Role Of Drugs That Affect Renin Angiotensin System 6h141r

CLINICAL PHARMACOLOGY OF HYPERTENSION

ROLE OF DRUGS THAT AFFECT RENIN ANGIOTENSIN SYSTEM

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Drugs affecting renin angiotensin system

ACE inhibitor Angiotensin II receptor antagonist Direct renin inhibitor

Angiotensin converting enzyme inhibitors • Used as first line antihypertensive drugs Captopril Perindopri l

Enalapril Ramipril

Lisinopril Benazepril

• Mechanism of action I. Inhibit generation of angiotensin ll II. Inhibit degradation of bradykinin III. Stimulate synthesis of vasodilating prostaglandin through bradykinin

Pharmacokinetic • istration : Given orally IV in emergency • Food reduces absorption • Poorly cross blood-brain barrier (BBB) • Metabolized in liver • Excreted in urine

Features of ACE inhibitors Drug

Captopri l

Enalapril Lisinopri Perindop Ramipril l ril

Active/ prodrug

Active

Prodrug

Active

Absorption

Wellabsorbed, decrease with food

Rapidly absorbed. Undergoes extensive first metabolis m. Food does not reduce absorption

Slowly and Poorly incomplete absorbed. ly absorbed. Food does not affect Food does absorption not affect absorption

Rapidly absorped

24 hours

>24 hours

> 24 hours

Duration of 8-12 hours action

Prodrug

>24 hours

Prodrug

Adverse effect • • • • • • • • •

Cough Angioedema Proteinuria Teratogenic effect Severe hypotension Neutropenia Rashes Itching Loss of taste sensation

Contraindication • Bilateral renal artery stenosis • Patient with single kidney with renal stenosis

Drug interaction • Potassium-sparing diuretics – Simultaneous istration leads to hyperkalemia

• Lithium – ACE inhibitor retards renal elimination of lithium and potentiate its toxicity

• NSAIDs – NSAIDs inhibit PG synthesis, promote Na+ and water retention – Decrease antihypertensive effect on ACE inhibitors

Therapeutic use • • • • •

Hypertension Congestive cardiac failure Acute myocardial infarction Diabetic nephropathy Scleroderma renal crisis

Angiotensin receptor blocker (ARBs) Losartan

Candesart an Irbesartan

Valsartan

Telmisarta n

• Angiotensin receptor antagonist • AT1 and AT2 • Vasoconstrictor, aldosterone secretion and release of adrenaline from sympathetic nerve ending Angiotensi n ll (agonist)

Angiotensin receptor (AT1) (competitiv e antagonism

ARBs (antagoni st)

Adverse effect • • • • • •

Headache Hypotension Weakness Rashes Teratogenic effect Less likely to produce cough/ angioedema

Therapeutic use • Hypertension • Congestive cardiac failure • Myocardial infarction

Indications • Patients who develop cough with ACE inhibitors • Patients with diabetes • Patients intolerant to ACE inhibitors

Direct renin inhibitor

Aliskire n • Angiotensinogen

angiotensin I

Renin • Inhibit renin, hence : – Decrease level of angiotensin l and angiotensin ll

• Uses : – Hypertension as monotherapy – Combination with diuretics

References • Principle of Pharmacology 2nd Edition by HL Sharma and KK Sharma