ACE Inhibitors and ARBs Flashcards
What stimulates renin release from the juxtaglomerular cell?
decreased sodium delivery at the macula densa, decreased renal blood flow, sympathetic activation (beta-1 receptors)
What are the key effects of angiotensin II?
vasoconstricts, enhances SNS activity centrally and peripherally, increases aldosterone, causes fluid retention, promotes growth, inhibits renin production (quick feedback)
What are the key effects of bradykinin?
vasodilation, natriuresis
What are the actions of ACE?
cleave Ang I to Ang II (acitvating); cleave bradykinin (inactivating)
Which ACE inhibitor has a sulfhydryl group at the zinc ligand site?
captopril
What is the general route of elimination for ACE inhibitors?
renal
Give an example of a carboxyl-containing ACEI.
lisinopril
Which ACEI has the shortest half-life?
captopril
Clinical indications for ACE inhibitors
HTN, CHF, chronic diabetic nephropathy, ischemic heart disease
What is the MOA of ACE inhibitors?
blocks the conversion of Ang I to Ang II and the degradation of bradykinin, decreasing SVR
How does ACEI lowering of SVR affect heart rate?
ACE inhibitors do not increase HR
How does plasma renin activity correlate with ACEI efficacy in treating HTN?
more effective in treating patients with normal to high renin
How do ACEIs help in treating CHF?
reduce afterload and systolic wall stress, increase CO w/o increasing HR, increase renal plasma flow-natriuresis
How do ACEIs help in treating diabetic nephropathy?
decrease glomerular capillary pressure, decrease proteinuria, anti-proliferative
Adverse effects of captopril
skin rash, neutropenia
Class-specific adverse effects of ACEIs
fetal anomalies, hypotension, hyperkalemia, cough, renal failure, angioedema
What is the mechanism of ACEI-induced renal failure?
perfusion (afferent areteriolar) pressure decreases in the setting of renal artery stenosis, e.g.; Ang II would maintain glomerular filtration by efferent arteriolar vasoconstriction, but it is blocked
ACEI drug interactions
K-sparing diuretics, K supplements, NSAIDs (interfere w/ anti-hypertensive effects), antacids (decrease bioavailability), capsaicin (cough)
What is an important difference between ACEIs and ARBs?
ACEIs increase bradykinin, ARBs may not affect to same degree (benefits vs. side effects of this)
Which ARB has an active metabolite?
losartan
adverse effects of ARBs
hypotension, hyperkalemia, GI, hepatotoxicity
What is the half-life of losartan?
2 h (prodrug), 9 h (metabolite)
Give an example of a renin inhibitor
aliskiren
Pharmocokinetics of aliskiren
low bioavailability, long half-life (44 h)
Important result from aliskiren study
increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension in patients taking aliskiren + ACEI or ARB
ARBs and ACEIs may reduce new onset of this disease
diabetes
