Alpha blockers

Alpha blockers

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  UNIT-II DRUGS ACTINGON AUTONOMIC NERVOUS SYSTEM Prepared by- Subham Kumar Vishwakarma (Asst. Prof., Department of Pharmaceutical Chemistry, UIPS, Ujjain (MP) P a g e 1 | 3 ADRENERGIC ANTAGONIST Adrenergic blockers are also called as antiadrenergic drugs or sympatholytics. Adrenergic blocking agents prevent the response of effector organs to endogenous as well as exogenous adrenaline and noradrenaline. These drugs block the actions of adrenergic drugs at alpha (α) or beta (β) adrenergic receptors. 1. Alpha Blocker • Alpha antagonist are preventing the interaction of endogenous NTS or Sympathomimetics wit corresponding adrenergic receptors. • Bind specifically to alpha receptor and interfere with catecholamines and sympathomimetics action. Role of alpha-1 and Alpha-2 antagonist Alpha-1 Alpha-2 • Vasoconstriction • Increased peripheral resistance • Increased Blood pressure • Inhibition of norepinephrine release • Inhibition of insulin Classification of Alpha blockers Alpha blockers Nonselective Selective Miscellaneous 1. Tolazoline It is an imidazoline derivative, nonselective α-adrenergic blocker MOA: - non-selective competitive Alpha- adrenergic receptor antagonist Phentolamine and tolazoline are competitive α adrenergic antagonists and block the receptor for 5-HT and it causes the release of histamine from the mast cells, which is a potent vasodilator. Action: Vasodilation, Pulmonary vasodilation Irreversible • Phenoxybenzamine Reversible (competitive) • Phentolamine • Tolazoline Alpha-1 Blocker Prazosin Terazosin Doxazosin Alpha-2 Blocker Yohimbine Ergot alkaloid Dihydroergotamine Methysergide
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  UNIT-II DRUGS ACTINGON AUTONOMIC NERVOUS SYSTEM Prepared by- Subham Kumar Vishwakarma (Asst. Prof., Department of Pharmaceutical Chemistry, UIPS, Ujjain (MP) P a g e 2 | 3 Uses: • Used to increase blood flow in peripheral vasospastic condition like Raynaud's syndrome (area of body feel numb, and cool). • Tolazoline used in persistent pulmonary hypertension of the newborn. • Cerebral vascular accident • Scleroderma- skin hardening and tightening of skin. Side effect: vertigo, Hypotension Synthesis 2. Phentolamine MOA: Phentolamine have both alpha 1 and alpha 2 blocking activity and produce tachycardia. The blocking action of these agents at presynaptic alpha 2 - receptors, contributes to their cardiac stimulatory effects by enhancing release of NE. Uses: Phentolamine is used to prevent or control hypertensive episodes, It is an α- adrenergic blocker used in urgent heart failure. Side effect: Tachycardia increased gastrointestinal motility and hyperchlorhydria 3. Phenoxybenzamine It is a Beta halo alkyl amines derivative MOA: it is an irreversible alpha blocker and blocks both alpha-1 and alpha- 2 receptor. Phenoxybenzamine inhibits the uptake of catecholamine from the nerve terminals. How covalent: - Initial step involves the formation of an intermediate aziridinium ion which will form reversible complex with the receptor. The positively charge aziridinium ion electrophile then reacts with a nucleophilic group on the receptor resulting in the formation of covalent bond between the drug receptor which will lead to alkylated receptor
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  UNIT-II DRUGS ACTINGON AUTONOMIC NERVOUS SYSTEM Prepared by- Subham Kumar Vishwakarma (Asst. Prof., Department of Pharmaceutical Chemistry, UIPS, Ujjain (MP) P a g e 3 | 3 Uses: treatment of Hypertension, urinary retention, pheochromocytoma (catecholamine-secreting tumor derived from adrenal medulla) Side effect: nasal congestion, broncho constriction, reflex tachycardia, congestive heart failure, cerebral stroke, or kidney failure 4. Prazosin It is a Quinazoline derivative, Selective Alpha-1 antagonist MOA: It has potent alpha 1 - adrenoreceptor blocking activity Uses: Used in treatment of hypertension and heart attack. Side effect: nasal congestion, dizziness, tiredness, nausea, drowsiness, orthostatic hypotension 5. Dihydroergotamine Mechanism of action: Dihydroergotamine increases the a - blocking potency and reduces the smooth muscle stimulant activity. Uses: used in the treatment of migraine and vasoconstriction, overdose headache. Side effect: Vomiting blurred vision, nasal stiffness, dizziness and upset stomach 6. Methysergide MOA: it blocks the Alpha 1 receptor, and Methysergide interacts with serotonin (5-HT) receptors. Its therapeutic effect in migraine prophylaxis has been associated with its antagonism at the 5-HT receptor. Uses: It is used to treat headache, carcinoid syndrome and serotonin syndrome. Side effect: Its common side effect is retroperitoneal fibrosis.