Cardiovascular Drug Agents

1. Cardiovascular Drug Agents .

2. Contents • Cardiac glycosides • Antidysrhythmic agents • Anti-anginal drugs • Anti-hypertensive drugs • Anti-lipemic agents • Anti-coagulants • Anti-platelets

3. Cardiac glycosides • Cardiac glycosides are drugs that increase the rate at which the heart beats is known as positive inotropic effects. • Cardiac glycosides used to solve the problems of congestive heart failure (CHF). • In patients with congestive heart failure occurs when the ejection fraction compared with the total amount of blood in the ventricle is decreased.

4. Continue • Cardiac glycosides are one of the oldest and most effective groups of drugs. • They were originally obtained from either digitalis purpurea or digitalis lanata plants both commonly referred to as foxglove. • The cardiac glycosides have been the mainstay of therapy for CHF for more than 200 years and they continue to be one of the most frequently used positive inotropic agents.

5. Drugs 1.Digoxin: is the most prescribed drug in this group, it has less side effects. 2. Digitoxin: not frequently used because of it is side effects.

6. Mechanism of action • The primary beneficial effect of digitalis is thought to be an increase in myocardial contractility. • By doing this cellular sodium concentration and calcium concentration increases.

7. Digoxin • Digoxin is the most commonly prescribed digitalis glycoside. • It is highly effective agent in the treatment of CHF. • May also used clinically to improve myocardial contractility and thus reverse Cardiogenic shock.

8. Continue • Digoxin is contraindicated in patients who have shown in: • Hypersensitivity • Tachycardia • Digoxin is available in: 50microgram elixir, 50,100, 200 microgram liquid filled capsule, 125, 250, 500 microgram tablet and 100, 200 microgram per mal injection.

9. Continue • Adult dosage is 1-1.5mg/day, 0.125-0.5 mg. • Premature dosage is 0.015-0.025mg/kg.

10. Side-effects • Anorexia • Nausea • Vomiting • Confusion • Colored vision • Headache • Fatigue

11. Toxicity and management overdose • Discontinue the drug. • Determine digoxin and electrolyte level. • Administer potassium supplements for hypokalemia. • Start ECG monitoring. • Administer digibind for severe overdose.

12. Anti-dysrhythmic Agents • A dysrhythmia is any deviation from the normal rhythm of the heart, thus the more accurate term for an irregular heart rhythm is dysrhythmia. • There are many conditions in which dysrhythmia can develop: • Myocardial infraction • Cardiac surgery as a result of coronary disease.

13. Continue • There are numerous drug available to treat dysrhytmias and these are classified based on where and how they affect cardiac cells. • The most commonly used system is the Vaughan Williams classification.

14. Classification of Drugs • Class one • Class 1A • Disopyramide • Procainamide • Quinidine

15. Continue Class 1B • Lidocaine • Phenytoin • Tocainide • Mexiletine

16. Continue • Class 1C • Propafenone • Flecainide • Entainide Class Two • Propranaolol • Esmolol • sotalol

17. Continue • Class three • Amiodarone • Bretylium • Class four • Adenosine • Verpamil • Diltiazem

18. Side-Effects • Hypersensitivity • Nausea • Vomiting • Diarrhoe • Dizziness • Headache • Blurred vision

19. Toxicity management of overdose • The main toxic affects of the anti-dysrhythmics involve: • Heart • Circulation • CNS • Speacific antidotes are not available and the management of an overdose involves maintaining adequate circulation and respiration.

20. Quinidine • Quinidine has both direct action on the electrical activity of the heart and indirect (ant cholinergic) effect. • It is ant cholinergic results in inhibition of the parasympathetic nervous system.

21. Continue • Significant adverse effects of the agent include • Cardiac asystole • Arterial embolism • Ventricular ectopic beats • Contraindicated • Hypersensitivity • AV block • Abnormal rhyths

22. Continue • Quinidine is available in 324mg quinidine gluconate tablets, 275 mg quinidine polygalacturonate tablets, 300mg quinidine sulfate tablets. • Parentrally quinidine gluconate comes as an 80mg/ml injection. • Adult dosage is 324 – 648 mg q8h-q12h, IM 600mg followed by 400mg q2h.

23. Procainamide • It is similar to that of Quinidine but it differs from Quinidine in that it is indirect effect (anticholinergic is weaker). • Procainamide is useful in the management of atrial and ventricular tachydysrhymias. • It is a pregnancy category C drug.

24. Continue • Available 250, 375, 500mg capsules, 500, 750, 1000mg film coated tablets and 100, 500mg/ml injection

25. Disopyramide • Disopyramide is used primarily for the treatment of ventricular dysrhymias. • It can produce significant side-effects including: • Anticholinergic effects • Cardiovascular depression For these reasons it is use is limited, especially in patients with poor left ventricular function.

26. Continue • Significance adverse reactions from it are hypotension and widening of the QRS interval on ECG. • It is available orally in 100- 150mg capsules • Adult dosage is 150mg q6h.

27. Lidocaine (1B) • It is one of the most effective drugs for the treatment of ventricular dysrhytmias. • It can only administer intravenously because it has extensive first pass effect, that is when taken orally, the liver metabolizes most of it. • It is accomplished by blockade of sodium channels.

28. Continue • Lidocaine is the drug of choice for treating the acute ventricular dysrhymias. • Available 100mg/ml IM injection, 10, 20, 40, 100, 200mg/ml IV injection.

29. Propafenone( 1C) • Propafenone reduces sodium current in purkinje fibers and to lesser extent in myocardial fibers. • Propafenone has a mild beta-blocking effects. • It is also believed to have calcium channel blocking effects, which contributes to propafenone mild negative inotropic effects.

30. Continue • It should be used with causion in patients with congestive heart failure, because of it is beta-blocking agents and it is mild inotropic effects. • The most frequently reported adverse reaction is dizziness.

31. Continue • Patients may also complain • Metallic taste • Constipation • Headache • Nausea

32. Continue • Propafenone is contraindicated: • Bradycardia • Hypersensitivity • Bronchial asthma • Hypotension • Available orally as 150, 300mg, and the adult dosage is 150mg q8h.

33. Quinidine Case Study • ID/CC: A 56 year old male comes to the cardiology unit for evaluation of ringing in his ears (Tinnitus), dizziness, GI distress (nausea, vomiting, diarrhea), and headaches. • HPI: He also complains of blurred vision and impaired hearing. The patient had a myocardial infarction one year ago and has been receiving oral Quinidine antiarrhythmic therapy. • Labs: CBC: normal, widening QRS.

34. Continue • Treatment: Monitor ECG and vital signs, discontinue the drug, change to different antiarrhythmic drug. Treat cardio toxic effects with sodium lactate.

35. Continue • Discussion: Quinidine, Procainamide, and Disopyramide are class 1A antiarrhythmic that acts by blocking sodium channels, increasing the effective refractory period. They are used for both atrial and ventricular arrhythmias. All these agents have low therapeutic toxic ratios and may produce severe adverse reactions. Cinchonism is commonly produced by drugs that are cinchona derivatives, such as Quinidine and quinine. The effects may occur with only one dose.

36. Atenalol (Tenormin) class II • It is a cardio-selective beta blocker that means it blocks the beta one adrenergic receptor. • Atenalol also activates beta two in the lungs and could therefore exacerbate a pre-existing case of asthma or COPD. • It is also useful in the treatment of hypertension and angina pectoris. • It is available orally 25, 50, 100mg tablets, 0.5mg/ml IV injection.

37. Propranolol (class II) • Propranolol is one of the first beta blockers introduced into clinical practice and this occurred in 1967. • It was then primarily used in the treatment of dysrhymias. • Propranolol is a non-speacific blocker that blocks both beta one and beta two adrenergic receptor in the heart and the lungs.

38. Continue • Propranolol is the oldest of this class of drugs, there are now many indications of It is use: • Hypertension • Angina pectoris • Dysarrythemia

39. Continue • Available as 10, 20, 40, 60, 80, 90 mg tablets, 60, 80, 120, 160 mg capsules, 20, 40, mg/5ml oral solution, 1mg/ml injection.

40. Amiodarone • Amiodarone markedly prolongs the APD (action potential duration) and ERP (effective refractory period). • Amiodarone also known to block both the alpha and beta adrenergic receptors. • Amiodarone is a very lipophilic, there fore it may cause un wanted effects.

41. Continue • Amiodarone can cause • Hypothyrodism • Hyperthyrodism • Amoidarone is contraindicated in patients • Hypersensitivity • Severe bradycardia • Second or third degree of heart block.

42. Continue • Amiodarone is available 200mg orally tablets. • Amiodarone is a pregnancy category C agent.

43. Diltiazem • Diltiazem is primarily indicated for the temporary control of a rapid ventricular response in a patient with atrial fibrillation. • It is a pregnancy category C drug. • It is available both orally and parenterally, 30, 90, 120 mg tablets and 5mg/ml injection.

44. Verpamil • Verpamil inhibits calcium ion influx across the slow calcium channels in cardiac conduction tissue. • Usually decreases the heart beat at least 20 percent. • Verpamil is also used to treat: • Angina pectoris • Hypertension

45. Continue • It is available 40, 80, 120mg tablets, and 2.5 mg/ml injection parenterally. • It is a pregnancy category C.

46. Adenosine • It is an unclassified antidysarhythmic drug. • It is naturally occuring nucleoside that slows the electrical conduction rate. • It is contraindicated in patients with second and third heart block. • It is extremely short half life of less than 10 seconds, for this reason it is only administered by IV.

47. Continue • It is available parenterally as a 3mg/ml injection. • It is a pregnancy category C.

48. Verpamil Case Study • ID/CC: A 73 year old widow visits her cardiologist complaining of difficulty moving her bowels for the past week, she also reports facial flushing. • HPI: She had been regular until she began taking verapamil for an irregular heart beat one month ago. • PE: Mild lower leg edema, constipation. • Labs: CBC: normal

49. Continue • Treatment: increase fluids in diet, regular exercise, fruits high bulk foods or laxatives. If persistent, change to another calcium channel blocker.

50. Continue Discussion: Verapamil is one of the agents that block voltage dependant calcium channels, consequently reducing muscle contractility. Verapamil acts more specifically on myocardial fibers than on arteriolar smooth muscle. It is widely used for as an antihypertensive, as antiarrhythmic, and for the treatment of angina pectoris. Constipation is common side-effect, other side-effect include dizziness, facial flushing and peripheral edema.