Detailed note on pharmacotherapy for hypertension

1. Pharmacotherapy
Hypertension
RVS Chaitanya koppala

2. Defined as:
Condition where blood pressure is elevated to an extent that
clinical benefit is obtained from blood pressure lowering
&
140/90 mmHg is considered the upper limit of normal
(treatment threshold or targets)

3. • Hypertension is largely a condition of older individuals
• Diastolic pressure peaks at age of 50
• Systolic pressure continues to increase with advancing age
• Risk of cardiovascular disease double for every 20/10mmHg rise in
blood pressure

4. Most common and important cardiovascular complications associated
with hypertension are stroke and myocardial infarction
↑5mmHg in usual diastolic blood pressure is associated with 35-40%
↑ risk of stoke
Risk of heart failure is increased with six fold in hypertensive subjects
↓ blood pressure of 10/6mmHg associated with 38% ↓ stoke and 16%
↓ coronary events
↓5 mmHg blood pressure is associated with 25% ↓ renal failure

5. Complications of hypertension:
Myocardial infarction
Stroke
Cerebral/brainstem infarction
Cerebral haemorrhage
Lacunar syndromes
Multi infarct disease
Hypertensive encephalopathy/ malignant hypertension
Dissection aortic aneurysm
Hypertensive nephroscelrosis
Peripheral vascular disease

6. Epidemiology
10-25% population are expected to benefit from the drug treatment
90-95% of cases of hypertension , there is no underlying medical illness to
cause high blood pressure= essential hypertension
Essential = compensation mechanism to maintain adequate circulation
Genetic factors also clearly plays a role, but not a single gene is responsible
for hypertension except in Polycystic kidney disease /Liddle’s syndrome
More common in black people of African (Caribbean origin)

7. Causes of hypertension
PRIMARY HYPERTENSION : Essential hypertension
SECONDARY HYPERTENSION
Renal diseases Drugs:
Endocrine disease Sympathomimetic amines
Steroid excess: hyperaldosteronism, hypercorticoidism
Growth hormone excess
Catecholamine excess
Pre clampsia
Oestrogens (?)
Ciclosporin
Erthyropoietin
NSAIDS
Steroids
Vascular causes: Renal artery stenosis: fibromuscular
hyperplasia, renal artery atheroma
High salt
Alcohol intake
Obesity

9. Regulation of Blood pressure
Mean blood pressure is the product of Cardiac output and total
peripheral resistance
In most hypertensive individuals no change in cardiac output but
increase in peripheral resistance (?)
Control of blood pressure is important and number of homeostatic
reflexes are evolved to provide the BP homeostatis

10. Minute to minute increase in BP – baroreceptor reflex
Longer term regulation – renin-angiotensin- aldosterone system(salt,
water and blood pressure control)
Long term increase in shear stress also causes the vascular remodeling
Nitric oxide overcome by increased sensitivity to vasoconstrictor
endothelin (increases peripheral resistance)
Atrial natriuretic peptide
Bradykinin
Antidiuretic hormone

12. Clinical presentation
• Severe cases may present – Headache, visual disturbance or evidence
of target organ damage ( stroke, ischaemic heart disease or renal
failure)
• Malignant hypertension : accelerated/uncommon/ emergency, usually
>220/120mmHg evidence of Small vessel damage

13. • Fundoscopy: papilloedema (optic disc swelling), haemorrhages and
exudates
• Renal damage: haematuria, proteinuria and impaired renal function
• Hypertensive encephalopathy: small vessel damage in brain/ cerebral
oedema- confusion, headache, visual loss, seizures and coma
• MRI shows extensive white matter changes
• Requires hospital admission and rapid control of blood pressure over
12-24h towards normal levels

14. Management of hypertension
Diagnosis of hypertension:
All adults have their blood pressure check for every 5 years
Those with high blood pressure 130-139mmHg systolic and 85-89 mmHg
diastolic should have annual measurement
Measurement of blood pressure:
Well maintained sphygmomanometer of validated accuracy
Measured in both arms
In sitting and standing positions
In relaxed condition
Accurate sized cuff should be used
White coat hypertension (?)

15. Assessment of hypertensive patient
Secondary causes
Contributing factors:
Evidence of end organ damage
Determination of cardiovascular risk

16. Secondary causes
Renal damage (haematuria, polyuria)
Phaeochromocytoma (headache, postural dizziness, syncope)
Physical examination: abdominal bruits (renal artery stenosis)
Radiofemoral delay (coarctation of aorta)
Palpable kidneys (polycystic kidney disease)
Laboratory analysis (full blood count, electrolytes , urea , creatinine
and urinalysis)
Ultrasound of abdomen
Isotope regimen for suspected renal disease

17. • Renin levels suppressed by Beta blockers
• Aldosterone by ACE inhibiotors and receptor antagonists
• Very high aldosterone /renin ratio- conn’s syndrome or primary
hyperaldosteronism, cause by benign adenoma/ simple hyperphlasia
• CT/ MRI scanning shows images of tumours

18. Contributing factors:
Should be assessed for possible contributing factors and possible
factors such as obesity, excess alcohol or excess salt intake and lack of
exercise
Provoked by use of drugs (OTC drugs cold and flu remedies)
Smoking, diabetes and hyperlipidaemia
Family history of cardiovascular disease

19. Evidence of end organ damage:
Optic fundi- retinal damage
ECG – detect left ventricular hypertrophy/ ischaemic heart disease
Urine analysis for microalbuminaria (indicator of higher risk of future
end stage renal disease and overall vascular risk)

20. Determination of cardiovascular risk:
Patients with documented atheromatous vascular disease
(MI/Stroke/angina/ peripheral vascular disease)
Type 2 Diabetes over 40 years of age = coronary equivalent
Non diabetic patients with MI
Non diabetic patients without cardiovascular disease necessary to
estimate the cardiovascular risk (microalbuminuria increase 2-3 folds
cardiovascular risk)

21. Treatment
Non pharmacological approaches
Pharmacological approaches
Ancillary drug treatment

22. Non pharmacological treatment
• Patients with mild hypertension in the range of 140-159/90-100mmHg
offered lifestyle advice
• Over weight- weight loss reduces BP about 2.5/1.5mmHg/kg
• DASH (dietary approaches to stop hypertension) found to lower BP
significantly 4.5/2.7mmHg
• DASH- fruit, vegetables, low fat dairy products, fish, low fat poultry
and whole grains, minimizing red meat, confectionary and sweetened
drinks

23. • Subjects should reduce their salt intake (6g NaCl)
• Significant hidden salt in the processed meat, ready meals, cheese and even
bread
• Control intake of calories and saturated fat
• Regular aerobic exercise (min 30mins)
• Alcohol intake 2 units for females and 3 units for male
• Smoking should be quit, or else reduce the units

24. Pharmacological approaches
Treatment thresholds:
S.NO Blood pressure threshold Approach
01 >220/120mmHg Treated immediately, dual therapy suggested for
>20mmHg increase then target
02 >160-220/100-120mmHg
(severity and end organ damage)
Monitored over several weeks, treated if BP remains
in this stage
03 >140-159/90-99mmHg
(severity and end organ damage)
Monitored annually unless evidence of target organ
damage, CVD, DM
04 >135-139/85-89mmHg Monitored annually/reassessed annually
05 Less then 135/89mmHg Rechecked every 5 years

28. Other agents:
Minoxidil: powerful antihypertensive drug, indicated in severe
peripheral oedema and reflex tachycardia (* women ?)
Hydralazine: add on for resistant hypertension therapy
Sodium nitroprusside: direct acting arterial and venous dilator /
intravenous infusion/ blood pressure during anaesthesia
Aliskiren: ? antagonist
Darusentan: endothelin antagonist undergoing clinical trials in
resistant hypertension.

29. Ancillary treatment
ASPIRIN:
• Use reduces CV events at the expense of an increase in GIT complications
• Blood pressure should be controlled (<150/90mmHg) before aspirin.
• It should be restricted to the patients who have no contraindication and
either :
Evidence of established vascular disease
No evident of CVD but who are over 50 yrs of age
No evident of target organ damage
10 year CVD risk >20%

30. Lipid lowering therapy:
• Increasing evidence from the clinical trials of the benefit of lipid
lowering drug treatment in patients with hypertension
• Atorvastatin 10mg reduction in CHD and stroke
• LLT with statins should be prescribed to patients
Under 80 years of age
With cholesterol >3.5mmol/L,
Pre existing vascular disease,
10 years CV risk of >20%

31. Drug selection:
Drugs should be chosen on the basis of efficacy, safety, convenience and
cost
Efficacy:
Evidence from the large scale clinical trials
Short term studies only generates hypothesis and should be used to change
current strategies
Safety:
Drugs need to take on long term, so should be with long established safety
records
Recognize the importance of symptomatic adverse effects since these may
reduce adherance

32. Convenience:
Once daily preparation is more adherence than more frequent regimens
Conscious of the cost of individual preparations
Combination of low doses of anti hypertensive drugs are often better
tolerated than single drugs taken in large doses

33. Algorithm for antihypertensive therapy
< 55 yrs and non blacks > 55 yrs and non blacks
ACE Inhibitors
(capto/enala/lisino/perindo/rami-PRIL)
Calcium channel blockers (nifedipine, amlodipine,
verapamil, diltiazem)
+
Diuretics (thiazides, loop diuretics)
A+C or A+D
A+C+D
Consider adding alpha/beta blocker, spironolactone
Seek specialist advice

34. Thank you