ACE InhibitorsACE InhibitorsTanvir islam Tanvir islam

HYPERTENSIONHYPERTENSION

HYPERTENSIONHYPERTENSION is defined as either a is defined as either a sustained systolic blood pressure (SBP) of sustained systolic blood pressure (SBP) of greater than 140 mm Hg or a sustained greater than 140 mm Hg or a sustained diastolic blood pressure (DBP) of greater than diastolic blood pressure (DBP) of greater than 90 mm Hg.90 mm Hg.

Hypertension results from increased Hypertension results from increased peripheral vascular smooth muscle tone, which peripheral vascular smooth muscle tone, which leads to increased arteriolar resistance and leads to increased arteriolar resistance and reduced capacitance of the venous system. reduced capacitance of the venous system.

CLASSIFICATION OF CLASSIFICATION OF ANTIHYPERTENSIVE DRUGS ANTIHYPERTENSIVE DRUGS ACEACE (Angiotensin Converting (Angiotensin Converting

Enzyme)inhibitor: Enzyme)inhibitor: Captopril,Enalapril, RamiprilCaptopril,Enalapril, Ramipril etc. .

Angiotensin (AT1 Receptor) blocker : Angiotensin (AT1 Receptor) blocker :

Losartan, Candesartan, Valsartan etc.Losartan, Candesartan, Valsartan etc. Calcium channel blocker : Calcium channel blocker : Verapamil, Verapamil,

Diltiazem, Nifedipine etc.Diltiazem, Nifedipine etc. Beta Adrenergic bocker : Beta Adrenergic bocker : Propanolol, Propanolol,

Atenolol,MetoprololAtenolol,Metoprolol..

CLASSIFICATION OF CLASSIFICATION OF ANTIHYPERTENSIVE DRUGS ANTIHYPERTENSIVE DRUGS

Alpha Adrenergic blocker : Alpha Adrenergic blocker : Prazosin,Terazosin.Prazosin,Terazosin.

Beta & Alpha Adrenergic blocker :Beta & Alpha Adrenergic blocker : Labetalol, Carvedilol.Labetalol, Carvedilol.

DiureticsDiuretics : : Thiazide : Thiazide : HydrochlorothiazideHydrochlorothiazide, , Chlorothiazide.Chlorothiazide.

High ceiling : High ceiling : Furosemide.Furosemide. Potassium sparing: Potassium sparing:

Spironolactone,Amiloride Spironolactone,Amiloride

CLASSIFICATION OF CLASSIFICATION OF ANTIHYPERTENSIVE DRUGS ANTIHYPERTENSIVE DRUGS

Central Sympatholytics :Central Sympatholytics : Clonidine, Clonidine, Methyldopa.Methyldopa.

Vasodilators :Vasodilators : Arteriolar :Arteriolar :Hydralazine,Minoxidil.Hydralazine,Minoxidil. Arteriolar & VenousArteriolar & Venous : : SodiumSodium nitroprusside.nitroprusside.

Adrenergic neurone blockerAdrenergic neurone blocker : : Reserpine,Reserpine, Guanethidine .Guanethidine .

►► ►► A.C.E. INHIBITOR ◄◄ A.C.E. INHIBITOR ◄◄ A.C.E.(Angiostensin converting enzyme) A.C.E.(Angiostensin converting enzyme)

inhibitor is an agent which block the angiotensin inhibitor is an agent which block the angiotensin converting enzyme which ultimately inhibit the converting enzyme which ultimately inhibit the conversion of Angiotensin- from Angiotensin- .ɪɪ ɪconversion of Angiotensin- from Angiotensin- .ɪɪ ɪ

Classification of ACE Inhibitor Classification of ACE Inhibitor

1. Direct action but internalized metabolite to 1. Direct action but internalized metabolite to disulfide group.Ex. disulfide group.Ex. captoprilcaptopril

2. Prodrug (ester dicarboxylic acid)2. Prodrug (ester dicarboxylic acid)

They have the effects when they are changed to They have the effects when they are changed to active metabolized .Ex active metabolized .Ex enalapril, benazepril,enalapril, benazepril,

3. Soluble in water and not change in the body3. Soluble in water and not change in the body

Ex Ex lisinoprillisinopril

►► ►► A.C.E. INHIBITOR ◄◄ A.C.E. INHIBITOR ◄◄

MECHANISM OF ACTION :MECHANISM OF ACTION : The ACE inhibitors lower blood pressure The ACE inhibitors lower blood pressure

by reducing peripheral vascular resistance.by reducing peripheral vascular resistance. Block the ACE that cleaves angiotensin I to Block the ACE that cleaves angiotensin I to

form the potent vasoconstrictor angiotensin form the potent vasoconstrictor angiotensin II. II.

ACE inhibitors decrease angiotensin II and ACE inhibitors decrease angiotensin II and increase bradykinin levels. increase bradykinin levels.

ACE inhibitors also decrease the secretion of ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium aldosterone, resulting in decreased sodium and water retention.and water retention.

►► ►► A.C.E. INHIBITOR ◄◄ A.C.E. INHIBITOR ◄◄

►► ►► A.C.E. INHIBITOR ◄◄ A.C.E. INHIBITOR ◄◄ ADVERSE EFFECT : ADVERSE EFFECT : Dry cough, rash, fever, Dry cough, rash, fever,

altered taste, hypotension (in hypovolemic altered taste, hypotension (in hypovolemic states), and hyperkalemia, fatigue, angioedema, states), and hyperkalemia, fatigue, angioedema, headache, dizziness.headache, dizziness.

CONTRAINDICATION & PRECAUTION : CONTRAINDICATION & PRECAUTION :

The ACE inhibitors are The ACE inhibitors are contraindicated in patients with:contraindicated in patients with:

Previous angioedema associated with ACE Previous angioedema associated with ACE inhibitor therapyinhibitor therapy

Hypersensitivity to ACE inhibitors. Hypersensitivity to ACE inhibitors.

►► ►► A.C.E. INHIBITOR ◄◄ A.C.E. INHIBITOR ◄◄

ACE inhibitors should be used with caution in ACE inhibitors should be used with caution in patients with:patients with:

Impaired renal function.Impaired renal function. Hypovolemia or dehydration.Hypovolemia or dehydration.

THERPEUTIC USES :Used in patients with THERPEUTIC USES :Used in patients with cardiac failure, renal disease or systemic cardiac failure, renal disease or systemic sclerosis .It also used to treat diabetic sclerosis .It also used to treat diabetic nephropathy and left ventricular nephropathy and left ventricular hypertrophy.hypertrophy.

▶▶▶▶ STUDY OF DRUGS UNDER STUDY OF DRUGS UNDER ACE INHIBITORS ◄◄ ACE INHIBITORS ◄◄

CAPTOPRIL :CAPTOPRIL :

Mechanism of action:Mechanism of action: Captopril prevents the conversion of angiotensin Captopril prevents the conversion of angiotensin

I to angiotensin II by inhibition of ACE.I to angiotensin II by inhibition of ACE. Decreased plasma angiotensin II.Decreased plasma angiotensin II. Increased plasma renin activity (PRA) resulting Increased plasma renin activity (PRA) resulting

from loss of negative feedback on renin release. from loss of negative feedback on renin release. Decreased aldosterone secretion.Decreased aldosterone secretion. small increases in serum potassium with sodium small increases in serum potassium with sodium

and fluid loss.and fluid loss.

CAPTOPRIL CAPTOPRIL Adverse effectsAdverse effects : Cough due to increase in the

plasma levels of bradykinin, angioedema, agranulocytosis, proteinuria, hyperkalemia, taste alteration, teratogenicity, acute renal failure and leukopenia..

Contraindication : Contraindication : Hypersensivity,stenosis,renal impairment,pregnancy..

Precaution : Precaution : Lactation, severe CHF. Lactation, severe CHF. Dose :Dose : 25 mg BD or 50 mg TDS. 25 mg BD or 50 mg TDS. Clinical use:Clinical use: vasodilation and inhibition of some vasodilation and inhibition of some

renal function activities .Used in renal function activities .Used in Hypertension,Cardiac conditions such as post Hypertension,Cardiac conditions such as post myocardial infarction and congestive heart failure.myocardial infarction and congestive heart failure.

ENALAPRIL ENALAPRIL Enalapril, an angiotensin-converting enzyme Enalapril, an angiotensin-converting enzyme

(ACE) inhibitor, is a prodrug which, when (ACE) inhibitor, is a prodrug which, when hydrolyzed by estarases to its active Enalaprilat.hydrolyzed by estarases to its active Enalaprilat.

Mechanism of action:Enalaprilat competes Mechanism of action:Enalaprilat competes with angiotensin I for binding at the angiotensin-with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of converting enzyme, blocking the conversion of angiotensin I to angiotensin II. angiotensin I to angiotensin II.

As angiotensin II is a vasoconstrictor and a As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood lower concentrations result in a decrease in blood pressure. Enalaprilat may also act on kininase pressure. Enalaprilat may also act on kininase II,that degrades the vasodilator bradykinin.II,that degrades the vasodilator bradykinin.

ENALAPRILENALAPRIL

Pharmacokinetic data : Pharmacokinetic data : Bioavailability - 60% (oral), Metabolism - Bioavailability - 60% (oral), Metabolism -

hepatic (to enalaprilat), Half-life - 11 hours hepatic (to enalaprilat), Half-life - 11 hours (enalaprilat), Excretion - renal.(enalaprilat), Excretion - renal.

Clinical uses :Management of hypertension. Clinical uses :Management of hypertension. In hypertensive patients with heart failure, In hypertensive patients with heart failure, postmyocardial infarction, high coronary postmyocardial infarction, high coronary disease risk etc.disease risk etc.

ENALAPRIL ENALAPRIL Adverse effects : Adverse effects : Hypotension, dizziness when Hypotension, dizziness when

standing up, and dry cough etc.standing up, and dry cough etc.Contraindication : Contraindication : Hypersensitivity , pregnancy, Hypersensitivity , pregnancy,

children. children. Special precaution :Special precaution :Impaired renal failure, Impaired renal failure,

hyperkalaemia hyperkalaemia Doses : Doses : The recommended initial dose in patients The recommended initial dose in patients

is 5 mg OD & should be adjusted according to blood is 5 mg OD & should be adjusted according to blood pressure response. pressure response.

The usual dosage range is 10 to 40 mg per day The usual dosage range is 10 to 40 mg per day administered in a single dose or two divided doses.administered in a single dose or two divided doses.

RAMIPRIL RAMIPRIL

RAMIPRIL : It is An inactive prodrug, RAMIPRIL : It is An inactive prodrug, ramipril is converted to ramiprilat in the liver ramipril is converted to ramiprilat in the liver and is used to treat hypertension and heart and is used to treat hypertension and heart failure, to reduce proteinuria and renal failure, to reduce proteinuria and renal disease and to prevent stroke, myocardial disease and to prevent stroke, myocardial infarction.infarction.

Mechanism of action: Mechanism of action:

•Ramiprilat competes with angiotensin I Ramiprilat competes with angiotensin I for binding at the angiotensin-converting for binding at the angiotensin-converting enzyme. blocking the conversion of enzyme. blocking the conversion of angiotensin I to angiotensin II. angiotensin I to angiotensin II.

RAMIPRILRAMIPRIL

As angiotensin II is a vasoconstrictor and a As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin negative-feedback mediator for renin activity Lower concentrations result in a activity Lower concentrations result in a decrease in blood pressure and an increase decrease in blood pressure and an increase in plasma reninin plasma renin. .

• Ramiprilat may also act on kininase II, an Ramiprilat may also act on kininase II, an enzyme identical to ACE that degrades the enzyme identical to ACE that degrades the vasodilator bradykinin.vasodilator bradykinin.

RAMIPRIL RAMIPRIL

Pharmacokinetic data:Pharmacokinetic data: Bioavailability : 28%, Protein binding :73% Bioavailability : 28%, Protein binding :73%

(ramipril)(ramipril)56% (ramiprilat), Metabolism : Hepatic, to 56% (ramiprilat), Metabolism : Hepatic, to ramiprilat Half-life : 2 to 4 hours, Excretion : ramiprilat Half-life : 2 to 4 hours, Excretion : Renal (60%) and fecal (40%).Renal (60%) and fecal (40%).

Contrindication : Contrindication :

Renovascular disease, severe renal impairment, Renovascular disease, severe renal impairment, volume-depleted patients, history of angioedema volume-depleted patients, history of angioedema while on an ACE inhibitor, pregnancy, while on an ACE inhibitor, pregnancy, hypotension.hypotension.

RAMIPRILRAMIPRIL

Adverse effects: Adverse effects: low blood sugar, dry low blood sugar, dry cough ,dizziness and light-headedness, mouth cough ,dizziness and light-headedness, mouth dryness, tiredness and fatigue,nausea, dryness, tiredness and fatigue,nausea, vomiting, diarrhea.vomiting, diarrhea.

Doses :Doses : Initial dose of 2.5 mg OD for 1 Initial dose of 2.5 mg OD for 1 week, 5 mg OD for the next 3 weeks, and then week, 5 mg OD for the next 3 weeks, and then increased as tolerated. Maintenance dose :10 increased as tolerated. Maintenance dose :10 mg OD.mg OD.

RAMIPRILRAMIPRIL

• As angiotensin II is a vasoconstrictor and a As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin negative-feedback mediator for renin activity.activity.

• Lower concentrations result in a decrease Lower concentrations result in a decrease in blood pressure and an increase in plasma in blood pressure and an increase in plasma renin. renin.

• Ramiprilat may also act on kininase II, an Ramiprilat may also act on kininase II, an enzyme identical to ACE that degrades the enzyme identical to ACE that degrades the vasodilator bradykinin.vasodilator bradykinin.

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