Aliskiren, a direct renin inhibitor

Question 1

Aliskiren

Answer 1

Only DRI available

Question 2

Direct Renin Inhibitor Mechanism

Answer 2

-Act on renin to inhibit the conversion of angiotensinogen into angiotensin 1
-by decreasing the production of angiotensin 1, DRIs can suppress the entire RAAS

Question 3

DRI Therapeutic Uses

Answer 3

Only approved for Hypertension
-may be used alone or in combination with other antihypertensives
-maximal effects developed within 2 weeks

Question 4

DRI pharmacokinetics

Answer 4

-administered orally
-Dosing with high fat meal makes availability much lower (0.8%)
-undergoes some metabolism by CYP 3A4
-about 25% of the drug is eliminated in the urine
-half-life is 24 hours

Question 5

Adverse effects DRI

Answer 5

-angioedema and cough (less risk than ACE inhibitors)
-GI effects (can cause dose-dependent diarrhea; older adults and women are more susceptible)
-Hyperkalemia (if combined with other ace inhibitors, k sparing diuretics and K supplements)
-fetal injury and death