5. ï· Like the agonists, the adrenergic antagonists are classified
according to their relative affinities for α1 or α2 receptors .
ï· Drugs that block α-adrenoceptors profoundly affect blood
pressure, resulting in decreased peripheral vascular resistance.
ï· Because normal sympathetic control of the vasculature occurs
in large part through agonist actions on α-adrenergic receptors
ï· This induces a reflex tachycardia resulting from the lowered
blood pressure.
Alpha-Adrenergic Blockers
6. Alpha-Adrenergic Blockers Classification
I. Type of blockade
1. Irreversible (non-competitive) :
Phenoxybenzamine; slow onset and long duration.
2. Reversible (competitive): All the rest
II. Selectivity: α1 or α2 receptors .
-Nonselective: Phenoxybenzamine and phentolamine
-Selective:
1. alpha-1 selective: Prazosin, terazosin, others
2. alpha-2 selective: Yohimbine
3. alpha/beta blockers: Labetalol
-Others: phenothiazines, haloperidol, tricyclic antidepressants
trazodone
9. Pharmacological Effects - Phenoxybenzamine
1. Cardiovascular system
âą âPR: â Blood pressure: reflex tachycardia:
âą Furthermore, the ability to block presynaptic
inhibitory α2-receptors in the heart will
result in more norepinephrine release,
which stimulates ÎČ- receptors on the heart
to increase cardiac output.
âą It reduces BP when sympathetic tone is
high upright posture, reduced blood volume
11. Epinephrine reversal:
⹠All α-adrenergic blockers reverse the α-agonist
actions of epinephrine. the vasoconstrictive action of
epinephrine is interrupted, but vasodilation of other
vascular beds caused by stimulation of ÎČ2 receptors
is not blocked.
âą Therefore, the systemic blood pressure decreases in
response to epinephrine given in the presence of
phenoxybenzamine. âŠ.Why?
âą The actions of norepinephrine are not reversed but
are diminished, âŠwhy?
12. Pharmacological Effects â
Phenoxybenzamine
2. Eye â miosis
3. Nasal stuffiness
4. GI tract â Increased motility
5. Urinary bladder â decreased tone in sphincter
6. Metabolic effects â increased insulin secretion
7. It also blocks histamine, serotonin and cholinergic
receptors
13. Clinical uses -
Phenoxybenzamine
1. Pheochromocytoma: a catecholamine-
secreting tumor of cells derived from the adrenal
medulla
2. Raynaud; peripheral vascular disease
3. Autonomic hyperreflexia which predisposes
paraplegics to strokes
4. BPH
14. Adverse effects
Phenoxybenzamine
âą Postural hypotension
âą Tachycardia it is contraindicated in patients with
decreased coronary perfusion.
âą Sedation, fatigue
âą Nasal stuffiness
âą Miosis
âą Impotence (inhibits ejaculation)
âą Exercise care in hypovolemic patients.
15. Imidazoline derivatives â phentolamine (5-7hr)
produces a competitive block of α1 and α2-
receptors.
1. Block serotonin receptors
2. Stimulate H1 & H2
3. Stimulate M1; Parasympathomimetic
âą Increased gastric motility & acid secretion
âą Increased secretion from exocrine glands, such as
salivary, sweat, lacrimal, pancreatic
âą Cardiac stimulation reflex and direct!!
âą it can be injected intracavernosally to produce
vasodilation of penile arteries (rarely used)
16. Alpha-1 selective blockers
Prazosin, terazosin, doxazosin, alfuzosin, and tamsulosin
âą the first three drugs are useful in the treatment of
hypertension.
âą Alfuzosin & Tamsulosin are indicated for the treatment
of benign prostatic hypertrophy
âą Prazosin (t1/2 3hrs): No significant tachycardia
Used in CHF and in hypertension but tolerance develops
with time, may be due to fluid retention.
âą Adverse effects: First dose phenomenon.
âą Favorable effect on plasma lipids: increase HDL/LDL
ratio
âą Terazosin (t1/2 9-12 hrs)
17.
18. Other α -adrenoceptor antagonists
âą Indoramin: antihypertensive.
⹠Urapidil is an α1 antagonist (its primary effect) that
also has weak α2-agonist and 5-HT1A-agonist actions
and weak antagonist action at ÎČ1 receptors. It is used
in Europe as an antihypertensive agent and for BPH.
âą Labetalol has both α1-selective and ÎČ-antagonistic
effects.
âą Neuroleptic drugs such as chlorpromazine and
haloperidol are potent dopamine receptor antagonists
but are also antagonists at α-receptors.
⹠Antidepressant: trazodone block α1 receptors.
19. ïĄ2 - selective antagonists Yohimbine
Chief active compound in Pausinystalia yohimbine
(bark), Effects opposite of Clonidine
Enters CNS => increased sympathetic output =>
increased HR, BP, can cause severe tremors
Ingredient in many weight loss products
Enhances sexual activity â aphrodisiac
Blocks other receptors: serotonin, dopamine, Increases
ADH release
Experimental uses in Treatment of :
1. Raynaud's phenomenon to inhibit smooth muscle
contraction,
2. type 2 diabetes (α2 receptors inhibit insulin
secretion),
3. depression.