The document discusses hypertension and its treatment with angiotensin converting enzyme (ACE) inhibitors. It defines hypertension and describes how it results from increased vascular resistance. It then discusses several classes of drugs used to treat hypertension, focusing on ACE inhibitors. Specific ACE inhibitors discussed include captopril, enalapril, and ramipril. Their mechanisms of action involve blocking the conversion of angiotensin I to the vasoconstrictor angiotensin II. This decreases blood pressure by reducing angiotensin II levels and increasing bradykinin. Their clinical uses and adverse effects are also summarized.

1. Rasel Mahbub
Dept of pharmacy
Jagannath University

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

3.  1.ACE (Angiotensin Converting
Enzyme)inhibitor:
Captopril,Enalapril, Ramipril etc.
 2.Angiotensin (AT1 Receptor) blocker :
Losartan, Candesartan, Valsartan etc.
 3.Calcium channel blocker : Verapamil,
Diltiazem, Nifedipine etc.
 4.Sympatholytic agent:
 Beta Adrenergic bocker : Propanolol,
Atenolol,Metoprolol.

4.  Alpha Adrenergic blocker : Prazosin,Terazosin.
 Beta & Alpha Adrenergic blocker : Labetalol,
Carvedilol.
 Central Sympatholytic agent: Clonidine, Methyldopa.

 5.Diuretics :
.. Thiazide : Hydrochlorothiazide, Chlorothiazide.
.. High ceiling{loop diuretics} : Furosemide.
.. Potassium sparing: Spironolactone,Amiloride
.. Osmotic diuretics:glycine,mannitol,urea
..CA inhibitor:Acetozolamide

5.  6.Direct Vasodilators :
Arteriolar :Hydralazine,Minoxidil.
Arteriolar & Venous : Sodium nitroprusside.
 7.Adrenergic neurone blocker : Reserpine,
Guanethidine

6.  A.C.E.(Angiostensin converting enzyme) inhibitor is
an agent which block the angiotensin converting
enzyme which ultimately inhibit the conversion of
Angiotensin-ɪɪ from Angiotensin-ɪ.
Classification of ACE Inhibitor
1. Direct action but internalized metabolite to disulfide group.Ex.
captopril
2. Prodrug (ester dicarboxylic acid)
They have the effects when they are changed to active
metabolized .Ex enalapril, benazepril,
3. Soluble in water and not change in the body
Ex lisinopril

7.  MECHANISM OF ACTION :
The ACE inhibitors lower blood pressure by reducing
peripheral vascular resistance.
 Block the ACE that cleaves angiotensin I to form the potent
vasoconstrictor angiotensin II.
 ACE inhibitors decrease angiotensin II and increase
bradykinin levels.
 ACE inhibitors also decrease the secretion of aldosterone,
resulting in decreased sodium and water retention.

9.  Angiotensin is a peptide hormone that causes
vasoconstriction and a subsequent increase in
blood pressure. It is part of the renin-
angiotensin system, which is a major target for
drugs that lower blood
pressure. Angiotensin also stimulates the
release of aldosterone, another hormone, from the
adrenal cortex.
 Angiotensin is a alpha2 globulin with a m/w of
58000,it contains 452 amino acid and is
continuosly snthesized by the liver

10.  Bradykinin is a non a peptides those acts locally
&produce pain also cause of
 Vasodilation
 Bronchoconstriction
 Increase vascular permeability
 Stimulate prostaglandin synthesis

11.  The hormone acts mainly in the functional unit of the
kidneys to aid in the conservation of sodium,
secretion of potassium, water retention and to
stabilize blood
pressure. ... Aldosterone helps maintain blood
pressure (BP) and water and salt balance in the
body by helping the kidneys retain sodium and
excrete potassium.
 aldosterone.>Na&water retention>increase
CO>increase BP

12.  Aldosterone also causes water to be
reabsorbed along with sodium; this increases
blood volume and therefore blood pressure.
Thus, aldosterone indirectly
regulatesblood levels of electrolytes (sodium,
potassium and hydrogen) and helps to maintain
the blood pH.

14.  ADVERSE EFFECT :
Dry cough, rash, fever, altered taste, hypotension (in
hypovolemic states), and hyperkalemia, fatigue, angioedema,
headache, dizziness.
 CONTRAINDICATION & PRECAUTION :
The ACE inhibitors are contraindicated in patients with:
◦ Previous angioedema associated with ACE inhibitor therapy
 Hypersensitivity to ACE inhibitors.

15. ACE inhibitors should be used with caution
in patients with:
 Impaired renal function.
 Hypovolemia or dehydration.
THERPEUTIC USES :Used in patients
with cardiac failure, renal disease or
systemic sclerosis .It also used to treat
diabetic nephropathy and left ventricular
hypertrophy.

16.  CAPTOPRIL :
Mechanism of action:
 Captopril prevents the conversion of angiotensin I to angiotensin II by
inhibition of ACE.
 Decreased plasma angiotensin II.
 Increased plasma renin activity (PRA) resulting from loss of negative
feedback on renin release.
 Decreased aldosterone secretion.
 small increases in serum potassium with sodium and fluid loss.

17.  Adverse effects : Cough due to increase in the
plasma levels of bradykinin, angioedema,
agranulocytosis, proteinuria, hyperkalemia, taste
alteration, teratogenicity, acute renal failure and
leukopenia.
 Contraindication : Hypersensivity,stenosis,renal
impairment,pregnancy.
 Precaution : Lactation, severe CHF.
 Dose : 25 mg BD or 50 mg TDS.
 Clinical use: vasodilation and inhibition of some
renal function activities .Used in Hypertension,Cardiac
conditions such as post myocardial infarction and
congestive heart failure.

18. Enalapril, an angiotensin-converting enzyme (ACE)
inhibitor, is a prodrug which, when hydrolyzed by estarases
to its active Enalaprilat.
Mechanism of action:
Enalaprilat competes with angiotensin I for binding at the
angiotensin-converting enzyme, blocking the conversion of
angiotensin I to angiotensin II.
As angiotensin II is a vasoconstrictor and a negative-
feedback mediator for renin activity, lower concentrations
result in a decrease in blood pressure. Enalaprilat may also
act on kininase II,that degrades the vasodilator bradykinin.

19.  Pharmacokinetic data :
Bioavailability - 60% (oral), Metabolism -
hepatic (to enalaprilat), Half-life - 11 hours
(enalaprilat), Excretion - renal.
 Clinical uses :Management of hypertension. In
hypertensive patients with heart failure,
postmyocardial infarction, high coronary
disease risk etc.

20.  Adverse effects : Hypotension, dizziness when
standing up, and dry cough etc.
Contraindication : Hypersensitivity , pregnancy,
children.
Special precaution :Impaired renal failure,
hyperkalaemia
 Doses : The recommended initial dose in patients is
5 mg OD & should be adjusted according to blood
pressure response.
The usual dosage range is 10 to 40 mg per day
administered in a single dose or two divided doses.

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

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

23.  Pharmacokinetic data:
Bioavailability : 28%, Protein binding :73%
(ramipril)
56% (ramiprilat), Metabolism : Hepatic, to
ramiprilat Half-life : 2 to 4 hours, Excretion :
Renal (60%) and fecal (40%).
 Contrindication :
Renovascular disease, severe renal
impairment, volume-depleted patients, history
of angioedema while on an ACE inhibitor,
pregnancy, hypotension.

24.  Adverse effects: low blood sugar, dry cough
,dizziness and light-headedness, mouth dryness,
tiredness and fatigue,nausea, vomiting, diarrhea.
 Doses : Initial dose of 2.5 mg OD for 1 week, 5
mg OD for the next 3 weeks, and then increased
as tolerated. Maintenance dose :10 mg OD.

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

26. THANK YOU
TO
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