Angiotensin and Adrenergic Antagonist: PHarmacology

Question 1

Vicious cycle of HFrEF (cycle 1)

Answer 1

1) Myocardial disease
2) decr SV/Cardiac output
3) arteriolar vasoconstriction
4) incr systemic vascular resistance
5) incr afterload

Question 2

Vicious cycle of HFrEF (cycle 2)

Answer 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

Question 3

Hydralazine action

Answer 3

Direct arterial vasodilation (decr afterload)

Question 4

Side effects of hydralazine

Answer 4

drug induced SLE

Question 5

isosorbide dinitrate

Answer 5

NO vasodilator = venous vasodilation

decr preload

Question 6

Side effects of isosorbide dinitrate

Answer 6

hypotension
headache
dizziness

Question 7

side effects of combined hydralazine and isosorbide dintrate

Answer 7

headache

Question 8

which is better used, ACE inhibitor or hydralazine ISDN combo

Answer 8

ACE inhibitor

Question 9

when do you specifically use hydralazine ISDN combo

Answer 9

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

Question 10

why do african americans have lots of problems with HF?

Answer 10

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)

Question 11

how do ACE inhibitors function?

Answer 11

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

Question 12

how is bradykinin produced

Answer 12

1) bradykninogen (produced in liver)
2) kallikrenin convert bradykininogen to bradykinin
3) kinase II (ACE II) convert bradykinin to inactive filaments

Question 13

why does high bradykinin lead to cough

Answer 13

bradykinin = pulmonary irritant

potent vasodilator

Question 14

Effect of angiotensin II in vascular smooth muscle

Answer 14

incr arteriolar constriction

incr arterial blood pressure

Question 15

Effect of angiotensin II in CNS and PNS?

Answer 15

facilitate sympathetic activity

incr CO

incr arterial blood pressure

Question 16

Effect of angiotensin II in adrneal cortex

Answer 16

incr aldosterone secretion

incr Na reabsoprtion

incr arterial blood pressure

Question 17

Effect of angiotensin II in kidney tubules

Answer 17

incr Na reabsorption

incr arterial blood pressure

Question 18

Effect of angiotensin II in kidney arterioles

Answer 18

change GFR
incr filtration fraction

incr Na+ and H2O retention
incr arterial blood pressure

Question 19

Effect of angiotensin II in brain

Answer 19

incr ADH
incr thirst
incr H2O absorption/ingestion
incr arterial blood pressure

Question 20

ACE inhibitors names

Answer 20

captopril
enalapril
lisinopril

Question 21

dosing of captopril

Answer 21

shortest half life = 3x /day

Question 22

dosing of enalapril

Answer 22

BID

Question 23

dosing of lisinopril

Answer 23

longest half life

once daily

Question 24

Side effects of ACE inhibitors

Answer 24

1) cough
2) hyperkalemia
3) angioedema
4) renal dysfunction
5) neutropenia
6) hypotension

Question 25

Drug interactions with ACE inhibitors

Answer 25

1) lithium 2) NSAIDs (incr serum Na affecting afterload and preload) 3) Salt substitute 4) loop diuretics 5) K+ sparing diuretics

Question 26

Contraindications of ACE inhibitors

Answer 26

``` pregnancy bilat renal artery stenosis renal failure angioedema hyperklaemia ``` CAUTION WITH ELDERLY

Question 27

When is ACE inhibitor good?

Answer 27

Good for NYHA good for class 2-4 (more sick) and starts right away also can reduce risk of HF

Question 28

Is ACE inhibitors dose dependent?

Answer 28

NO SIGNIFICANCE

Question 29

what is the angiotensin escape?

Answer 29

aldosterone continues to incr even though you are blocking angiotensin

Question 30

why does angiotensin escape occur with ACE inhibitors?

Answer 30

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)

Question 31

where is angiotensin 1a found

Answer 31

lung smooth muscle liver brain kidney

Question 32

where is angiotensin 1b found

Answer 32

adrenals | pituitary gland

Question 33

where is angiotensin 2 found

Answer 33

midbrain/thalamus adrenal gland (medulla) embryonic tissue

Question 34

actions of angiotensin?

Answer 34

1) incr aldosterone 2) vasoconstriction 3) renal/inotropic response 4) growth promoting

Question 35

Side effects of angiotensin

Answer 35

ACE INHIBITOR WITHOUT COUGH and LESS ANGIOEDEMA other side effects = hyperkalemia

Question 36

any precautions/contraindications

Answer 36

same as ACE incl gout and angioedema

Question 37

Any difference in ACE inhibitors or ARBs?

Answer 37

NO DIFFERENCE IN ALL CAUSE MORTALITY

Question 38

benefit of ACE inhibitors + ARBs

Answer 38

decr all cause mortality, cardiac arrest, HF hospitalization, or need for inotropes

Question 39

when use ARBs?

Answer 39

HFrEF NYHA 2-4

Question 40

what are guidelines for ARBs?

Answer 40

1) HFrEF pts who can't use ACE inhibitors 2) Equal to ACE inhibitors 3) HFrEF patients treated with ACE inhibitor + beta blocker

Question 41

Relationship btwn plasma NE and survival in HF

Answer 41

incr in plasma NE due to incr in sensitivity of baroreceptors assoc with incr mortality

Question 42

what happens with adrenergic activation?

Answer 42

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

Question 43

Beta blockers help how?

Answer 43

1) upregulate b1 receptors 2) prevent apoptosis/oxid stress (cell death) 3) decr arrhythmias 4) decr hypertrophy/fibrosis

Question 44

First gen beta blockers

Answer 44

not selective for b1/b2 propanolol timolol

Question 45

examples of first gen beta blockers

Answer 45

propanolol | timolol

Question 46

2nd gen beta blockers

Answer 46

selective for b1 or b2 block metoprolol atenolol bisoprolol

Question 47

example of second gen beta blockers

Answer 47

metoprolol atenolol bisoprolol

Question 48

3rd gen beta blockers

Answer 48

selective or nonselective with additional property carvedilol bucindolol = mostly b1 + alpha 1 block nebivolol (b1)

Question 49

examples of 3rd gen beta blocker

Answer 49

carvedilol bucindolol = mostly b1 + alpha 1 block nebivolol (b1)

Question 50

best b1 selective inhibitors (2)

Answer 50

1) nebivolol | 2) bisoprolol

Question 51

which patients are appropriate candidates for therapy?

Answer 51

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

Question 52

When should treatment with beta blocker be started?

Answer 52

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

Question 53

Effect of metoprolol long lasting form in chronic HF

Answer 53

decr all cause mortality and prevents worsening HF

Question 54

When to use beta blockers

Answer 54

use of beta blocker recommended for all patient with HFrEF

Question 55

what is neprilysin?

Answer 55

inhibitor of BNP degradation

Question 56

BNP effects

Answer 56

1) vasodilation 2) decr BP 3) decr symp tone 4) decr aldosterone

Question 57

why is new drug (neprilysin inhibitor so effective)

Answer 57

keeps BNP around longer and also block angiotensin II