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
ARBs can be used to treat:
•Hypertension
•Heart failure
•Kidney failure in diabetes
•Chronic kidney diseases
Side effects of ARBs
•Dizziness
•Elevated blood potassium level (hyperkalemia)
•Localized swelling of tissues (angioedema)
•Orthostatic hypotension (early in the treatment)
Newer pathways of Angiotensin I metabolism
What drugs are Useful in patients who cannot tolerate ACE inhibitors
ARBs
What drug Can be detected in the kidneys for up to 3 weeks after
discontinuation of treatment (whereas its plasma levels become
undetectable at an earlier time)
Aliskiren
What drug is Thought to be more effective in reducing blood pressure and ventricular hypertrophy
Aliskiren
Administration of ACE inhibitors is accompanied by:
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