Renin angiotensin system

pharmacology

1. DRUGS INHIBITING
THE RENIN-
ANGIOTENSIN
SYSTEM

2. •Renin release is stimulated in response
to:
•1.
↓
Arterial Pressure
•2. Dehydration, hemorrhage
•3. Hyponatremia

3. DRUGS INHIBITING THE RENIN-
ANGIOTENSIN SYSTEM
•ACE Inhibitors
Captopril Benazepril
Enalapril Quinapril
Lisinopril Ramipril
FosinoprilTrandolapril
Angiotensin Receptor Blockers
Losartan Valsartan
CandesartanEprosartan
IrbesartanTelmisartan
Drugs which block Renin secretion
Beta-blockers
Clonidine
Alpha-methyldopa

4. ACE INHIBITORS (ACEIS)-
MECHANISM OF ACTION
1-These drugs inhibit the enzyme
Angiotensin Converting Enzyme.
This leads to decreased formation of
Angiotensin II causing decreased
vasoconstriction and decreased
release of aldosterone and hence less
salt and water retention

5. 2-This enzyme in the name of plasma kininase inactivates
bradykinin, a potent vasodilator.
By inhibiting this enzyme, the breakdown of bradykinin
decreases, thus increasing its concentration and hence
increasing vasodilatation.

7. ANGIOTENSIN RECEPTORS
•AT1 GPCR
• to date, effects of AII, AIII are believed to
•be mediated by this receptor
•• stimulates phospholipase C (PLC)
→ ↑
Ca2+,
•protein kinase C (PKC) activation
•• inhibits adenylyl cyclase, stimulates
•phospholipase A2 (PLA2)
•AT2 GPCR
•• Does not activate PLC or Ca2+ signaling
•• Function (?)
•AT3 GPCR
•• Also mediates
↑
Ca2+

8. ANGIOTENSIN RECEPTOR
BLOCKERS (ARBS)-MECHANISM
OF ACTION
These drugs are competitive
antagonists at Angiotensin II Type 1
Receptors.
They provide a much more complete
inhibition of Angiotensin II because
there are pathways other than ACE
that are capable of generating
Angiotensin II

10. OTHER ACTION (BOTH ACEI
AND ARBS)
They decrease proteinuria and stabilize renal function
This is due to improved intrarenal hemodynamics with
decreased glomerular efferent arteriolar resistance and a
resulting reduction of intraglomerular capillary pressure

11. •These drugs also decrease cardiac
remodeling
•Increased Angiotensin causes increased
aldosterone secretion and increased salt
and water retention that causes cardiac
remodeling
•Cardiac remodeling is dilation & other
structural changes that occur in the
stretched myocardium (ultimately
myocytes may die through apoptosis)

12. USES OF HYPERTENSION
1. Hypertension
By decreasing TPR due to decreased formation of
Angiotensin II and decreased CO due to decreased salt
and water retention and thus decreased EDV and hence
Stroke volume
BP = CO X TPR
2. CCF

13. 3. Diabetic Nephropathy
This is due to improved intrarenal hemodynamics with
decreased glomerular efferent arteriolar resistance and a
resulting reduction of intraglomerular capillary pressure
4.Used even in those patients with diabetic nephropathy who
are not hypertensive
5.Post myocardial infarction
6.Scleroderma crisis
7.Captopril test
8-Portal hypertension (receptor blockers are used)

14. ADVERSE EFFECTS
1. Severe Hypotension
2. Acute Renal Failure (Especially in Bilateral Renal
Artery Stenosis)
3. Hyperkalemia
4. Dry cough, wheezing and angioedema (Due to
bradykinin and Substance P); seen only with ACE
Inhibitors
5. Altered sense of taste( dysguesia), allergy
6. Fetopathic

15. CONTRAINDICATIONS
2
nd
and 3
rd
Trimester of Pregnancy
because of the risk of fetal
hypotension, anuria, and renal failure
and fetal malformations and death

16. DRUG INTERACTIONS
1.With potassium supplements and with other drugs that
cause hyperkalemia like Potassium Sparing Diuretics that
can result in Hyperkalemia
2. NSAIDs by inhibiting synthesis of Prostaglandins, may
impair the hypotensive effects of ACE Inhibitors by blocking
bradykinin-vasodilatation which is Prostaglandin mediated

17. Character
ACE Inhibitor Angiotensin
Receptor Blocker
Mechanism of
Action
Inhibit ACE and
decrease
Formation of
Ang. II
Competitive
Antagonist at
Ang. II blockers
Bradykinin
Metabolism
Decreased
breakdown by
inhibiting
Kininase
No effect
Block of Non-ACE
Pathways
NO YES

18. Character ACE InhibitorsAng. Rec.
Blockers
Adverse EffectsCough,
Wheezing Due to
Bradykinin
No
Drug InteractionDecreased action
with NSAIDs
No