CARDIOVASCULAR AGENTS. Dr.P.Valentina, professor, HOD Department of pharmaceutical chemistry SRM college of pharmacy

Transcription

1 CARDIOVASCULAR AGENTS Dr.P.Valentina, professor, HOD Department of pharmaceutical chemistry SRM college of pharmacy

2 System = heart, blood vessels (arteries & veins), Blood Blood rich w/ O2 & nutrients moves through vessels called arteries to narrower arteriols to capillaries where the rich blood is absorbed by bodies cells & waste products are absorbed (CO2, urea, Cr, ammonia) deoxygenated blood returned to circulation via venules to veins for elimination through lungs & kidneys

3 Cardiac disorders Heart = * 4 chambers R & L atria, R & L ventricles * Blood from circulation to R atrium to R ventricle to pulmonary artery to lungs for gas exchange (CO2 & O2) to L atrium to L ventricle to aorta to systemic circulation Heart muscle = myocardium & surrounds the atria & ventricles

4 Pericardium = fibrous covering around the heart that protects it from injury & infection Endocardium = 3 layered membrane that lines the inner part of the heart chambers Valves = 4 two atrioventricular (tricuspid & mitral) & 2 semilunar (pulmonic & aortic) control blood. flow between atria & ventricles & pulmonary artery & the aorta

5 Right Ventricle

6 Cardiac disorders Conduction = Generated & conducted by the myocardium usually * Originates in sinoatrial (SA) node pacemaker atrioventricular (AV) node bundle of HIS purkinje fibers ventricular muscle tissue contraction from apex upward forcing blood to lungs & circulatory system

7 Cardiac disorders Blood flow & Heart Rate (HR) * Ave. HR = beats/min. (adult) * Ave. BP = 120/80 mm/hg resistance to blood flow through systemic arterial circulation Arterial BP determined by Cardiac Output (CO) = the volume of bld. expelled form the heart in 1 min. calculated by mult. HR by stroke volume Ave. CO = 4 8 l/min.

8 Stroke Volume (SV) = amt. of bld ejected from the L vent. w/ each heart beat Ave. = 70ml/beat SV determined by 3 factors: Preload blood flow force that stretches the ventricle Contractility force of ventricular contraction Afterload Resistance to vent. ejection of blood caused by opposing pressures in aorta & systemic circulation Specific drugs can or preload & afterload, affecting both SV & CO most vasodilators dec. preload & afterload a dec. in arterial pressure & CO

9 Cardiac Glycosides Digitalis One of the oldest drugs (1200 AD) Effective in treating congestive heart failure (CHF) CHF = when the heart muscle weakens & enlarges loss of ability to pump blood through the heart & into the systemic circulation = heart failure (or pump failure) peripheral & lung tissues become congested = CHF

10 Cardiac Glycosides CHF can be left sided or right sided Cardiac glycosides = digitalis glycosides inhibits the Na K pump inc. intracellular Ca cardiac muscle fibers contract more efficiently Digitalis = 3 effects on the heart 1) + inotropic action (inc. myocard. contraction) 2) chronotropic action (dec. HR) #) dromotropic action (dec. conduction of the heart cells

11 Cardiac Glycosides The inc. in myocardial contractility = inc. card., peripheral, & kidney function by inc. CO, dec. preload, improving bld flow to periphery & kidneys, dec. edema, & inc. fluid excretion fluid retention in lung & extremities is decreased Digitals also used to correct atrial fibrillation & atrial flutter (cardiac dysrhythmias)

12 Cardiac Glycosides Digoxin (Lanoxin) Protein binding low, t1/2 = 36 hrs drug accumulation can occur monitor SE & serum levels closely metabolized by liver & excreted by kidneys kidney dysfunction can affect excretion of dig. Do not confuse digoxin & digitoxin digitoxin = highly protein bound w/ a long t1/2 seldom prescribed

13 Digoxin (Lanoxin) Action = inc. myocardial contraction (+ inotrophy), and slows HR ( chronotropy), therefore regulating the rate & rhythm of the heart Therapeutic serum levels = ng/ml Use = moderate/severe systolic CHF, arrythmias SE = Dig. toxicity bradycardia (pulse < 60), anorexia, diarrhea, N&V, blurred vision, lethargy older adults more prone to toxicity DI Other heart meds

14 Heart Failure Other drugs = * Vasodilators dec. venous blood return to the heart & dec. cardiac filling, ventricular stretching & O2 demand * Angiotensin converting enzyme (ACE) inhibitors dilate venules & arterioles & improves renal bld flow & dec. bld fluid volume * Diruetics first line = reduces fluid volume

15 Antianginal Drugs Used to treat angina pectoris ( acute cardiac pain caused by inadequate bld flow resulting from plaque occlusion in the coronary arteries of the myocardium or from spasms of the coronary arteries) described as tightness, pressure in center of chest, pain radiating down L arm attacks may lead to an MI 3 Types of angina pectoris 1. Classic (stable) stress or exercise 2. Unstable (preinfarction) frequently over day, severity 3. Variant (Prinzmetal, vasospastic) during rest

16 Antianginal Drugs Action Inc. blood flow by inc. O2 supply, or by dec. O2 demand by the myocardium Nitrates, beta blockers, calcium channel blockers Nitrates & calcium channel blockers effective in treating variant or vasospastic angina (not beta blockers) beta blockers effective in treating stable angina Non pharm Rx = avoid heavy meals, smoking, extremes in weather changes, strenuous exercise, stress Proper nutrition, moderate exercise, adequate rest & relaxation techniques

17 Antianginals Nitrates First agents used Nitroglycerine (NTG) Action acts directly on the smooth muscle of blood vessels = relaxation & dilation. Dec. cardiac preload & afterload & reduces O2 demand dilation of veins = less blood return to the heart dilation of arteries = less vasoconstriction & resistance Onset of Action sublingual (under the tongue) & IV = 1 3 min. transderm nitro patch = min

18 Antianginals SE = Headaches less frequent w/ continued use, hypotension, dizziness, weakness, faintness Beta Blockers Block the beta receptor site Atenolol (Tenormin), Metoprolol tartrate (Lopressor), Nadolol (Corgard), Propranolol HCL (Inderal) Action Dec. the effects of the sympathetic nervous system by blocking release of epi. & norepi dec. HR & BP reduce the need for O2 & the pain of angina Nonselective (beta 1 & beta 2) Inderal, Corgard, Visken Selective (beta 1) Tenormin, Lopressor

19 Antianginals SE Dec. in HR & BP Closely monitor vital signs Calcium Channel Blockers (Calcium Blockers) Newest Amlodipine (Norvasc), Diltiazem HCL (Cardizem), Nifedipine (Procardia, Adalat), Verapamil (Calan, Isoptin) Action Ca activates myocard. contraction; inc. workload of heart. Calcium blockers dec. cardiac contractility ( inotropic) & the workload of the heart = dec. O2 need

20 Calcium Blockers Use long term Rx of angina SE Headache, Hypotension, dizziness, flushing of the skin Bradycardia w/ verapamil (Calan) Hypotension esp. w/ Nifedipine (most potent) promotes vasodilation of coronary & peripheral arteries Calcium blockers can cause changes in liver & kidney function Check liver enzymes periodically Can be given w/ nitrates to prevent angina

21 Antidysrhythmics Cardiac dysrhythmia (arrhythmia) = any deviation from the normal rate or pattern of the heartbeat. HR s too slow (bradycardia), fast (tachycardia), or irregular Electrocardiogram (ECG) identifies the type of dysrhythmia P wave = atrial activation QRS complex = ventricular depolarization T wave = ventricular repolarization PR interval = atrioventricular conduction time QT interval = ventricular action potential duration

22 Antidysrhythmics Atrial dysrhythmias = prevent proper filling of the ventricles & dec. CO by 1/3 Ventricular dysrhythmias = life threatening d/t ineffective filling of the ventricle = dec. or absent CO Dysrhythmias can occur after an MI, from hypoxia (lack of O2 to body tissue), hypercapnia (inc. CO2 in the bld.), excess catecholamines (epi, norepi), or electrolyte imbalance

23 Antidysrhythmic Drugs 2 major classifications of dysrhythmias * Above bundle of HIS = supraventricular A flutter, a fib., PAC s * Below bundle of HIS = Ventricular PVC s, Vent. tachycardia, V fib. Desired action = restoration of normal cardiac rhythm 4 Classes: 1. Fast (sodium) Channel Blockers dec. the fast Na influx to the cardiac cells, so dec. conduction time of cardiac tissue, dec. likelihood of ectopic foci, inc. repolarization 3 subgroups of fast channel blockers

24 Antidysrhythmics Class 1A Procainamide (Pronestyl, Procan), Quinidine Sulfate (Quinidex) slows conduction & prolongs repolarization Use = Control PVC s, vent. tachycardia SE = Anorexia, headache, dizziness, weakness Class 1B Lidocaine (Xylocaine), Mexiletine (Mexitil) Slows conduction & shortens repolarization Use = Ventricular arrythmias associated w/ acute MI s IM & IV IV bolus then a drip started (1 4 mg/min.)

25 Antidysrhythmics Class 1C Flecainide (Tambocor) Prolongs conduction w/ little to no effect on repolarization Use Life threatening vent. dysrhythmias, supraventricular tachycardia, a fib or flutter Beta Blockers dec. conduction velocity Prolong Repolarization Amiodarone (Cordarone) emergency Rx of ventricular dysrhythmias. Inc. refractory perios & prolong action potential duration Calcium Channel Blockers inc. refractory period of the AV node, dec. vent. response

26 Congestive heart failure (CHF) is inability of the heart to pump blood effectively at the rate that meets the need of metabolizing tissues. This results in the reduced contractility which causes a decrease in cardiac output, increasing the blood volume of the heart. As a result the systemic and renal blood flow decreases, which causes edema and renal failure.

27 CARDIAC GLYCOSIDES Cardiac glycosides are important class of naturally occurring drugs used in the treatment of CHF and associated edema. They occur mainly in plants and in animals such as poisonous toads. Digitalis purpurea or the foxglove plants, Digitalis lanata, Strophanthus gratus and Strophanthus Kombe are the major plant

28 Glycosides Secondary products formed from one or more sugar molecules added to a non sugar biologically active molecule Sugar most commonly found is glucose Non sugar molecule known as the aglycone and may be amino acid derivatives steroids triterpenes

29 Glycosides Most common types Saponins Cardiac Glycosides (Cardenolides) Cyanogenic Glycosides Anthraquinone Glycosides Glucosinolates technically not glycosides Most glycosides function as deterrents to herbivores

30 Cardiac glycosides Structurally similar to saponins with similar detergent properties Distinguished by presence of a lactone ring and rare sugars Wide distribution found in over 200 species (55 genera in 12 families) Best known are digitoxin and digoxin from Digitalis (foxglove) 30 glycosides

31 Digitoxin

32 Sugars in digitoxin 2 molecules of digitose 1 molecule of 1 acetyl digitose 1 molecule of glucose Digitose

33 Action of Cardiac Glycosides In medicinal doses, cardiac glycosides increase the contractions of heart and the force of the heart beat Increases cardiac output Improved circulation, decreases edema, and increases kidney output Most effective for congestive heart failure Toxic doses cause arrhythmias or even cardiac arrest fine line between medicinal and toxic

34 Aglycone Aglycone portion is a steroid nucleus with a unique set of fused rings. R C D HO A B OH

35 Digoxin (Lanoxin) O OH O H Tri Digitoxose O H H OH Digitoxigenin

36 Dobutamine HO CH 2 - CH 2 - NH - CH - CH 2 - CH 2 OH CH 3 HO It resembles Dopamine chemically, but possesses a bulky aromatic residue on the amino group despite the absence of a b OH group. The (+) isomer has potent b agonist action. The ( ) isomer has potent a 1 agonist and poor b agonist actions.