ALPHA ANTAGONISTS

Classification
• Non-equilibrium α-adrenergic blockers :
β Haloalkylamine - Phenoxybenzamine
• Equilibrium type (Competitive): Non Selective
ERGOT • ERGOTAMINE
ALKALOIDS • ERGOTOXINE

HYDROGENATED • DHE
ERGOT
ALKALOIDS • DIHYDROERGOTOXINE

IMIDAZOLINE • PHENTOLAMINE
MISCELLANEOUS • CHLORPROMAZINE
Selective α1-adrenergic blockers

• Prazosin
• Doxazosin
• Tamsulosin
• Terazosin
• Silodosin
• Alfuzocin
Selective α2-adrenergic blockers

• Yohimbine

Alpha and beta blockers : Carvedilol and

Labetolol
GENERAL EFFECTS OF α BLOCKERS
• Blockade of vasoconstrictor α1 (also α2)
vasodilation→ reduces peripheral resistance
→pooling of blood in capacitance vessel
→venous return and cardiac output ↓
→ fall in BP.
Postural reflex is interfered with
• marked hypotension occurs on standing
• dizziness and syncope
VASOMOTOR REVERSAL OF DALE
• The α blockers abolish the pressor action of
Adr, which then produces
only fall in BP due to β2 mediated
vasodilation
GENERAL EFFECTS cond…
• Reflex tachycardia
• Nasal stuffiness and miosis
• Intestinal motility is increased
• renal blood flow ↓ leads to ↓sed g.f.r.

more complete reabsorption of Na and water

Na retention and increase in blood volume.

 GENERAL EFFECTS COND…
• Tone of smooth muscle in bladder trigone,
sphincter and prostate reduced by blockade of
α1 receptors

urine flow in patients with benign hypertrophy of

prostate (BHP) is improved.

• Inhibition of ejaculation
 PHENOXYBENZAMINE
– Oral abs. incomplete.. im & sc painful
– Long duration of action (48 hours)
– Binds covalently to its receptors
– Only slightly alpha1 selective
– Short elimination half life
– Postural hypotension
– Shifts blood from pulmonary to systemic
circulation
– Shifts blood from extravascular to vascular comp.
 Therapeutic uses & adverse effects
1. Pheochromocytoma
2. Secondary shock
3. Perepheral vascular disease
S/E
a) Postural hypotension
b) Palpitation
c) Nasal blockage
d) Miosis, inhibition of ejaculation
 ERGOT ALKALOIDS
• Ergotoxine,Ergotamine,Dihydroergotamine,
Dihydroergotoxine

• Natural ergot alkaloids produce vasoconstriction

• Hydrogenated ones have α-blocking activity

USES
1. Migraine

2. Cognition enhancer
 PHENTOLAMINE
– Nonselective (alpha1=alpha2)
– Duration of action(short),quick acting.
• Oral (2-4 hours)
• IV (20-40 minutes)
USES
1. Diagnosis and intraoperative management
of pheochromocytoma.
2. Clonidine withdrawl
3. Cheese reaction
4. Counteract vasoconstriction by
extravasated NA/DA during I/V infusion.
 PRAZOSIN
– Prototype, orally effective, high PPB
– Selective reversible alpha1 blocker
– Duration of action 6-8 hours
– Doxazosin, terazosin and tamsulosin
– NA release not ↑sed (no α2 blockade)
– First dose effect: Arteriolar dilatation more.
USES
Antihypertensive
Raynaud’s disease
BHP
 Benefits of Selective blockers

• Fall in BP with mild tachycardia

• Postural hypotension less marked (dilates arterioles

more than veins)

• Mild side effects(miosis, nasal stuffiness, inhibition of

ejaculation)
• TERAZOSIN

1. Similar to prazosin

2. Higher bioavailability

3. Longer half life

USES
 BHP (Preferred)

(Single daily dose, apotosis promoting effect on

prostrate)
 TAMSULOSIN
• Uroselective,α1A : α1D selective

• Better tolerated α blocker in BHP.

• No significant changes in BP and Heart rate

• Dizziness and retrograde ejaculation(S/E)

• Plasma half life 6-9 hrs.

• Once daily dosing.

 SILODOSIN
• Longer acting orally effective tamsulosin analogue

• Incidence of retrograde ejaculation more

• Dizziness & Postural hypotension may occur

 NAFTOPIDIL
• Second generation α1 blocker

• Higher selectivity for α1D receptor responsible

for symptoms due to storage & bladder irritability

• Indicated for dysuria associated with BHP

 YOHIMBINE
– Prototype

– Selective alpha2 competitive blockers

– Heart rate and BP ↑sed.

– Excitation and tremor,nausea, vomitting.

– Used primarily in research application

 USES OF α-BLOCKERS
Pheochromocytoma : Tumour of adrenal medullary cells.
• Excess CAs are secreted which can cause intermittent or
persistent hypertension

1. Diagnostic: Phentolamine
2. Therapeutic : Phenoxybenzamine

 To normalize blood volume and distribution of body water.

 To prevent excessive rise in BP during operation.
 To prevent fall in BP after tumour removal.
 USES CONTD……
• Hypertension : Prazocin (α1– selective)
Clonidine withdrawl
Cheese reaction
• Benign Hypertrophy of Prostrate:
 Terazocin
 Doxazocin Once a day dose.
 Tamsulosin
Apoptosis promoting effect
Less vascular side effects.
 BHP CONTD…..
• Blockade of α1 adrenoceptors in bladder

trigone, prostate and prostatic urethra decreases smooth

muscle tone

• Symptomatic relief is faster (within 2 weeks)

• Voiding symptoms (hesitancy, narrowing of stream,

dribbling & inc residual urine)are relieved better than
irritative symptoms (urgency, frequency, nocturia)
 USES CONTD……
• Secondary Shock:
a) To counteract reflex vasoconstriction

b) To shift blood from pulmonary to systemic circuit.

c) To shift blood from extravascular to vascular

comp.
• PVD – PRAZOSIN or PHENOXYBENZAMINE
Raynauds phenomenon
vasoconstriction
Acrocynosis relieved
 USES COND……
• CHF
Prazosin (vasodilatory action) for short term relief

• Impotence
Papaverine/ Phentolamine therapy
Reserved for selected situations with proper
facilities