ACE Inhibitors and ARBs DSA I Flashcards
ANP
vasodilator - inhibits RAAS
renin
released with sympathetic activation of beta-1 receptors on JG cells
angiotensinogen
synthesized in liver
> ANG I (renin)
-can be increased in inflammation, corticosteroids, insulin, estrogen, thyroid, ANG II
ANG I
> ANG II (ACE)
ANG II
activates GPCRs
-rate of synthesis - depends on renin
EFFECTS
- vasoconstriction vas. smooth m
- adrenal - aldosterone
- renin inhibition from kidney (- feedback)
- heart - hypertrophy/remodeling
- brain - baroreceptor to higher set point
ACE
activates ANG I > ANG II
inactivates bradykinin > inactive metabolite
ANG II receptor
GPCRs - AT1 and AT2
AT1 - major in adults
-PLC > IP3 and DAG > smooth m. contraction
AT2 - bradykinin and NO production (vasodilation)
aldosterone
increased reabsorption of Na - DCT and collecting tubules
increased ENaC and Na/K ATPase
-increased Na reabsorption and K secretion
ACE inhibitors
inhibit ANG II formation and bradykinin inhibition
-decrease TPR ** (good in physically active patients)
BP agents for athletes
ACE inhibitors
ACE inhibitor clinical use
HTN, nephropathy, heart failure, left V dysfunction, AMI, prophylaxis of CVD events
ACE inhibitor toxicity
hypotension ARF (renal a stenosis ) hyperkalemia cough** angioedema
ACE inhibitor contraindication
pregnancy
-fetal hypotension, anuria, renal failure, fetal malformation, tetarogen during first trimester
ACE inhibitor drug drug interactions
potassium supps and K sparing diuretics
-hyperkalemia
NSAIDs - block hypertensive effects (bradykinin prostaglandin mediated)
ARBs
selective blockade of AT1 receptors
-decreased smooth m contraction
AT1 receptors
GPCR > PLC > IP3 and DAG > smooth muscle contraction
ARB clinical use
HTN, diabetic nephropathy, HF, left ventricular dysfunction, AMI, prophylaxis for CV events
effects of ARBs
(-) of ANG II
- block smooth m contraction
- decreases pressor response
- decreased aldosterone
- changed renal function
- decreased cellular hypertrophy and hyperplasia
ACE (-) vs. ARB
ARB - only at AT1 receptors
ARB toxicity
- lower cough and angioedema
- not recommended during pregnancy
losartan
metabolized by CYP450 to more potent metabolite
clonidine
alpha-2 agonist in brainstem - blocks renin secretion
propanolol
non-selective beta agonist
- block JG cell beta-1 release of renin
- decrease blood pressure
aliskiren
direct renin inhibitor
-decreased ANG I, ANG II, and aldosterone
fetal and neonatal morbidity in pregnancy
use with caution in patients with kidney insufficiency
