Angiotensin and Adrenergic Antagonist: PHarmacology Flashcards
Vicious cycle of HFrEF (cycle 1)
1) Myocardial disease
2) decr SV/Cardiac output
3) arteriolar vasoconstriction
4) incr systemic vascular resistance
5) incr afterload
Vicious cycle of HFrEF (cycle 2)
1) Myocaridal disease
2) decr SV/CO
3) incr NaCl and H2O retention –> incr renin angiotensin/aldosterone –> incr arterial vasoconstriction
4) incr blood volume –> peripheral edema
5) incr LV preload
Hydralazine action
Direct arterial vasodilation (decr afterload)
Side effects of hydralazine
drug induced SLE
isosorbide dinitrate
NO vasodilator = venous vasodilation
decr preload
Side effects of isosorbide dinitrate
hypotension
headache
dizziness
side effects of combined hydralazine and isosorbide dintrate
headache
which is better used, ACE inhibitor or hydralazine ISDN combo
ACE inhibitor
when do you specifically use hydralazine ISDN combo
in african ameicans with NYHA 3-4 HFrEF in combo with beta blocker, ACE inhibitor, and a aldosterone antagonist
OR in HFrEF when can’t take ACE inhibitor or ARB
why do african americans have lots of problems with HF?
1) TGFB = incr type 1 and type 2 collagen –> incr fibrosis
2) incr endothelin (vasoconstrictor)
3) decr renin angiotensin system
4) decr in NO (vasodilator)
how do ACE inhibitors function?
1) angiotensinogen (zymogen produced in liver)
2) renin (produce in kidney in response to low BP/Na) convert angiotensinogen to angiotensin 1
3) ACE (produce in lungs) convert angiotensin 1 to 2
how is bradykinin produced
1) bradykninogen (produced in liver)
2) kallikrenin convert bradykininogen to bradykinin
3) kinase II (ACE II) convert bradykinin to inactive filaments
why does high bradykinin lead to cough
bradykinin = pulmonary irritant
potent vasodilator
Effect of angiotensin II in vascular smooth muscle
incr arteriolar constriction
incr arterial blood pressure
Effect of angiotensin II in CNS and PNS?
facilitate sympathetic activity
incr CO
incr arterial blood pressure
Effect of angiotensin II in adrneal cortex
incr aldosterone secretion
incr Na reabsoprtion
incr arterial blood pressure
Effect of angiotensin II in kidney tubules
incr Na reabsorption
incr arterial blood pressure
Effect of angiotensin II in kidney arterioles
change GFR
incr filtration fraction
incr Na+ and H2O retention
incr arterial blood pressure
Effect of angiotensin II in brain
incr ADH
incr thirst
incr H2O absorption/ingestion
incr arterial blood pressure
ACE inhibitors names
captopril
enalapril
lisinopril
dosing of captopril
shortest half life = 3x /day
dosing of enalapril
BID
dosing of lisinopril
longest half life
once daily
Side effects of ACE inhibitors
1) cough
2) hyperkalemia
3) angioedema
4) renal dysfunction
5) neutropenia
6) hypotension
Drug interactions with ACE inhibitors
1) lithium
2) NSAIDs (incr serum Na affecting afterload and preload)
3) Salt substitute
4) loop diuretics
5) K+ sparing diuretics
Contraindications of ACE inhibitors
pregnancy bilat renal artery stenosis renal failure angioedema hyperklaemia
CAUTION WITH ELDERLY
When is ACE inhibitor good?
Good for NYHA good for class 2-4 (more sick)
and starts right away
also can reduce risk of HF
Is ACE inhibitors dose dependent?
NO SIGNIFICANCE
what is the angiotensin escape?
aldosterone continues to incr even though you are blocking angiotensin
why does angiotensin escape occur with ACE inhibitors?
Angiotensinogen can be convert directly to angiotensin II via non-renin (tP factor, cathepsin G and tonin)
Angiotensin 1 can be convert to angiotensin II via non-ACE (chymase, CAGE, cathepsin G)
where is angiotensin 1a found
lung
smooth muscle
liver
brain kidney
where is angiotensin 1b found
adrenals
pituitary gland
where is angiotensin 2 found
midbrain/thalamus
adrenal gland (medulla)
embryonic tissue
actions of angiotensin?
1) incr aldosterone
2) vasoconstriction
3) renal/inotropic response
4) growth promoting
Side effects of angiotensin
ACE INHIBITOR WITHOUT COUGH and LESS ANGIOEDEMA
other side effects =
hyperkalemia
any precautions/contraindications
same as ACE
incl
gout and angioedema
Any difference in ACE inhibitors or ARBs?
NO DIFFERENCE IN ALL CAUSE MORTALITY
benefit of ACE inhibitors + ARBs
decr all cause mortality, cardiac arrest, HF hospitalization, or need for inotropes
when use ARBs?
HFrEF NYHA 2-4
what are guidelines for ARBs?
1) HFrEF pts who can’t use ACE inhibitors
2) Equal to ACE inhibitors
3) HFrEF patients treated with ACE inhibitor + beta blocker
Relationship btwn plasma NE and survival in HF
incr in plasma NE due to incr in sensitivity of baroreceptors assoc with incr mortality
what happens with adrenergic activation?
1) incr CNS sympath outflow
2) incr cardiac, kidney and blood vessel activity
3) activ beta 1, 2 (cardiac), alpha 1 receptor (kidney/blood vessel)
4) myocyte death/incr arrhythmia/decr beta1 receptor
alpha 1 receptor also leads to vasoconstriction/Na retention
Beta blockers help how?
1) upregulate b1 receptors
2) prevent apoptosis/oxid stress (cell death)
3) decr arrhythmias
4) decr hypertrophy/fibrosis
First gen beta blockers
not selective for b1/b2
propanolol
timolol
examples of first gen beta blockers
propanolol
timolol
2nd gen beta blockers
selective for b1 or b2 block
metoprolol
atenolol
bisoprolol
example of second gen beta blockers
metoprolol
atenolol
bisoprolol
3rd gen beta blockers
selective or nonselective with additional property
carvedilol
bucindolol = mostly b1 + alpha 1 block
nebivolol (b1)
examples of 3rd gen beta blocker
carvedilol
bucindolol = mostly b1 + alpha 1 block
nebivolol (b1)
best b1 selective inhibitors (2)
1) nebivolol
2) bisoprolol
which patients are appropriate candidates for therapy?
1) mild to mod heart failure (NYHA 2-4)
2) systolic dysfunction of LV
3) treatment with ACE inhibitor + diuretic
4) CAD or nonischemic dilated cardiomyopathy
5) COPD without reactive airway disease
6) diabetic or nondiabetic
When should treatment with beta blocker be started?
1) treat with diuretic (to decr fluid retention)
2) with ACE inhibitor for 2 wk+
3) no recent IV vasodilators or positive inotropic agents (acute HF)
4) systolic BP >/ 90 mmHg
5) HR > 60 bpm
5) no end organ failure
Effect of metoprolol long lasting form in chronic HF
decr all cause mortality and prevents worsening HF
When to use beta blockers
use of beta blocker recommended for all patient with HFrEF
what is neprilysin?
inhibitor of BNP degradation
BNP effects
1) vasodilation
2) decr BP
3) decr symp tone
4) decr aldosterone
why is new drug (neprilysin inhibitor so effective)
keeps BNP around longer and also block angiotensin II
