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JESSEN GEORGE KM PHARM PART 1PHARMACY PRACTICECPS, MEDICAL COLLEGE TVM

HYPERTENSION

CONTENTS INTRODUCTION EPIDEMIOLOGY TYPES OF HYPERTENSION ETIOLOGY PATHOPHYSIOLOGY CLINICAL PRESENTATION & DIAGNOSIS MANAGEMENT OF HYPERTENSION SPECIAL POPULATION PATIENT COUNSELLING REFERENCES

INTRODUCTION Hypertension is defined by persistently elevated

arterial blood pressure. Elevated systolic and diastolic blood pressure -

(≥ 140/90 mm of Hg). In diabetic patient (≥ 130/80 mm of Hg).

Classification Systolic Blood Pressure (mm Hg)

Diastolic Blood Pressure (mm Hg)

Normal <120 <80

Pre hypertension 120-139 80-89

Stage1 HT 140-159 90-99

Stage 2 HT Greater than or equal to160

Greater than or equal or100

JNC 7 Classification of blood pressure in adults

EPIDEMIOLOGY Prevalence of HT increases with age & greater among

African Americans than Caucasians. In US, 68% of adults have HT, only 53% are on

treatment & only 27% have achieved control of BP. Prevalence of HT in India is about 26.2% in men &

23.6% in women. Hypertension is similar between men and women of the

same race.

TYPES OF HYPERTENSION

Essential hypertension. Secondary hypertension. White coat hypertension. Isolated systolic hypertension. Gestational hypertension. Hypertensive crisis.

a) Hypertensive urgencies.

b) Hypertensive emergencies.

ETIOLOGY

Essential or Primary hypertension

- 90 % .

- sedentary lifestyle - smoking, alcohol intake, stress, obesity.

- inherited genetic mutation, ageing etc.

- cannot be cured, but can be controlled.

Secondary hypertension.

- 10 % .

- Due to either a co morbid disease or a drug.

- Diseases : chronic kidney disease, cushing's syndrome, coarctation of aorta, pheochromocytoma, primary aldosteronism, thyroid disease etc.

- Drugs :Oral contraceptives, phenylpropanolamine, cyclosporine, corticosteroids, MAO inhibitors, antidepressants etc.

PATHOPHYSIOLOGY BP = CO x TPR.

CO - major determinant of SBP.

TPR - determines DBP.

POTENTIAL MECHANISMS OF PATHOGENESIS

1 ) Humoral mechanisms.

a) RAAS system

b) Natriuretic hormone

c) Hyperinsulinemia

2) Neuronal regulation.

3) Peripheral autoregulatory components.

4) Vascular endothelial mechanism.

5) Electrolytes and other chemicals.

b) Natriuretic Hormone :

inhibit sodium and potassium ATPase block the active transport of sodium increase intracellular conc of Na.

c) Hyperinsulinemia :

Increased insulin concentration elevate BP by,

- increased renal Na retention.

- enhanced sympathetic NS activity.

- increased intracelllar Ca increase vascular resistance.

2) Neuronal mechanisms :

- Stimulation of α1 (arterioles and venules) : vasoconstrictions.

- Stimulation of α2 : decrease sympathetic outflow.

- Stimulation of β1 (heart, JG cells in kidney) : increase in heart rate and contractility, renin release.

- Stimulation of β2 (lungs, liver, arteriolar smooth muscles, pancreas) : vasodilation, bronchodilation.

- Baroreceptor reflex system

BR: nerve endings lying in the walls of large arteries, especially in carotid arteries and aortic arch.

Transmit impulse through 9 th cranial nerve and vagus nerves.

3) Peripheral autoregulatory components

- Kidney : maintain normal BP

- BP drops --- kidney increase retention of Na --- PV expansion --- BP increases (viceversa)

4) Vascular endothelial mechanism

- Deficiency in local synthesis of vasodilating substances (eg : prostacyclin and bradykinin)

- Excess vasoconstricting substances (eg : angiotensin 2 and endothelin 2 )

- Deficiency in NO release (from endothelium )

5) Electrolytes and other chemicals

- Excess sodium Intake

- Potassium depletion --- increase peripheral VR.

CLINICAL PRESENTATION & DIAGNOSIS

HT is usually asymptomatic. BP measured using sphygmomanometer. HT is confirmed when the average of two or more DBP

measurements is 90mm Hg or higher & average of two or more SBP measurements is consistently greater than 140 mm Hg.

Initial assessment include a complete history and physical examination.

If hypertension seems reasonable, tests as echocardiogram and electrocardiogram should be done to measure the electrical activity of heart.

Laboratory tests can also be performed to identify possible causes of secondary hypertension.

(Eg : serum creatinine, fasting blood glucose, serum potassium, urinalysis etc)

SIGNS AND SYMPTOMS

Mild to moderate essential hypertension

- asymptomatic Secondary hypertension

- Hyperthyroidism : weight loss, tremors, heart rate abnormalities, reddening of the palms and increased sweating.

- Hyperaldosteronism : numbness, excessive urination, excessive sweating, electrolytes imbalance , dehydration and elevated blood alkalinity.

In pregnancy

- Pre Eclampsia, Eclampsia. In newborns and neonates

- Failure to thrive, seizures, irritability, lack of energy and difficulty breathing.

In children

- Headache, fatigue, blurred vision, nosebleeds, and facial paralysis.

MANAGEMENT OF HYPERTENSION

1) Non pharmacologic therapy

- Weight reduction

- Dietary approaches

- Regular aerobic physical activity

- Avoid alcohol consumption

- Smoking cessation

- Potassium supplementation

- Magnesium supplements

- Stress reduction

KEY MODIFICATIONS

RECOMMENDED ACTIONS Approximate BP reduction

Physical activity → Get at least 30 minutes of moderate to vigorous activity (such as brisk walk) at least 4days/week

4-9mm of Hg

Healthy diet (Adopt DASH eating plan )

→ Eat plenty of fruit and vegetables , low fat dairy products with a reduced content of saturated and total fat, ,whole grains,fish. lean poultry and nuts.→Reduce sodium Intake (≤ 2.4 gm/day)→maintain adequate dietary potassium

8-14 mm of Hg

Weight reduction Maintain normal body weight (body mass index,18.5-24.9 kg/m2 )

5-20 mm of Hg per 10 kg weight loss.

Life style modifications

PHARMACOTHERAPY

A) PRIMARY ANTIHYPERTENSIVES

1) DIURETICS

a) Thiazides - eg : chlorthalidone, indapamide (lozol),

hydrochlorothiazide (esidrix ).

b) Loops - eg : furosemide (Lasix), torasemide.

c) Potassium sparing

(1) Inhibitors of renal epithelial Na channel -

eg : amiloride, triamterene.

(2) Aldosterone antagonist - eg : spironolactone,

(aldactone).

2) ACE INHIBITORS

eg : captopril, enalapril (vasotec), lisinopril, perindopril.

3) ANGIOTENSIN ∏ RECEPTOR BLOCKERS.

eg : losartan, valsartan, telmesartan, candesartan

4) β-BLOCKERS.

a) Cardioselective (β1) - eg : atenolol (tenormin),

metoprolol, bisoprolol.

b) Nonselective (β1 & β2)

- without ISA eg : propranolol ( inderal), timolol

- with ISA eg : pindolol

- with additional α blocking eg : carvidilol,

labetolol

5) CALCIUM CHANNEL BLOCKERS.

a) Dihydropyridines - eg : amlodipine, nifedipine,

felodipine.

b) Nondihydropyridines - eg : diltiazem, verapamil.

B) ALTERNATIVE ANTIHYPERTENSIVE

AGENTS

1) α1 blockers - eg : prazosin (minipress),

terazosin

2) Central α2 agonist - eg : clonidine , methyldopa

3) Peripheral adrenergic antagonist - eg : reserpine

4) Direct arterial vasodilators : eg : sodium nitroprusside,

hydralazine, minoxidil

5) Renin inhibitors – eg : aliskiren (tekturna), remikiren.

1) DIURETICS : Reduces plasma volume and stroke volume & thus CO

& BP is reduced. Thiazides most prefered. ( also se TPR ) loop prefered in patients with decreased renal

function, in cardiac failure & in elderly ADR : hypokalemia, hyperglycemia, hyperuricemia,

dyslipidemia. DOSE - hydrochlorothiazide 25-50mg daily

- furosemide 40- 80mg daily

- spironolactone 25-50mg daily

- low dose or combine with K sparing diuretics .

2) ACE INHIBITORS Blocks the conversion of Ang I to Ang II. Also stimulate the synthesis of vasodilating

substances (prostaglandin E2 and prostacyclin) Contraindicated in bilateral artery stenosis also in

pregnancy. ADR : renal failure, dry cough, hypotension,

angioedema, dysgeusia, foetopathic, hyperkalaemia.

DOSE : captopril initially 12.5 mg bid, max 50mg tid

enalapril initially 5mg at bedtime.

3) ANGIOTENSIN RECEPTOR BLOCKERS ARB directly block angiotensin type I receptor (AT 1)

which mediates the effect of angiotensin II. Stimulation of AT II– vasodilation Angiotensin II from RAAS and an alternative

pathway through the enzyme chymase.

ADR : edema, headache, renal failure DOSE : losartan K 50-100mg in two divided doses,

telmesartan 40 mg OD, max 80 mg/day

4) β-BLOCKERS Decrease CO through –ve chronotropic & inotropic

effect. Patient with asthma, COPD, and diabetes :

cardioselective safer than non selective β-blockers. Abrupt cessation may cause rebound HT ADR- bradycardia, conduction abnormalities,

broncospasm, dizziness, drowsiness.

DOSE : atenolol 25-100 mg OD

propranolol 160- 480 mg b.i.d

5) CALCIUM CHANNEL BLOCKERS Blocks voltage sensitive Ca channels & cause relaxation

of cardiac & smooth muscles vasodilation & fall in BP.

a) Dihydropyridines ADR : flushing, edema, headache DOSE : amlodipine 5mg OD

nifedipine 10-40 mg bid

b) Non dihydropyridines ADR : bradycardia, heart block, constipation DOSE : verapamil 240 mg daily in 2-3 div doses

diltiazem 60-120 mg bid.

1) α-1 BLOCKERS

- prevent noradrenaline induced vasoconstriction se TPR & BP.

ADR : edema, postural hypotension, depression

DOSE : terazosin 2-10mg OD

2) CENTRAL α2 AGONIST

- stimulation of α2 adrenergic receptors in brain

reduce sympathetic outflow from vasomotor

centre increase in vagal tone.

ADR : depression, sedation , drymouth

DOSE : methyl dopa -initially 250 mg bid/tid

clonidine 50-100 mcg tid.

3) PERIPHERAL ADRENERGIC ANTAGONIST Depletes norepinephrine from sympathetic nerve

endings & blocks transport of NE into storage granules

ADR : mental depression, nasal conjestion, headache DOSE : 250 mcg daily

4) DIRECT ARTERIAL VASODILATORS Direct arterial smooth muscle relaxation Hydralazine ADR : dermatitis, headache

DOSE : 20-100 mg/day Minoxidil ADR : reversible hypertrichosis on

face,arms etc

SITES OF ACTION OF MAJOR

ANTIHYPERTENSIVE AGENTS

1) ACE inhibitors

2) ARB

3) β-blockers

4) CCB

5) Diuretics

6) Aldosterone antagonist

7) Renin inhibitors

SPECIAL POPULATION

HT IN ELDERLY :

Treatment initiated with a small dose of diuretic hydrochlorothiazide 12.5 mg & increased gradually then an ACE inhibitor added in small dose & gradually increased.

HT IN PULMONARY DISEASES

Non selective β blockers should be avoided in asthma ,COPD

HT IN PREGNANCY :

- methyldopa - drug of choice.

- β-blockers,labetalol and CCB - other alternatives

- ACE inhibitors and ARB - contraindicated.

HT with DYSLIPIDEMIA

- Thiazides, β blockers without ISA : affect serum lipids (raise triglyceride level and LDL/HDL ratio)

- ACE inhibitors, CCBs prefered.

PATIENT COUNSELLING

Silent killer. Should advice the importance of taking medications

regularly at the same time. Advice the patient not to stop medication abruptly Should monitor the side effects & give necessary

advices Should council the patient regarding

-life style modifications

-regular exercise

-reducing weight

- sodium & calorie restriction

- restriction of saturated fats

- increased intake of dietary fibres

- restriction of alcohol

- smoking cessation

- avoid stress

- caution while using cold remedies

containing sympathomimetics

METHODS TO IMPROVE ADHERENCE TO

DRUG THERAPY

- simplifying the drug regimen

- avoid side effects by starting with low doses

- schedule drug doses once/twice daily

- label prescriptions clearly & indicate the purpose of drug

- provide written schedules/ pill box for patients taking multiple drug

- encourage the use of calenders to remind the patient to take medication

REFERENCES

Clinical pharmacy and Therapeutics- Eric T Herfindal

7th edition page no.401-425 Pharmacotherapy. A pathophysiologic approach- 6th

edition ,Joseph T Dipiro page no.157-181 Essentials of medical pharmacology – K D Tripathi page

no. 539 – 554. Clinical pharmacy and Therapeutics-Rojer wallker page

no.295-309

All data were collected from various sources

Only for educational purpose.

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