Hypertensive drugs

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
ALL OF
YOU