (BHP)
• Two classes of drugs are available:• • α1 adrenergic blockers (prazosin like): decrease
tone of prostatic/bladder neck muscles.• •5-α reductase inhibitor (finasteride): arrest
growth/reduce size of prostate.
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Secondary shock
• Shock due to blood or fluid loss is accompanied by reflex vasoconstriction.
• (Phenoxybenzamine i.v.) can help by:• (i) Counteracting vasoconstriction.• (ii) Shifting blood from pulmonary to systemic circuit.• (iii) Returning fluid from extravascular to the vascular
compartment so that cardiac output improves.
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Peripheral Vascular Disease(PVD)
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Peripheral vascular diseases
• When vasoconstriction is a prominent feature (Raynaud’s phenomenon, acrocyanosis), good symptomatic relief is afforded by prazosin or phenoxybenzamine.
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Side effects of blockers
• Postural hypotension.• Palpitation.• Nasal blockage.• Miosis. • Inhibition of ejaculation.
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Thank You