Pharmacotherapy for hypertension

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 h aemorrhage 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

8. 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

9. 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

10. 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

11. 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

12. 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 (?)

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

14. Secondary causes R enal 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

15. R enin 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

16. 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

17. 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)

18. 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)

19. Treatment Non pharmacological approaches Pharmacological approaches Ancillary drug treatment

20. 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

21. 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

22. 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

23. 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.

24. 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%

25. 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 U nder 80 years of age W ith cholesterol >3.5mmol/L, P re existing vascular disease, 10 years CV risk of >20%

26. 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

27. Convenience: O nce 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

28. 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

29. Thank you