Pharmacology of ACEIs, ANG2 Receptor Blockers and Renin Inhibitors

Question 1

what is the goal of antihypertensive therapy

Answer 1

reduce cardiovascular and renal morbidity and mortality

Question 2

what agents affects renin angiotensin system and what do they do

Answer 2

ACEIs- ‘-prils’
ANG2/AT1R antagnoists
prevent generation or binding of ANG2

Question 3

what do Thiazide diuretcs do and give example

Answer 3

increase salt and water excretion
bendroflumethiazide

Question 4

calcium channel antagonists

Answer 4

vasodilate arteries to reduce pressure

Question 5

what do β-adrenoceptor antagonists do

Answer 5

decreases sympathetic stimulation on β1 receptors to reduce renin production
‘-olols’

Question 6

what is RAAS

Answer 6

renin-angiotensin-aldosterone system, a hormone system essential to regulate blood pressure and fluid balance

Question 7

what are the 3 main hormones of the RAAS

Answer 7

renin
angiotensin 2
aldosterone

Question 8

name 4 antihypersensitive drugs used on the RAAS to lower blood pressure and how it does it

Answer 8

renin inhibitors-stops angiotensin 1 production
ACE inhibitors- stops angiotensin 1 to angiotensin 2
ARBs- stops angiotensin 2 producing aldesterone
aldesterone receptor antagonists- stops aldesterone from binding and causing harmful effects
these drugs reduce cardiac output/decreasing peripheral resistance

Question 9

how do antihypersensitive drugs lower blood pressure

Answer 9

decreases ouput of sympathetic nervous system
vasodilates blood vessels
reduces sodium and water retention

Question 10

how does ANG2 cause hypertension via AT1 receptor

Answer 10

vasoconstricts afferent arterioles
reduces synthesis of vasodilator nitrous oxide
stimulates release of aldesterone

Question 11

How do ACE inhibitors work

Answer 11

competitively antagonices ACE enzyme which reduces conversion of ANG1 to ANG2
this dampens AT1 receptor
reduces vascular tone, increases bradykinin which increases NO and Na+ output which leads to vasodilation
this decreases aldesterone release and Na+ reabsorption

Question 12

how do ARBs work

Answer 12

competitively antagonises AT1 receptors in vasculature, adrenal and neuronal tissue to stop ANG2 from binding
this reduces vascular resistance, aldesterone release and Na+ reabsorption

Question 13

How do renin inhibitors work

Answer 13

renin inhibitors ‘aliskiren’ competitively antagonises renin and stops angiotensinogen to ANG1
this reduces ANG2 production and dampens AT1 activation
which then leads to similar results and ACEIs

Question 14

side affects of ACEIs

Answer 14

dry cough
hyperkalaemia- high potassium
skin rash
hypotension- reduced BP
altered taste
dont give to pregnant patients or patients with renal diseases including renal artey sterosis

Question 15

side affects of ANG2 antagonists (ARBS)

Answer 15

Hyperkalaemia
hypotension
rare but serious allergic skin reaction
dont give to pregnant patients or patients with renal diseases including renal artey sterosis and severe hepatic impairment

Question 16

side affects of renin inhibitors

Answer 16

diarrhoea
cough (less than ACEIs)
‘aleskrin’ is suseptible to many drug interactions so be careful with other medication
dont give to pregnant patients or combine with ACE inhibitor or ARB

Question 17

ACEIs pharmacokinetics

Answer 17

usually oral administration
55-75% absorption
mostly excreted by kidney

Question 18

ARBs pharmacokinetics

Answer 18

oral administration
valsartan(parent) -t½:6h- excreted unchanged
losartan(parent)-t½:2-6h
candestaran(prodrug)-t½:10h
last 2 mostly excreted with active metabolites by kidney