W3, 6 Pharma RAAS Flashcards
Components of the Renin-Angiotensin System
RAS is also expressed locally. In what organs & systems?
RAAS system
What’s the advantage of ARBs over ACEI ?
What are Alternate pathways of angiotensin II production? (Not involving ACE)
Angiotensin acts through what receptors?
- AT 1-receptors
- AT2-receptors
what are Pharmacological actions of Angiotensin II ?
Ang II type 1 (AT1R) receptor
A. What type of receptor?
B. Where is it expressed?
C. Action?
Pharma cological ations of AngII mediated by AT1- receptors
- Constriction of resistance vessels to increase systemic vascular resistance and blood pressure
- Stimulation of vascular, cardiac and renal hypertrophy
- Stimulation of sodium transport (Na/H+ exchanger) at several regions of the tubule leading to sodium and water retention
- Stimulation of antidiuretic hormone (vasopressin) release - water retention
- Enhancement of sympathetic nerve activity
- Contraction of intestinal smooth muscles
What are Selective antagonists of AT1R?
losartan, valsatan, telmisartan (drugs ending “tan” are selective AT1R blockers)
Ang II type 2 (AT2R) receptor
A. Type
B. Location
C. Action
Ang II type 2 (AT2R) receptor selective agonist & antagonist
• Selective antagonists –PD 123319
• Selective agonist -CGP42112
Pharmacological actions mediated by AT2-receptor activation
- Vasodilation – by increasing production of bradykinin, Nitric oxide and cGMP.
AT2-receptor activation reduces BP when AT1-receptor is blocked. - Inhibition of growth and cardiac remodeling
- Possible mediation of some beneficial effects of AT1-receptor blockade
Renin Inhibitors drug is
e.g. Aliskiren
Aliskiren
A. Used to trat …
B. What Type of inhibitor
Aliskiren
A. Orally active or not?
B. Peak Plasma concentration is reached within … hours?
C. Metabolized by ..?
D. Elimination?
A. Aliskirenis orally active with a very low bioavailability (~2.5%).
B. reached within 1–6 hours after oral administration
C. metabolized by cytochrome P450 enzyme 3A4.
D. More than 90% is eliminated unchanged in the feces, <2% is
eliminated as oxidized metabolites, and <1% is eliminated in the urine.
Common adverse events of aliskiren include:
• Headache
• Dizziness
• Fatigue.
• Dose-related gastrointestinal events.
• A slight increase in cough (much less than ACE inhibitors).
• Hyperkalemia which is worsened when used in combination with an ACE inhibitor.
What drug is useful in hypertensive diabetic patients?
ACE inhibitors
Actions of ACE inhibitors
• Prevent the conversion of AngI into AngII –reduce systemic vascular resistance, reduce intravascular volume
What’s the main Side effect of ACEI?
•Decrease bradykinin degradation –high levels of bradykinin - cough
Uses of ACE inhibitors
•Mild to severe hypertension
•Congestive heart failure
•Diabetic nephropathy.
Side effects of ACEI ?
- Hypotension
- Cough
- Hyperkalemia
- Renal failure
- Fetal anomalies
- Angioedema
- Neutropenia
Angio tensin receptor blockers
e.g. losartan,valsartan
ARBs administration and action
These are orally effective competitive antagonists of AT1 receptors – reduce blood pressure. They also reduce arteriolar and ventricular remodeling
