Ace Inhibitors and receptor blockers classification of drugs.

1. ACE Inhibitors
PRESENTED BY: MUHAMMAD HAIDER ALI
ROLL NO: 43

2. What is ACE??
"ACE" stands for Angiotensin-Converting Enzyme. ACE is an enzyme that plays a
crucial role in the regulation of blood pressure and fluid balance in the body.
The primary function of ACE is to convert angiotensin I, an inactive precursor
formed in response to the release of renin, into angiotensin II.
Angiotensin II is a potent vasoconstrictor, meaning it causes blood vessels to
constrict, leading to an increase in blood pressure. It also stimulates the release of
aldosterone, a hormone that promotes the retention of sodium and water in the
kidneys, further contributing to increased blood volume and pressure.

3. ACE Inhibitors:
Angiotensin-Converting Enzyme (ACE) inhibitors are a class of medications that
block the action of the angiotensin-converting enzyme, a key enzyme in the renin-
angiotensin-aldosterone system. By inhibiting this enzyme, ACE inhibitors reduce
the production of angiotensin II, a potent vasoconstrictor, leading to vasodilation,
decreased blood pressure, and improved cardiovascular function.

4. Mechanism of Action of ACE Inhibitors:
ACE inhibitors dilates the blood vessels and lower the blood pressure by inhibiting
the action of angiotensin-converting enzyme(ACE), an enzyme that helps regulate
blood pressure. ACE inhibitors prevents the conversion of angiotensin 1 to
angiotensin 2(potent vasoconstrictor) which disrupts he renin-angiotensin-
aldosterone system(RAAS).
ACE inhibitors block the break down of bradykinin(a vasodilator) and increases the
amount of bradykinin and thus causing vasodilation(decrease BP).

5. RAAS(Renin-Angiotensin-Aldosterone System)

6. Classification of ACE Inhibitors:
ACE Inhibitor drugs ends with “pril”
Captopril
Enalapril
Lisinopril
Perindopril
Fosinopril
Ramipril
Quinapril

7. Captopril: (Pharmacokinetics)
About 70% of orally administered captopril is absorbed.
 Presence of food in stomach reduces its bioavailability.
 Penetration in brain is poor.
It is partly metabolized and partly excreted unchanged in urine.
 The plasma t½ is ~2 hours, but actions last for 6–12 hours.

8. 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 resulting from the loss of negative feedback
on renin release.
Decreased aldosterone secretion.
Small increase in potassium with sodium.

9. Adverse Effects:
Hypotension: an initial sharp fall in BP occurs especially in diuretic treated and CHF
patients.
Hyperkalemia: This is likely in patients with impaired renal function and in those
taking K+ sparing diuretics, NSAIDs or β blockers.
Cough: a persistent brassy cough occurs in 10–16% patients within 1–8 weeks
Dysgeusia: reversible loss or alteration of taste sensation

10. Contraindication:
1) Hypersensitivity
2) Stenosis
3) Renal impairment
4) Pregnancy
Dose: 25mg BD or 50mg TDS.

11. Enalapril (Pharmacokinetics):
This is the second ACE inhibitor to be introduced.
It is a prodrug, deesterified in the liver to enalaprilat (a tripeptide analogue), which
is not used as such orally because of poor absorption
Its absorption is not affected by food.
 Onset of action is slower (due to need for conversion to active metabolite), less
liable to cause abrupt first dose hypotension.
 Has a longer duration of action.

12. 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 rennin
activity, lower concentrations result in a decrease in blood pressure. Enalaprilat may
also act on kininase II, that degrades the vasodilator bradykinin.

13. Dose: effective dose 5–20 mg OD or BD.
Side effects:
1) Hypotension
2) Dizziness when standing up and dry cough.
Special precautions:
1) Impaired renal failure
2) Hyperkalaemia

14. Ramipril (Pharmacokinetics):
Bioavailability: 28%
Protein binding: 73% (Ramipril) , 56% (Ramiprilat)
Metabolism: Hepatic to Ramiprilat
Half Life: 2-4 hrs.
Excretion: Renal(60%) , Fecal(40%)

15. Contraindication: Reno vascular diseases, severe renal impairment, history of
angioedema while on an ACE inhibitor, hypotension
Side effects: low blood sugar, drug cough, dizziness and light headedness,
omitting, diarrhea
Doses: Initial dose of 2.5mg OD for week,5mg OD for next 3 weeks, and
maintenance dose: 10mg OD

17. Uses:
1. Hypertension: The ACE inhibitors are first line drugs in all grades of
hypertension, but the angiotensin receptor blockers (ARBs) have now surpassed
them in popularity.
2. CHF: ACE inhibitors cause both arteriolar and venodilation in CHF patients;
reduce afterload as well as preload on heart and improve all hemodynamic
parameters.
3. Diabetic nephropathy: Prolonged ACE inhibitor therapy has been found to
prevent or delay end-stage renal disease in type I as well as type II diabetics.

18. 4. Myocardial infarction (MI): Several mega trials have established that oral ACE
inhibitors administered while MI is evolving (within 24 hr. of an attack) and
continued for 6 weeks reduce early as well as long-term mortality, irrespective of
presence or absence of systolic dysfunction, provided hypotension is avoided.

19. Angiotensin Receptors:
AT 1
found in blood vessels, heart, kidneys,
and adrenal glands
GPCR
Mediates vasoconstriction in blood
vessels.
Stimulates aldosterone release from
adrenal glands.
Promotes sodium and water
retention.
AT 2
Foetus, Adrenal Medulla- Adults
GPCR
Counteracts AT1 effects, promoting
vasodilation.
Associated with anti-proliferative
effects.
May play a role in tissue repair.

20. Angiotensin Receptor Blockers:
ARBs treat high blood pressure(hypertension), heart failure, chronic kidney disease,
kidney failure in diabetes.
Classification of ARBs: ARBs ends with “Sartan”
Losartan
Valsartan
Candesartan
Irbesartan
Telmisartan
Olmesartan
Azilsartan

21. Mechanism of Action:
Angiotensin receptor blockers block the action of angiotensin II by blocking
the activation of angiotensin II receptor type 1 (AT1) which disrupts RAAS.
Angiotensin receptors are found in smooth muscle cells of vessels, adrenal
gland etc. As a result, ARBs allows your veins and arteries to dilate reduces
secretion of vasopressin which decreases the BP and make it easier for the
heart to pump blood.

22. Losartan (Pharmacokinetics):
Oral absorption of losartan is not affected by food.
but bioavailability is only 33%
It is partially carboxylated in liver to an active metabolite (E3174)
peak plasma levels are attained at 1 hr. for losartan and at 3–4 hours for
E3174.
98% plasma protein bounding.
The plasma t½ of losartan is 2 hr., but that of E3174 is 6–9 hr.

23. Side effects:
1)Hypotension
2)Hyperkalemia
3) Nausea
4) Vomiting
5) Diarrhea
Dose: 50 mg OD, in liver disease or volume depleted patients 25 mg OD

24. Candesartan (Pharmacokinetics):
Candesartan has an oral bioavailability of approximately 15-40%
Elimination occurs by both hepatic metabolism and renal excretion
Half-life of candesartan is relatively long, averaging around 8-12 hours
Action lasts 24 hours
Dose: 8 mg OD liver/kidney impairment 4 mg OD.