Anti hypertensive

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??BRAIN

STROKE

HEART FAILURE

,Coronary

Heart Disease

RETINOPATHY

RENAL FAILUR

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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%.

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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

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1. What is blood pressure?2. Regulation of blood pressure3. Parameters on which blood pressure depends4. What is Hypertension?5. Types of Hypertension6. Classification of Blood Pressure7. What is Antihypertensive?8. Classification of Antihypertensive9. Treatment of Hypertension10. Antihypertensive models11. Hypertension in Ayurveda12. Research updates13. Discussion14. Conclusion15. References

Content

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What is Blood Pressure?

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Regulation of Blood PressureBy 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.

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

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Contd…

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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)

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What is Hypertension?

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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.

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What are the types of Hypertension?

Types ofHypertension

Essential Secondary

A disorder of unknown origin affecting theBlood Pressure regulating mechanisms Secondary to other disease processes

Environmental Factors

Stress Na+ Intake Obesity Smoking

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Classification of Blood PressureThe JNC 7 (2003)- 7th 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 HgDiastolic BP in mm of Hg

Normal < 120 < 80Prehypertension 120- 139 80- 89Hypertension Stage I 140 -159 90 - 99Hypertension Stage II ≥ 160 ≥ 100

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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

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CLASSIFICATION OF ANTIHYPERTENSIVE Drugs

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Antihypertensive Drugs

4. Direct renin inhibitor

Aliskiren

2.ACE inhibitorsEg. Captopril, Enalapril, Lisinopril etc.

3. Angiotensin ( AT1 receptor) blockersEg. Losartan, Candesartan etc.

1. DiureticsThiazides:

Hydroclorothiazide, etc

High ceiling: Furosemide, etc.

Potassium Sparing: Spironolactone, Amiloride

5. Calcium channel blockers

Verapamil, Diltiazem, Nifedipine, Lacidipine, etc.

6. Beta Adrenergic blockers Propranolol, Metoprolol, Atenolol, etc

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Classification contd….

7. Beta+ alpha Adrenergic blockers

Labetalol, Carvedilol

8. Alpha Adrenergic blockersPrazosin, Terazosin, Doxazosin etc.

9. Cenral SympatholyticsClonidine, Methyldopa

10. VasodilatorsArteriolar : Hydralazine, Minoxidil, DiazoxideArteriolar + Venous : Sodium nitroprusside

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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

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Diuretics ….site of action

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ACE InhibitorsMOA: ↓ ang II ↓ vasocostriction ↓ degradation of Bradykinin ( vasodilator)

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Adverse effects of ACE inhibitors

C APTOP R IL

Cough (dry Cough)AngioedemaProteinuriaTaste changesHypotensionContraindicated in PregnancyRashesIncreased K+ LevelsLow Ang II and Aldosterone levels

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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

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Upper respiratory infections Headache May cause occasional dizziness, inability

to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue

SIDE EFFEECTS OF ANGIOTENSIN BLOCKER

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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.

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Calcium channel blockers

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Calcium channel blocker ..contd…

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Side effects of Calcium channel blockersCalcium Channel Blockers Cardiovascular

◦ hypotension, palpitations, tachycardia

Gastrointestinal◦ constipation, nausea

Other◦ rash, flushing, peripheral edema, dermatitis

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Beta blockers :Selectives: Metoprolol, AtenololAdverse Effect: Dizziness, Drowsiness, Fatigue, DiarrheaNon-Selectives: PropranololAdverse Effect: Drowsiness, Sedation, Asthma

βAdrenergic Blockers

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Mixed blockersActing on Alpha as well as on Beta receptors.

Labetolol, Carvidolol, BucindololAdverse Effects: Drowsiness, Fatigue, Insomnia, Orthostatic Hypotension

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Alpha Adrenergic blockersSelectives: Prazosine, terazosin

Adverse Effect: Orthostatic Hypotension

Non-Selectives: Phenoxybenzamine, Phentolamine

Adverse Effect: Tachycardia, PalpitationAdvantages- improvement in carbohydrate

metabolism, lowers LDL, increases HDLDose- available as 0.5, 1, 2.5 and 5 mg. 1-4

mg TDS

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Central Sympatholytics

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Directly relaxes arteriolar smooth muscle Result: decreased systemic vascular response,

decreased afterload, andPERIPHERAL 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

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Treatment of Hypertension

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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

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1.Renovascular hypertension2. Dietary hypertension3. Endocrine hypertension4. Neurogenic hypertension5. Psychogenic hypertension6. Genetic hypertension7. Other models

Types of animal models of hypertension

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GOLDBlAtT HYPERTENSIONIschemia of kidney Blood pressure

RENIN ANGIOTENSIN MECHANISM

Clamping of Renal artery for 4 hours and reopening

Accumulated Renin is released

ACUTE HYPERTENSION

RENOVASCULAR MODEL…

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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)

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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.

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AYUREDIC CONCEPT ABOUT HYPERTENSION AND ANTIHYPERTENSIVE

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Hypertension in Ayurveda may fall underPittavruta 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

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RESEARCH UPDATES ABOUT ANTIHYPERTENSIVE HERBS

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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

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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

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1. Annona muricataHindi name – Lakshman phalaFamily- AnnonaceaeParts used – fruit, leaves, barkThe leaf extract of the plant has been reported to lower an elevated BP by decreasing the peripheral vascular resistance.2. Apium graveolens Family: ApiaceaeSanskrit name- AjmodaParts used - FruitThe 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

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3. Cassia occidentalisFamily- CaesalpiniaceaeSanskrit name- KasmardaParts 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 Ca2+ influx through receptor-operated channel and voltage-sensitive channel, showing its nonselectivity on these Ca2+ channels.

4. Cuscuta reflexaFamily- Cuscutaceae Sanskrit name- AmarvelaParts 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….

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5. Moringa oleifera Family- MoringaceaeSanskrit name- ShigruParts 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 amarusFamily- EuphorbiaceaeSanskrit name- Bhoomi AamalkiParts used- whole plantintravenous 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…

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Name of the Journal- World journal of Pharmaceutical research, Vol.3(8): 769- 777Name of Authors- V.Velpandian*, N.Anbu, S.Elangovan, M.

Mohamed MusthafaConclusion- 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 INHYPERTNSIVE RATS FOLLOWING RENAL GOLD BLATTOCCLUSION METHOD

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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.

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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.

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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

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1. Tripathi. KD, Essential of Medical Pharmacology

2. Nahida Tabassum and Feroz Ahmad, Pharmacogn.Rev. 2011Jan-June; 5(9): 30-40

3. Dr.G.H.ANANTHASAYANA, MANAGEMENT OF ESSENTIAL HYPERTENSION IN AYURVEDIC PERSPECTIVES, ( Desertation work submitted to RGUHS)

4. D.K. BADYAL, H. LATA*, A.P. DADHICH, Indian Journal of Pharmacology 2003; 35: 349-362

5. V.Velpandian*, N.Anbu, S.Elangovan, M. Mohamed Musthafa, wjpr, Vol.3(8): 769- 777

6. www.google searh.net.

REFERENCES

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