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CVS PHARMACOLOGY

CVS PHARMACOLOGY. Drugs to treat myocardial ischemia. Etiology 1. Decrease in myocardial oxygen supply [determined by oxygen-carrying capacity of blood & coronary blood flow]; 2. Increase in myocardial oxygen demand

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CVS PHARMACOLOGY

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  1. CVS PHARMACOLOGY

  2. Drugs to treat myocardial ischemia Etiology • 1. Decrease in myocardial oxygen supply [determined by oxygen-carrying capacity of blood & coronary blood flow]; • 2. Increase in myocardial oxygen demand [Determined by heart rate & ventricular contractility] or both. Angina Pectoris is a common manifestation of Ischemia characterized by pressing discomfort ( & pain) radiating to left shoulder, arm, jaw.

  3. Organic Nitrates • Examples –Nitroglycerine, Isosorbidedinitrate and iso-sorbidemononitrate • Pharmacologic Properties: • Reduce myocardial oxygen demand • In low concentration produce dilation of vein • Nitrates have also relaxing effect on large coronary vessels

  4. Organic Nitrates • Do not directly alter inotropic or chronotropic state of heart rather • decrease preload and after-load as a result of venous capacitance and arterial resistance vessels thus reduce myocardial oxygen demand and relief symptoms of angina. • M/A: Leads to formation of reactive free radical NO, activate guanylyl cyclase, increase synthesis of cyclic GMP in smooth muscle and other tissues of heart. Cyclic GMP-dependent protein kinase catalyse phosphorylation of various proteins and regulates contractile state in smooth muscle.

  5. Calcium Channel blockers • Mechanism of vascular smooth muscle contraction due to influx of Ca+2 • i) voltage-sensitive Ca+2 channels open in response to depolarization of membrane. • ii) agonist induced contraction result from formation iP3, which acts as a second messenger to release intracellular Ca+2 • iii) receptor operated • An increase in cytosolic Ca+2 results in enhanced binding of Ca+2 to protein calmodulin. This complex in turn activates myosin light-chain kinase allowing phosphorylation of Myosin. Such phosphorylation promote interaction between actin and myosin and contraction of smooth muscle. • Mechanism of calcium channel blockers [Amlodipine, Nifedipine, Verapamil]: Inhibit voltage –dependent Ca+2 channels in vascular smooth muscle

  6. β-adrenergic receptor antagonists • Efficacious for angina pectoris, acute myocardial infarction and congestive heart failure • Adrenaline is vasoconstrictor. It’s blockage results in blocking of vasoconstriction. • Reduce oxidative stress in myocardium and improve efficiency of myocardium • Example: propranolol,carvidolol, metoprolol

  7. Drugs to treat heart failure Consequence of cardiac failure & Drugs used Reduced cardiac output Sympathetic nervous system activation Vasoconstriction Elevated cardiac pressure β blockers, nitrates Renin Vasodilators like nitrates Angiotensin-I Sodium & water retention ACE inhibitor (enalapril, captopril) Angiotensin-II ARBs (Losartan, Candesartan) Diuretics Aldosteron Spironolactone

  8. Role of aldosterone to initiate heart failure

  9. Drugs to treat hypertension Classification • 1. Diuretics: thiazides (chlorthalidone), loop diuretics (furosemide), K+ spearing diuretic (spironolactone) • 2. Sympatholytic : α-adrenergic antagonist (prozosin), β -adrenergic antagonist (metoprolol), Mixed-carvedilol, adrenergic neuron blocking (reserpine) • 3. Vasodilators: Arterial (hydralazine, minoxidil), venous (nitroprusside) • 4. Calcium channel blockers: Verapamil, Diltiazim, nifedipine, amlodipine • 5. ACE inhibitor: Captopril, Ramipril, Enalapril • 6. Angiotensin-II receptor blockers (ARBs ): Losartan, Valsartan, Candesartan

  10. CNS PHARMACOLOGY

  11. Pathophysiology and management of • Parkinson’s disease • Alzheimer’s disease • Stroke

  12. Drugs used in different CNS pathological conditionsM/A, Clinical use and S/E Antipsychotics • 1. Phenothiazines: Fluphenazine, Chlorpromazine • 2. Butyrophenons: Haloperidol • 3. Clozapine-type : Olanzapine, Loxapine • 4. Other heterocyclics: Resperidone Antiepileptics: Carbamazepine, Valproic Acid, Phenytoin, Gabapentine Sedative-hypnotics: Benzodiazepines (Diazepam, Clonazepam etc. ) & Barbiturates (pentobarbital, phenobarbital etc.)

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