Antihypersensitive drugs

Hypertension is defined as either a sustained systolic blood pressure (SBP)of greater than 140 mm Hg or a sustained diastolic blood pressure of greater than 90 mm of Hg.

An agent that reduces high blood pressure is called as an ANTIHYPERTENSIVES.
Prehypertension-systolic between 120 to 139 mm/Hg and diastolic between 80 to 89 mm/Hg.

1. Antihypertensive drugs Presented By: Gandham Malasree M Pharmacy I year I sem Regd no: 620209502002 Dept of Pharmaceutical Chemistry AU COLLEGE OF PHARMACEUTICAL SCIENCES, VISAKHAPATNAM

2. Hypertension is defined as either a sustained systolic blood pressure (SBP)of greater than 140 mm Hg or a sustained diastolic blood pressure of greater than 90 mm of Hg. An agent that reduces high blood pressure is called as an ANTIHYPERTENSIVES. Prehypertension-systolic between 120 to 139 mm/Hg and diastolic between 80 to 89 mm/Hg. Hypertension

3. Causes: It results from: Increased arterial resistance Reduced capacitance Increased peripheral vascular smooth Muscle tone Effects of Hypertension Increases risk of heart disease , heart failure, kidney disease, blindness, and stroke. Primary Hypertension- No known reason. Secondary Hypertension-due to some cause such as kidney disease, abnormalities of adrenal glands will try nonpharmacological methods first.

4. ACE INHIBITORS Sulfhydryl containing drugs- Captopril Dicarboxylate containing drugs- Enalapril, Lisinopril, Perindopril, Quinapril , Ramipril. Phosphate containing drugs- Phosinopril 2) ANGIOTENSIN RECEPTOR BLOCKERS Losartan, Candesartan, Irbesartan. 3) CALCIUM CHANNEL BLOCKERS a)1,4 Dihydropyridines- Nifedipine, Amlodipine, b)Diphenyl alkylamine- Verapamil, c) Benzothiazipine - Diltiazem. d)Diamino propanol ethers - Bepridil DRUG CLASSIFICATON

5. 4) DIURETICS : a) Thiazide diuretics – Hydrochlorthiazide , Chlorthalidone. b) High-ceiling/Loop diuretics – Furosemide, Torsemide. c) K+ sparing diuretics – Spironolactone, Eplerenone. d) Xanthines – Theophylline, Theobromine , Caffeine e) Carbonic anhydrase inhibitors- Acetazolamide, Metazolamide . f) Osmotic diuretics- Mannitol , Urea g) Organo mercurales – Mercaptomerin , Chlormeridine

6. 5) SYMPATHOLYTICS: a) Beta Adrenergic blockers: Atenolol, Propranolol, Esmolol, Metoprolol. b) Selective Alpha-1 Adrenergic blockers: Prazosin, Terazosin. c) Alpha + Beta Adrenergic blockers: Labetalol, Carvediol d) Centrally-acting sympatholytics : Clonidine, Methyl-D-dopa. 6) GANGLIONIC BLOCKERS: Pentolinium, Trimethaphan , Clonidium . 7) ADRENERGIC NEURONAL BLOCKERS: Reserpine, Guanethidine. 8)VASODILATORS: a) Arteriolar – Diazoxide, Minoxidil. b) Arteriolar + Venodilator – Sodium-nitroprusside.

7. MECHANISM OF ACTION

8. Ace inhibitor’s Phosphonate containing drugs Sulfhydryl containing drugs

9. Dicarboxylate containing drugs

10. MECHANISM OF ACTION:  - Inhibit generation of AT-2  - Inhibit degradation of Bradykinin, which is a potent vasodilator  - Dilate both arteries and veins  - Blood flow to vital organs increases  - Decrease aldosterone production indirectly PHARMACOKINETICS: Well absorbed orally; poorly cross BBB; metabolized in liver; excreted through urine. Duration of action of Captopril – 8-12 hrs. ADRs: Cough, Teratogenic, Skin rashes, Loss of taste sensation, Hyperkalemia. Uses: Hypertension, CHF, MI, Diabetic nephropathy

11. ANGIOTENSIN RECEPTOR BLOCKERS

12. MECHANISM OF ACTION: Competitively inhibit binding of AT-2 to AT-1 receptors. ADRs and Uses are almost similar to that of the ACEIs, except that, ARBs do not increase bradykinin levels and so, the ACEI related cough isn’t encountered. Angioedema and taste disturbance is also rare.

13. CALCIUM CHANNEL BLOCKERS

14. Diphenylalkylamine derivatives : Diamino propanol ethers :

15. It inhibits cellular influx of Ca, which is responsible for muscle contraction. Calcium channel blockers protect tissue by inhibiting entrance of Ca into cardiac & smooth muscle cells of coronary & systemic arterial beds. All Ca channel blockers are vasodilators that ultimately cause dilation of coronary & peripheral arteries,reduce heart rate. MECHANISM OF ACTION:

16. DIURETICS Loop diuretics

17. Thiazides :

18. Potassium Sparing Diuretics :

19. Carbonic anhydrase inhibitors Osmotic diretics

20. MECHANISM OF ACTION: Inhibit Na+ - Cl- symport in early DCT → Promote Na+ and water retention → Decrease Na+ conc. in vascular smooth muscles → Decrease in plasma volume and peripheral resistance → Decrease in BP ADRs: Hypokalemia, Hypercalcemia, Hyperglycemia, etc. Uses: Hypertension, Renal dysfunction, nephrogenic diabetes insipidus.

21. GANGLIONIC BLOCKERS

22. MECHANISM OF ACTION: Act on, and block sympathetic ganglia → interrupt adrenergic control of arterioles → Vasodilation → Decrease BP ADRs: Hypotension, Neuromuscular blockade, Dry mouth, Constipation. Uses: Hypertension, Peripheral vascular diseases.

23. ADRENERGIC NEURONAL BLOCKERS

24. MECHANISM OF ACTION: They act by blocking adrenergic receptors in target organs, or by inhibiting the synthesis, storage, or release of endogenous catecholamines (mainly Norepinephrine), and cause decrease in CO and vascular resistance. ADRs: Mild postural hypotension Uses: Hypertension, Anti-psychotic, Anti-emetic

25. VASODILATORS

26. Minoxidil: Opens K+ channel → Hyperpolarization of vascular smooth muscles → Vasodilation → Decreases BP Diazoxide: Activates Ca+ channel in the arteriolar smooth muscle → Direct smooth muscle relaxation → Decreases BP ADRs: Chest pain, Heart palpitations (fluttering or pounding heartbeat), Dizziness, Headache, etc. Uses: Hypertension, Angina, Heart failure. MECHANISM OF ACTION:

27. BETA BLOCKERS

28. MECHANISM OF ACTION:

29. Catecholamines : Reserpine

30. Alpha blockers

31. SAR OF CALCIUM CHANNEL BLOCKERS

32. SAR OF LOOP DIURETICS

33. SAR OF ACE INHIBITORS

34. ANTIHYPERTENSIVES IN PREGNANCY Drugs to be avoided:  Diuretics – Risk of placental wastage, still birth.  ACEIs – Risk of foetal damage, growth retardation.  Beta-blockers – Neonatal bradycardia, hypoglycaemia .  Safe drugs: Hydralazine, Alpha-methyldopa, CCBs, Prazosin, Clonidine, Cardioselective beta-blockers.

35. CONCLUSION Choice of drugs for any patient should be individualized. Patients undergoing antihypertensive medications in diabetes, or during pregnancy are at higher risk of clinical cardiovascular events and benefit more from antihypertensive therapy, compared to the non-diabetic/ non-pregnant patients. It is thus, important for the clinicians to monitor these patients so that, they can be conscientiously treated.

36. Thank you