1 / 25

Adrenoceptor antagonist drugs

Adrenoceptor antagonist drugs. Pawitra Pulbutr M.Sc. In Pharm (Pharmacology). Objectives.

Download Presentation

Adrenoceptor antagonist drugs

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Adrenoceptor antagonist drugs Pawitra Pulbutr M.Sc. In Pharm (Pharmacology)

  2. Objectives • นิสิตมีความรู้ความเข้าใจถึงเภสัชวิทยา กลไกการออกฤทธิ์ เภสัชจลนศาสตร์ การใช้ประโยชน์ทางคลินิก การเกิดปฏิกิริยาระหว่างยา ของยาที่ออกฤทธิ์ต้านระบบประสาทซิมพาเทติกทั้งชนิด -receptor antagonist และชนิด -receptor antagonist

  3. Adrenoceptor blocking agent • Affect many physiological & pathophysiological functions • In the past… may be called “Sympatholytics”… Not appropriate • Antagonist or Blocker >>> More appropriate •  blocker… • Pheochromocytoma, Primary hypertension •  blocker… • Hypertension, Ischemic heart disease, Arrhythmia, Other endocrine disorder

  4. Relative selectivity of antagonist for adrenoceptors

  5. Basic Pharmacologyof -blockers • Binding with -receptor • Reversible • Competitive with catecholamine • Phentolamine, Tolazoline, Prazosin, Labetalol • Irreversible • Covalent binding • Phenoxybenzamine • Nitrogen mustard like structure • Form reactive ethyleneimmonium compound

  6. Reversible blocker Irreversible blocker Dose-response curve to NE in the presence of two different -blockers.

  7. Pharmacologic effects • CVS • -receptor control • Arteriolar tone • Venous tone • -receptor antagonist • Decrease peripheral vascular resistance (TPR) • Decreased BP • May cause postural hypotension or reflex tachycardia (esp. if 2 also blocked … increase NE secretion… more tachycardia) • Body compensation in long term use … Increase blood volume

  8. Other -blocking effects • Bladder base & Prostate • -blocker … • Decrease resistance • Increase urine flow • Use in benign prostatic hyperplasia (BPH)

  9. -blockers • Irreversible blockers • Phenoxybenzamine • Reversible blockers • Non-selective blocker • Phentolamine, Tolazoline • Selective 1-blocker • Prazosin family • Doxazosin, Terazosin, Alfuzosin, Tamsulosin • Selective 2-blocker • Yohimbine

  10. Clinical Pharmacology • Pheochromocytoma • Hypertensive emergencies • Chronic hypertension • Peripheral vascular disease • Local vasoconstrictor excess • Urinary obstruction >> BPH • Male sexual dysfunction

  11. Chronic hypertension • Prazosin family • 1-selective blockers • Treatment of mild to moderate hypertension • ADRs • Postural hypotension esp. First dose • Not use non-selective -blocker • 2 blocker … Increase NE release

  12. Urinary obstruction • Benign prostatic hyperplasia (BPH) • Mostly found in elderly male • Treatment • Surgery • Drug therapy • 1-blocker • Partial reversal of smooth muscle contraction at prostate and bladder base • Prazosin, Doxazosin, Terazosin, Tamsulosin • Good effective esp. in hypertensive patients

  13. Basic Pharmacology of -blockers • Competitive binding to -receptor • “Isoproterenol” like structure • Difference affinity to 1 or 2 receptor • Pure antagonist • Pure -blocker • Partial agonist • -blocker with intrinsic sympathomimetic activity (ISA) • Activate -RC… not to maximal response • Interfere endogenous ligand to bind -RC • -blocker with -blocker activity (Mixed) • Labetalol & Carvedilol

  14. Properties of several Beta-blockers

  15. Pharmacological effects • CVS • Decrease BP • Heart • Negative chronotropic & inotropic • Slow arterioventricular conduction • Prolong PR interval (AV node suppression) • Renin Angiotensin Aldosterone (RAA) system… decrease renin release • Vascular resistance • Inhibit 2-mediated vasodilation • Acute effect >>> Vasoconstriction • Prolong action …. Decrease peripheral vascular resistance • Decrease renin (RAA)

  16. Respiratory tract • 2-receptor blocking activity • Bronchoconstriction • Danger in asthmatic patients !! • Should select 1-selective blocker… less bronchoconstriction • Acebutolol, Atenolol, Betaxolol, Bisoprolol, Celiprolol, Esmolol, Metoprolol • Use with caution in asthma

  17. Eyes • -blocker … decrease aqueous humor production …decrease intraocular pressure • Use in glaucoma • Metabolic & endocrine effects • -blocker … Inhibit lipolysis • Inhibit glycogenolysis in liver • May affect hypoglycemia correction ? • Should be use with caution in DM esp. Type 1 • Increase LDL • Decrease HDL • Decrease HDL/ LDL ratio • Increase risk of CVS disease • Partial agonist … less effects • - blockers … No effect

  18. Effects not related to -blockade • Intrinsic sympathomimetic activity of partial agonist • -blocker with ISA (partial agonist) • Acebutolol, Carteolol, Celiprolol, Labetalol, Penbutolol, Pindolol • May be useful in asthmatic & bradycardia patients • Less bronchoconstriction • Less bradycardia

  19. Clinical Pharmacology • Hypertension • Ischemic heart disease • Cardiac arrhythmia • Other CVS disorder • Glaucoma • Hyperthyroidism • Neurologic disease • Miscellaneous

  20. Choice of -blocker • Specific activity of each agent • Benefit or Risk of each agent • 1-selective • Partial agonist • May not be replaced with others • Only pure antagonist is used in hyperthyroidism

  21. ADRs • Propranolol • Rash, Fever, Drug allergy • Sedation, Sleep disturbance, Depression • Less in hydrophillic -blocker…Nadolol, Atenolol • Unwanted -blocking effect • Bronchoconstriction (2)… Asthma • Vasospasm (2)… Peripheral vascular dz. • Use selective 1-blocker

  22. ADRs • Use with caution in CHF patient • Reversal of life threatening -blocker effect • Isoproterenol, Glucagon • Drug Interaction • Ca++ channel blocker • Severe hypotension, Severe bradycardia, Heart failure • Taper dose • Prolong use …“RC upregulation” • Sudden stop … RC over stimulation … Danger ! • Slowly stop using -blocker in ischemic heart disease • Especially in short half-life … propranolol, metoprolol

  23. Use with caution in Type 1 DM • -blocker may interfere hypoglycemia recovery • 2 activation >>> Glycogenolysis • Use selective 1-selective blocker • Mask disease/ symptom manifestation • Mask hypoglycemia sign … tachycardia • Mask hyperthyroidism symptom

  24. -blockers • Pure antagonists • Propranolol, Nadolol, Sotalol, Timolol • Selective 1-antagonists • Metoprolol, Esmolol, Celiprolol, Acebutolol, Atenolol, Betaxolol, Bisoprolol (MEC 2A 2B) • Partial agonist (Blockers with ISA) • Labetalol, Acebutolol, Carteolol, Celiprolol, Penbutolol, Pindolol (LA 2C 2P) • Mixed antagonist ( and -blockers) • Labetalol, Carvedilol

  25. Q & A

More Related