L8: B-adrenergic blockers

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Text of L8: B-adrenergic blockers

  • 1. -Adrenergic Blockers Dr. Hiwa K. Saaed Ph.D. Pharmacology & Toxicology

2. -Adrenergic Blockers -Blockers are effective in treating : angina, cardiac arrhythmias, myocardial infarction, congestive heart failure, hyperthyroidism, and glaucoma, prophylaxis of migraine headaches. Note: The names of all -blockers end in olol except for labetalol and carvedilol. 3. -Blockers All are competitive antagonists Propranolol is prototype Although all -blockers lower blood pressure in hypertension, they do not induce postural hypotension, because the -adrenoceptors remain functional. 4. A. Classification and Mechanisms Selectivity (1>2) Partial agonist activity (Intrinsic Sympathomimetic Activity ISA) Lipid solubility (CNS effect) Membrane stabilizing activity (MSA) (local anesthetic action) Capacity to block alpha adrenoceptors. K+ channel blockade (sotalol) 5. A. Classification: Selectivity (1>2) 1 selective (cardioselective) Atenolol Acebutolol Bisoprolol Esmolol (short t1/2) Metoplrolol Advantage: HTN with asthma, peripheral vascular disease (coldness of extremities), NIDDM 6. A. Classification and Mechanisms Selective 2 Butoxamine (experimental) Nonselective (1 & 2) Nadolol Propranolol Timolol 7. Combined ( & ): peripheral vasodilation Labetalol Carvedilol Useful in Rx HTN patients for whom increased Peripheral resistance is undesirable (elderly or black) Labetalol in Rx preeclampsia, pheochromocytoma They do not alter serum lipid or blood glucose levels Carvedilol also decreasees lipid peroxidation and vascular wall thickening (benefit in heart failure) 8. Partial agonist activity ISA Pindolol Acebutolol Labetalol less bradycardia & diminished effect on COP, less disturbances of lipid and carbohydrate metabolism Advantages: HTN with asthma, HTN with moderate bradycardia HTN+DM 9. A. Classification and Mechanisms 3. Local anesthetic activity (membrane-stabilizing activity): Is a disadvantage when used topically in the eye because it decreases protective reflexes and increases the risk of corneal ulceration Timolol, atenolol, carvedilol &nadolol: no Local anesthetic activity 10. 4. Lipid solubility responsible for CNS adverse effects: propranolol Lipid soluble Pharmacokinetic properties Water soluble Pharmacokinetic properties Propranolol Highly metabolized Large Vd CNS penetration Shorter t1/2 Acebutolol Excreted unchanged by kidney Less 1st pass effect Small Vd Longer t1/2 except esmolol Timolol Atenolol Pindolol Esmolol Metoprolol Nadolol Labetalol 11. K+ channel blockade: sotalol Sotalol is a nonselective receptor antagonists, that lack LA action but has marked class III antiarrhythmia effect reflecting k+ channel blockade 12. B. Pharmacological Effects and Clinical Uses 1. CVS: A. Heart: both decreased HR, force of contraction (ve inotropic & chronotropic effect) decreased A-V conduction, PR interval Decrease CO, work & O2 consumption Rx: Angina and Supraventricular tachycardia 13. Reflex peripheral vasoconstriction!? B. Vascular system: prevent 2 mediated vasodilation reduction in COP (because of cardiac effect) decrease BP reflex vasoconstriction. On balance there is gradual reduction of both systolic and diastolic BP 14. 2. Respiratory: bronchoconstriction; contraindicated in asthma 3. Eye: reduce IOP especially in Glaucomatous eyes decrease aqueous humor production B. Pharmacological Effects and Clinical Uses 15. 4. metabolic and endocrine effects: A. Increased Na+ retention, how? Reduced blood pressure causes a decrease in renal perfusion, resulting in an increase in Na+ retention and plasma volume In some cases, blood pressure. For these patients, -blockers are often combined with a diuretic to prevent Na+ retention. Also by inhibiting receptors, renin production is also prevented, contributing to Na+ retention. B. Pharmacological Effects and Clinical Uses 16. B. inhibit lipolysis: plasma VLDL, HDL, LDL HDL/LDL ratio coronary heart disease C. partially inhibit glycogenolysis and decrease glucagon secretion Great caution in IDDM (Type 1)? Because pronounce hypoglycemia may occur after insulin injection, blockers also attenuate the normal physiologic response to hypoglycemia, furthermore they mask signs of hypoglycemia; tremor, palpitation.. B. Pharmacological Effects and Clinical Uses 17. B. Clinical Uses Cardiovascular and ophthalmic applications are extremly important A. CVS: -angina pectoris cardiac work & O2 demand, -Chronic hypertension, CO, TPR, inhibition of renin release NB: blockers are not used for acute or emergency Rx of HTN,? ma y increase diastolic pressure Labetalol is effective in emergency 18. -Arrhythmia (supraventricular tachycardias), -prophylaxis after MI: 1) early use within 6-12 hrs for 3-4 wks 2) Late use within 4 days- 4 wks after onset of infarction and continued for at least 2 years useful for secondary prevention from another MI - congestive heart failure* B. Clinical Uses 19. B. Eye: Glaucoma: reduce aqueous humor secretion (timolol) C. Endocrine use: Thyroid storm, thyrotoxicosis: propranolol D. CNS: propranolol 1. Anxiety with somatic symptoms 2. Migraine headache prophylaxis: 3. Famillial tremor, other types of tremor, stage fright: 4. Alcohol, opioids acute withdrawal symptoms B. Clinical Uses 20. C. Adverse effects CVS: bradycardia, A-V blockade, CHF Arrhythmias: never stop Rx with blockers suddenly Bronchoconstriction: Patients with airway disease: asthmatic attack Sexual dysfunction?? Indep of blockade CNS effects: sedation, fatigue, sleep alterations 21. Thank You