Sympatholytics I

Dr. Pramod Bhalerao

Receptor location in the body

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

Receptor location

α1 α2Selective agonist Phenylephrine ClonidineSelective antagonist Prazosin Yohimbine

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)

blockers

• These drugs inhibit adrenergic responses mediated through the α adrenergic receptors without affecting those mediated through β receptors.

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

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.

General effects of blockers

• Fall in BP due to blockers menifest as postural hypotension.

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

General effects of blockers

• Nasal stuffiness result from blockade of α receptors in nasal blood vessels

General effects of blockers

• Miosis result from blockade of α receptors in radial muscles of iris.

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.

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.

Phenoxybenzamine

• Nonequilibrium (irreversible) type of α blockade.

• Uses: Pheochromocytoma,Secondary shock.

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.

Prazocin

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).

Prazosin

• Prazosin is effective orally (bioavailability ~60%).• Its plasma t½ is 2–3 hours.

Terazosin

• Higher bioavailability (90%) and longer plasma t½ (~12 hr)

• Single daily dose.

Doxazosin

• Long acting (t½ 18 hr).• Single daily dose.

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.

Uses of blockers

Pheochromocytoma

Pheochromocytoma

• A tumour of adrenal medullary cells.

• Excess CAs are secreted which can cause intermittent or persistent hypertension.

• Rx-Phenoxybenzamine /Phentolamine.

Hypertension

• blockers improve lipid profile.

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.

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.

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.

Peripheral Vascular Disease(PVD)

Peripheral vascular diseases

• When vasoconstriction is a prominent feature (Raynaud’s phenomenon, acrocyanosis), good symptomatic relief is afforded by prazosin or phenoxybenzamine.

Side effects of blockers

• Postural hypotension.• Palpitation.• Nasal blockage.• Miosis. • Inhibition of ejaculation.

Thank You