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 [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.

Organic Nitrates Examples –Nitroglycerine, Isosorbide dinitrate and iso-sorbide mononitrate Pharmacologic Properties: Reduce myocardial oxygen demand In low concentration produce dilation of vein Nitrates have also relaxing effect on large coronary vessels

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. Organic Nitrates

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

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

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

Role of aldosterone to initiate heart failure MechanismPathological effect Increased sodium and water retention Edema, elevated cardiac pressure Potassium & magnesium lossArrythmogenesis Reduced uptake of NEArrythmogenesis & Vasoconstriction Alteration in sodium channel expression Incrased excitability & contractility of cardiac myocytes

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 Drugs to treat hypertension

CNS PHARMACOLOGY

Pathophysiology and management of Parkinson’s disease Alzheimer’s disease Stroke

Drugs used in different CNS pathological conditions M/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.)