ANTIHYPERTENSIVE

DRUGS

Presentation by-Diksha Kumari

B.pharm 6th sem

22

Gurunanak institute of

pharmaceutical science

and technology

Definition-Hypertension is common cardiovascular disease

determined by increase blood pressure (pressure exerted by

blood against the wall of a blood vessel )in arteries.

Normal blood pressure-

120/80 mmHg systolic/diastolic

Symptoms that may occur include:•Confusion•Ear noise or buzzing•Fatigue•Headache•Irregular heartbeat•Nosebleed•Vision changes

BP= CO X SVR

BP = Blood pressure

CO =Cardiac output

SVR=Systemic vascular

resistance

Category Systolic Blood

Pressure(mmHg)

Diastolic Blood

Pressure(mmHg)

Pre-hypertension 120-139 80

Hypertension – Stage 1 140-159 90-99

Hypertension – Stage 2 160-179 100-109

Hypertension – Stage 3 >180 >110

CATEGORIES OF HYPERTENSION

ACCORDING TO EUROPEAN SOCIETY

OF CARDIOLOGY.

Types of

Hypertension

Essential Secondary

A disorder of unknown origin affecting the

Blood Pressure regulating mechanismsSecondary to other disease processes

RISK FACTORS-

•Hyperlipidaemia –more LDL content

•Tension and stress

•Smoking-more nicotine intake

•Diabetes mellitus

•Imbalance between vasoconstrictor and

vasodilators peptides

Treatment-Why???

Global Mortality 2000: Impact of hypertension and other health risk factors

Adapted from Ezzati et al. Lancet 2002;360:1347–60

Attributable mortality (in millions (total: 55,861,000)

Developing region

Developed region

0 87654321

Antihypertensive Drug Therapy

DIURETICS :

EXAMPLES:Thiazides: chlorthalidoneHigh ceiling:FurosemideK+ sparing:Spironolactone,

MOA: Act on V-2 receptor in kidneys (vasopressin receptor) having an antediuretic function---- leads to diuresis----increased secretion of Na & H2O decrease in blood volume ----decreased CO----decreased BP.Adverse Reactions

•dizziness,

•electrolyte

imbalance/depletion,

•hypokalemia,

•hyperlipidemia,

•hyperglycemia

(Thiazides)

Contraindications•hypersensitivity,

•compromised kidney

function

•hyponatremia

Central Sympatholytics (a-2

Agonists)Drugs: clonidine, methyldopa Site of Action:CNS medullary ,cardiovascular

centersMOA: CNS a-2 adrenergic stimulation----

autoinhibitory feed back mechanism----

decreased sympathetic outflow----decreased

norepinephrine release----vasodilatation----

decreased PR---- decreased BP.Adverse Effect:dry mouth; sedation; drowsiness;nasal

congestion

SYMPATHOLYTIC DRUGS

a-1 Adrenergic blockers (Antagonists)

Drugs:Prazocin,Terazocin

Site of Action: peripheral arterioles, smooth muscle

MOA:Blocks a-1 receptor(in post synaptic neurone as

well as in vascular smooth muscles)---- cause

vasodialatation due to relaxation of vascular smooth

muscles---- decreased PR----also reduces preload by

pooling of blood----decreased CO ---- decreased BP.

Adverse Effects:nausea; drowsiness; postural

hypotension;headache

b -ADRNERGIC BLOCKERS(ANTAGONISTS)

Drugs: Non Selective– Propranolol,Timolol, Pindolol

Cardioselective –Atenolol, Metoprolol(acts only on

beta-1 receptor )

Site of Action: heart,kidney.

MOA: 1.heart:blocks b -1receptor---reduce heart rate ----

decreased CO---- decreased BP2.kidney:decreased renin production(mediated by b- 1

receptor)----depresses RAS system---- decreased PR----decreased BP

Advantages:No postural hypotension;No salt and water retention

Low incidence of side effects

Adverse Effects:impotence; bradycardia; fatigue; exercise

intolerance

Contraindication: asthma;bradycardia;hypersensitivity

b-1

DUAL ALPHA & BETA RECEPTOR ANTAGONISTS

Drugs: Labetalol (3:1 ratio of beta:alpha blocking activity),CarvedilolIT IS USEFUL IN HYPERTENSIVE EMERGENCIES

VASODIALATOR

Drugs: Arteriolar – HydralazineArterio-venular: Sodium Nitroprusside (USED IN EMERGENCY

SITUATION)MOA: Releases NO ----stimulation of guanylyl cyclase---- more conversion of GTP to cGMP-----activate

protein kinase----inhibit MLCK phosphorylation---- myosin phosphorylation & combination with

actin inhibited----relaxation of vascular smooth muscles----vasodialatation.

CALCIUM CHANNEL BLOCKERS

(CCBs)Drugs: verapamil ; nifedipine ; diltiazem ;

amlodipine:felodipineSite of Action- Vascular

smooth muscle

KCaN

aMOA:Blocks long acting

voltage sensitive calcinm

channels

Advantages:

No sedation or other CNS effects

Can be given to asthma patients &

angina patients

No impairment of renal perfusion

No deleterious effect on uric acid

level& electrolyte

balance

Side effects:

flushing; headache; tachycardia;

peripheral oedema

gastroesophageal reflux

Contraindications:

Congestive heart failure;

Pregnancy and lactation

DRUGS ACTING ON RENIN

ANGIOTENSIN SYSTEM

(RAS)1ACE inhibitors: captopril;enalapril;

lisinopril

2 renin inhibitors: Aliskiren; remikinen

3 AT1 receptor antagonists:losartan

;candesartan

1st line of Drug:No postural hypotension or electrolyte imbalance (no fatigue or weakness)Safe in asthmatics and diabeticsPrevention of secondary hyperaldosteronism and K+ lossReverse the ventricular hypertrophy and increase in lumen size of vesselNo hyperuraecemia or deleterious effect on plasma lipid profile

Side effects:Dry cough;Steep fall in BP with 1st doseSkin rashAngioneurotic oedema

Reference-

1)Essentials of medical pharmacology sixth edition K.D Tripathi MD

2010. Jaypee brothers medical publishers. Page no-539 to 554.

2)Introduction to pharmacology by S.K kulkarni updated seventh

edition. Page no-286 to 302