ACE Inhibitors and ARBs Flashcards Preview

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Flashcards in ACE Inhibitors and ARBs Deck (29)
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1
Q

Where is angiotensinogen synthesized and what increases its production?

A

Synthesized in liver

Production increased by corticosteroids, estrogens, thyroid hormones and angiotensin II

2
Q

What is angiotensin I?

A

Substrate for ACE that has minimal biologic activity

3
Q

Where does angiotensin II exert its effects?

A

Vascular smooth muscle (contraction)
Adrenal cortex (stimulate aldosterone synthesis)
Kidney (inhibits renin secretion)
Heart (cardiac hypertrophy)
Brain (resets baroreceptor reflex of HR to higher pressure)
Regulates fluid/electrolyte balance and arterial BP

4
Q

How does AT II compare to epinephrine in terms of vasoconstriction?

A

It is 40x more potent

5
Q

What determines the rate of synthesis of AT II and what removes it from circulation?

A

Secretion of renin from kidneys

Angiotensinase removes it rapidly

6
Q

What 2 substrates does ACE act on and where is it found in the body?

A
AT I (cleaves carboxy-terminal two AA) + bradykinin (vasodilator)
Found in luminal surface of vascular endothelial cells in most tissues
7
Q

What are the 2 receptors for AT II and what are the effects?

A

AT1 (more common) = Gq that results in smooth muscle contraction
AT2 = bradykinin/NO production that results in vasodilation

8
Q

What does aldosterone act on and what are its end effects?

A

Increases activity of ENaC and basolateral Na/K ATPase in DCT and cortical collecting renal tubules
Results in increase in Na reabsorption and K secretion –> retention of water, increase in blood V, increase in BP and hypokalemia

9
Q

What is the MOA of ACEi?

A

Inhibit ACE and prevent inactivation of bradykinin

10
Q

How to ACEi lower BP?

A

Decrease peripheral vascular resistance with minimal effects on CO (makes it good drug for athletes)

11
Q

What are ACEi used for?

A

HTN, nephropathy (+/- diabetes), heart failure, left ventricular dysfunction (after MI), AMI and prophylaxis of cardiovascular events

12
Q

Adverse effects of ACEi

A

Hypotension, acute renal failure (esp in pts with renal A stenosis), hyperkalemia (more likely in renal insufficiency/diabetes), dry cough, angioedema

13
Q

How does ACEi cause acute renal failure?

A

Both afferent and efferent arterioles are dilated and GFR is not maintained in hypoperfused states

14
Q

What is the most common side effect of ACEi?

A

Dry cough since it interferes with breakdown of bradykinin

15
Q

What can ACEi cause if given during pregnancy?

A

Teratogenicity in 1st trimester

Fetal hypotension, anuria, renal failure, fetal malformations and even death in 2nd/3rd trimesters

16
Q

What other drugs can interact with ACEi and what results?

A

K+ supplements/K+ sparing diuretics –> hyperkalemia

NSAIDs –> may block bradykinin-mediated vasodilation

17
Q

What 2 ACEi do not have an active metabolite?

A

Captopril (half life 2 hours)

Lisinopril (half life 12 hours)

18
Q

Which ACEi is used for hypertensive emergencies?

A

Enalaprilat (active metabolite of Enalapril)

19
Q

MOA of angiotensin receptor blockers (ARBs)?

A

Selective blockage of AT1 receptors with no effect on bradykinin metabolism

20
Q

What are the effects of ARBs?

A

Relaxation of vascular smooth M, pressor responses, blockage of aldosterone secretion, changes in renal function, cellular hypertrophy and hyperplasia

21
Q

Differences between ARBs and ACEi?

A

ARBs block AT1 more effectively and promote AT2 activity

ACEi increase levels of bradykinin

22
Q

Adverse effects/contraindications of ARBs?

A

Similar to ACEi with lower rates of cough and angioedema
Do not use with K supplements or K sparing diuretics
Do not give during pregnancy or in patients with nondiabetic renal disease

23
Q

Which ARB is metabolized to more potent metabolite?

A

Losartan - shortest half life of 2 hours and peak plasma levels after 1 hr

24
Q

If I want to block the secretion of renin, what drugs would I want?

A

Clonidine and propranolol

25
Q

MOA of clonidine?

A

a2-agonist at brainstem

Inhibit sympathetic vasomotor centers resulting in reduction in sympathetic activity by decreasing renin secretion

26
Q

MOA of propranolol?

A

B1-antagonist at juxtaglomerular cells
Decreases renin release –> decreases BP
Decreases CO which also contributes to BP decrease

27
Q

What’s the name of an oral renin inhibitor and how is different from ACEi, ARBs and diuretics?

A

Aliskiren
Produces dose-dependent REDUCTION in plasma activity (whereas other drugs increase plasma renin activity)
See antihypertensive effects within 2 weeks
Do not use in pregnancy or patients with kidney insufficiency

28
Q

Why use polytherapy in HTN?

A

Monotherapy may not be effective - want to add on another drug with different MOA/pattern of toxicity

29
Q

Where is renin synthesized, what stimulates its release and what does it do?

A

Synthesized/stored in juxtaglomerular apparatus in nephron
Activation of B1- adrenergic receptors stimulates release
Cleaves decapeptide angiotensin I from angiotensinogen