Antihypertensive Drugs.pptx

1.Introduction
2.Types of Hypertension
3.Risk factors
4.Classification of Anti-hypertensive Drugs

1.Diuretics :-
(a)Thiazides :-
Hydrochlorothiazide, Chlorthalidone, Indapamide
(b)Loop diuretics :-
Furosemide, Bumetanide, Torasemide
(c)Potassium sparing diuretics :- Spironolactone, Amiloride,

2. ACE inhibitors :-
Captopril,, Lisinopril, Enalapril, Ramipril,

3. Angiotensin blockers :-
Losartan, Candesartan ,Valsartan

4. Renin inhibitors :-
Aliskiren , Remikiren

5. β-adrenergic blockers :-
(a)Non selective :- Propranolol, Metoprolol Timolol,
(b)Selective :- Bisoprolol, Metoprolol, Atenolol

6. α-adrenergic blockers :-
(a)Selective :- Prazosin, Terazosin, Doxazosin
(b)Non Selective :- Phentolamine, Phenoxybenzamine

7. α-β, adrenergic blockers :-
Labetalol, Carvedilol

8. Calcium channel blockers :-
(a)L Type –Verapamil, Diltiazem, Efonidipine,
(b)Dihydropyridine -Nifedipine, Nicardipin, Lacidipine

9. Potassium channel openers :-
Minoxidil, Diazoxide,

10. Vasodilators :-
(a)Arteriolar dilator:- Hydralazine, Minoxidil,
(b)Arteriolar venodilator :- Sodium Nitroprusside

11. Centrally acting sympatholytics :-
Clonidine, α- methyldopa,

1. Antihypertensive Drugs Prepared By – Undhad Tushar C. Masters Of Pharmacy Sem – 1 (Pharmacology) R.K. University Under The Guidance Of – ujjval vaghela M. Pharm - Pharmacology, Professor, School Of Pharmacy, RK University Tushar Undhad Antihypertensive Drugs 1 Tushar Undhad Antihypertensive Drugs 1 Prepared By – Undhad Tushar C. Masters Of Pharmacy Sem – 1 (Pharmacology) Antihypertensive Drugs

2. CONTENTS 1.Introduction 2.Types of Hypertension 3.Risk factors 4. Classification of Anti-hypertensive Drugs 5.Pharmacology of Antihypertensive drugs 6.Reference Tushar Undhad Antihypertensive Drugs 2

3. 1.INTRODUCTION Hypertension is an elevation of systolic and diastolic BP above 140/90 mm of Hg. Hypertension the heart is working harder than normal putting extra strain on the heart and vessels. Tushar Undhad Antihypertensive Drugs 3

4. 1.INTRODUCTION Systolic blood pressure :- The amount of pressure against the artery walls each time the heart contract Diastolic blood pressure :- The amount of pressure inside the artery when heart is at rest, in between heartbeats. Tushar Undhad Antihypertensive Drugs 4

5. 1.INTRODUCTION Blood pressure is determined by cardiac output (CO) and total peripheral vascular resistance (PVR). Prolonged hypertension damages the blood vessels of the heart, brain and the kidneys and may result in several complications like stroke, coronary artery disease or renal failure. Tushar Undhad Antihypertensive Drugs 5

6. 1.INTRODUCTION Blood pressure is controlled by baroreceptor reflexes acting through autonomic nervous system along with the renin-angiotensin-aldosterone system. Tushar Undhad Antihypertensive Drugs 6

7. Low blood pressure Baroreceptor sense low BP Parasympathetic sympathetic Vasoconstriction Vasoconstriction Increase cardiac output, BP Release of Renin of kidney Angiotensinogen Angiotensin-1 ACE Vasoconstriction Angiotensin -2 Tushar Undhad Antihypertensive Drugs 7

8. 2.Type Types of Hypertension 1.Primary (Essential) Hypertension:- where the cause is not known. 2.Secondary:- Cause are known kidney problem, Adrenal gland tumor - aldosteronism, Thyroid problem - increase ca+ Tushar Undhad Antihypertensive Drugs 8

9. 3.Risk factors: Risk with increase age (above 65 years) Family history Tobacco Smoking Diet-High salt and oil intake and alcohol Stress condition Tushar Undhad Antihypertensive Drugs 9

10. 4.Classification of Anti-hypertensive Drugs 1 . Diuretics :- (a)Thiazides :- Hydrochlorothiazide, Chlorthalidone , I ndapamide (b)L oop diuretics :- F urosemide, Bumetanide , Torasemide (c)Potassium sparing diuretics :- Spironolactone, Amiloride, Tushar Undhad Antihypertensive Drugs 10

11. 4.Classification of Anti-hypertensive Drugs 2. ACE inhibitors :- Captopril,, Lisinopril , Enalapril, Ramipril, 3. Angiotensin blockers :- Losartan, Candesartan , Valsartan 4. Renin inhibitors :- Aliskiren , Remikiren Tushar Undhad Antihypertensive Drugs 11

12. 4.Classification of Anti-hypertensive Drugs 5. β- adrenergic blockers :- (a)Non selective : - Propranolol, Metoprolol Timolol, (b)Selective :- Bisoprolol, Metoprolol, Atenolol Tushar Undhad Antihypertensive Drugs 12

13. 4.Classification of Anti-hypertensive Drugs 6. α - adrenergic blockers :- (a)Selective :- Prazosin, Terazosin, Doxazosin (b)Non Selective :- Phentolamine, Phenoxybenzamine Tushar Undhad Antihypertensive Drugs 13

14. 4.Classification of Anti-hypertensive Drugs 7. α - β, adrenergic blockers :- Labetalol, Carvedilol 8. Calcium channel blockers :- (a)L Type –Verapamil, Diltiazem, Efonidipine, (b)Dihydropyridine -Nifedipine, Nicardipin, Lacidipine Tushar Undhad Antihypertensive Drugs 14

15. 4.Classification of Anti-hypertensive Drugs 9. Potassium channel openers :- Minoxidil, Diazoxide, 10. Vasodilators :- (a)Arteriolar dilator:- Hydralazine, Minoxidil, (b)Arteriolar venodilator :- Sodium Nitroprusside Tushar Undhad Antihypertensive Drugs 15

16. 4.Classification of Anti-hypertensive Drugs 11. Centrally acting sympatholytics :- Clonidine, α - methyldopa, Tushar Undhad Antihypertensive Drugs 16

17. 1 . Diuretics :- (a)Thiazides :- Hydrochlorothiazide, Chlorthalidone , I ndapamide MOA: Diuretics enhance the excretion of sodium and water. Tushar Undhad Antihypertensive Drugs 17

18. (a)Thiazide diuretics :- Acts on early part of distal tubules. Inhibit Na + -Cl - symporter at the luminal membrane. Increase NaCl excretion. Na + exchanges with K + in the DT. Tushar Undhad Antihypertensive Drugs 18

19. (a)Thiazide diuretics :- 1. ↓ Plasma volume → ↓ cardiac output → ↓ BP 2. ↓ Body sodium → relaxation of vascular smooth muscles (due to Na+ depletion in the vascular smooth muscle) - ↓ PVR → ↓ BP. Tushar Undhad Antihypertensive Drugs 19

20. (a)Thiazides diuretics :- Pharmacokinetic action : Extensively protein-bound All are excreted in the urine, mainly by tubular secretion Their action starts within 1 hrs but the duration varies from 8-12hrs Tushar Undhad Antihypertensive Drugs 20

21. (a)Thiazides diuretics :- ADR: Hypokalaemia Hyperuricemia Hyperglycemia Hypercalcemia Tushar Undhad Antihypertensive Drugs 21

22. (a)Thiazides diuretics :- Therapeutic uses: CHF Hypertension Edema Tushar Undhad Antihypertensive Drugs 22

23. (b)L oop diuretics :- Furosemide, Bumetanide , Torasemide MOA: The major site of action is the thick AscLH, Inhibits Na+ - K+ -2Cl- cotransport Tushar Undhad Antihypertensive Drugs 23

24. (b)L oop diuretics :- Pharmacokinetic action : Absorbed orally ( 1 hrs. ) Bioavailability is 60% Lipid solubility is low Highly bound to plasma proteins Tushar Undhad Antihypertensive Drugs 24

25. (b)L oop diuretics :- ADR: Hypokalaemia. Excessive Na+ and water loss are common. Metabolic alkalosis. Tushar Undhad Antihypertensive Drugs 25

26. (b)L oop diuretics :- Therapeutic uses: These agents are rarely used alone to treat hypertension, but they are commonly used to manage symptoms of heart failure and edema. Hypercalcaemia and renal calcium stones. Tushar Undhad Antihypertensive Drugs 26

27. (c)Potassium sparing diuretics :- Spironolactone, Amiloride MOA: Amiloride inhibitors of epithelial sodium transport at the late distal and collecting ducts. spironolactone are aldosterone receptor antagonists. All of these agents reduce potassium loss in the urine. Tushar Undhad Antihypertensive Drugs 27

28. (c)Potassium sparing diuretics :- Pharmacokinetic action : Oral bioavailability of 70% Highly bound to plasma proteins. Completely metabolized in liver. Plasma half - 10 min. Tushar Undhad Antihypertensive Drugs 28

29. (c)Potassium sparing diuretics :- ADR: Hyperkalaemia Gastrointestinal upset menstrual disorders Tushar Undhad Antihypertensive Drugs 29

30. (c)Potassium sparing diuretics :- Therapeutic uses: Potassium-sparing diuretics are sometimes used in combination with loop diuretics and thiazides to reduce the amount of potassium loss induced by these diuretics. Heart failure. Primary Hyperaldosteronism. Tushar Undhad Antihypertensive Drugs 30

31. Ras system Tushar Undhad Antihypertensive Drugs 31 Angiotensinogen Angiotensin-1 Liver secretion Angiotensin-2 Angiotensin-2 Type 1 receptor Kidney secretion ACE Inhibitor Kidney ↑Na+ reabsorption ↑Aldosterone effect ↑vasoconstriction CNS ↑sympathetic activity Vessels ↑vasoconstriction ↑atherosclerosis Renin ACE Direct renin inhibitor

32. Tushar Undhad Antihypertensive Drugs 32 Bradykinin Nitric oxide prostaglandin (PGE2&PGI2) vasodilation Blood pressure

33. 2. ACE inhibitors :- Captopril, Lisinopril , Enalapril, Ramipril MOA: Angiotensin II is a powerful vasoconstrictor. Aldosterone also raises the BP by increasing the plasma volume Tushar Undhad Antihypertensive Drugs 33

34. 2. ACE inhibitors :- ACE inhibitors prevent the formation of angiotensin II and (indirectly) aldosterone. There is vasodilation and decrease in PVR resulting in a fall in BP. As ACE also degrades bradykinin, ACE inhibitors raise the bradykinin levels which is a potent vasodilator. This also contributes to the fall in BP Tushar Undhad Antihypertensive Drugs 34

35. 2. ACE inhibitors :- Tushar Undhad Antihypertensive Drugs 35

36. 2. ACE inhibitors :- Pharmacokinetic action : Better oral bioavailability t½ is 2 hrs. ADR: Hypotension, Acute renal failure Proteinuria, Angioedema, Hyperkalaemia Tushar Undhad Antihypertensive Drugs 36

37. 2. ACE inhibitors :- Therapeutic uses: Hypertension Coronary artery disease Chronic renal failure Congestive heart failure Left ventricular systolic dysfunction Tushar Undhad Antihypertensive Drugs 37

38. 3. Angiotensin receptor blockers (ARBs) :- Losartan, Candesartan ,Valsartan MOA: Angiotensin II receptors— AT1 and AT2 . Losartan has high affinity for AT1 receptors when compared to AT2 receptors. By blocking AT1 receptors, losartan blocks the effect of angiotensin II. Tushar Undhad Antihypertensive Drugs 38

39. 3. Angiotensin receptor blockers (ARBs) :- It cause relaxes vascular smooth muscles, promotes salt and water excretion and reduces plasma volume. Angiotensin converting enzyme is not inhibited cause increase in bradykinin levels and its associated adverse effects like dry cough and angioedema. Tushar Undhad Antihypertensive Drugs 39

40. 3. Angiotensin receptor blockers (ARBs) :- Pharmacokinetic action : High first pass metabolism Highly bound to plasma proteins Absorption is not affected by food t½ -6 hrs. Tushar Undhad Antihypertensive Drugs 40

41. 3. Angiotensin receptor blockers (ARBs) :- ADR: Risks of cough and angioedema Hypotension and hyperkalaemia Therapeutic uses: Hypertension Cardiac failure Diuretic Tushar Undhad Antihypertensive Drugs 41

42. 4. Renin inhibitors Aliskiren , Remikiren MOA: Renin inhibitors bind to active site of renin and prevent the formation of ang1 and age 2. Resulting decrease blood pressure. Tushar Undhad Antihypertensive Drugs 42

43. 4. Renin inhibitors Tushar Undhad Antihypertensive Drugs 43 Mechanism of action:

44. 4. Renin inhibitors Pharmacokinetic action : It is orally active, t½ is about 24 hrs. It is reduce plasma renin activity by 50-80%, It is metabolised by liver and excreted by the kidneys. Tushar Undhad Antihypertensive Drugs 44

45. 4. Renin inhibitors ADR: Diarrhea ,cough and angioedema Hyperkalaemia Therapeutic uses: Heart attacks, Kidney failure Tushar Undhad Antihypertensive Drugs 45

46. 5. β- adrenergic blockers :- (a)Selective :- Prazosin, Terazosin, Doxazosin (b)Non Selective :- Phentolamine, Phenoxybenzamine Tushar Undhad Antihypertensive Drugs 46

47. 5. β- adrenergic blockers :- MOA: Blockade of cardiac β1 receptors results in decreased myocardial contractility and cardiac output. They reduce the BP due to a fall in the cardiac output. They also lower plasma renin activity and have an additional central antihypertensive action. Tushar Undhad Antihypertensive Drugs 47

48. 5. β- adrenergic blockers :- Tushar Undhad Antihypertensive Drugs 48 Mechanism of action:

49. 5. β- adrenergic blockers :- Pharmacokinetic action : β- blockers are orally active Metabolised in the liver t½ is 3-7 hrs. Tushar Undhad Antihypertensive Drugs 49

50. 5. β- adrenergic blockers :- ADR: Bradycardia Fatigue Insomnia Sexual Dysfunction Hypotension Tushar Undhad Antihypertensive Drugs 50

51. 5. β- adrenergic blockers :- Therapeutic uses: Previous myocardial infarction, Angina pectoris Chronic heart failure Hypertension Tushar Undhad Antihypertensive Drugs 51

52. 6. α - adrenergic blockers :- (a)Selective :- Prazosin, Terazosin, Doxazosin (b)Non Selective :- Phentolamine, Phenoxybenzamine Tushar Undhad Antihypertensive Drugs 52

53. 6. α - adrenergic blockers :- MOA: Blocks alpha adrenergic receptors - vasodilatation & decrease in BP Tushar Undhad Antihypertensive Drugs 53

54. 6. α - adrenergic blockers :- Pharmacokinetic action : It is orally bioavailability is 60%, Highly bound t plasma proteins, Metabolised in liver and excreted primarily in bile, t½ is 2-3 hrs Tushar Undhad Antihypertensive Drugs 54

55. 6. α - adrenergic blockers :- ADR: Palpitation, Nasal blockade Hypotension Reflex tachycardia Tushar Undhad Antihypertensive Drugs 55

56. 6. α - adrenergic blockers :- Therapeutic uses: Used in hypertension CHF It may be added to a diuretic + blocker in those not achieving target BP. Tushar Undhad Antihypertensive Drugs 56

57. 7. α - β, adrenergic blockers :- Labetalol, Carvedilol MOA: Blocking both α and β receptors. Fall in bp ( both systolic and diastolic ) is due to α1 and β2 blocked as well as β2 agonism (vasodilation ). Tushar Undhad Antihypertensive Drugs 57

58. 7. α - β, adrenergic blockers :- Alpha-blockers work on norepinephrine or noradrenaline, while beta-blockers work on epinephrine or adrenaline. Alpha-blockers affect only blood pressure levels, while beta-blockers affect both the heart and blood pressure. Tushar Undhad Antihypertensive Drugs 58

59. 8. Calcium channel blockers :- (a)L Type:- Verapamil, Diltiazem, Efonidipine, (b)Dihydropyridine:- -Nifedipine, Nicardipin, Lacidipine Tushar Undhad Antihypertensive Drugs 59

60. 8. Calcium channel blockers :- MOA: The intracellular concentration of calcium plays an important role in maintaining the tone of smooth muscle and in the contraction of the myocardium. Calcium enters muscle cells through special voltage sensitive calcium channels. Tushar Undhad Antihypertensive Drugs 60

61. 8. Calcium channel blockers :- This triggers release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium. Calcium channel blocker block L-type calcium channels in the heart and in smooth muscle of the coronary and peripheral arteriolar. Tushar Undhad Antihypertensive Drugs 61

62. 8. Calcium channel blockers :- This causes vascular smooth muscle to relax, dilating mainly arterioles. Calcium channel blockers do not dilate veins Tushar Undhad Antihypertensive Drugs 62

63. 8. Calcium channel blockers :- Pharmacokinetic action : Most of these agents have short half-lives (3 to 8 hours) Metabolized in liver Excreted in urine Tushar Undhad Antihypertensive Drugs 63

64. 8. Calcium channel blockers :- ADR: Dizziness, headache, and a feeling of fatigue caused by a decrease in blood pressure Peripheral edema is another commonly reported side effect of this class. Tushar Undhad Antihypertensive Drugs 64

65. 8. Calcium channel blockers :- Therapeutic uses: Hypertension Treatment of angina Arrhythmias Tushar Undhad Antihypertensive Drugs 65

66. 9. Potassium channel openers :- Minoxidil, Diazoxide, MOA: Opening these channels hyperpolarizes the smooth muscle, which closes voltage-gated calcium channels and decreases intracellular calcium. This leads to relaxation and vasodilation. Tushar Undhad Antihypertensive Drugs 66

67. 9. Potassium channel openers :- Tushar Undhad Antihypertensive Drugs 67

68. 9. Potassium channel openers :- ADR: Headaches, flushing, Reflex tachycardia Fluid and salt retention Tushar Undhad Antihypertensive Drugs 68

69. 9. Potassium channel openers :- Therapeutic uses: Hypertension Smooth muscle relaxing activity Vasodilator to treat angina Tushar Undhad Antihypertensive Drugs 69

70. 10. Vasodilators :- (a)Arteriolar dilator:- Hydralazine, Minoxidil, (b)Arteriolar venodilator :- Sodium Nitroprusside Tushar Undhad Antihypertensive Drugs 70

71. 10. Vasodilators :- MOA: Hydralazine molecules combine with receptors in the endothelium of arterioles – NO release – relaxation of vascular smooth muscle – fall in BP Tushar Undhad _Antihypertensive Drugs 71

72. 10. Vasodilators :- ADR: Hypotension, salt & water retention It may precipitate angina in some patients because increased o2 demand due to reflex tachycardia and decreased myocardial blood supply due to peripheral vasodilatation Headache (caused by cerebral vasodilation) Tushar Undhad Antihypertensive Drugs 72

73. 10. Vasodilators :- Therapeutic uses: Heart failure Angina and myocardial infarction Ability to inhibit platelet aggregation Tushar Undhad Antihypertensive Drugs 73

74. 11. Centrally acting sympatholytics :- Clonidine, α - methyldopa, MOA: Centrally acting sympatholytic block sympathetic activity by binding to and activating alpha ( α 2) adrenoceptors Tushar Undhad Antihypertensive Drugs 74

75. 11. Centrally acting sympatholytics :- This reduces sympathetic outflow to heart thereby decreasing cardiac output by decreasing heart rate and contractility ,which causes vasodilation and reduced systemic vascular resistance, which decreases arterial pressure. Tushar Undhad Antihypertensive Drugs 75

76. 11. Centrally acting sympatholytics :- ADR: Bradycardia (not good for emergency), Dryness of mouth, Vertigo Bradycardia (not good for emergency), Dryness of mouth, Tushar Undhad Antihypertensive Drugs 76

77. 11. Centrally acting sympatholytics :- Therapeutic uses: Preferred for pts. with chronic renal disease & hypertensive emergencies Now used only in HTN associated with pregnancy since it is safe. Tushar Undhad Antihypertensive Drugs 77

78. Advance drugs in hypertension Genericart Amlodipine+Atenolol 5mg/50mg Tablet ( 01-Oct-2021) Prescription Required MANUFACTURER Swast Aushadhi Seva Generic Medicine Store SALT COMPOSITION Amlodipine (5mg) + Atenolol (50mg) Tushar Undhad _Antihypertensive Drugs 78

79. Combination antihypertensives Combination antihypertensives include combined agents from the following pharmacologic classes:  diuretics and potassium-sparing diuretics , beta blockers and diuretics, angiotensin-converting enzyme (ACE) inhibitors and diuretics, angiotensin-II antagonists and diuretics, and calcium channel blockers and ACE inhibitors. Tushar Undhad _Antihypertensive Drugs 79

80. Combination antihypertensives agent The recommendation for first-line therapy for hypertension remains a beta blocker or diuretic given in a low dosage. A target blood pressure of less than 140/90 mm Hg is achieved in about 50 percent of patients treated with monotherapy; two or more agents from different pharmacologic classes are often needed to achieve adequate blood pressure control Tushar Undhad _Antihypertensive Drugs 80

81. Combination antihypertensives agent Tushar Undhad _Antihypertensive Drugs 81 Diuretic combinations Brand name - Moduretic Amiloride and hydrochlorothiazide (5 mg/50 mg) Beta blockers and diuretics Brand name - Tenoretic Atenolol and chlorthalidone (50 mg/25 mg, 100 mg/25 mg) ACE inhibitors and diuretics Brand name - Lotensin HCT Benazepril and hydrochlorothiazide (5 mg/6.25 mg, 10 mg/12.5 mg, 20 mg/12.5 mg, 20 mg/25 mg)

82. References: Essentials Of Medical Pharmacology 8th Edition 2018 By KD Tripathi Lippincott's pharmacology Padmaja Uday Kumar Professor and Head Department of Pharmacology Fr. Muller Medical College, Mangalore Karnataka India Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11 th -Edition 2006 Rang & Dale’s Pharmacology, Eighth edition Tushar Undhad Antihypertensive Drugs 82

83. Tushar Undhad Antihypertensive Drugs 83