1. Hypertension is defined as systolic blood pressure (SBP) of 140 mmHg or greater, diastolic blood pressure (DBP) of 90 mmHg or greater, or taking antihypertensive medication. VI JNC, 1997

2. Types of hypertension Essential hypertension  90%  No underlying cause Secondary hypertension  Underlying cause

3. Causes of Secondary Hypertension Renal  Parenchymal  Vascular  Others Endocrine Neurogenic Miscellaneous Unknown

4. Hypertension: Predisposing factors Age > 60 years Sex (men and postmenopausal women) Family history of cardiovascular disease Smoking High cholesterol diet Co-existing disorders such as diabetes, obesity and hyperlipidaemia High intake of alcohol Sedentary life style

5. 1999 WHO-ISH Guidelines : Definitions and Classifications of BP Levels SBPDBP Category*(mm Hg)(mm Hg) Optimal< 120< 80 Normal< 130< 85 High-normal130-13985-89 Grade 1 hypertension (mild)140-15990-99 Borderline subgroup140-14990-94 Grade 2 hypertension (moderate)160-179100-109 Grade 3 hypertension (severe)> 180> 110 ISH> 140< 90 Borderline subgroup140-149< 90 WHO-ISH Guidelines Subcommittee J Hypertens 1999; 17:151

6. 1999 WHO-ISH Guidelines: Stratification of risk to Quantify Prognosis Degree of hypertension (mm Hg) Risk factors andGrade 1-mildGrade 2-moderateGrade3-severe disease history(SBP 140-159(SBP 160-179(SBP > 180 or DBP 90-99)or DBP 100-109)or DBP > 110) INo other riskLow riskMed riskHigh risk factors II1-2 risk factorsMed riskMed riskVery high risk III> 3 risk factors orHigh riskhigh riskVery high risk target organ disease or diabetes IVAssociatedVery high riskVery high riskVery high risk Clinical conditions WHO-ISH Guidelines Subcommittee J Hypertens 1999;17:151

7. Diseases Attributable to Hypertension HYPERTENSION Gangrene of the Lower Extremities Heart Failure Left Ventricular Hypertrophy Myocardial Infarction Hypertensive Encephalopathy Aortic Aneurym Blindness Chronic Kidney Failure Stroke Preeclampsia/ Eclampsia Cerebral Hemorrhage Coronary Heart Disease Adapted from Dustan HP et al. Arch Intern Med. 1996; 156: 1926-1935

8. 1999 WHO-ISH Guidelines: Desirable BP Treatment Goals Optimal or normal BP (< 130/85 mm Hg) for  Young patients  Middle-age patients  Diabetic patients High-normal BP (< 140/90 mm Hg) desirable for elderly patients Aggressive BP lowering may be necessary in patients with nephropathy, chronic renal failure, particularly if proteinuria is  < 1 g/d - 130/80 mm Hg  > 1 g/d - 125/75 mm Hg

9. Significant benefits from intensive BP reduction in diabetic patients Major CV events / 100 patient-yr Lancet 1998, 351, 1755

10. Relative risks of specific types of clinical complications related to tight and less tight BP Control Patients with Absolute risk aggregate (events/1000 and points patients-yr) TightLess tightLessRR for controlcontrolTighttighttight control Clinical end point(n=758)(n=390)controlcontrolp(95% Cl) Any diabetes-related25917050.967.40.00460.76 (0.62-0.92) end point Deaths related to826213.720.30.0190.68 (0.49-0.94) diabetes All cause mortality1348322.427.20.170.82 (0.63-1.08) Myocardial infarction1076918.623.50.130.79 (0.59-1.07) Stroke38346.511.60.0130.56 (0.35-0.89) Peripheral vascular881.42.70.170.51 (0.19-1.37) disease Microvascular disease685412.019.20.0092063 (0.44-0.89) Ref : UK Prospective Diabetes Study Group BMJ 1998; 317:703

11. Life style modifications Lose weight, if overweight Limit alcohol intake Increase physical activity Reduce salt intake Stop smoking Limit intake of foods rich in fats and cholesterol

12. Factors affecting choice of antihypertensive drug The cardiovascular risk profile of the patient Coexisting disorders Target organ damage Interactions with other drugs used for concomitant conditions Tolerability of the drug Cost of the drug

13. Drug therapy for hypertension Class of drugExampleInitiating doseUsual maintenance dose DiureticsHydrochlorothiazide 12.5 mg o.d.12.5-25 mg o.d.  -blockersAtenolol 25-50 mg o.d.50-100 mg o.d. CalciumAmlodipine2.5-5 mg o.d.5-10 mg o.d. channel blockers  -blockersDoxazosin1 mg o.d.1-8 mg o.d. ACE- inhibitors Lisinopril2.5-5 mg o.d.5-20 mg o.d. Angiotensin-IILosartan25-50 mg o.d.50-100 mg o.d. receptor blockers

14. Diuretics Example: Hydrochlorothiazide Act by decreasing blood volume and cardiac output Decrease peripheral resistance during chronic therapy Drugs of choice in elderly hypertensives Drawbacks Hypokalaemia Hyponatraemia Hyperlipidaemia Hyperuricaemia (hence contraindicated in gout) Hyperglycaemia (hence not safe in diabetes) Not safe in renal and hepatic insufficiency

15. Beta blockers Example: Atenolol Block  1 receptors on the heart Block  2 receptors on kidney and inhibit release of renin Decrease rate and force of contraction and thus reduce cardiac output Drugs of choice in patients with co-existent coronary heart disease Drawbacks Adverse effects: lethargy, impotency, bradycardia Not safe in patients with co-existing asthma and diabetes Have an adverse effect on the lipid profile

16. Calcium channel blockers Example: Amlodipine Block entry of calcium through calcium channels Cause vasodilation and reduce peripheral resistance Drugs of choice in elderly hypertensives and those with co-existing asthma Neutral effect on glucose and lipid levels Drawbacks Adverse effects: Flushing, headache, Pedal edema

17. ACE inhibitors Example: Lisinopril, Enalapril Inhibit ACE and formation of angiotensin II and block its effects Drugs of choice in co-existent diabetes mellitus Drawbacks Adverse effect: dry cough, hypotension, angioedema

18. Angiotensin II receptor blockers Example: Losartan Block the angiotensin II receptor and inhibit effects of angiotensin II Drugs of choice in patients with co-existing diabetes mellitus Drawbacks Adverse effect: dry cough, hypotension, angioedema

19. Alpha blockers Example: Doxazosin Block  -1 receptors and cause vasodilation Reduce peripheral resistance and venous return Exert beneficial effects on lipids and insulin sensitivity Drugs of choice in patients with co-existing hyperlipidaemia, diabetes mellitus and BPH Drawbacks Adverse effects: Postural hypotension

20. Antihypertensive therapy: Side-effects and Contraindications Class of drugsMain side-effectsContraindications/ Special Precautions DiureticsElectrolyte imbalance,Hypersensitivity, Anuria (e.g. Hydrochloro-  total and LDL cholesterol thiazide) levels,  HDL cholesterol levels,  glucose levels,  uric acid levels  -blockersImpotence, Bradycardia,Hypersensitivity, (e.g. Atenolol)FatigueBradycardia, Conduction disturbances, Diabetes, Asthma, Severe cardiac failure

21. Class of drugMain side-effectsContraindications/ Special Precautions Calcium channel blockersPedal edema, HeadacheNon-dihydropyridine (e.g. Amlodipine,CCBs (e.g diltiazem)– Diltiazem)Hypersensitivity, Bradycardia, Conduction disturbances, Congestive heart failure, Left ventricular dysfunction. Dihydropyridine CCBs– Hypersensitivity  -blockersPostural hypotensionHypersensitivity (e.g. Doxazosin) ACE-inhibitorsCough, Hypertension,Hypersensitivity, Pregnancy, (e.g. Lisinopril)Angioneurotic edemaBilateral renal artery stenosis Angiotensin-II receptorHeadache, DizzinessHypersensitivity, Pregnancy, blockers (e.g. Losartan)Bilateral renal artery stenosis Antihypertensive therapy: Side-effects and Contraindications (Contd.)

22. Choosing the right antihypertensive ConditionPreferred drugsOther drugsDrugs to be that can be usedavoided AsthmaCalcium channel  -blockers/Angiotensin-II  -blockers blockersreceptor blockers/Diuretics/ ACE-inhibitors Diabetes  -blockers/ACECalcium channel blockersDiuretics/ mellitusinhibitors/  -blockers Angiotensin-II receptor blockers High cholesterol  -blockersACE inhibitors/ Angiotensin-II  -blockers/ levelsreceptor blockers/ CalciumDiuretics channel blockers Elderly patientsCalcium channel  -blockers/ACE- (above 60 years)blockers/Diuretics inhibitors/Angiotensin-II receptor blockers/  - blockers BPH  -blockers  -blockers/ ACE inhibitors/ Angiotensin-II receptor blockers/ Diuretics/ Calcium channel blockers

23. Limitations on use of antihypertensives in patients with coexisting disorders CoexistingDiuretic  -blockerACEAllCCB   -blocker Disorderinhibitorantagonist DiabetesCaution/xCaution/x     Dyslipidaemiaxx     CHD       Heart failure  3/Caution   Caution  Asthma/COPD  x  /Caution    Peripheral  CautionCautionCaution   vascular disease Renal artery   xx   stenosis

24. Effect of various antihypertensives on coexisting disorders TotalLDL-HDL-SerumGlucoseInsulin cholesterolcholesterolcholesteroltriglyceridestolerancesensitivity Diuretic   -blockers-  -- ACE inhibitors----  All antagonists----  CCBs------  -blockers 

25. Combination therapy for hypertension – Recommended by JNC-VI guidelines and 1999 WHO-ISH guidelines With any single drug, not more than 25–50% of hypertensives achieve adequate blood pressure control J Hum. Hypertens 1995; 9:S33–S36 For patients not responding adequately to low doses of monotherapy Increase the dose of drug. This, however, may lead to increased side effects Substitute with another drug from a different class Add a second drug from a different class (Combination therapy) Add second drug from different class (Combination therapy) If inadequate response obtained

26. Advantages of fixed-dose combination therapy Better blood pressure control Lesser incidence of individual drug’s side-effects Neutralisation of side-effects Increased patient compliance Lesser cost of therapy

27. Fixed-dose combinations as recommended by JNC-VI (1997) guidelines and 1999 WHO-ISH guidelines Calcium channel blocker and  -blocker (e.g. Amlodipine and Atenolol) Calcium channel blocker and ACE-inhibitor (e.g. Amlodipine and Lisinopril) ACE-inhibitor and Diuretic (e.g. Lisinopril and Hydrochlorothiazide)  -blocker and Diuretic (e.g. Atenolol and Hydrochlorothiazide)

28. Blood Pressure (mm Hg) Reduces BP effectively Safe and well tolerated  Adverse events were reported in 7.9% of patients  Common side effects included edema, fatigue and headache Indian Practitioner 1997; 50: 683-688. % responders 175.4+ 19.4 143.8 + 13.2 106.8 + 10.5 88.2 + 7.6 80.5% Efficacy and Tolerability of a fixed-dose combination of amlodipine and atenolol (Amlopres-AT) in Indian Hypertensives (n=369)

29. Efficacy and Tolerability of combined amlodipine and lisinopril (Amlopres-L) in Indian hypertensives (n=330) Blood Pressure (mm Hg) Reduces BP effectively Safe and well tolerated  Adverse events were reported in 9.7% of patients  Side effects commonly reported included cough and edema  Only 1.76% of patients withdrew from the study. Indian Practitioner 1998; 51: 441-447. % responders 175.4+ 19.4 143.8 + 13.2 106.8 + 10.5 88.2 + 7.6 77.65

30. Drugs in special conditions Condition Pregnancy Coronary heart disease Congestive heart failure Preferred Drugs Nifedipine, labetalol, hydralazine, beta-blockers, methyldopa, prazosin Beta-blockers, ACE inhibitors, Calcium channel blockers ACE inhibitors, beta-blockers 1999 WHO-ISH guidelines

31. Summary Hypertension is a major cause of morbidity and mortality, and needs to be treated It is an extremely common condition; however it is still underdiagnosed and undertreated Hypertension is not controlled with monotherapy in at least 50% of patients; in these patients combination therapy is required