ADRENERGIC(SYMPATHETIC)BLOCKERS
In this post, we deal with those drugs which antagonize or block the adrenergic receptors at the postganglionic sympathetic nervous system directly or indirectly.
Remember antagonizing or blocking the adrenergic postganglionic receptors will result in unopposed domination of cholinergic postganglionic effects.
General Mechanism of these drugs is that they block the intracellular response by binding at the adrenergic receptors.
Classifications
1.Alpha-blockers
2.Beta-blockers
3.Indirect acting
Alpha (a) Blockers
1.Prazosin, Terazosin, Doxazosin,and Tamsulosin
These compounds selectively and competitively block the alpha-1 adrenergic receptors.
Among the above, the tamsulosin is having an advantage of selectively blocking alpha-1-A receptors and thereby acting selectively on the prostate gland and not affecting blood vessels. Tamsulosin is the drug of choice in the treatment of Benign Prostate Hyperplasia (Enlargement of Prostate) with minimum side effects.
Physiological Effects Of Alpha Blockade
1. The alpha-1 blockade on vascular smooth muscles (alpha-1-B) results in vasoconstriction of arterioles and veins. This causes reduced peripheral vascular resistance followed by hypotension.
2. The blockade of the alpha-1 receptor in prostate and urinary bladder muscles (alpha-1-A) results in relaxation and decreased resistance to urine flow.
Uses
1.Treatment of Hypertension
2.Enlargement of Prostate.
Side effects
1.GI hypermotility because of the unopposed cholinergic effects.
2.Orthostatic hypotension especially after the initial dose. This effect is nill or negligible with tamsulosin because of its selectivity on alpha-1-B receptors.
3.Sexual defects
4.Dry mouth
5.Dizziness
2.Phenoxybenzamine
It is unique in action by non competitively block both presynaptic (alpha-2) and postsynaptic(alpha-1) receptors. The effect on the alpha-2 receptor is very little or negligible.
Because of this unique action of blocking presynaptic alpha-2 blockade, it causes a partial sympathomimetic activity by preventing noradrenaline reabsorption at the presynaptic level but is minor importance. Hence it causes peripheral vasodilation and reflex tachycardia.
Administered by mouth.
This drug acting on the receptor noncompetitively by strong covalent bonds and hence it has a prolonged duration of action up to 14 hours.
Therapeutics
1.Treatment of Pheochromocytoma induced hypertension.
Pheochromocytoma is a tumor that occurs in the adrenal gland. Because of the tumor, the gland gets hyperstimulation to release excess catecholamines like adrenaline and noradrenaline which causes a hypertensive crisis for which Phenoxybenzamine is the drug of choice because of its long duration of actions.
2. Treatment of BPH as uniquely this drug reduces the size of the prostate along with its hypotensive effects. But be careful about its other side effects.
3.In spinal cord injuries which causes hyperreflexia that results in elevated blood pressure. Phenoxybenzamine blunts these effects.
4. Treatment of Reynaud's disease, in which there is reduced blood flow at the fingertips causes numbness in response to high cold weather or stress.
Side effects
1.Orthostatic hypotension
2. Reflex tachycardia-hence it may cause anginal pain and contraindicate in patients with CHD.
3.Inhibition of ejaculation due to over-relaxation of smooth muscles in vas deferens
3.Yohimbine
It is selective alpha-2 presynaptic receptors that cause excessive collection of noradrenalin at the synapsis as a result of the adrenergic crisis.
It is sometimes used to treat impotency by direct penile injection.
This drug in lower dosage block majorly the alpha-2 receptor only and cause hypertension but in higher dosage, it blocks alpha-1 receptors predominantly and causes serious hypotension.
4.Phentolamine
It is an imidazole compound.
It reversibly blocks alpha-1and alpha-2 receptors
Hence the effects are with dosage adjustments. As this drug primarily block alpha-1 receptors at low dosages and hence causes hypotension. But in high doses, it blocks alpha-2 also and may cause hypertension.
It can be administered by I.V and I.M as poor absorption orally.
Uses
Because of its short duration of action (4 hours), it can be used for short courses of pheochromocytoma induced hypertension in low dosages.
Side effects
1.Orthostatic hypotension in low doses.
2.Peptic ulcer due to GI hypermotility due to unopposed cholinergic effects.
3.Tachycardia-due to reflex adrenergic response
4.Heart attacks-,,,,,,
5.Arrhythmias -,,,,,,
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