Drugs that affect Renin Angiotensin System

Question 1

ACEIs:

names

Answer 1

“prils”

Question 2

ACEIs:

MOA

Answer 2

block ACE conversion of Ang I to Ang II

block ACE degredation of bradykinins, ect.

Hypotensive effects result from inhibiting the action of angiotensin II (AII) and stimulating action on the Kallikerin-kinin system.

decrease aldosterone secretion some

Production of renin and AI is increased
– Accumulating AI is directed down alternative metabolic routes,
resulting in increased production of vasodilator peptides as to Ang1-7,
which are believed to be protective (in HF?)

ACEI increases renal blood flow via vasodilation of afferent and efferent arterioles
increase RBF occurs w/out increase in
GFR: thus filtration fraction is decreased

Question 3

ACEIs:

Effects

Answer 3

Decrease TPR and BP in HTN states
dilates arteries and veins

baroreceptors remain in tact
postural Hypotension not a problem

Question 4

ACEIs:

Decrease in BP is&raquo_space; in pts w/…

Answer 4

Na retention OR

high renin

Question 5

ACEIs:

especially good for pts w/..

Answer 5

HF

Question 6

Captopril

Answer 6

increased synthesis of vasodilatory prostaglandins in vascular and renal endothelium

(Delays/ prevents progression of kidney disease in type I diabetics!!!)

renoprotective

Question 7

Enalapril

Answer 7

prodrug converted to enalaprilat

Potent
IV for HTN emergencies

NOT renoprotective

Question 8

Lisinopril

Answer 8

a lysine derivative of enalaprilat; renoprotective.

Question 9

Ramipril

Answer 9

prodrug, activated by deesterification

Long half-life
given once daily

Question 10

ACEIs:

Side effects

Answer 10

1. Hypotension in hypovolemic and/or Na+
   -depleted patients
   – Precipitous first-dose hypotension unless dose is gradually increased.
2. Hyperkalemia (especially with renal insufficiency, or in pts receiving K-sparing diuretics or K supplements).
3. Dry cough (most common),angioneurotic edema or angiodema; both related to bradykinin actions.
   – Bradykinin activates stretch receptors in the trachea, which might causes dry cough in ~10-15% of patients receiving ACEI.
4. Angioedema: (fluid and red blotches in face) infrequent but potentially fatal.
   – Reported with all ACEIs.
5. Fetotoxicity: contraindicated in the 2nd and 3rd trimesters of pregnancy.

Question 11

ARBs:

names

Answer 11

sartans

Question 12

ARBs:

MOA and effects

Answer 12

1. Selectively block AT II type 1 receptors, which are responsible for all of the vascular, renal and central effects of AII.
2. Cause vasodilation and increase Na and H20 excretion. Thus, they decrease TPR, plasma volume, CO, and BP.
3. Have no effect on bradykinin, therefore they are THE substitute when ACEI cause cough.
4. Do not block the action of AII on AT2 receptors, which are thought to be protective.

Question 13

Losartan

Answer 13

prodrug
–One metabolite, EXP 3174, has increased potency as an AT1 receptor antagonist.

• Competitive antagonist of thromboxane A2
receptor; attenuates platelet aggregation.

• Unique in that it increases uric acid urinary excretion (Uricosuric). HTN gout treatment!!
• Inhibits CYP activity.

Question 14

ARB prodrugs

Answer 14

Losartan

Valsartan

Question 15

ARB w/ shortest half-life

Answer 15

Losartan

Valsartan

Question 16

ARB w/ longest half-life

Answer 16

Telmisartan

Question 17

ARB NO renal clearance

Answer 17

Telmisartan

so prefered drug for Rx of HTN in pts w/ renal failure

Question 18

ARB that increases excretion of uric acid

Answer 18

Losartan

Question 19

ARB metabolized by CYP3A4

Answer 19

Losartan

Question 20

Number one selling ARB

Answer 20

Telmisartan

b/c taken once a day [long half-life], w/ no effect with food, CYP3A4, or kidneys

Question 21

ARBs:

side effects

Answer 21

Hypotension
• In hypovolemic and/or Na-depleted patients.

Hyperkalemia
• Especially in renal insufficiency, or in patients using K-sparing diuretics or K supplements.

Hepatic dysfunction
• Reported with Losartan and Valsartan.

Fetotoxicity
• Like ACE inhibitors should not be given to pregnant
women.

Question 22

Renin Inhibitor:
Aliskiren

MOA

Answer 22

Nonpeptide inhibitor of renin (involved in generation of AI from angiotensinogen).

deccreased AII levels.

Question 23

Renin Inhibitor:
Aliskiren

clinical effects

Answer 23

• An effective antihypertensive agent that induces significant dose-dependent decrease in BP.
• As effective as ACEI and ARBs in decreasing BP.

Question 24

Renin Inhibitor:
Aliskiren

Therapeutic uses

Answer 24

Used with other antihypertensive agents such as ACEI or ARB and with a diuretic such as HCTZ.
– Not used as monotherapy

Question 25

Angiotensin II actions

Answer 25

1. Systemic vasoconstriction
2. renal PCT sodium and H20 retention
3. stimulates adrenal cortex–>aldosterone
4. Increases thirst
5. Cardiac and vascular hypertropy (intimal thickening)