Anti hypertensive

Antihypertensive drugs and screening methods are dealt

1. ?? BRAIN STROKE HEART FAILURE , Coronary Heart Disease RETINOPATHY RENAL FAILURE 1

2. One in three adults worldwide, according to the report, has raised blood pressure – a condition that causes around half of all deaths from stroke and heart disease. Overall prevalence for hypertension in India is 29.8%. 2

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4. Presented by- Guided by- Dr. Puneshwar Keshari Dr. Harini A. P.G. IInd Year Associate Professor& HOD Department of Dravya Guna SDM College of Ayurveda & Hospital Hassan ANTIHYPERTENSIVE 4

5. What is blood pressure? Regulation of blood pressure Parameters on which blood pressure depends What is Hypertension? Types of Hypertension Classification of Blood Pressure What is Antihypertensive? Classification of Antihypertensive Treatment of Hypertension Antihypertensive models Hypertension in Ayurveda Research updates Discussion Conclusion References Content 5

6. What is Blood Pressure? 6

7. Regulation of Blood Pressure By definition, BP = CO X PVR Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites: arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid . 7

8. Baroreceptor reflex (aortic arch and carotid sinuses ) Contd …. 8

9. Contd … 9

10. Parameters on which blood pressure depends Cardiac output Total Peripheral Resistance Stroke Volume And Heart Rate SYSTOLIC BP DIASTOLIC BP Preload: Preload can be defined as the initial stretching of the cardiac myocytes prior to contraction (EDV) Afterload : Afterload is the load against which the heart has to pump(TPR) 10

11. What is Hypertension? 11

12. HYPERTENSION: Hypertension can be defined as: A sustained rise in blood pressure. It is a condition in which the arteries have persistently high blood pressure, making harder for the heart to pump blood in the vessels. Basically it has 2 main components; the SYSTOLIC and the DIASTOLIC blood pressure. 12

13. What are the types of Hypertension? Types of Hypertension Essential Secondary A disorder of unknown origin affecting the Blood Pressure regulating mechanisms Secondary to other disease processes Environmental Factors Stress Na+ Intake Obesity Smoking 13

14. Classification of Blood Pressure The JNC 7 (2003)- 7 th Report of Joint National Committee(of USA) on prevention, detection, evaluation and treatment of high blood pressure, Classified HTN as follows- BP Classification Systolic BP in mm of Hg Diastolic BP in mm of Hg Normal < 120 < 80 Prehypertension 120- 139 80- 89 Hypertension Stage I 140 -159 90 - 99 Hypertension Stage II ≥ 160 ≥ 100 14

15. What is Antihypertensive? The drugs used in the treatment of hypertension act by reducing the cardiac output and/or reducing the total peripheral resistance, without correcting the cause 15

16. CLASSIFICATION OF ANTIHYPERTENSIVE Drugs 16

17. Antihypertensive Drugs 4. Direct renin inhibitor Aliskiren 2.ACE inhibitors Eg . Captopril, Enalapril , Lisinopril etc. 3. Angiotensin ( AT1 receptor) blockers Eg . Losartan, Candesartan etc. Diuretics Thiazide s : Hydroclorothiazid e , etc High ceiling : Furosemide , etc. Potassium Sparing : Spironolacton e , Amiloride 5 . Calcium channel blockers Verapamil, Diltiazem, Nifedipine , Lacidipine , etc . 6. Beta Adrenergic blockers Propranolol, Metoprolol, Atenolol, etc 17

18. Classification contd …. 7. Beta+ alpha Adrenergic blockers Labetalol, Carvedilol 8. Alpha Adrenergic blockers Prazosin, Terazosin, Doxazosin etc . 9. Cenral Sympatholytics Clonidine, Methyldopa 10. Vasodilators Arteriolar : Hydralazine, Minoxidil , Diazoxide Arteriolar + Venous : Sodium nitroprusside 18

19. MOA: 1- ↑ renal excretion of Na & water ↓ plasma volume ↓ C.O. 2- ↓ peripheral resistance ( desensitize smooth muscles to action of catecholamine) Advantage : Effective in controlling blood pressure in long term. Controls BP in Supine as well as standing positions so postural hypotension doesn’t occur. Disadvantage : Of Thiazides include, hypokalemia, hyperuricemia; Of Loop Diuretics include, Ototoxicity; Of Potassium Sparing group include, Gastric upsets, Gynecomastia in males, Menstrual irregularities in females Diuretics 19

20. Diuretics ….site of action 20

21. ACE Inhibitors MOA : ↓ ang II ↓ vasocostriction ↓ degradation of Bradykinin ( vasodilator) 21

22. Adverse effects of ACE inhibitors C A P T O P R I L Cough (dry Cough) Angioedema Proteinuria Taste changes Hypotension Contraindicated in Pregnancy Rashes Increased K+ Levels Low Ang II and Aldosterone levels 22

23. Angiotensin ( AT1 receptor ) Blockers Specific angiotensin receptors have been discovered, grouped and abbreviated as – AT1 and AT2 They are present on the surface of the target cells Most of the physiological actions of angiotensin are mediated via AT1 receptor Losartan is the specific AT1 blocker Available as 25 and 50 mg tablets 23

24. Upper respiratory infections Headache May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue SIDE EFFEECTS OF ANGIOTENSIN BLOCKER 24

25. Direct Renin Inhibitors Aliskiren the only available member . Acts by blocking catalytic activity of renin and inhibiting production of Ang I and Ang II. Second line antihypertensive when established ACE inhibitors or ARBs cannot be used, or to supplement them. 25

26. Calcium channel blockers 26

27. Calcium channel blocker .. contd … 27

28. Side effects of Calcium channel blockers Calcium Channel Blockers Cardiovascular hypotension, palpitations, tachycardia Gastrointestinal constipation, nausea Other rash, flushing, peripheral edema, dermatitis 28

29. Beta blockers : Selectives : Metoprolol , Atenolol Adverse Effect : Dizziness, Drowsiness, Fatigue, Diarrhea Non- Selectives : Propranolol Adverse Effect : Drowsiness, Sedation, Asthma β Adrenergic Blockers 29

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31. Mixed blockers Acting on Alpha as well as on Beta receptors. Labetolol , Carvidolol , Bucindolol Adverse Effects: Drowsiness, Fatigue, Insomnia, Orthostatic Hypotension 31

32. Alpha Adrenergic blockers Selectives : Prazosine , terazosin Adverse Effect: Orthostatic Hypotension Non- Selectives : Phenoxybenzamine , Phentolamine Adverse Effect: Tachycardia, Palpitation Advantages- improvement in carbohydrate metabolism, lowers LDL, increases HDL Dose- available as 0.5, 1, 2.5 and 5 mg. 1-4 mg TDS 32

33. Central Sympatholytics 33

34. Directly relaxes arteriolar smooth muscle Result: decreased systemic vascular response, decreased afterload , and PERIPHERAL VASODILATION Eg .- Hydralazine ( Hypertension in Pregnancy, Dose 25-50 mg OD) , Minoxidil , Sodium nitroprusside Adverse effects- Hydralazine- Dizziness, Dyspnoea , oedema etc. Sodium nitroprusside - Bradycardia Vasodilators 34

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36. Treatment of Hypertension 36

37. In the past, most studies on experimental hypertension were carried out on Dogs. Currently, rat is the preferred animal species Spontaneous hypertensive rat (SHR), the genetic strain of hypertensive rat, is the animal of choice Antihypertensive Screening Model 37

38. 1.Renovascular hypertension 2. Dietary hypertension 3. Endocrine hypertension 4. Neurogenic hypertension 5. Psychogenic hypertension 6. Genetic hypertension 7. Other models Types of animal models of hypertension 38

39. GOLDBlAtT HYPERTENSION Ischemia of kidney Blood pressure RENIN ANGIOTENSIN MECHANISM Clamping of Renal artery for 4 hours and reopening Accumulated Renin is released ACUTE HYPERTENSION RENOVASCULAR MODEL… 39

40. Sprague – Dawley Rats (300gm) are anesthetized ĉ Hexobarbital sodium (100mg/kg) Intra peritonially . Cannulate the trachea for respiration and the Jugular vein for test compound administration. A transducer is connected to the carotid artery for recording the pressure. A PVC coated clip is placed in the left hilum of the kidney by fixing with the back muscle for 3.5 - 4hr. Pentolinium is administered for ganglionic block. Relaese the clip and record the rise in B.P. Administer the test drug through I.V. and monitor the pressure continuously. Increase in B.P after releasing the clip and reduction after the drug administration is determined. Compare using percentage values Contd ….( 2Kidney 1 clip method) 40

41. CHRONIC RENAL HYPERTENSION (1 Kidney- I -Clip Method) -Sprague – Dawley Rats (200 - 300gm) are anesthetized ĉ - Phenobarbitone sodium (100mg/kg) Intra peritonially . -A flank parallel incision is made in the left lumbar area. -Renal artery is dissected, cleaned and ‘U’ shaped silver clip is slipped around near the aorta. -The internal gap b/w the clip is adjusted to 0.25 – 0.38 nm. -The right kidney is removed after tying off the renal pedicel. -After 4-5 weeks the B.P is measured and the animals are divided into groups of different doses. -Test drug is administered for 3 days -Pressure before and after drug administration(3min) are recorded. -Percent reduction in pressure is calculated and compare to the Std. 41

42. AYUREDIC CONCEPT ABOUT HYPERTENSION AND ANTIHYPERTENSIVE 42

43. Hypertension in Ayurveda may fall under Pittavruta udana (Su.S.Ni.1/35) Raktagata vata ( Ch.Chi . 28/31), Pittavruta vata , Raktavruta vata , Pranavruta udana , Rakta vega vridhi , Rasa bhara , Rakta Samvardhana , Vyanabala , Uccharaktachapa , Siragata vata , Bhrama (Ch.su.20/10.Ma.Ni.17/1), Raktamada ( Ch.su . 24/34), Moorcha (Ma.Ni.17), Sanyasa , Dhamanipratichaya , Raktabhara Vridhi etc Hypertension in Ayurveda 43

44. RESEARCH UPDATES ABOUT ANTIHYPERTENSIVE HERBS 44

45. Name of the Journal- Pharmacogn.Rev . 2011Jan-June; 5(9): 30-40 Name of the Authors- Nahida Tabassum and Feroz Ahmad Total 49 plants are reviewed for Antihypertensive effect by experimental, Clinical and Phytochemical evaluations Role of natural herbs in the treatment of hypertension 45

46. Agathosma betulina   Cassia occidentalis   Hibiscus sabdariffa  Pueraria lobata   Allium sativum Castanospermum australe Lavandula stoechas   Punica granatum Annona muricata Coleus forskohlii   Lepidium latifolium   Raphanus sativus   Apium graveolens Commelina virginica   Linum usitatissimum   Rauwolfia serpentina   Aristolochia manshuriensis Crataegus pinnatifida   Lumnitzera racemosa   Rhaptopetalum coriaceum oliver   Artocarpus altilis Crinum glaucum   Lycopersicon esculentum Sesamum indicum   Avena sativa Cuscuta reflexa   Moringa oleifera   Solanum sisymbriifolium Blond psyllium Daucus carota   Musanga cecropiodes Theobroma cacao Camellia sinensis Desmodium styracifolium   Ocimum basilicum Triticum aestivum Capparis cartilaginea Fuchsia magellanica   Peganum harmala   Uncaria rhynchophylla   Carum copticum Glycine max   Phyllanthus amarus   Viscum album   Cassia absus   Gossypium barbadense   Pinus pinaster   Vitex doniana Contd … Zingiber officinale 46

47. Annona muricata Hindi name – Lakshman phala Family- Annonaceae Parts used – fruit, leaves, bark The leaf extract of the plant has been reported to lower an elevated BP by decreasing the peripheral vascular resistance. 2. Apium graveolens   Family : Apiaceae Sanskrit name- Ajmoda Parts used - Fruit The juice was mixed with equal amount of honey and about 8 ounces were taken orally three times each day for up to one week. It has also been reported to reduce systolic and diastolic BP. Antihypertensive herbs 47

48. 3. Cassia occidentalis Family- Caesalpiniaceae Sanskrit name- Kasmarda Parts used- Seeds, Panchanga   In vitro  studies of the leaf extract have  shown a relaxant effect on the aortic rings. The studies revealed that cassia extract may be relaxing smooth muscle and reducing BP by inhibiting Ca 2+  influx through receptor-operated channel and voltage-sensitive channel, showing its nonselectivity on these Ca 2+  channels. 4 . Cuscuta reflexa Family- Cuscutaceae Sanskrit name- Amarvela Parts used- whole plant Crude extract of  C. reflexa  has been reported to cause a decrease in systolic and diastolic BP as well as HR in anesthetized rats. Contd …. 48

49. 5. Moringa oleifera Family- Moringaceae Sanskrit name- Shigru Parts used- Leaves, Fruit, Root In anesthetized rats, the crude extract of the leaves of  M. oleifera  caused a fall in systolic, diastolic, and mean BP in a dose-dependent manner. 6. Phyllanthus amarus Family- Euphorbiaceae Sanskrit name- Bhoomi Aamalki Parts used- whole plant intravenous administration of the aqueous extract of the leaves of this plant (5-80 mg/kg) to anesthetized NMT male rabbits produced a significant fall in mean diastolic, systolic, and mean arterial pressures in a graded dose-response manner. Contd … 49

50. Name of the Journal- World journal of Pharmaceutical research, Vol.3(8): 769- 777 Name of Authors- V.Velpandian *, N.Anbu , S.Elangovan , M. Mohamed Musthafa Conclusion- Drug- Sadamanjil Chooranam ( Nardostachys jatamansi ) Dose - 500mg and 1000mg/kg body weight Route- Oral Method of screening- 2 kidney 1 clipped, Gold Blatt occlusion method Result - statistically significant decrease in systolic and diastolic blood pressure in renovascular hypertensive rat through the action on renin angiotensin system. ANTIHYPERTENSIVE ACTIVITY OF Nardostachys jatamansi IN HYPERTNSIVE RATS FOLLOWING RENAL GOLD BLATT OCCLUSION METHOD 50

51. DISSCUSSION - The prevalence of Hypertension(HTN) is growing on day by day. - Both Primary and Secondary HTNs are directly or indirectly related with food habit, sedentary life styles and consumption of various drugs. - The antihypertensive drugs are classified according to their site of action, their target receptors and their mode of actions. - Older drugs for Hypertension are outdated due to their various adverse effects and newer are going on to be incorporating in treatment schedule. 51

52. Contd … - All types of antihypertensive drugs are only able to do symptomatic decrease in blood pressure. They are not able to treat the real cause of Hypertension. - Hypertension can be correlated with various Vata and Raktagata vyadhi but the exact terminology is not dealt in classical Ayurvedic texts. - There are various herbs which are proven as safe and better antihypertensive and search for new one should be done on the basis of scientifically proven and widely accepted Screening models of Antihypertensive . 52

53. Hypertension is becoming a global burden and the world is looking towards natural remedies system like Ayurveda , even though there are various antihypertensive drugs in contemporary system of medicine. So it is a high time to adopt proper screening model of antihypertensive and search for best solution from herbs for HTN. CONCLUSION 53

54. Tripathi . KD, Essential of Medical Pharmacology Nahida Tabassum and Feroz Ahmad, Pharmacogn.Rev . 2011Jan-June; 5(9): 30-40 Dr.G.H.ANANTHASAYANA , MANAGEMENT OF ESSENTIAL HYPERTENSION IN AYURVEDIC PERSPECTIVES, ( Desertation work submitted to RGUHS) D.K. BADYAL, H. LATA*, A.P. DADHICH, Indian Journal of Pharmacology 2003; 35: 349-362 V.Velpandian *, N.Anbu , S.Elangovan , M. Mohamed Musthafa , wjpr , Vol.3(8): 769- 777 www.google searh.net. REFERENCES 54

55. THANK YOU 55