NUB Pharmacology Sympathetic Depressants II PDF

Pharmacology SYMPATHETIC DEPRESSANTS II BY Staff Members Pharmacology Department, Faculty of Medicine , NUB Code of the module 17/11/2019 Issue 1/2018 17/11/2019 17/11/2019 1 Code of conduct...

Pharmacology SYMPATHETIC DEPRESSANTS II BY Staff Members Pharmacology Department, Faculty of Medicine , NUB Code of the module 17/11/2019 Issue 1/2018 17/11/2019 17/11/2019 1 Code of conduct Effective interaction Switch off Mutual mobile respect phones Smile Appreciate Struggle to our be on time differences Focus on topic 17/11/2019  BETA BLOCKERS They are competitive blockers of -adrenoceptors. They Abolish hypotension of Isoprenaline. & Augment HTN of Adrenaline Some have Intrinsic Sympathetic Activity (ISA) (Partial Agonistic Activity)  Initial  then -receptors & Some have local anesthetic (LA) effect  Classification according to selectivity (LOL) 1st generation 2nd generation 3rd generation (Nonselective) (Selective) (Vasodilating BB) Pindolol Acebutalol Nonselective Selective Oxprenolol Atenolol Propranolol Bisoprolol Labetalol Celiprolol Sotalol Betaxolol Carvediolol Nebivolol Nadolol Metoprolol Carteolol Betaxolol Timolol Esmolol Bucindolol 17/11/2019 1  Selective B-2 blocker: Butoxamine is used experimentally only BB With ISA: Pindolol – Oxprenolol – Acebutalol – Carteolol – Celiprolol Esmolol is ultrashort acting metabolised by esterase & used IV infusion in emergency HTN 3rd generation having additional effects: α-1 adrenergic receptor blockade (labetalol, carvedilol, bucindolol) β2 agonist (celiprolol, carteolol)  production of NO (celiprolol, carteolol, nebivolol,) Ca2+ entry block (carvedilol, betaxolol) antioxidant action (carvedilol) 17/11/2019 1 Classification of according to Lipid solubility Lipophilic Hydrophilic G.I.T. Absorption: - Well Absorbed. - Poorly absorbed. Passage across B.B.B.: - Pass BBB - Not pass BBB - has CNS effects. - has little CNS effect Metabolism: - Extensive hepatic. - Mainly Renal. Duration of Action: - Short (4-6 Hours) - Longer (12-24 Hs) Examples: - Propranolol. - Nadolol. - Oxprenolol. - Atenolol. - Metoprolol. - Sotalol. - Timolol - Bisoprolol 17/11/2019 1 Action & Dynamics I. Bata- Blocking Effects: CVS.... EYE..... BRONCHI.... METABOLISM.. II. CNS Effects: Some B  Lipophilic  Pass BBB  Sedation & antianxiety action III. Cell Membrane Stabilization: Some B block Na+ -channel, so they have: Direct myocardial depressant effect (Quinidine-like effect). Local anesthetic effect 17/11/2019 1 Action & Dynamics I. Bata- Blocking Effects: A) C.V.S.: i) Heart (-1) 1. –ve inotropic , -ve Chronotropic , -ve Dromotropic 2. COP,  cardiac work & O2 needs 3.  Excitability & Automaticity ii) Blood Vessels (-2): VC due to unopposed α-receptor activity:  - Blood flow to all organs except the brain: - Cold extremities & intermittent claudication. - Hepatic blood flow  non-specific enzyme inhibition. - Prinzmetal angina 17/11/2019 1  iii) Blood Pressure: anti-hypertensive effect after long use > 4ws: Block -l of Heart  COP. Block -1 of CNS  Sympathetic outflow. Block -1 of Kidney Renin. Block Pre-synaptic  Release of Nor-adr.  Prostacyclin (VD) synthesis 17/11/2019 1  B) Eye: IOP: Aqueous humor formation (especially Timolol). (They do not affect pupil size) C) Bronchi: Non-selective BB  Bronchospasm, esp. in BA E) Metabolism: Block -2 in Liver   Glycogenolysis  Hypoglycemia. Block p-2 in Pancreas   Release of Insulin. Block -2 in Sk.m.  Block Hypokalemia induced by Adrenaline. Block -1 & -3 in Adipose tissues   Lipolysis. -Blockers   VLDL &  HDL. 17/11/2019 1  Uses of B-blockers: 1- CVS: Heart: 1. Angina Pectoris (Stable & Unstable Angina but never in variant): -B do NOT produce coronary VD BUT  Cardiac work  O2 demand 2. Acute myocardial infarction ( infarct size) 3. Arrhythmias (Atrial & Ventricular) Hypertrophic obstructive cardiomyopathy: -B may  COP. 4. 5. Heart failure: ?? Small doses of cardioselective BB to protect the heart from the cardiotoxic effect of high catecholamines that occur in HF esp. in diastolic HF Blood Vessels: Acute dissecting aortic aneurysm. Blood Pressure.: HTN: Better avoid in pregnancy Portal HTN & esophageal varices. 17/11/2019 1 2- Eye: Open Angle Glaucoma: Topical Timolol, Betaxolol & Levobunolol. 3-CNS: 1. Essential Tremors & Anxiety 2. Prophylaxis of Migraine headache. 4- Endocrine: 1. Thyrotoxicosis: use BB without ISA due to Supersensitivity: - Treat (tachycardia &  cardiac work) of thyrotoxicosis. - Propranolol peripheral conversion of T4 to the more active T3. NB.: Propranolol is life saving drug in ttt of thyrotoxic crisis 2. With -blockers in Pheochromocytoma, Never alone. 17/11/2019 1 Side effects & contraindications of BB: System Side effects Contraindications I. CNS: Sedation - depression – sleep disturbance Severe depression (only in lipophilic BB crossing BBB) (use hydrophilic BB) II. CVS: Heart Heart failure (HF) - Heart block (HB) - - HF - HB- severe bradycardia Bradycardia - With Verapamil  H.F & HB B.V: Cold extremities, Raynaud's phenomenon - Variant angina. numbness, tingling - Raynaud's phenomenon & PVD & alone in pheochromocytoma Bl pr. Hypotension - Hypotension III. Respiration - Precipitate acute attack of B.A. in asthmatics - Bronchial asthma (use cautiously selective B1) IV. Metabolism Hypoglycemia (due to block of -2, severe in - Hypoglycemia in insulin or oral patient receiving insulin or oral hypoglycemic hypoglycemic treatment. [coma can occur without warning symptoms (silent death)] Hyperkalemia Atherosclerosis ( HDL &  triglycerides) V. Others Sudden withdrawal withdrawal syndrome  - Never stop suddenly. sympathetic over activity and precipitation of 17/11/2019 anginal attack even myocardial infarction 1  *Drug interactions of BB: 1- Kinetic interactions: Enzyme inhibitors  the effect of propranolol Enzyme inducers  the effect. 2- Dynamic interactions: NSAIDs may antagonize the hypotensive effect. They  the severity of Clonidine withdrawal HTN. 17/11/2019 1 17/11/2019