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L7 ans pharmacology 17 18

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L7 ans pharmacology 17 18

  1. 1. Drugs Affecting The Autonomic Nervous System(ANS) β-Adrenergic Blockers ANS Pharmacology Lecture 7 Dr. Hiwa K. Saaed College of Pharmacy/University of Sulaimani 2017-2018
  2. 2. β-Adrenergic Blockers • β-Blockers are effective in treating: • angina, • cardiac arrhythmias, • myocardial infarction, • congestive heart failure, • hyperthyroidism, • and glaucoma, • as well as serving in the prophylaxis of migraine headaches. • Note: The names of all β-blockers end in “olol” except for labetalol and carvedilol. • All are competitive antagonists • Propranolol is prototype • Although all β-blockers lower blood pressure in hypertension, they do not induce postural hypotension!? because the α-adrenoceptors remain functional.
  3. 3. A. Classification and Mechanisms • Selectivity (β1>β2) • 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)
  4. 4. 1. Selectivity (β1>β2) β1 selective (cardioselective) • Atenolol • Acebutolol • Bisoprolol • Esmolol (short t1/2) • Metoplrolol Advantage: HTN with asthma, peripheral vascular disease (coldness of extremities), NIDDM Selective β2 • Butoxamine (experimental) Nonselective (β1 & β2) • Nadolol • Propranolol • Timolol
  5. 5. 2, Combined (α & β): 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)
  6. 6. 3. Partial agonist activity ISA Pindolol, Acebutolol & Labetalol less bradycardia & diminished effect on CO, less disturbances of lipid and carbohydrate metabolism Advantages: • HTN with asthma, • HTN with moderate bradycardia • HTN+DM 4. 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
  7. 7. 5. Lipid solubility Lipid soluble • Propranolol. Timolol. Pindolol Metoprolol. Labetalol Pharmacokinetic properties • Highly metabolized • Large Vd • CNS penetration • Shorter t1/2 WATER SOLUBLE • Acebutolol, Atenolol, Esmolol, Nadolol Pharmacokinetic properties • Excreted unchanged by kidney • Less 1st pass effect • Small Vd • Longer t1/2 except esmolol
  8. 8. 6. K+ channel blockade: sotalol • Sotalol is a nonselective β receptor antagonists, • that lack Local Anesthetic action • but has marked class III antiarrhythmia effect reflecting k+ channel blockade
  9. 9. 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 B. Vascular system: prevent β2 mediated vasodilation→ reduction in CO (because of cardiac effect) → decrease BP → reflex vasoconstriction. On balance there is gradual reduction of both systolic and diastolic BP
  10. 10. 2. Respiratory: bronchoconstriction; contraindicated in asthma 3. Eye: reduce IOP especially in Glaucomatous eyes decrease aqueous humor production 4. metabolic and endocrine effects: A. Increased Na+ retention, how? • Reduced BP causes a decrease in renal perfusion, resulting in an increase in Na+ retention and ↑plasma volume → In some cases, ↑BP. • For these patients, β-blockers are often combined with a diuretic to prevent Na+ retention. • Also by inhibiting β receptors, renin production is also prevented, contributing to Na+ retention. B. Pharmacological Effects and Clinical Uses
  11. 11. 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, β blockers also attenuate the normal physiologic response to hypoglycemia, furthermore they mask signs of hypoglycemia; tremor, palpitation.. 4. metabolic and endocrine effects:
  12. 12. B. Pharmacological Effects and 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: β blockers are not used for acute or emergency Rx of HTN,? may increase diastolic pressure Labetalol is effective in emergency HTN -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*
  13. 13. 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. Pharmacological Effects and Clinical Uses
  14. 14. C. Adverse effects • CVS: bradycardia, A-V blockade, CHF • Arrhythmias: never stop Rx with β blockers suddenly • Bronchoconstriction: Patients with airway disease: asthmatic attack • Sexual dysfunction?? Independent of β blockade • CNS effects: sedation, fatigue, sleep alterations