Angiotensin receptor blockers

1. ANGIOTENSIN RECEPTOR BLOCKERS [ARBS]
DR PADMAVATHI S
ASSOCIATE PROFESSOR - DEPT OF PHARMACOLOGY

2. ANGIOTENSIN
ANTAGONISTS

4. ANGIOTENSIN RECEPTORS
AT1
 VASCULAR S. M, MYOCARDIUM
 GPCR
 VASOCONSTRICTION
CELL GROWTH IN HEART & ARTERIES
SECRETION OF ALDOSTERONE
PERIPHERAL SYM. ACTIVITY INCREASED
AT2
 FOETUS, ADRENAL MEDULLA – ADULTS
 GPCR
 VASODILATATION
ANTI-PROLIFERATIVE
APOPTOSIS

5. COMPETITIVE blockers

6. ARBS  SARTANS
 LO SARTAN
 CANDESARTAN
 IRBESARTAN
 VALSARTAN
 OLMESARTAN
 TELMISARTAN

7. MAJOR ADVERSE EFFECT DUE TO TREATMENT WITH ACE INHIBITORS
NOT SEEN WITH
ARBS
?

8. ARBS VS ACE INHIBITORS
 DO NOT INTERFERE WITH DEGRADATION OF BRADYKININ – COUGH IS RARE
 COMPLETE INHIBITION OF AT1 RECEPTOR ACTIVATION
 INDIRECT AT2 ACTIVATION

9. INDIVIDUAL DRUGS
 LOSARTAN – HIGH FIRST PASS METABOLISM,
NO DOSE ADJUSTMENT – RENAL / LIVER DISEASE
 CANDESARTAN – NON COMPETITIVE ANTAGONISM
 VALSARTAN – ABSORPTION AFFECTED BY FOOD
 OLMESARTAN – NO DOSE ADJUSTMENT
PRODRUG

10. ADVERSE EFFECTS
HYPOTENSION
HYPERKALEMIA
TERATOGENECITY

11. USES
 HYPERTENSION
 CONGESTIVE HEART FAILURE
 MYOCARDIAL INFARCTION
 DIABETIC NEPHROPATHY

12. PREVENTS
REMODELING

13. Bilateral

15. CAN WE COMBINE
ARBS WITH ACE INHIBITORS?

16. THEORETICAL REASONS
 MORE COMPLETE SUPPRESSION OF RAS
 ANGIOTENSIN II GENERATED BY ALTERNATE PATHWAYS BLOCKED BY ARBS
 ACE INHIBITORS – BRADYKININ RELATED VASODILATATION
 ARBS – COMPENSATORY RISE IN ANG II  checked by ACEI

18. DIRECT RENIN INHIBITOR
ALISKIREN