This document summarizes adrenergic receptor antagonists. It describes the different types of α-adrenergic receptors and how they mediate various physiological functions. It discusses selective and non-selective α-blockers, their mechanisms of action, and examples of commonly used drugs for each category. Specific drugs discussed include prazosin, terazosin, doxazosin, tamsulosin, yohimbine, and phentolamine. The document also reviews uses of α-blockers for conditions like hypertension, Raynaud's phenomenon, benign prostatic hyperplasia, and treatment of pheochromocytoma.

1. Adrenergic Receptor
Antagonists

2. Recap……

3. α Adrenergic Receptor Antagonists
• The α adrenergic receptors mediate many of the important actions of
endogenous catecholamines.
• The α1 receptors mediate contraction of arterial, venous, and visceral
smooth muscle.
• The α2 receptors are involved in suppressing sympathetic output,
increasing vagal tone, facilitating platelet aggregation, inhibiting the
release of NE and acetylcholine from nerve endings, and regulating
metabolic effects (e.g., suppression of insulin secretion and inhibition
of lipolysis).
• The α2 receptors also mediate contraction of some arteries and veins.

4. • Some of α adrenergic antagonist have markedly different
affinities for α1 and α2 receptors. For example,
• prazosin is much more potent in blocking α1 than α2 receptors
(i.e., α1 selective), whereas
• yohimbine is α2 selective;
• phentolamine has similar affinities for both of these receptor
subtypes.
• More recently, agents that discriminate among the various
subtypes of a particular receptor have become available; for
example, tamsulosin has higher potency at α1A than at α1B
receptors.

5. • Catecholamines increase the output of glucose from the liver; in
humans, this effect is mediated predominantly by β receptors,
although α receptors may contribute.
• The α receptor antagonists therefore may reduce glucose release.
• Receptors of the α2A subtype facilitate platelet aggregation; the
effect of blockade of platelet α2 receptors in vivo is not clear.
• Activation of α2 receptors in the pancreatic islets suppresses insulin
secretion; conversely, blockade of pancreatic α2 receptors may
facilitate insulin release.

7. Non-selective α- blockers Selective α- blockers
Reversible
 Phentolamine
 Tolazoline
(priscoline)
 Ergot alkaloid:
Ergotamine,
Ergotoxine,
Dihydroergotamin
e (DHE),
Dihydroergotoxine
Irreversible
 Phenoxy-
benzamine
α1- selective α2- selective
 Prazosin
 Terazosin
 Doxazosin
 Alfuzosin
 Tamsulosin
 Silodosin
 Yohimbine
 Idazoxan

11. Heart

23. Ergotamine and ergotoxine
• These are partial agonists and antagonists at α adrenergic,
serotonergic and dopaminergic receptors.
• These drugs produce long lasting vasoconstriction which
predominates over their α blocking action.
• Ergotism: Peripheral vascular insufficiency and gangrene of
toes and fingers.
• Ergotoxine is a more potent α blocker and less potent
vasoconstrictor than ergotamine.

24. • Uses
• Migraine
• Induce labour
• Ergometrine should be avoided in—
• patients with vascular disease, hypertension, toxaemia.
• presence of sepsis—may cause gangrene.
• liver and kidney disease.
• They are contraindicated during pregnancy and before 3rd
stage of labour.

25. Indoramin
• Indoramin is a selective, competitive α1-selective receptor
antagonist that also antagonizes H1 and 5HT receptors.
• Indoramin lowers blood pressure with minimal tachycardia.
• Indoramin is used for the treatment of hypertension and BPH
and in the prophylaxis of migraine.
• The drug also decreases the incidence of attacks of Raynaud
phenomenon.
• Some of the adverse effects of indoramin include sedation, dry
mouth, and failure of ejaculation.

26. • Ketanserin
• Although developed as a 5HT receptor antagonist,
ketanserin also blocks α1.receptors.
• Urapidil
• Urapidil is a selective α1 receptor antagonist that has a
chemical structure distinct from those of prazosin and
related compounds.
• Blockade of peripheral α1 receptors appears to be
primarily responsible for the hypotension produced by
urapidil, although it has actions in the CNS as well.

27. • Bunazosin
• Bunazosin is an α1-selective antagonist of the quinazoline
class that has been shown to lower blood pressure in
patients with hypertension.
• Neuroleptic Agents
• Chlorpromazine, haloperidol, and other neuroleptic drugs
of the phenothiazine and butyrophenone types produce
significant blockade of both α and D2 receptors in humans.

35. Papaverine/Phentolamine Induced Penile
Erection (PIPE) therapy for impotence
• In patients unable to achieve erection, injection of papaverine (3–20
mg) with or without phentolamine (0.5–1 mg) in the corpus
cavernosum has been found to produce penile tumescence to permit
intercourse.
• Priapism occurs in 2–15% cases
• Repeated injections can cause penile fibrosis
• Other complications are
• local haematoma, infection, paraesthesia and penile deviation.

37. Drugs Dose Special features
PHENOXYBENZAMINE 20–60 mg/day oral,
1 mg/kg slow i.v. infusion over 1hr.
 Used in the preoperative management of Pheochromocytoma.
 It causes postural hypotension and impotence.
PHENTOLAMINE 5 mg i.v. repeated as required  Used in diagnosis & intra-operative management of
Pheochromocytoma and cheese reaction.
PRAZOSIN Start with 0.5–1 mg at bedtime;
usual dose 1–4 mg BD or TDS.
 Used as an antihypertensive, Raynaud’s disease and BPH.
 ‘First dose effect’ in the form of postural hypotension and
syncope attack occurs on the initiation of therapy & decreases
with time due to tolerance.
TERAZOSIN Usual maintenance dose
2–10 mg OD.
 Same as prazosin.
 It has longer duration of action; hence, single daily dose is
sufficient.
DOXAZOSIN 1 mg OD initially, increase upto 8
mg BD.
 Used as an antihypertensive and BPH.
TAMSULOSIN 0.4 mg, 1 cap (max 2) in the
morning with meals.
 It is uroselective (α1A), bladder and prostate specific.
ALFUZOSIN 2.5 BD-QID or 10 mg OD as
modified release tab.
 Short acting and used for symptomatic treatment of BPH
SILODOSIN 4-8 mg /day  α1A- antagonist (uroselective) for prostate.
 No orthostatic hypotension is seen.
 Loss of seminal emission.
YOHIMBINE 2 mg oral.  No valid indications for its use are there.
 Previously it was used as aphrodisiac.