ACE Inhibitors and ARBs Flashcards
Where is angiotensinogen synthesized and what increases its production?
Synthesized in liver
Production increased by corticosteroids, estrogens, thyroid hormones and angiotensin II
What is angiotensin I?
Substrate for ACE that has minimal biologic activity
Where does angiotensin II exert its effects?
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
How does AT II compare to epinephrine in terms of vasoconstriction?
It is 40x more potent
What determines the rate of synthesis of AT II and what removes it from circulation?
Secretion of renin from kidneys
Angiotensinase removes it rapidly
What 2 substrates does ACE act on and where is it found in the body?
AT I (cleaves carboxy-terminal two AA) + bradykinin (vasodilator) Found in luminal surface of vascular endothelial cells in most tissues
What are the 2 receptors for AT II and what are the effects?
AT1 (more common) = Gq that results in smooth muscle contraction
AT2 = bradykinin/NO production that results in vasodilation
What does aldosterone act on and what are its end effects?
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
What is the MOA of ACEi?
Inhibit ACE and prevent inactivation of bradykinin
How to ACEi lower BP?
Decrease peripheral vascular resistance with minimal effects on CO (makes it good drug for athletes)
What are ACEi used for?
HTN, nephropathy (+/- diabetes), heart failure, left ventricular dysfunction (after MI), AMI and prophylaxis of cardiovascular events
Adverse effects of ACEi
Hypotension, acute renal failure (esp in pts with renal A stenosis), hyperkalemia (more likely in renal insufficiency/diabetes), dry cough, angioedema
How does ACEi cause acute renal failure?
Both afferent and efferent arterioles are dilated and GFR is not maintained in hypoperfused states
What is the most common side effect of ACEi?
Dry cough since it interferes with breakdown of bradykinin
What can ACEi cause if given during pregnancy?
Teratogenicity in 1st trimester
Fetal hypotension, anuria, renal failure, fetal malformations and even death in 2nd/3rd trimesters
What other drugs can interact with ACEi and what results?
K+ supplements/K+ sparing diuretics –> hyperkalemia
NSAIDs –> may block bradykinin-mediated vasodilation
What 2 ACEi do not have an active metabolite?
Captopril (half life 2 hours)
Lisinopril (half life 12 hours)
Which ACEi is used for hypertensive emergencies?
Enalaprilat (active metabolite of Enalapril)
MOA of angiotensin receptor blockers (ARBs)?
Selective blockage of AT1 receptors with no effect on bradykinin metabolism
What are the effects of ARBs?
Relaxation of vascular smooth M, pressor responses, blockage of aldosterone secretion, changes in renal function, cellular hypertrophy and hyperplasia
Differences between ARBs and ACEi?
ARBs block AT1 more effectively and promote AT2 activity
ACEi increase levels of bradykinin
Adverse effects/contraindications of ARBs?
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
Which ARB is metabolized to more potent metabolite?
Losartan - shortest half life of 2 hours and peak plasma levels after 1 hr
If I want to block the secretion of renin, what drugs would I want?
Clonidine and propranolol
