Adrenergic Drugs - Part-II (Beta Antagonists) PDF

Adrenergic drugs Remember  Adrenergic receptors; Location and functions Receptor Organ Effect 1 heart Increase in heart rate Increase in conductivity...

Adrenergic drugs Remember  Adrenergic receptors; Location and functions Receptor Organ Effect 1 heart Increase in heart rate Increase in conductivity Increase in the force of contraction 2 Heart Stimulation Smooth muscles of bronchi, Relaxation uterus, GIT, GUT and BV Skeletal muscles glycogenolysis, tremors & K+ uptake Pancreas insulin secretion Liver glycogenolysis & gluconeogenesis 3 adipose tissues lipolysis  Beta-blockers Competitively blocks beta adrenergic receptors.  Beta-blockers classifications Nonselective Block all  receptors Propranolol Nadolol Selective  1 Block 1 Atenolol (Cardio-selective) Metoprolol Antagonists with partial agonist Intrinsic sympathomimetic Pindolol activity activity Acebutolol With direct VD activity Block 1, 2 and Labetalol α1 receptors carvedilol Non-Selective BB: Pharmacodynamics 1- Heart (1): -ve Inotropic -ve Chronotropic -ve Dromotropic  COP  Cardiac work & O2 consumption  Excitability &  Automaticity  Non-Selective BB: Pharmacodynamics (Cont.) 2- Blood vessels (2):  V.D. Unopposed  V.C. 3- Anti-hypertensive:  COP  Sympathetic outflow from CNS  Renin 4- Bronchi (2) Bronchospasm Contraindication in patients with COPD or bronchial asthma Non-Selective BB: Pharmacodynamics (Cont.) 5. Na+ retention: ↓BP→↓↓ renal perfusion→ ↑Na retention and plasma volume (add diuretic) 6. I.O.P.: ↓synthesis of aqueous humor 7. Metabolism:  2  Glycogenolysis  1 & 3  Lipolysis Non-Selective BB: Pharmacodynamics (Cont.) 8- C.N.S. Lipophilic -Blockers  Anxiety  Tremors 9- Local anesthetic action: (Some -Blockers) Na+ Channel Block Membrane stabilizer Direct Myocardial Depressant Non-Selective BB: Therapeutic Uses 1. Hypertension 2. Angina ( Classic angina) Cardiac work & O2 consumption Never Variant angina Propranolol decreases the oxygen requirement of heart muscle, therefore is effective in reducing chest pain in angina. 3. Myocardial infarction (prophylactic use): to protect against a second heart attack and sudden arrhythmic death. 4. Arrhythmia Atrial or ventricular Tachycardia e.g. Thyrotoxicosis Catecholamines Digitalis toxicity Non-Selective BB: Therapeutic Uses 5. -blockers in Pheochromocytoma 6. Glaucoma (Timolol) 7. Migraine headache (Propranolol) 8. Hyperthyroidism 9. Familial tremors Non-Selective BB: Side Effects 1. Bronchoconstriction Nonselective β blockers are potentially lethal in asthma and COPD 2. Arrhythmias Never stop suddenly (can worsen angina, hypertension, or precipitate arrhythmia) withdraw gradually 3. Sexual impairment: Impotence 4. Block manifestations and impair recovery of hypoglycemia in type 1 diabetes In diabetic patient receiving insulin, careful monitoring of blood glucose is essential, because pronounced hypoglycaemia may occur after insulin injection. 𝝱1 Selective Blocker (Cardio-selective) Examples:  Atenolol, acebutolol, metoprolol, esmolol  Acebutolol has intrinsic sympathomimetic activity  Cardioselectivity can be lost at high doses They lack the unwanted broncho-constrictive and hypoglycemic effects of non-selective blockers Advantage:  Less effect on pulmonary function, peripheral resistance, and glucose homeostasis 𝝱1 Selective Blocker (Cardio-selective) (Cont.) Esmolol Ultra-short-acting beta blocker Destroyed by plasma esterase Given by IV Use in hypertension: Can be used with monitoring in asthmatics Less vasoconstriction Useful in diabetic hypertensive patients Acute, short-term control of hypertension and arrhythmias during medical procedures or emergencies. Antagonists with partial agonist activity Pindolol, Acebutolol Partial agonists Stimulate β receptors first then block them Advantages: Less decrease in HR and CO Fewer disturbances in glucose and lipid metabolism Antagonists of both α and 𝝱 receptors (with VD activity) Labetalol, Carvedilol  Produce vasodilation via blockade of α1  Useful in treating hypertension with Peripheral vascular resistance (PVD)  Don not affect lipid or glucose Adverse effects:  Orthostatic hypotension and dizziness Antagonists of both α and 𝝱 receptors Labetalol 1. Useful in elderly hypertensives. 2. Alternative to methyldopa in pregnancy-induced hypertension. 3. Useful in an emergency: rapid ↓ in BP. Carvedilol ↓ lipid peroxidation and vessel wall thickening, useful in HF.  Butaxamine It is a selective 2 blocker, not used clinically  Drugs affecting neurotransmitter release or uptake Reserpine Amphetamine, Guanethidine tyramine cocaine Drugs affecting neurotransmitter release or uptake Reserpine  plant alkaloid Mechanism of action:  Prevent storage of NE, dopamine, and 5-HT into vesicles by Blocking the Mg/ ATP-dependent transport. ↓BP, HR Used to treat hypertension resistant to other drugs Has a slow onset and long duration of action Drugs affecting neurotransmitter release or uptake Guanethidine: 1. Block release of NE inhibits the effect of indirect-acting sympathomimetics. 2. Displaces NE from storage vesicles, leading to its depletion. 3. ↓BP, HR, and ↑ parasympathetic tone of GIT. 4. Causes orthostatic hypotension, and impairment of male sexual function. 5. This can result in hypertensive crises in patients with pheochromocytoma. Drugs affecting neurotransmitter release or uptake Cocaine 1. Local anesthetic. 2. Inhibit reuptake of epinephrine and NE 3. ↑ the action of catecholamines.