Drugs used for the prevention of hypertension. In the presentation mainly the drugs based on ACE inhibitors are discussed. The presentation will be useful for the M.Sc. candidates.

1. CARDIOVASCULAR
DRUGS BASED ON ACE
INHIBITORS
Presented By- Mohd Sufiyan Ashraf
M.Sc. Biotechnology

2. CARDIOVASCULAR DISEASES
▶ Cardiovascular disease (CVD) is a general term for conditions
affecting the heart or blood vessels.
▶ There are many different types of CVD. Four of the main types
are-
▶ Coronary heart disease
▶ Strokes
▶ Peripheral arterial disease
▶ Aortic disease
▶ Causes of CVD
▶ The exact cause of CVD isn't clear, but there are lots of things that
can increase your risk of getting it. These are called "risk factors".
▶ Major risk factor is High blood pressure

3. HYPERTENSION
▶ Hypertension is defined as either a sustained systolic blood
pressure of greater than 140 mmHg or a sustained diastolic blood
pressure of greater than 90 mmHg.
▶ Hypertension results from increased peripheral vascular smooth
muscle tone, which leads to increased cases of Cardiovascular
Diseases.

4. CLASSIFICATION OF
ANTIHYPERTENSIVE DRUGS
▶ ACE(Angiotensin Converting Enzyme) Inhibitor:
▶ Captopril, Enalapril, Ramipril etc.
▶ Angiotensin(AT1 Receptor) Blocker:
▶ Losartan, Candesartan, Valsartan etc.
▶ Calcium Channel Blocker:
▶ Verapamil, Diltiazem, Nifedipine etc.
▶ Vasodilators:
▶ Hydralazine, Minoxidil, Sodium nitroprusside etc.

5. RENIN-ANGIOTENSIN-ALDOSTERONE
SYSTEM
▶ A system which works to increase blood pressure when the
pressure within the kidney drops.
▶ As a result of low blood pressure and/or oxygenation in the
nephron, renin is released from the juxtaglomerular cells.
▶ Renin travels to the liver via the cardiovascular system and
combines with angiotensinogen to form angiotensin I.
▶ Angiotensin I travels through the cardiovascular system and
arrives at the lungs where it is changed into Angiotensin II.
▶ The alveoli use Angiotensin Converting Enzyme also known as
kinase II to cause this conversion.

6. ▶ Angiotensin II is a powerful vasoconstrictor which causes a rise in
peripheral resistance and increases pressure.
▶ Angiotensin II works to increase the release of aldosterone from
the adrenal glands.
▶ Aldosterone causes renal retention of sodium and water, which
further increases blood pressure by increasing volume.

7. RENIN-ANGIOTENSIN-ALDOSTERONE
SYSTEM
▶ The Renin-Angiotensin-Aldosterone System(RAAS) is a hormone
system that regulate blood pressure and fluid balance.
▶ The renin-angiotensin-aldosterone system(RAAS) plays an
important role in regulating blood volume and systemic vascular
resistance, which together influence cardiac output and arterial
pressure.

9. ACE(ANGIOTENSIN CONVERTING
ENZYME) INHIBITOR
▶ ACE Inhibitor is an agent which block the angiotensin
converting enzyme which ultimately inhibit the
conversion of angiotensin II from angiotensin I.
▶ Classification of ACE Inhibitor
▶ Direct action but internalized metabolites to disulfide group.
▶ E.g.- Captopril
▶ Prodrug- They have the effects when they are changed to
active metabolized.
▶ E.g.- Enapril, benazepril.
▶ Soluble in water and not change in the body.
▶ E.g.- Lisinopril

10. 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.

11. ▶ ADVERSE EFFECT:
▶ Dry cough, rash, fever, altered taste, hypotension, fatigue,
angioedema, headache, dizziness.
▶ CONTRADICTION & PRECAUTION:
▶ Contradicted in patient with:
▶ Previous angioedema associated with ACE inhibitor therapy.
▶ Hypersensitivity to ACE Inhibitors.
▶ Should be used with caution in patients with:
▶ Impaired renal function
▶ Dehydration.
▶ THERAPEUTIC USES:
▶ Used in patients with cardiac failure, renal disease or systemic
sclerosis.

12. STUDY OF DRUGS UNDER ACE
INHIBITORS
▶ Captopril-
▶ 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.

13. ▶ Adverse Effects: Cough due to increase in the plasma
levels of bradykinin, angioedema, agranulocytosis,
proteinuria, taste alteration, teratogenicity, acute renal
failure and leukopenia.
▶ Contradiction: Hypersensitivity, stenosis, renal impairment,
pregnancy.
▶ Precaution: Lactation
▶ Dose: 25mg BD or 50mg 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.

14. ▶ ENALAPRIL-
▶ A prodrug when hydrolyzed by esterases to its active
enalaprilat.
▶ Mechanism of action: Enalaprilat competes with
angiotensin I for binding at the ACE, 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.

15. ▶ Pharmacokinetic data:
▶ Bioavailability- 60% (oral)
▶ Metabolism- Hepatic
▶ Half life: 11 hours
▶ Excretion- Renal
▶ Clinical uses: Management of hypertension
▶ Adverse effects: Hypotension, dizziness when standing
up, dry cough etc.
▶ Contradiction: Hypersensitivity, pregnancy, children.
▶ Special Precaution: Impaired renal failure,
hyperkalemia.
▶ Doses: 5mg OD

16. ▶ RAMIPRIL-
▶ Inactive prodrug
▶ Converted to ramiprilat in liver
▶ 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

17. ▶ Pharmacokinetic data:
▶ Bioavailability: 28% protein binding:73%(ramipril)
56%(ramiprilat)
▶ Metabolism: Hepatic
▶ Half life: 2 to 4 hours
▶ Excretion: Renal(60%) and Fecal (40%)
▶ Contradiction: Renovascular disease, severe renal
impairment, volume depleted patients, history of
angioedema while on an ACE inhibitor, pregnancy,
hypotension.
▶ Adverse effects: Low blood sugar, dry cough, dizziness
and light headedness, mouth dryness, tiredness and
fatigue, nausea, vomiting, diarrhoea.
▶ Doses: Initial 2.5mg OD for 1 week and 5mg OD for
next 3 week.

18. BENEFITS OF ACE INHIBITORS
▶ Lowering blood pressure
▶ Can slow the progression of kidney disease
▶ Can slow the progression of Atherosclerosis.

19. THANK YOU