α blockers work by inhibiting adrenergic responses mediated through α adrenergic receptors. They reduce peripheral resistance and blood pressure by blocking vasoconstrictor α1 receptors. Common side effects include reflex tachycardia, nasal stuffiness, miosis, and reduced ejaculation. Phenoxybenzamine is irreversibly binds to receptors. Prazosin is highly selective for α1 receptors. It is used to treat hypertension and benign prostatic hyperplasia. Tamsulosin is relatively selective for α1A/α1D receptors in the bladder and prostate and causes fewer side effects than non-selective α blockers. α blockers are used to treat pheochromocytoma,

1. Adrenergic Antagonists
α blockers
Dr. Pramod P Bhalerao (M.D.)
Asst. Professor
Dept. of Pharmacology

2. α Adrenergic blocking drugs
• These drugs inhibit adrenergic responses mediated through the α
adrenergic receptors.

4. General effects of α blockers
• 1. Blockade of vasoconstrictor α1 (also α2) receptors reduces
peripheral resistance and causes pooling of blood in capacitance
vessels → venous return and cardiac output are reduced → fall in
BP.
• Postural reflex is interfered with → marked hypotension occurs on
standing → dizziness and syncope.

5. General effects of α blockers
• 2. Reflex tachycardia occurs due
to fall in mean arterial pressure
and increased release of NA due
to blockade of presynaptic α2
receptors.

6. General effects of α blockers
• 3. Nasal stuffiness result from blockade of α receptors in nasal blood
vessels.

7. General effects of α blockers
• 4. Miosis result from blockade of α receptors in radial muscles of iris.

8. General effects of α blockers
• 5. 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.

9. Benign Hypertrophy of Prostate

10. General effects of α blockers
• 7. 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.

11. α Blockers

12. Phenoxybenzamine
• It cyclizes spontaneously in the body
giving rise to a highly reactive
ethyleniminium intermediate which
reacts with α adrenoceptors and other
biomolecules by forming strong covalent
bonds.
• The α blockade is of nonequilibrium
(irreversible) type.
• Used primarily in Pheochromocytoma.

13. Phentolamine
• This is a rapidly acting α blocker with short duration of action (in
minutes).
• It is used as a quick and short acting α blocker for diagnosis and
intraoperative management of pheochromocytoma.

14. Pheochromocytoma
• Pheochromocytoma (PCC) is a neuroendocrine tumor of the medulla
of the adrenal glands that secretes high amounts of catecholamines,
mostly norepinephrine.

15. Prazosin
• It is first of the highly selective α1 blockers having α1 : α2 selectivity
ratio 1000:1.
• All subtypes of α1 receptor (α1A, α1B, α1D) are blocked equally.
• Postural hypotension is less marked, occurs especially 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) are also milder.

16. Postural Hypotension due to Prazosin

17. Prazosin
• Pharmacokinetics
• Prazosin is effective orally (bioavailability ~60%).
• Its plasma t½ is 2– 3 hours; effect of a single dose lasts for 6–8 hours.

18. Prazosin-Uses
• Prazosin is primarily used as an antihypertensive.
• Other uses are— Benign hypertrophy of prostate (BHP).
• Prazosin blocks α1 receptors in bladder trigone and prostatic smooth
muscle, thereby improves urine flow, reduces residual urine in bladder.
• Dose: Prazosin GITS (gastrointestinal therapeutic system) 2.5 mg and
5 mg tablets; 1 tab OD.

19. Terazosin
• Higher bioavailability (90%) and longer plasma t½ (~12 hr);
• a single daily dose lowers BP over 24 hrs.
• Terazosin is more popular for use in BHP due to single daily dose and
a probable apoptosis promoting effect on prostate.

20. Doxazosin
• Another long acting (t½ 18 hr) congener of prazosin with
pharmacological profile, similar to terazosin, including the apoptosis
promoting effect on prostate.
• It is used in hypertension and BHP.

21. Tamsulosin (Uroselective)
• This relatively uroselective α1A/ α1D blocker (α1A : α1B affinity 7–
38 fold) has been found as effective as terazosin in improving
BHP symptoms, because α1A subtype predominate in the bladder base
and prostate.
• However, it lacks the prostatic apoptosis promoting property of
terazosin and doxazosin.
• Tamsulosin does not cause significant changes in BP or HR at doses
which relieve urinary symptoms, and it is not used as an
antihypertensive.

22. Tamsulosin
• It may be a better tolerated α1 blocker for BHP in patients who
continue to suffer postural hypotension with terazosin/doxazosin.
• Dose: 0.4 mg MR cap; 1 cap (max 2) in the morning with meals.

23. Uses of α blockers 1. Pheochromocytoma
• It is a tumour of adrenal medullary cells.
• Excess CAs are secreted which can cause
intermittent or persistent hypertension.
• Phenoxybenzamine can be used as
definitive therapy for inoperable and
malignant pheochromocytoma.
• Prazosin is an alternative.

24. Uses of α blockers 1. Pheochromocytoma
• When surgical removal of the tumour is contemplated, it is desirable to
give phenoxybenzamine orally for 1–2 weeks preoperatively and
infuse it i.v. during surgery.
• The rationale is:
(i) Due to excess circulating CAs blood volume is low (they shift fluid
from vascular to extravascular compartment). Treatment with α
blocker normalizes blood volume and distribution of body
water.
• (ii) Handling of the tumour during surgery may cause outpouring of
CAs in blood → marked rise in BP. This is prevented by
phenoxybenzamine given pre and intraoperatively.

25. Uses of α blockers 2. Hypertension
• α blockers other than those selective for α1 (prazosin-like) have been a
failure in the management of essential hypertension,
because vasodilatation is compensated by cardiac stimulation.
• Moreover, postural hypotension, impotence, nasal blockage and other
side effects produced by nonselective α blockers are unacceptable.

26. Uses of α blockers 3. Benign hypertrophy of
prostate (BHP)
• The urinary obstruction caused by BHP has a static component due to
increased size of prostate and a dynamic component due to increased
tone of bladder neck/prostate smooth muscle.
• 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

27. Benign Hypertrophy of Prostrate

28. Uses of α blockers 3. Benign hypertrophy of
prostate (BHP)
• Terazosin, doxazosin and tamsulosin are the peferred α1 blockers
because of once daily dosing.
• There is some evidence that terazosin and doxazosin promote
apoptosis in prostate.
• Tamsulosin appears to cause fewer vascular side effects because of
relative α1A /α1D selectivity.

29. Thank You