Pharmacotherapy Hypertension

RVS Chaitanya koppala

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)

• 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

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

Complications of hypertension:Myocardial infarction Stroke

Cerebral/brainstem infarction Cerebral haemorrhageLacunar syndromesMulti infarct disease

Hypertensive encephalopathy/ malignant hypertension Dissection aortic aneurysmHypertensive nephroscelrosisPeripheral vascular disease

Epidemiology10-25% 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)

Causes of hypertensionPRIMARY HYPERTENSION : Essential hypertension

SECONDARY HYPERTENSION

Renal diseases Drugs:Endocrine disease Sympathomimetic aminesSteroid excess: hyperaldosteronism, hypercorticoidismGrowth hormone excessCatecholamine excess Pre clampsia

Oestrogens (?)CiclosporinErthyropoietinNSAIDSSteroids

Vascular causes: Renal artery stenosis: fibromuscular hyperplasia, renal artery atheroma

High saltAlcohol intakeObesity

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

Minute to minute increase in BP – baroreceptor reflexLonger term regulation – renin-angiotensin- aldosterone system(salt,

water and blood pressure control)Long term increase in shear stress also causes the vascular remodelingNitric oxide overcome by increased sensitivity to vasoconstrictor

endothelin (increases peripheral resistance)Atrial natriuretic peptideBradykininAntidiuretic hormone

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

• 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

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 measurementMeasurement of blood pressure:Well maintained sphygmomanometer of validated accuracyMeasured in both armsIn sitting and standing positionsIn relaxed conditionAccurate sized cuff should be usedWhite coat hypertension (?)

Assessment of hypertensive patient

Secondary causes

Contributing factors:

Evidence of end organ damage

Determination of cardiovascular risk

Secondary causesRenal 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

• 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

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

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)

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)

Treatment Non pharmacological approaches

Pharmacological approaches

Ancillary drug treatment

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

• 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

Pharmacological approachesTreatment thresholds:S.NO Blood pressure threshold Approach01 >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 annually05 Less then 135/89mmHg Rechecked every 5 years

Other agents:Minoxidil: powerful antihypertensive drug, indicated in severe

peripheral oedema and reflex tachycardia (* women ?)Hydralazine: add on for resistant hypertension therapySodium nitroprusside: direct acting arterial and venous dilator /

intravenous infusion/ blood pressure during anaesthesiaAliskiren: ? antagonistDarusentan: endothelin antagonist undergoing clinical trials in

resistant hypertension.

Ancillary treatmentASPIRIN:• 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 diseaseNo evident of CVD but who are over 50 yrs of ageNo evident of target organ damage10 year CVD risk >20%

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%

Drug selection:

Drugs should be chosen on the basis of efficacy, safety, convenience and costEfficacy: Evidence from the large scale clinical trialsShort term studies only generates hypothesis and should be used to change

current strategiesSafety: Drugs need to take on long term, so should be with long established safety

recordsRecognize the importance of symptomatic adverse effects since these may

reduce adherance

Convenience:

Once daily preparation is more adherence than more frequent regimensConscious of the cost of individual preparationsCombination of low doses of anti hypertensive drugs are often better

tolerated than single drugs taken in large doses

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

Thank you