ACE inhibitors and ARBs Flashcards
1
Q
ACE inhibitors
A
Benazepril Captopril Enalapril Enalaprilat Fosinopril Lisinopril Moexipril Perindopril Quinapril Ramipril Trandolapril
2
Q
Angiotensin receptor blockers
A
Azilsartan Candesartan Eprosartan Irbesartan Losartan Olmesartan Telmisartan Valsartan
3
Q
Drugs that block renin secretion
A
Clonidine
propranolol
4
Q
Renin inhibitor
A
Aliskiren
5
Q
Renin
A
- Aspartyl protease
- Catalyzes conversion of angiotensinogen to angiotensin 1
- Synthesized and stored in the juxtaglomerular apparatus of the nephron
- Sympathetic stimulation activates B1 adrenergic receptors on juxtaglomerular cells, stimulates the release of renin
6
Q
Angiotensinogen
A
- Synthesized in the liver
- Cleaved by renin into angiotensin 1
- Angiotensinogen increased by corticosteroids, estrogens, thyroid hormones, and angiotensin II
7
Q
Angiotensin I
A
- Cleaved to angiotensin II by angiotensin converting enzyme (ACE)
- Pharmacological responses to these peptides are indistinguishable due to the rapid conversion
8
Q
Angiotensin II
A
- Exerts actions at vascular smooth muscle (contraction), adrenal cortex (aldosterone synthesis), kidney (renin secretion inhibition), heart (hypertrophy), and brain (reset baroreceptor)
- Angiotensin II 40x more potent vasoconstrictor than epi
- Most active angiotensin peptide
- Activates GPCR angiotensin II receptor
- Rate determined by renin
- Removed rapidly by angiotensinase
9
Q
Converting Enzyme (ACE)
A
- Converts angiotensin I to angiotensin II
- Bradykinin (vasodilator) is inactivated by ACE
- Widely distributed and on luminal surface of vascular endothelial cells
10
Q
Angiotensin II receptors
A
- AT1 is the major receptor in adults. AT2 is also a receptor. Both GPCR
- AT1 is Gq activating IP3 and DAG causing smooth muscle contraction
- AT2 activates bradykinin and NO causing vasodilation
11
Q
Aldosterone
A
- Promotes reabsorption of Na from distal convoluted tubule
- Increases ENaC and Na/K ATPase to increase Na reabsorption and K secretion
- Causes increased H2O retention, increased blood volume, increased BP and hypokalemia
12
Q
What drugs inhibit the RAAS system?
A
Ace inhibitors and ARBs
13
Q
ACEIs MOA
A
- Inhibition of ACE to conversion to angiotensin II
- Lower BP by decreasing peripheral vascular resistance
- They don’t impact cardiac output or HR
- Approved for HTN, nephropathy, heart failure, left ventricular dysfunction, AMI, prophylaxis of cardiovascular events
- Dosing based on half life
14
Q
Angiotensin receptor blockers (ARBs) MOA
A
- Selective blockade of AT1-type receptors
- No effect on bradykinin metabolism
- Tx for HTN, diabetic nephropathy, HF, left ventricular dysfunction, prophylaxis of cardiovascular events
- Blockade of angiotensin II induced contraction of vascular smooth muscle, pressor responses, aldosterone secretion, changes in renal function, cellular hypertrophy and hyperplasia
15
Q
Differences between ARBs and ACEIs
A
- ARBs reduce activation of AT1 receptors more effectively than do ACEIs
- ARBs permit activation of AT2 receptors
- ACEIs increase the levels of number of ACE substrates including bradykinin
16
Q
ARB toxicities and adverse effects
A
- Cough and angioedema occur at lower rates
- Not recommended in patients with non diabetic renal disease or pregnancy
- Avoid use with potassium supplements or potassium sparing diuretics
17
Q
Clonidine MOA
A
- Agonist of a2-receptors in the brainstem
- a2-receptors cause inhibition of sympathetic vasomotor centers resulting in a centrally mediated reduction in renal sympathetic nerve activity
- Ultimate effect is reduction in renin secretion
18
Q
Propranolol MOA
A
- Nonspecific antagonist of adrenergic B-receptors
- Block B1-receptors on juxtaglomerular cells which release renin and thereby decrease BP
- Also decreases cardiac output and decreases sympathetic outflow from CNS
19
Q
Aliskiren
A
- Renin inhibitor
- Dose-dependent reduction in plasma renin activity, decreased angiotensin I and II and aldosterone concentrations
- *Decrease in baseline renin is in contrast to the rise seen from ACEIs, ARBs, and diuretics
- 85-90% of the effect is in 2 weeks of therapy starting
- Possible fetal and neonatal morbidity and mortality when used during pregnancy
- Use caution in patients with kidney insufficiency
20
Q
Polypharmacy
A
-When HTN doesn’t respond to a regimen enough from one drug, a second is added with a different MOA in order to try and lower it more
21
Q
ACEI adverse effects and contraindications
A
- Adverse effects: hypotension, acute renal failure, renal stenosis, hyperkalemia, dry cough, angioedema
- Common side effect: cough
- Contraindicated in pregnancy: fetal hypotension, anuria, renal failure in 2-3 trimesters; malformations, death 2-3 trimesters; teratogenicity 1st trimester
- Avoid K supplements or K sparing diuretics and NSAIDs
