Adrenergic Drugs - Alpha Receptor Antagonists PDF

# Adrenergic Drugs ## Adrenergic Receptor Antagonists - **α Receptor Antagonists** - Nonselective - phenoxybenzamine - phentolamine - α₁-selective - prazosin - terazosin - doxazosin - alfuzosin - tamsulosin - indoramin...

# Adrenergic Drugs ## Adrenergic Receptor Antagonists - **α Receptor Antagonists** - Nonselective - phenoxybenzamine - phentolamine - α₁-selective - prazosin - terazosin - doxazosin - alfuzosin - tamsulosin - indoramin - urapidil - bunazosin - α₂-selective - yohimbine - **β Receptor Antagonists** - Nonselective (First Generation) - nadolol - penbutolol - pindolol - propranolol - timolol - sotalol - levobunolol - metipranolol - β₁-selective (Second Generation) - acebutolol - atenolol - bisoprolol - esmolol - metoprolol - Nonselective (Third Generation) - carteolol - carvedilol\* - bucindolol - labetalol\* - β₁-selective (Third Generation) - betaxolol - celiprolol - nebivolol \* Also block α receptors. ## Sympatholytic Drugs that inhibit nerve impulses of the sympathetic nervous system. ## Alpha Blockers - Blockade of α-adrenergic receptors ↓ the sympathetic tone of blood vessels (BV) → vasodilation → ↓ peripheral resistance (PR) → ↓ blood pressure (BP) - ↓ BP → reflex tachycardia. ### 1. Nonselective α-blockers - phenoxybenzamine - phentolamine - Have limited clinical applications - Used in the treatment of pheochromocytoma ### 2. Selective α₁ blockers - Prazosin - Terazosin - Doxazosin - Used in the treatment of hypertension and benign prostatic hypertrophy (BPH) ## Phenoxybenzamine (Dibenzyline) - Non-selective, α₁ > α₂ adrenergic antagonist - **Mechanism of action:** - Irreversible non-competitive blocking agent. - The body has to synthesize new adrenoceptors to overcome the block - A long-acting (24 h) - Must be converted to the active form (delayed onset). ## Phenoxybenzamine Actions ### 1. Block α₁ - Prevents vasoconstriction of peripheral blood vessels by endogenous catecholamines. - ↓ PR → reflex tachycardia. ### 2. Block α₂ (inhibitory) - Activation of the α₂ receptor decreases production of cyclic adenosine monophosphate (cAMP) leading to an inhibition of further release of norepinephrine from the neuron. **So, blood pressure lowering is not maintained.** ## Epinephrine Reversal The following graph demonstrates the effect of epinephrine and how alpha blockers can affect the vasoconstrictive effect of epinephrine. It shows that alpha blockers can block the vasoconstrictive effect of epinephrine, leading to vasodilation. - **Top graph:** The first line shows a baseline. The next line shows an increase in blood pressure after injection of adrenaline (epinephrine). The third line shows a decrease in blood pressure after injection of an alpha blocker. The fourth line shows an increase in blood pressure after injection of epinephrine. And the fifth line shows a decrease in blood pressure after injection of a beta blocker. - **Bottom image:** This image shows that the alpha blocker will block the vasoconstrictive effect of epinephrine, leading to vasodilation. ## a-Adrenergic Blockers - **α-Adrenergic blockers have no effect on the actions of isoproterenol, which is a pure β agonist.** - **α-Adrenergic blockers reverse the vasoconstrictive action of epinephrine.** ## Phenoxybenzamine - Indications - **Pheochromocytoma:** - For treatment & pre-operative (to avoid hypertensive (HT) crisis) - Chronic treatment - Combined with β-blocker - **Raynaud's disease (Peripheral vascular disease):** - May be used to relieve vasoconstriction. - **Autonomic hyperreflexia:** - Which predisposes paraplegics to strokes. ## Phenoxybenzamine - Side Effects - **α blocking:** - Postural hypotension - Tachycardia - Inhibition of ejaculation - Nasal congestion - Nausea and vomiting - **Contraindications:** - Conditions where a fall in blood pressure is undesirable - As ↓ coronary perfusion ## Phentolamine (Regitine) - A competitive blocker of α₁ and α₂ receptors. - Duration of action: 4 hours (short duration). - It produces postural hypotension and causes epinephrine reversal. - Reflex cardiac ++ and tachycardia - May cause arrhythmias and anginal pain - Contraindicated in patients with decreased coronary perfusion. ## Phentolamine - Indications - Short-term treatment of pheochromocytoma - Phentolamine + papaverine intravenous injection (I.V) → induce erection. ## Selective α₁ blockers - **Example:** Prazosin, Terazosin, Doxazosin and Tamsulosin - They are competitive blockers of the α₁ receptor. - Prazosin, Terazosin, and Doxazosin useful in the treatment of hypertension. - **Tamsulosin** is indicated for the treatment of benign prostatic hypertrophy. - Doxazosin is the longest-acting of these drugs (secreted in feces). ## Selective α₁ blockers (Cont.) - Cardiovascular effects: - ↓ PR & ↓ BP by causing the relaxation of both arterial and venous smooth muscle. - Tamsulosin has the least effect on blood pressure. - Cause minimal changes in cardiac output, renal blood flow, and the glomerular filtration rate. ## Selective α₁ blockers - Therapeutic Uses - **Hypertension:** - No tolerance for the antihypertensive effect - a "first-dose" effect. - **Benign prostatic hypertrophy (BPH):** - Alternative to surgery in patients with symptomatic. - ↓ the tone in the smooth muscle of the bladder neck and prostate and improves urine flow. - Tamsulosin is a more potent inhibitor of the α₁ receptors found on the smooth muscle of the prostate. ## Tamsulosin - **The following image shows the zones of the prostate gland.** - Selective α₁ more effective in BPH. ## Selective α₁ blockers - Adverse Effects - Dizziness, a lack of energy, - Nasal congestion, - Headache, drowsiness, - Orthostatic hypotension. - Prazosin: - Tendency of salt & water retention. - Use a diuretic. - Male sexual function is not as severely affected as in phenoxybenzamine. ## Selective α₂ blockers - **Yohimbine (Yocon):** - Selective Alpha-2 Receptor Blocker of plant origin. - Act at CNS level. - **Indication:** - No established clinical role. - May be used to relieve vasoconstriction (VC) in Raynaud's disease. - Aphrodisiac: improve erection & treat impotence. - **Contraindication:** in Central Nervous System (CNS) & Cardiovascular System (CVS) diseases (stimulant). ***