Pharmacology of drugs acting on Renin-Angiotensin-Aldosterone System (RAAS) Easy memorization of drugs using various mnemonics Pictorial representation of drug's mechanism of action Self Assessment questions to understand the topic in better way

1. RENIN-ANGIOTENSIN-
ALDOSTERONE SYSYEM ( RAAS)
INHIBITORS
BY:
Dr. Meenu
Assistant Professor
Pharmacology
NIIMS

3. Actions of AGII

4. Drugs acting on RAAS
Beta blockers
Renin inhibitors
ACE inhibitors
AT1 antagonists ( ARBs)
Aldosterone antagonists
Act by
decreasing
the activity of
RAAS

5. Renin Inhibitors
• Aliskiren
• Remikiren
• Enalkiren.
Can be used orally for the treatment of chronic
hypertension.
Side effects: Diarrhea ( Alsikiren higher dose), cough,
angioedema
Decrease the activity of
RAAS causing fall in blood
pressure

6. Angiotensin Converting Enzyme
Inhibitors (ACEI)
Captopril
( Prototype)
Enalapril
Lisinopril
Ramipril
Perindopril
Trandolapril
Fosinopril
Moexipril
Inhibits the enzyme kininase II or ACE.
Decrease the activity of RAAS
Potentiate the vasodilatory action of
bradykinin.

7. Actions of ACEIs

8. Main Actions of ACEIs

9. CAPTOPRIL
( Prototype)
Important differences between Captopril & other ACEIs
CAPTOPRIL
Less potent
Fast onset
Short duration of action
Less absorption in presence of food in GIT.
Because of short and fast action, it can cause
postural hypotension which is not seen with
other ACEI.

10. IMPORTANT POINTS OF ACEIs
All ACEI are prodrugs except
captopril and lisinopril.
Other drugs like enalapril are
converted to its active metabolite
(enalaprilat) and thus are slow
acting.
Enalaprilat is available
as a separate drug meant for use in
hypertensive emergencies by i.v. route
Perindopril is longest acting
captopril is shortest acting

11. Uses of ACEIs
Hypertension
CHF
Evolving MI
Diabetic nephropathy
Diabetic retinopathy
Non-diabetic renal disease: reduce proteinuria in diabetic
as well as non-diabetic renal disease
Scleroderma crisis. prevent the manifestations of scleroderma
crisis which are mediated by angiotensin II

12. Most frequent adverse effect. Reduced by iron supplements& asprin
Dry
elevated levels of bradykinin
elevated levels of bradykinin

14. An increase in serum creatinine upto 30% within
2-5 days can be expected in most patients
started on ACE inhibitors. It stabilizes in 2-3
weeks and is reversible on stopping drug
therapy

15. CONTRAINDICATIONS
• Pregnancy
• When serum creatinine is more than 3.5
mg/dl.

17. Angiotensin Receptor Blockers
(ARBs)
• Losartan
• Valsartan
• Irbesartan
• Candesartan
• Telmisartan
• Eprosartan
act by
antagonizing the action of
angiotensin II at AT1
receptors.
ARB can be combined with ACEI for various indications as:
ARB act at a distal site, so these will inhibit the activity of RAAS
even when angiotensin II is generated by non-ACE pathway.

18. Special features of losartan are:
– Produce active metabolite
– Has anti-platelet action due to competitive antagonism of TXA2.
– Mild uricosuric effect
Telmisartan has additional PPAR-g agonistic activity.
This activity can help in patients with dysglycemia.
Telmisartan is longest acting
Eprosartan is shortest acting ARB.
All indications, adverse effects and contra-indications of ACEI also
apply to ARB except that incidence of cough and angioedema is
less with ARB(not increase in bradykinin).

19. ALDOSTERONE ANTAGOINSTS ( K+
sparing diuretics)
Spironolactone(reduces
cardiac mortality)
Eplerenone
Block aldosterone hormone
Increase urination
Less fluid in the body--- less BP
Uses
Hypertension
Heart Failure after MI

20. SIDE EFFECTS OF ALDOSTERONE
ANTAGONISTS
• Hyperkalamia
• Dizziness
• Fatigue
• Abnormal Pain
• Gynacomastia
• Cough

23. Which of the following potassium sparing
diuretic reduces cardiac mortality?
(a) Spironolactone
• (b) Amiloride
• (c) Triamterene
• (d) All of these

24. Which of the following antihypertensive drugs
is contra-indicated in pregnancy?
• (a) Amlodipine
• (b) Labetalol
• (c) Enalapril
• (d) Hydralazine

25. Which of the following angiotensin receptor
antagonist contains additional PPAR gamma
agonistic activity?
(a) Olmesartan
• (b) Telmisartan
• (c) Candesartan
• (d) Losartan

26. 179. Which of the following statements regarding
ACE inhibitors is true?
• (a) These inhibit the conversion of
angiotensinogen to angiotensin-1
• (b) Omission of prior diuretic dose decreases the
risk of postural hypotension
• (c) Lisinopril is shorter acting than enalapril
• (d) These are contra-indicated in diabetic
patients.

27. Which of the following ACE inhibitor is NOT a
prodrug?
• (a) Fosinopril
• (b) Enalapril
• (c) Ramipril
• (d) Lisinopril

28. Q . Angiotensin II causes all except:
• (a) Stimulates release of ADH
• (b) Increases thirst
• (c) Vasodilation
• (d) Stimulates aldosterone release

29. Q: All the following statements are true regarding
losartan except:
(a) It is a competitive angiotensin receptor antagonist
(b) It has a long acting metabolite
(c) Associated with negligible cough
(d) Causes hyperuricemia
Q: Enalapril is contraindicated in all of the following
conditions except:
• (a) Diabetic nephropathy with albuminuria
• (b) Single kidney
• (c) Bilateral renal artery stenosis
• (d) Hyperkalemia

30. Q: The most significant adverse effect of ACE
inhibition is:
• (a) Hypotension
• (b) Hypertension
• (c) Hypocalcemia
• (d) Hypercalcemia
Q: All of the following are indications for the use of
ACE inhibitors except:
• (a) Hypertension
• (b) Myocardial infarction
• (c) Left ventricular dysfunction
• (d) Pheochromocytoma

31. Q: ACE inhibitors are contraindicated in:
• (a) Diabetes mellitus
• (b) Hypertension in old age groups
• (c) Scleroderma
• (d) Bilateral renal artery stenosis
Q: Indication of ACE inhibitor in diabetes mellitus is:
• (a) Diabetic nephropathy
• (b) Nephropathy unrelated to diabetes
• (c) Both
• (d) None

32. Q: Cough and angioedema in a patient receiving ACE
inhibitors is due to:
• (a) Bradykinin
• (b) Renin
• (c) Angiotensin-II
• (d) All
Q: The drug of choice in scleroderma induced
hypertensive crisis is:
• (a) ACE inhibitors
• (b) Thiazides
• (c) b-blockers
• (d) Sodium nitroprusside