HYPERTENSION

G.RAYYAPA REDDY M.PHARM(COLOGY )

CONTENTS
DEFINITION CLASSIFICATION OF HYPERTENSION STAGES OF HYPERTENSION MECHANISMS FOR CONTOLING B.P TREATMENT STRATIGIES CLASSIFICATION OF DRUGS

DEFINITION
Hypertension is, defined as a repeatedly elevated blood pressure exceeding 140 over 90 mmHg -- a systolic pressure above 140 with a diastolic pressure above 90. B.P=C.O * TPR C.O = S.V * H.R

CLASSIFICATION OF HYPER TENSION

PRIMARY HYPER TENSION: In

which no specific cause can be identified. Greater than 90% of all cases of systemic hypertension comes under this.

SECONDARY HYPERTENSION:

Resulting from identifiable cause, Such as renal diseases or adrenal hyper function.

STAGES OF HYPERTENSION
NORMAL: S.B.P <120, D.B.P < 80. PREHYPERTENSION: S.B.P 120-139,
D.B.P 80-89.

STAGE 1 HYPERTENSION: S.B.P 140-159,

D.B.P 90-99.

STAGE 2 HYPERTENSION: S.B.P 160,

D.B.P 100.

MECHANISM FOR CONTROLING B.P

TREATMENT STRATIGIES
The goal of anti-hyper therapy is to reduce
cardio vascular and renal morbidity and mortality.

Mild hypertension can be control with single

drug, however most patient require more than one drug to achieve blood pressure control.

Individualized care, certain hypertensive

patients responds better one class of drug then than other, ex: black patients respond well to diuretics and calcium channel blockers, compared to -blockers and ACE inhibitors.

CLASSIFICATION OF DRUGS
Diuretics -adrenoceptor blocking agents ACE inhibitors Angiotensin 2 receptor antagonist Renin inhibitors Calcium channel blockers -adrenoceptors blocking agents - sdrenoceptors blocking agents Central acting adrenergic drugs vasodilators

DIURETICS
This can be used as first line drug
therapy of hypertension, they are safe and inexpensive. They are effective in preventing M.I and C.H.F All diuretics drug are effective in treating hypertension but thiazides are widely used.

Thiazide diuretics: ex; chlorthiazide

They decrease B.P initially by increasing sodium and

water excretion, this causes decrease in ECV resulting in decrease in C.O and renal blood flow.

Adverse Effects: Hypokalemia Hyperuresimia Hyperglycemia Interactions: NSAIDS interact to diminish the anti-hypertensive effect DOSE: Chlorthiazide 250-500mg

LOOP DIURETICS: ex; furosemide

These are specially used in patients
with poor renal function these act primarily on the ascending loop of henle hence called as loop diuretic These decrease sodium reabsorption Interaction: NSAID Dose: furosemide 20-80 mg

POTASSIUM SPARING DIURETICS: Ex; amiloride

These cause potassium retension, these

are not so potent compared to other diuretics.

Interactions: when these drugs are coadministerd with ACE inhibitors or potassium supplements potasiium levels shuld be monitoered due to risk of hyperkalemia.

-ADRENOCEPTOR BLOCKER

These blockers reduce B.P primarily by

AGENTS

decreasing cardiac output, they can also inhibit release the renin from kidney. Thus decrease in the formation of angiotensin2 and secretion of aldosterone.

PROPRANOLOL: These drug acts on both 1 and 2. Selective blockers of 1 such as metaprolol and atenolol are commonly used. Adverse Effect: Hypotension Bradycardia Fatigue and insomnia.

ACE INHIBITORS
These are preferred when first line
drugs like diuretics -blockers are contra-indicated or ineffective.

Adverse Effects:

Dry cough Hypekalemia Hypotension Fetotoxic Skin rash Fever

ANGIOTENSIN2 RECEPTOR ANTAGONIST

ARBs are alternative to ace inhibitors

these drugs block the AT1 receptors ex; losartan They did not increase bradykinin levels. ARBs decrease nephrotoxicity of diabetes. There adverse effects are similar to ACE inhibitors, although risk of cough and angioedema are significantly decreased.

RENIN INHIBITOTRS
Aliskiren directly inhibits renin
and thus acts earlier to renin angiotensin aldosterone system it lowers B.P as effectively as ARBs and ACE inhibitors This drug is contradicted on pregnancy

CALCIUM CHANNEL BLOCKERS

These drugs are recommended, when the
first line drugs are contra-indicated or ineffective. These are effective in treating hypertension in patients with angina diabetes.

Classes of calcium channel blockers Diphenylalkalylamines: ex; verapamil is the only member of this class that is currently approved. It is the least selective of any calcium channel blocker due to its significant effects on cardiac and vasculoar smooth muscle. It is used to treat angina supra ventricular arrhythmias and migraine .

 Benzothiazepines: ex; diltiazem is the

only member in this class currently approved effects both cardiac and smooth muscle it has less pronounced ionotropic effect on hearty compared to verapamil.

Dihydropyridines: this class includes

first generation drugs like nifedipine and second generation agents for trreating cardio vascular disease. Ex; amlodipine, felodipine, nicardipine. These dihydropyridines have greater affinity for vascular calcium channel

Actions: Intracellular concentration of calcium place important role in maintain tone smooth muscle and in contraction of myocardium. Calcium enters to cell through voltage sensitive calcium channels and trigger the release of calcium from sarcoplasmic reticulum and mitochondria which further increase cytosol level of calcium. Calcium channel antagonist block by binding to L-type calcium channel in heart and smooth muscle this causes vascular smooth to relax and dilating mainly arterioles. Pharmacokinetics: Most of these drugs have short half-life 3-8 hrs. By oral dose treatment is required three times a day. Sustain relaease preparation are also available.

Adverse Effects: Constipation when treated with verapamil. Verampamil should be avoided in case of C.H.F due to negative ionotropic effect and dromtropic effect. Dizziness headache fatigue hypotension in case dihydropyridines. Dose: Verampamil 120-480mg. Nefidipine 30-90mg.

-ADRENOCEPTOR BLOCKERS
Prazosin, doxazosin, terazosin,
produce competitive block of 1 adrenoceptors. They decrease peripheral vascular resistance and lower arterial blood pressure by causing relaxation of both arterial and Venus smooth muscle. Tamsulosin an 1 blocker with greater selectivity for prostate muscle, has been used in the treatment of prostate hyperplasia.

--Adrenoceptor Blocking Agents

Labetalol and carvedilol block both

1- and 1-2-receptors. Carvedilol has been mainly used in the treatment of heart failure. Centrally acting adrenergic drugs ex; clonidine, methyldopa, guanbnz. Post ganglionic adrenergic drugs ex; reserpine. Dose: 0.05mg

VASODILATORS
These are second line drugs, these act by
producing relaxation of vascular smooth muscle which decreases resistance and therefore blood pressure decrease. Vasodilators also increase plasma renin concentration resulting in sodium water retention. These undesirable effect is countered by using diuretics. Ex; hydralazine these drug causes direct vasodilation acting directly on arteries and arterioles

Adverse Effect: Tachycardia Nausea and headache

 Minoxidil a more potent vasodilator

than hydralazine acts directly by relaxing arterioles smooth muscle and thus cause decrease in peripheral resistance.

Adverse Drug Effect: Hypertrychosis is a common side effect a particularly taken more than 4 weeks. Dose: 2.5-80mg