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 Secondary 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
SBP DBP
Category* (mm Hg) (mm Hg)
Optimal < 120 < 80
Normal < 130 < 85
High-normal
Grade 1 hypertension (mild)
Borderline subgroup
Grade 2 hypertension (moderate)
Grade 3 hypertension (severe) > 180 > 110
ISH > 140 < 90
Borderline subgroup < 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 and Grade 1-mild Grade 2-moderate Grade3-severe
disease history (SBP (SBP (SBP > 180
or DBP 90-99) or DBP ) or DBP > 110)
I No other risk Low risk Med risk High risk
factors
II 1-2 risk factors Med risk Med risk Very high risk
III > 3 risk factors or High risk high risk Very high risk
target organ disease
or diabetes
IV Associated Very high risk Very high risk Very high risk
Clinical conditions
WHO-ISH Guidelines Subcommittee J Hypertens 1999;17:151

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

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)
Tight Less tight Less RR for
control control Tight tight tight control
Clinical end point (n=758) (n=390) control control p (95% Cl)
Any diabetes-related ( )
end point
Deaths related to ( )
diabetes
All cause mortality ( )
Myocardial infarction ( )
Stroke ( )
Peripheral vascular ( )
disease
Microvascular disease ( )
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 drug Example Initiating dose Usual maintenance dose
Diuretics Hydrochlorothiazide mg o.d mg o.d.
-blockers Atenolol mg o.d mg o.d.
Calcium Amlodipine mg o.d mg o.d.
channel
blockers
-blockers Doxazosin 1 mg o.d. 1-8 mg o.d.
ACE- inhibitors Lisinopril mg o.d mg o.d.
Angiotensin-II Losartan mg o.d 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 b1 receptors on the heart
Block b2 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 a-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 drugs Main side-effects Contraindications/ Special Precautions
Diuretics Electrolyte imbalance, Hypersensitivity, Anuria (e.g. Hydrochloro- ­ total and LDL cholesterol thiazide) levels, ¯ HDL cholesterol
levels, ­ glucose levels, ­ uric acid levels
b-blockers Impotence, Bradycardia, Hypersensitivity, (e.g. Atenolol) Fatigue Bradycardia, Conduction disturbances, Diabetes, Asthma, Severe cardiac failure

21. Antihypertensive therapy: Side-effects and Contraindications (Contd.)
Class of drug Main side-effects Contraindications/ Special
Precautions
Calcium channel blockers Pedal edema, Headache Non-dihydropyridine (e.g. Amlodipine, CCBs (e.g diltiazem)– Diltiazem) Hypersensitivity, Bradycardia, Conduction disturbances, Congestive heart failure, Left ventricular dysfunction.
Dihydropyridine CCBs– Hypersensitivity
a-blockers Postural hypotension Hypersensitivity (e.g. Doxazosin)
ACE-inhibitors Cough, Hypertension, Hypersensitivity, Pregnancy, (e.g. Lisinopril) Angioneurotic edema Bilateral renal artery stenosis
Angiotensin-II receptor Headache, Dizziness Hypersensitivity, Pregnancy, blockers (e.g. Losartan) Bilateral renal artery stenosis

22. Choosing the right antihypertensive
Condition Preferred drugs Other drugs Drugs to be that can be used avoided
Asthma Calcium channel a-blockers/Angiotensin-II b-blockers blockers receptor blockers/Diuretics/ ACE-inhibitors
Diabetes a-blockers/ACE Calcium channel blockers Diuretics/ mellitus inhibitors/ b-blockers Angiotensin-II receptor blockers
High cholesterol a-blockers ACE inhibitors/ Angiotensin-II b-blockers/ levels receptor blockers/ Calcium Diuretics channel blockers
Elderly patients Calcium channel -blockers/ACE- (above 60 years) blockers/Diuretics inhibitors/Angiotensin-II
receptor blockers/- blockers
BPH a-blockers b-blockers/ ACE inhibitors/
Angiotensin-II receptor
blockers/ Diuretics/
Calcium channel blockers

23. Limitations on use of antihypertensives in patients with coexisting disorders
Coexisting Diuretic b-blocker ACE All CCB a1-blocker Disorder inhibitor antagonist
Diabetes Caution/x Caution/x    
Dyslipidaemia x x    
CHD      
Heart failure  3/Caution   Caution 
Asthma/COPD  x  /Caution   
Peripheral  Caution Caution Caution   vascular disease
Renal artery   x x   stenosis

24. Effect of various antihypertensives on coexisting disorders
Total LDL- HDL- Serum Glucose Insulin cholesterol cholesterol cholesterol triglycerides tolerance sensitivity
Diuretic ­ ­ ¯ ­­ ¯ ¯
b-blockers - ­ ¯¯ ­­­ - -
ACE inhibitors ­ ­
All antagonists ­ ­
CCBs
a-blockers ¯ ¯ ­ ¯ ­ ­

25. (Combination therapy)
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)
If inadequate response obtained
Add second drug from different class (Combination therapy)

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 b-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)
b-blocker and Diuretic (e.g. Atenolol and Hydrochlorothiazide)

28. Reduces BP effectively
Efficacy and Tolerability of a fixed-dose combination of amlodipine and atenolol (Amlopres-AT) in Indian Hypertensives (n=369)
Reduces BP effectively
80.5%
Blood Pressure (mm Hg)
% responders
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:

29. Reduces BP effectively
Efficacy and Tolerability of combined amlodipine and lisinopril (Amlopres-L) in Indian hypertensives (n=330)
Reduces BP effectively
77.65
Blood Pressure (mm Hg)
% responders
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:

30. Drugs in special conditions
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