ALPHA BLOCKERS block the ALPHA-receptors, thus inhibiting the ALPHA-receptor-mediated responses of sympathetic stimulation and adrenergic drugs.

1. ALPHA RECEPTOR
BLOCKERS
Dr. S P Srinivas Nayak, PharmD, (MSc).
Assistant Professor, Sultan-ul-Uloom
college of Pharmacy, Hyderabad,
Telangana, India.

2. ALPHA RECEPTORS
EFFECT OF ACTIVATION OF ALPHA1-RECEPTORS
Blood vessels: Constriction.
GI sphincter (anal): Increase in tone.
Urinary sphincter: Increase in tone.
Radial muscle (iris): Contraction (mydriasis).

3. EFFECT OF ACTIVATION OF
ALPHA 2 -RECEPTORS
1. Effect of activation of presynaptic Alpha 2 receptors:
Mediate negative-feedback control on NA secretion.
2. Effect of activation of postsynaptic alpha 2
receptors: Vasoconstriction and venoconstriction.
3. Effect of activation of alpha 2 –receptors on various
tissues:
a) Beta cells of islets of Langerhans in pancreas:
Decrease in insulin secretion.
b) Ciliary epithelium: Reduction of aqueous humor
secretion.
c) Sympathetic nerve endings: Decrease in NA release.

7. Pharmacology of Alpha Blockers
• PHENOXYBENZAMINE
• it is a nonselective irreversible alpha blocker that blocks
both alpha1 and alpha2-receptors.
• It binds covalently to alpha-receptors and causes
irreversible blockade. It also inhibits the reuptake of NA
into the adrenergic nerve endings.
Phrmacolgical Actions:(mixed action)
1. reduces Peripheral vascular resistance due to the blockade
of vascular alpha 1-receptors.
2. Increased release of NA from the adrenergic nerve endings
due to the blockade of presynaptic alpha 2-receptors. This
may cause cardiac stimulation and produce tachycardia,
palpitation, cardiac arrhythmias, etc.
Use: pheochromocytoma

10. PHENTOLAMINE
• Phentolamine is an imidazoline derivative. It competitively
blocks the effects of NA at both alpha 1 and alpha2
receptors. It can also block 5-HT receptors, K+ channels and
cause histamine release from mast cells.
• Phentolamine is given intravenously
and has rapid onset but short duration of action.
• It is used intraoperatively during surgery of
phaeochromocytoma and
• in hypertensive emergencies
• Adverse effects :They include tachycardia,
• palpitation, arrhythmias; angina and MI may be
precipitated.

11. SELECTIVE ALPHA 1-
BLOCKERS
• Prazosin is a potent and selective alpha1 blocker.
given orally. It is well absorbed from GI tract, but
undergoes Extensive first-pass metabolism.
First-dose phenomenon:
Within 30–90 min of oral administration of prazosin,
severe postural hypotension and syncopal attacks may be seen with
first dose. Therefore, the initial dose should be small (1 mg). It is
usually given at bed time so that the patient remains in bed for several
hours and the risk of syncopal attack is reduced.

12. OTHER SELECTIVE ALPHA1-
BLOCKERS
• Terazosin is similar to prazosin, but less potent
than prazosin. It is almost completely absorbed
after oral administration and has a longer
duration of action.
• Doxazosin is the longest-acting, selective alpha 1-
blocker. The haemodynamic effects,
bioavailability and extent of metabolism are
similar to prazosin.
• Alfuzosin blocks all subtypes of alpha 1-receptors
(alpha 1A, 1B and 1D). It is orally effective and
used in benign prostatic hyperplasia (BPH)

13. TAMSULOSIN
• Tamsulosin is an uroselective alpha 1-blocker (alpha 1A). At
low doses, it reduces the resistance to flow of urine with little
effect on BP. It is administered orally and is the preferred
alpha 1-blocker for the treatment of benign prostatic
hyperplasia (BPH) in normotensive patients. It may cause
retrograde ejaculation

14. YOHIMBINE
• Yohimbine An alkaloid from West African plant
Yohimbehe. It is a relatively selective α2 blocker with
short duration of action. Also blocks 5-HT receptors.
Heart rate and BP are generally elevated due to
increased central sympathetic outflow as well as
peripheral NA release.
• Other CNS effects include excitation, tremor, ADH
release (antidiuresis), nausea and vomiting. It may
cause congestion of genitals and has been claimed to
be an aphrodisiac. This effect is only psychological, but
can overcome psychogenic impotence in some
patients. There are no valid indications for clinical use
of yohimbine.

15. ERGOT ALKALOIDS
• The natural ergot alkaloids produce long lasting
vasoconstriction which predominates over their
α blocking action—peripheral vascular
insufficiency and gangrene of toes and fingers
occurs in ergotism.
• Ergotoxine is a more potent α blocker and less
potent vasoconstrictor than ergotamine.
• The α blockade produced by clinical doses of
ergot alkaloids is low grade and short lasting;
they are not employed for this purpose. The
principal use is in migraine

17. THERAPEUTIC USES OF ALPHA-
BLOCKERS
• Pheochromocytoma
• Hypertensive emergencies
• Essential hypertension
• Benign prostatic hyperplasia
• Tissue necrosis
• Kidney stones
• MIGRAINE

18. THANK YOU