ACE inhibitors and ARBs Flashcards
what cells produce renin
JG cells in the afferent artery in the kidney
why is renin produced
it is produced when the JG cells detect under perfusion to the afferent arterioles.
what does renin do
renin cleaves angiotensinogen (made by the liver) to angiotensin-1.
once produced what happens to AT1
in the lungs its converted to AT2 by ACE.
AT2 is a powerful vasoconstrictor
what does AT2 do
binds to the ATR
binding to the ATR1 causes smooth muscle contraction in the blood vessel - hence the powerful vasoconstrictor effects of AT2
AT2 stimulates the posterior pituitary to release ADH. ADH acts on the kindeys to increase water and Na+ uptake.
stimulates release of aldosterone from the adrenal cortex. acts on DCT increasing Na+ and thus water reabsorption.
so AT2 can increase blood pressure.
this at the ATR1
suffix of the ACE inhibitors and the ARBs
ACE inhibitor is the ‘pril drug
ARB is the ‘sartan drug
bradykinin is a vasodilator hormone, whats this got to do with anything
ACE breaks down bradykinin
what effects do ACE inhibitors such as enalapril have
decreased levels of AT2 means there is less vasoconstriction - thus reducing preload and afterload.
also less levels of ADH released as post pituitary isn’t stimulated so less Na+ and H20 retention.
less adrenal cortex stimulation so there is less aldosterone release so same as above.
(this does lead to K+ retention)
there is also increased levels of the vasodilator bradykinin.
enalapril pharmacokinetics
given orally with good oral absorption, cleared as an active metabolite.
enalapril is a prodrug which gets metabolised to enalaprilat via first pass metabolism in the liver
half life 11-14 hours and active 24-36 for enalaprilat.
what are our theraputic uses for ACE inhibitors such as enalparil
the main first-line indicated use is use in treating hypertension as dilation of arteies and veins reducing preload and afterload. there is also total volume loss in the kidneys
for same reason as above its good in CHF
adverse effects of ACE inhibitors
persistent dry cough, can rarely have angiodema - these first two are due to the increased bradykinin levels, also get rash, dysguesia,
how do the ARBs such as candesartan work
these block the ATR1 thus causing less pathological effect that occurs when AT2 binds to the ATR1. so there is less vasoconstriction, less aldosterone secretion, less ADH secretion, less sympathetic activation, less fibrosis of heart stuff.
all this plus less bradykinin build up.
why would the ARB be better than the ACE inhibitor
ARB blocks only the ATR1 so the AT2 can still bind to the ATR2 and have the positive health effects it needs to. also there is less bradykinin build up with ARBs so there is less dry cough and angiodema,
indications of ARBs
the same as ACE inhibitors. these are given when the ACE inhibitors are not greatly tolerated.
ARB side effects
Hypotension, dizziness, headache
Rash!
GI stuff – nausea, vomiting and diarrhoea
Cough! … But not usually
Hyperkalaemia (elevated K+ levels), due to inhibited aldo formation,
teratogenic
