Kruse ARBs

Question 1

Angiotensin receptor blockers (ARBs): MOA

Answer 1

blocks AT1 receptors, which cause vascular smooth muscle contraction. pressor effects counter angiotensin II vasoconstrictor effect.

cause selective blockade of angiotensin II receptors (AT1-type)

Question 2

AT1 receptors

Answer 2

blocked by ARBs: AT1 receptors are Gq-protein coupled receptors that, when activated, result in activation

of phospholipase C, production of inositol triphosphate (IP3) and diacylglycerol (DAG),

and smooth muscle contraction

Question 4

Angiotensin II receptor II blocker clinical indications

Answer 4

1. hypertension
2. diabetic nephropathy
3. acute myocardial infarction
4. heart failure
5. left ventricular dysfunction

Question 5

Inhibition of angiotensin II activity

Answer 5

Inhibition of angiotensin II activity includes

1. blockade of angiotensin II-induced contraction of vascular smooth muscle
2. pressor responses
3. aldosterone secretion
4. changes in renal function
5. cellular hypertrophy
6. hyperplasia

Question 6

Differences between ARBs and ACEIs

Answer 6

ARBs reduce activation of AT1 receptors more effectively than do ACEIs

ARBs permit activation of AT2 receptors

ACEIs increase the levels of a number of ACE substrates, including bradykinin

Question 7

Toxicity and adverse effects of ARBs

Answer 7

1. ARB adverse effects: similar to those of ACEIs but cough & angioedema occur at significantly lower rates
2. ARBs: not recommended during pregnancy or in patients with nondiabetic renal disease

Question 8

ARBs are not recommended for whom?

Answer 8

1. ARBs are not recommended during
   
   1. pregnancy
   2. in patients with nondiabetic renal disease
   3. patients with concomitant use of
      • potassium supplements
      • potassium sparing diuretics

Answer 9

1. Azilsartan
2. Candesartan
3. Eprosartan
4. Irbesartan
5. Losartan (active metabolite)
6. Olmesartan
7. Telmisartan
8. Valsartan

Question 10

Losartan

Answer 10

metabolized by CYP450 enzymes to a more potent metabolite (14% of dose)

Question 11

Renin secretion blockers

Answer 11

clonidine and propanolol

Question 12

clonidine

Answer 12

renin secretion blocker

(1) MOA: an agonist of α2-receptors in the brainstem
(2) When stimulated, α2-receptors cause inhibition of sympathetic vasomotor centers,

resulting in a centrally mediated reduction in renal sympathetic nerve activity (3) Ultimate effect is a reduction of renin secretion.

Question 13

propanolol

Answer 13

Propranolol (and other β-blockers)

(1) MOA: nonspecific antagonist of adrenergic β-receptors
(2) Act on juxtaglomerular cells by blocking β1-receptor stimulated release of renin and

thereby decreases blood pressure (also decreases BP by decreasing cardiac output and decreasing sympathetic outflow from the CNS)

Question 14

renin inhibitors

Answer 14

Aliskiren

• the first effective oral renin inhibitor
• approved by the FDA in 2007 for the treatment of hypertension

Question 15

Aliskiren MOA

Answer 15

Aliskiren produces a dose-dependent reduction in plasma renin activity, resulting in

decreased angiotensin I and II and aldosterone concentrations

requires around 2 weeks to produce up to a 90% effect on blood pressure

Question 16

in some drugs, plasma renin levels rise, in others they fall

Answer 16

aliskerin: renin inhibitor– causes renin levels to fall in the body

ACEI and ARBs–cause renin levels in the body to increase

Question 18

aliskerin clinical notes

Answer 18

1. Possible fetal and neonatal morbidity and mortality when used during pregnancy
2. use withcaution in patients with kidney insufficiency

Question 19

treating hypertension when one drug does not work

Answer 19

add another

In practice, when hypertension does not respond adequately to a regimen of one drug, a second drug from a different class with a different MOA and different pattern of toxicity is added