Hypertension is defined as systolic blood pressure SBP of 140 mmHg or greater, diastolic blood press

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• Hypertension is defined as systolic blood
  pressure (SBP) of 140 mmHg or greater, diastolic
  blood pressure (DBP) of90 mmHg or greater, or
  taking antihypertensive medication.
• VI JNC, 1997

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Types of hypertension

• Essential hypertension
• 90
• No underlying cause
• Secondary hypertension
• Underlying cause

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Causes of Secondary Hypertension

• Renal
• Parenchymal
• Vascular
• Others
• Endocrine
• Neurogenic
• Miscellaneous
• Unknown

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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

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1999 WHO-ISH Guidelines Definitions and
Classifications of BP Levels

• SBP DBP
• Category (mm Hg) (mm Hg)
• Optimal
• Normal
• High-normal 130-139 85-89
• Grade 1 hypertension (mild) 140-159 90-99
• Borderline subgroup 140-149 90-94
• Grade 2 hypertension (moderate) 160-179 100-109
• Grade 3 hypertension (severe) 180 110
• ISH 140
• Borderline subgroup 140-149
• WHO-ISH Guidelines Subcommittee J Hypertens 1999
  17151

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1999 WHO-ISH GuidelinesStratification of risk
to Quantify Prognosis

• Degree of hypertension (mm Hg)
• Risk factors and Grade 1-mild Grade
  2-moderate Grade3-severe
• disease history (SBP 140-159 (SBP 160-179 (SBP
  180
• or DBP 90-99) or DBP 100-109) 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
  199917151

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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
Preeclampsia/Eclampsia
Stroke
Adapted from Dustan HP et al. Arch Intern Med.
1996 156 1926-1935
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1999 WHO-ISH Guidelines Desirable BP Treatment
Goals

• Optimal or normal BP (
• Young patients
• Middle-age patients
• Diabetic patients
• High-normal BP (elderly patients
• Aggressive BP lowering may be necessary in
  patients with nephropathy, chronic renal failure,
  particularly if proteinuria is
• 1 g/d - 125/75 mm Hg

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Significant benefits from intensive BP
reductionin diabetic patients
Major CV events / 100 patient-yr
Lancet 1998, 351, 1755
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Relative risks of specific types of clinical
complicationsrelated 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 (n758) (n390) control control
  p (95 Cl)
• Any diabetes-related 259 170 50.9 67.4 0.0046 0.76
  (0.62-0.92)
• end point
• Deaths related to 82 62 13.7 20.3 0.019 0.68
  (0.49-0.94)
• diabetes
• All cause mortality 134 83 22.4 27.2 0.17 0.82
  (0.63-1.08)
• Myocardial infarction 107 69 18.6 23.5 0.13 0.79
  (0.59-1.07)
• Stroke 38 34 6.5 11.6 0.013 0.56 (0.35-0.89)
• Peripheral vascular 8 8 1.4 2.7 0.17 0.51
  (0.19-1.37)
• disease
• Microvascular disease 68 54 12.0 19.2 0.0092 063
  (0.44-0.89)
• Ref UK Prospective Diabetes Study Group BMJ
  1998 317703

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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

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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

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Drug therapy for hypertension

• Class of drug Example Initiating
  dose Usual maintenance dose
• Diuretics Hydrochlorothiazide 12.5 mg
  o.d. 12.5-25 mg o.d.
• ?-blockers Atenolol 25-50 mg o.d. 50-100 mg o.d.
• Calcium Amlodipine 2.5-5 mg o.d. 5-10 mg o.d.
• channel
• blockers
• ?-blockers Doxazosin 1 mg o.d. 1-8 mg o.d.
• ACE- inhibitors Lisinopril 2.5-5 mg o.d. 5-20 mg
  o.d.
• Angiotensin-II Losartan 25-50 mg o.d. 50-100 mg
  o.d.
• receptor blockers

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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

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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

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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

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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

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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

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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

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Antihypertensive therapySide-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, Hypersensitivit
  y, (e.g. Atenolol) Fatigue Bradycardia,
  Conduction disturbances, Diabetes, Asthma,
  Severe cardiac failure

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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, Hypersensitivi
  ty, 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

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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-blocke
  rs 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/Diur
  etics inhibitors/Angiotensin-II
• receptor blockers/?- blockers
• BPH a-blockers b-blockers/ ACE inhibitors/
• Angiotensin-II receptor
• blockers/ Diuretics/
• Calcium channel blockers

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Limitations on use of antihypertensives in
patientswith coexisting disorders

• Coexisting Diuretic b-blocker ACE All CCB a1-block
  erDisorder inhibitor antagonist
• Diabetes Caution/x Caution/x ? ? ? ?
• Dyslipidaemia x x ? ? ? ?
• CHD ? ? ? ? ? ?
• Heart failure ? 3/Caution ? ? Caution ?
• Asthma/COPD ? x ? /Caution ? ? ?
• Peripheral ? Caution Caution Caution ? ?
  vasculardisease
• Renal artery ? ? x x ? ? stenosis

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Effect of various antihypertensives on coexisting
disorders

• Total LDL- HDL- Serum Glucose Insulin cholestero
  l cholesterol cholesterol triglycerides tolerance
  sensitivity
• Diuretic
• b-blockers - - -
• ACEinhibitors - - - -
• Allantagonists - - - -
• CCBs - - - - - -
• a-blockers

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Combination therapy for hypertension
Recommended by JNC-VI guidelines and 1999 WHO-ISH
guidelines

• With any single drug, not more than 2550 of
  hypertensives achieve adequate blood pressure
  control
• J Hum. Hypertens 1995 9S33S36

For patients not responding adequately to low
doses of monotherapy
Substitute with another drug from a different
class
Increase the dose of drug. This, however, may
lead to increased side effects
Add a second drug from a different
class (Combination therapy)
If inadequate response obtained
Add second drug from different class (Combination
therapy)
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Advantages of fixed-dosecombination therapy

• Better blood pressure control
• Lesser incidence of individual drugs
  side-effects
• Neutralisation of side-effects
• Increased patient compliance
• Lesser cost of therapy

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Fixed-dose combinations as recommended byJNC-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)

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Efficacy and Tolerability of a fixed-dose
combination of amlodipine andatenolol
(Amlopres-AT) in Indian Hypertensives (n369)
Reduces BP effectively
80.5
175.419.4
143.8 13.2
Blood Pressure (mm Hg)
106.8 10.5
responders
88.2 7.6

• 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.

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Efficacy and Tolerability of combined amlodipine
andlisinopril (Amlopres-L) in Indian
hypertensives (n330)
Reduces BP effectively
77.65
175.419.4
143.8 13.2
Blood Pressure (mm Hg)
106.8 10.5
responders
88.2 7.6

• 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.

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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
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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