Ant ihypertensive

ANTIHYPERTENSIVE DRUGS

1. Antihypertensive Drug Presented by Monika Devi M.Sc.(N)

2. Antihypertensive Drugs Antihypertensives  are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction.

3. Antihypertensive Drugs Classification Diuretics. Beta adrenergic blockers. Calcium channel blockers. Angiotensin converting enzyme inhibitors. Angiotensin receptor blockers. Sympatholytic and adrenergic blockers. Direct arterial vasodilators.

4. Diuretics Diuretics, also called water pills, are medications designed to increase the amount of water and salt expelled from the body as urine. They’re often prescribed to help treat high blood pressure, but they're used for other conditions as well.

5. Types The three types of diuretic medications. All of them make the body excrete more fluids as urine. 1. Thiazide diuretics:- Are the most commonly prescribed diuretics. They’re most often used to treat high blood pressure. These drugs not only decrease fluids in the body, they also relax the blood vessels. Thiazides are sometimes taken with other medications used to lower blood pressure. Examples of thiazides include: Chlorothiazide Chlorthalidone Hydrochlorothiazide Metolazone Indapamide

6. Cont… 2. Loop diuretics :- Loop diuretics are often used to treat heart failure. Examples of these drugs include: Torsemide Furosemide Bumetanide Ethacrynic acid

7. Cont… 3. Potassium-sparing diuretics :- Potassium-sparing diuretics reduce fluid levels in the body without loosing  potassium. The other types of diuretics cause to lose potassium, which can lead to health problems such as  arrhythmia . Potassium-sparing diuretics may be prescribed for people at risk of low potassium levels, such as those who take other drugs that deplete potassium. Examples of potassium-sparing diuretics include: Amiloride Spironolactone Triamterene Eplerenone

8. Mechanism of Action Initial effects:- through reduction of plasma volume and cardiac output. Long term effect:- through decrease in total peripheral vascular resistance.

9. Advantages Documented reduction in cardiovascular morbidity and mortality. Least expensive antihypertensive drugs. Best drug for treatment of systolic hypertension and for hypertension in the elderly. Can be combined with all other antihypertensive drugs.

10. Side effects More common side effects the more common side effects of diuretics include: T oo little potassium in the blood Too much potassium in the blood (for potassium-sparing diuretics only) Low sodium levels Headache Dizziness Thirst Increased blood sugar Muscle cramps Increased cholesterol Skin rash Diarrhea

11. Cont… Serious side effects In rare cases, diuretics may cause serious side effects. These can include: Allergic reaction Kidney failure Irregular heartbeat

12. Drug interactions These include: Cyclosporine Antidepressants such as fluoxetine and venlafaxine Lithium Digoxin Other drugs for high blood pressure

13. 2. Beta - Adrenergic Blocking Agents Beta-adrenergic blocking agents, are a class of drugs that works by blocking the neurotransmitters   norepinephrine  and  epinephrine from binding to receptors. There are three known types of beta receptors, known as beta 1  (β 1 ), beta 2  (β 2 ) and beta 3  (β 3 ). β 1 -adrenergic receptors are located commonly in the  hear t and kidneys .  β 2 -adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver,  uterus,vascular  smooth muscle, and skeletal muscle.  β 3 - adrenergic receptors are located in fat cells.

14. Mechanisms of Action Initial decrease in cardiac output, followed by reduction in peripheral vascular resistance. Other actions include decrease plasma renin activity, resetting of baroreceptors, release of vasodilator prostaglandins, and blockade of pre-junctional beta-receptors.

15. Advantages Documented reduction in cardiovascular morbidity and mortality. Cardio protection: primary and secondary prevention against coronary artery events (i.e. ischemia, infarction, arrhythmias, death). Relatively not expensive.

16. Practical Considerations Beta blockers are used with caution in patients with bronchospasm. Contraindicated in heart block. Do not discontinue abruptly.

17. Side Effects Bronchospasm and obstructive airway disease. Bradycardia Coldness of extremities. Fatigue. Mask symptoms of hypoglycemia. Metabolic effects (raise triglycerides levels and decrease HDL cholesterol; may worsen insulin sensitivity and cause glucose intolerance). Increased incidence of diabetes mellitus.

18. Special Indications First line treatment for hypertension as an alternative to diuretics. Hypertension associated with coronary artery disease. Hypertension associated with supraventricular tachycardia, Migraine, essential tremors hypertrophic cardiomyopathy .

19. Calcium channel blockers  ( CCB ),or  calcium antagonists are medications that disrupt the movement of calcium (ca 2+ ) through calcium channels.  calcium channel blockers are used as antihypertensive drugs. 3. Calcium channel blockers

20. Types Dihydropyridine : used to reduce systemic vascular resistance and arterial pressure. This CCB class is easily identified by the suffix "- dipine ". Nifedipine Nimodipine ( nimotop ) this substance can pass the blood-brain barrier and is used to prevent cerebral vasospasm. Amlodipine Felodipine Lacidipine .

21. Cont… 2. Non dihydropyridine : The Non- dihydropyridine Calcium Chanal Blockers such as verapamil ( Isoptin ) and diltiazem ( Cardizem ) cause less vasodilation and more cardiac depression than dihydropyridine Calcium Chanal Blockers. They have negative effects at the SA and AV nodes, and cause reductions in heart rate and contractility. E.g Phenylalkylamine :- Verapamil . Benzothiazepine :- Diltiazem

22. Mechanisms of action Decrease in the concentration of free intracellular calcium ions results in decreased contraction and vasodilation. Diuretic effect through increase in renal blood flow and glomerular filtration rate. Inhibition of aldosterone secretion.

23. Advantages No metabolic disturbances: no change in blood glucose, potassium, uric acid and lipids. May improve renal function. Maintain optimal physical, mental, and sexual activities.

24. Special Indications Ischemic heart disease : when beta blockers are ineffective or contraindicated and in vasospastic angina. Elderly hypertensives: second agent of choice after diuretics. Peripheral vascular disease.

25. Side Effects Dihydropyridine: flushing, headache, and lower limb edema. Non dihydropyridine: aggravation of heart failure and heart block.

26. Practical considerations Short acting dihydropyridine should be combined with beta blockers in coronary artery disease, and should be avoided in stroke, and hypertensive crisis.

27. 4. Angiotensin Converting Enzyme Inhibitors Angiotensin -converting enzyme (ACE) inhibitors help relax blood vessels. ACE inhibitors prevent an enzyme in the body from producing angiotensin II, which narrows blood vessels and releases hormones that can raise blood pressure. This narrowing can cause high blood pressure and force the heart to work harder. Types:- Class I: C aptopril Class II (prodrug) : e.g., ramipril, enalapril, perindopril Class III ( water soluble) : lisinopril.

28. Advantages Reduction of cardiovascular morbidity and mortality in patients with atherosclerotic vascular disease, diabetes, and heart failure. Improvement in glucose tolerance and insulin resistance. Renal glomerular protection effect especially in diabetes mellitus. Do not adversely affect quality of life.

29. Special Indications Diabetes mellitus, particularly with nephropathy. Congestive heart failure. Following myocardial infraction.

30. Side Effects Cough (10 - 30%): a dry irritant cough with tickling sensation in the throat. Skin rash (6%). Postural hypotension in salt depleted or blood volume depleted patients. Renal failure: rare, high risk with bilateral renal artery stenosis . Hyperkaliemia

31. 5. Angiotensin receptor blockers The class of drugs called  angiotensin receptor blockers (ARBs), as the class name suggests, are drugs that block the action of  angiotensin . Mechanism of action:- They act by blocking type I angiotensin II receptors generally, producing more blockade of the renin - angiotensin - aldosterone axis.

32. Advantages Similar metabolic profile to that of ACE-I. Renal protection. They do not produce cough.

33. Practical Indications:- Patients with a compelling indication for ACE-I who can not tolerate them because of cough or allergic reactions.

34. 6. Sympatholytic And Alpha Adrenergic Blockers Sympatholytic drugs  : Drugs that inhibit nerve impulses in the sympathetic nervous system. They may block the effect of alpha-adrenergic receptors  which is used to reverse  pupillary  blockage or the effect of  beta- adrenergic receptors   called  beta-blockers ( which block beta 1 receptors;  timolol   maleate ,   levobunolol , metipranolol  and  carteolol  which block beta 1 and beta  2 receptors) Beta-blockers are used in the treatment of glaucoma.  Alpha 1-receptor blockers : prazocin , doxazocin . Centrally acting alpha 2- agonists: methyldopa, clonidine . Peripherally acting adrenergic antagonists: reserpine . Imidazoline receptor agonists: rilmenidine , moxonidine .

35. Advantages Alpha1- receptor blockers and imidazoline receptor agonists improve lipid profile and insulin sensitivity. Methyldopa: increases renal blood flow. Drug of choice during pregnancy. Reserpine: neutral metabolic effects and cheap.

36. Special indications Diabetes mellitus: alpha1- receptor blockers, imidazoline receptor agonists. Dyslipidemia: alpha 1- receptor blockers, imidazoline receptor agonists. Prostatic hypertrophy: alpha 1- receptor blockers. When there is a need for rapid reduction in blood pressure: clonidine.

37. Side Effects Prazocin : postural hypotension, diarrhea, occasional tachycardia, and tolerance (due to fluid retention). Methyldopa: sedation, hepatotoxicity, hemolytic anemia, and tolerance. Reserpine: depression, lethargy, weight loss, peptic ulcer, diarrhea, and impotence. Clonidine: dry mouth, sedation, bradycardia, impotence, and rebound hypertension if stopped suddenly.

38. 7. Direct Arterial Vasodilators These drugs act directly on the blood vessel walls, relaxing muscles to allow blood to flow more easily. Direct vasodilators are used only in individuals with hypertension that is  extremely difficult to control ; they are also sometimes used to  treat a hypertensive crisis hydralazine, diazoxide, nitroprusside, and minoxidil .

39. Patients’ compliance to antihypertensive medications:- Poor adherence to antihypertensive therapy remains a major therapeutic challenge contributing to the lack of adequate control of blood pressure in more than two thirds of patients with hypertension. One half of all patients discontinue antihypertensive medications within one year.

40. Causes of Poor Compliance Hypertension has no symptoms and treatment has to continue indefinitely. Poor communication with the patient. Very long intervals between follow-up visits, and frequent change of doctors impair the doctor-patient relationship. Logistic barriers e.g. expense of medications, inability to read instructions, complicated multi-dose regimens, etc …. Adverse drug effects.

41. Strategies to Improve Compliance Educate patients about the disease and involve their families in the treatment. Stress that treatment is life-long. Consider cost while prescribing. Consider adverse effects at initial prescription and follow up visits. Prescribe simple once-daily regimens. Allow extra visits for blood pressure measurement at no extra charge to the patient. Arrange follow-up visits at intervals no more than three months apart, during the first year. Encourage life style modifications.

42. BIBLIOGRAPHY (1) Kumar P. Pharmacology For Nurses Second Edition 2008 JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD new Delhi   (2) Kumar P. medical Pharmacology fifth edition 2017 CBS Publishers & Distributors PVT. LTD new.   (3)Shenoy S, Shanbhag T Pharmacology For medical Graduates 3 rd Edition, Elsevier Publication, RELX India Private Limited, Barakhamba road, LTD. ltd

43. Thank you