Hypertension, classification of anti hypertensives drugs,ACE inhibitor drugs. advantage ,disadvantage etc.

1. ACE InhibitorsACE Inhibitors
Tanvir islamTanvir islam

2. HYPERTENSIONHYPERTENSION
HYPERTENSIONHYPERTENSION is defined as either ais defined as either a
sustained systolic blood pressure (SBP) ofsustained systolic blood pressure (SBP) of
greater than 140 mm Hg or a sustainedgreater than 140 mm Hg or a sustained
diastolic blood pressure (DBP) of greater thandiastolic blood pressure (DBP) of greater than
90 mm Hg.90 mm Hg.
 Hypertension results from increasedHypertension results from increased
peripheral vascular smooth muscle tone, whichperipheral vascular smooth muscle tone, which
leads to increased arteriolar resistance andleads to increased arteriolar resistance and
reduced capacitance of the venous system.reduced capacitance of the venous system.

3. CLASSIFICATION OFCLASSIFICATION OF
ANTIHYPERTENSIVE DRUGSANTIHYPERTENSIVE 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..

4. CLASSIFICATION OFCLASSIFICATION OF
ANTIHYPERTENSIVE DRUGSANTIHYPERTENSIVE 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,AmilorideSpironolactone,Amiloride

5. CLASSIFICATION OFCLASSIFICATION OF
ANTIHYPERTENSIVE DRUGSANTIHYPERTENSIVE 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 .

6. ►►►► 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 angiotensininhibitor is an agent which block the angiotensin
converting enzyme which ultimately inhibit theconverting enzyme which ultimately inhibit the
conversion of Angiotensin- from Angiotensin- .ɪɪ ɪconversion of Angiotensin- from Angiotensin- .ɪɪ ɪ
Classification of ACE InhibitorClassification of ACE Inhibitor
1. Direct action but internalized metabolite to1. 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 toThey have the effects when they are changed to
active metabolized .Exactive 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

7. ►►►► A.C.E. INHIBITOR ◄◄A.C.E. INHIBITOR ◄◄
 MECHANISM OF ACTION :MECHANISM OF ACTION :
The ACE inhibitors lower blood pressureThe ACE inhibitors lower blood pressure
by reducing peripheral vascular resistance.by reducing peripheral vascular resistance.
 Block the ACE that cleaves angiotensin I toBlock the ACE that cleaves angiotensin I to
form the potent vasoconstrictor angiotensinform the potent vasoconstrictor angiotensin
II.II.
 ACE inhibitors decrease angiotensin II andACE inhibitors decrease angiotensin II and
increase bradykinin levels.increase bradykinin levels.
 ACE inhibitors also decrease the secretion ofACE inhibitors also decrease the secretion of
aldosterone, resulting in decreased sodiumaldosterone, resulting in decreased sodium
and water retention.and water retention.

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

10. ►►►► A.C.E. INHIBITOR ◄◄A.C.E. INHIBITOR ◄◄
 ADVERSE EFFECT :ADVERSE EFFECT :
Dry cough, rash, fever,Dry cough, rash, fever,
altered taste, hypotension (in hypovolemicaltered 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 areThe ACE inhibitors are
contraindicated in patients with:contraindicated in patients with:
 Previous angioedema associated with ACEPrevious angioedema associated with ACE
inhibitor therapyinhibitor therapy


11. ►►►► A.C.E. INHIBITOR ◄◄A.C.E. INHIBITOR ◄◄
ACE inhibitors should be used with caution inACE 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 withTHERPEUTIC USES :Used in patients with
cardiac failure, renal disease or systemiccardiac failure, renal disease or systemic
sclerosis .It also used to treat diabeticsclerosis .It also used to treat diabetic
nephropathy and left ventricularnephropathy and left ventricular
hypertrophy.hypertrophy.

12. ▶▶▶▶ STUDY OF DRUGS UNDERSTUDY OF DRUGS UNDER
ACE INHIBITORS ◄◄ACE INHIBITORS ◄◄
 CAPTOPRIL :CAPTOPRIL :
Mechanism of action:Mechanism of action:
 Captopril prevents the conversion of angiotensinCaptopril 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) resultingIncreased 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 sodiumsmall increases in serum potassium with sodium
and fluid loss.and fluid loss.

13. CAPTOPRILCAPTOPRIL

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 somevasodilation and inhibition of some
renal function activities .Used inrenal function activities .Used in
Hypertension,Cardiac conditions such as postHypertension,Cardiac conditions such as post
myocardial infarction and congestive heart failure.myocardial infarction and congestive heart failure.

14. ENALAPRILENALAPRIL
Enalapril, an angiotensin-converting enzymeEnalapril, 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 competesMechanism 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 ofconverting enzyme, blocking the conversion of
angiotensin I to angiotensin II.angiotensin I to angiotensin II.
As angiotensin II is a vasoconstrictor and aAs 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 bloodlower concentrations result in a decrease in blood
pressure. Enalaprilat may also act on kininasepressure. Enalaprilat may also act on kininase
II,that degrades the vasodilator bradykinin.II,that degrades the vasodilator bradykinin.

15. ENALAPRILENALAPRIL
 Pharmacokinetic data :Pharmacokinetic data :
Bioavailability - 60% (oral), Metabolism -Bioavailability - 60% (oral), Metabolism -
hepatic (to enalaprilat), Half-life - 11 hourshepatic (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 coronarypostmyocardial infarction, high coronary
disease risk etc.disease risk etc.

16. ENALAPRILENALAPRIL
 Adverse effects :Adverse effects : Hypotension, dizziness whenHypotension, 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,
hyperkalaemiahyperkalaemia
 Doses :Doses : The recommended initial dose in patientsThe recommended initial dose in patients
is 5 mg OD & should be adjusted according to bloodis 5 mg OD & should be adjusted according to blood
pressure response.pressure response.
The usual dosage range is 10 to 40 mg per dayThe 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.

17. RAMIPRILRAMIPRIL
 RAMIPRIL : It is An inactive prodrug,RAMIPRIL : It is An inactive prodrug,
ramipril is converted to ramiprilat in the liverramipril is converted to ramiprilat in the liver
and is used to treat hypertension and heartand is used to treat hypertension and heart
failure, to reduce proteinuria and renalfailure, to reduce proteinuria and renal
disease and to prevent stroke, myocardialdisease and to prevent stroke, myocardial
infarction.infarction.
 Mechanism of action:Mechanism of action:
•Ramiprilat competes with angiotensin IRamiprilat competes with angiotensin I
for binding at the angiotensin-convertingfor binding at the angiotensin-converting
enzyme. blocking the conversion ofenzyme. blocking the conversion of
angiotensin I to angiotensin II.angiotensin I to angiotensin II.

18. RAMIPRILRAMIPRIL
 As angiotensin II is a vasoconstrictor and aAs angiotensin II is a vasoconstrictor and a
negative-feedback mediator for reninnegative-feedback mediator for renin
activity Lower concentrations result in aactivity Lower concentrations result in a
decrease in blood pressure and an increasedecrease in blood pressure and an increase
in plasma reninin plasma renin..
• Ramiprilat may also act on kininase II, anRamiprilat may also act on kininase II, an
enzyme identical to ACE that degrades theenzyme identical to ACE that degrades the
vasodilator bradykinin.vasodilator bradykinin.

19. RAMIPRILRAMIPRIL
 Pharmacokinetic data:Pharmacokinetic data:
Bioavailability : 28%, Protein binding :73%Bioavailability : 28%, Protein binding :73%
(ramipril)(ramipril)
56% (ramiprilat), Metabolism : Hepatic, to56% (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 angioedemavolume-depleted patients, history of angioedema
while on an ACE inhibitor, pregnancy,while on an ACE inhibitor, pregnancy,
hypotension.hypotension.

20. RAMIPRILRAMIPRIL
 Adverse effects:Adverse effects: low blood sugar, drylow blood sugar, dry
cough ,dizziness and light-headedness, mouthcough ,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 1Initial dose of 2.5 mg OD for 1
week, 5 mg OD for the next 3 weeks, and thenweek, 5 mg OD for the next 3 weeks, and then
increased as tolerated. Maintenance dose :10increased as tolerated. Maintenance dose :10
mg OD.mg OD.

21. RAMIPRILRAMIPRIL
• As angiotensin II is a vasoconstrictor and aAs angiotensin II is a vasoconstrictor and a
negative-feedback mediator for reninnegative-feedback mediator for renin
activity.activity.
• Lower concentrations result in a decreaseLower concentrations result in a decrease
in blood pressure and an increase in plasmain blood pressure and an increase in plasma
renin.renin.
• Ramiprilat may also act on kininase II, anRamiprilat may also act on kininase II, an
enzyme identical to ACE that degrades theenzyme identical to ACE that degrades the
vasodilator bradykinin.vasodilator bradykinin.

22. THANK YOUTHANK YOU
TOTO
ALL OF YOUALL OF YOU