Drugs of the Renin-Angiotensin-Aldosterone System

Question 1

Renin-Angiotensin-Aldosterone System is a very important system in regards to controlling ______.

Answer 1

blood pressure

Question 2

what organ is involved in producing angiotensinogen?

Answer 2

liver

Question 3

Angiotensin II is a very important ______.

Answer 3

vasoconstrictor

Question 4

Angiotensin II is a very important vasoconstrictor, so if you are hypovolemic and the body senses that it needs to increase your blood pressure, you will start trying to convert more angiotensin I to angiotensin II. The enzyme that does this is ACE- angiotensin converting enzyme. And this enzyme is produced where?

Answer 4

in the lungs and kidneys

Question 5

angiotensinogen in the liver gets converted to angiotensin I by Renin, and renin is secreted by the kidneys in response to ____________.

Answer 5

adrenergic stimulation (epi, NE, drop in BP)

Question 6

Angiotensinogen –> angiotensin I–> (___) –>angiotensin II

Answer 6

ACE

Question 7

Why are kidneys controlling BP?

Answer 7

angiotensinogen in the liver gets converted to angiotensin I by Renin, and renin is secreted by the kidneys in response to adrenergic stimulation (epi, NE, drop in BP).

Renin responds to juxtaglomerular apparatus in the kidney, that’s what senses the amount of sodium and potassium that we are filtering and absorbing- that’s why kidneys are controlling BP.

Question 8

angiotensin II causes what 5 things to happen?

Answer 8

1. increased sympathetic activity
2. sodium and chloride reabsorption, potassium excretion, and water retention
3. aldosterone secretion
4. arterioler vasoconstriction = inc. in BP
5. ADH secretion–> water absorption in collecting duct

Question 9

ACE also breaks down bradykinin, which is a _______.

Answer 9

vasodilator

Question 10

ACE also breaks down bradykinin, which is a vasodilator. If you don’t need to increase the BP then you don’t need ACE, and if you don’t have ACE then bradykinin will keep - things ________. It is also involved in increasing certain prostaglandin production.

Answer 10

vasodilated

Question 11

If we use ACE INHIBITORS and block ACE, we don’t get angiotensin II made, but we also don’t get breakdown of______.

Answer 11

bradykinin

Question 12

ARBs are angiotensin receptor blockers/ antagonists and bind to receptors to not allow ______ to bind to its receptors on the target tissue.

Answer 12

angiotensin II

Question 13

Aldosterone antagonist (spironolactone) block where aldosterone will bind, so you don’t get activation of the ________.

Answer 13

sodium channels

Question 14

ACE causes _________ (vasoconstriction/vasodilation) and blocks _______ (vasoconstriction/vasodilation)

Answer 14

ACE causes vasoconstriction and prevents vasodilation

Question 15

ACE:
- Cleaves angiotensin I to form _______ (vasoconstrictor)
and Breaks down _______ (vasodilator)

Answer 15

angiotensin II

bradykinin

Question 16

Blocking ACE helps lower BP by reducing vasoconstriction and reducing secretion of _______.

Answer 16

aldosterone

Question 17

ACE inhibitors end in ___.

Answer 17

“pril”

Question 18

most common ACE inhibitor used

Answer 18

Lisinopril

Question 19

Ace inhibitors Actions on CV System

Answer 19

1. Decrease vascular resistance (total peripheral resistance), venous tone, and BP
2. Reduce preload and afterload (because of vasodilation, which increases cardiac output overall, especially in those with HF or MIs, as well as high BP
3. Blunt the usual angiotensin II-mediated sympathetic response and aldosterone secretion (BP and cardiac remodeling). By decreasing these things we can prohibit cardiac remodeling in patients with HF, which is why we like to use these drugs in HF and post MI

Question 20

Ace inhibitors indications for HTN

Answer 20

Ace inhibitors are a First-line option or as an add-on to almost every other class except for another renin angiotensin drug, but we do use them with aldosterone antagonists.

Question 21

Ace inhibitors indications for HF

Answer 21

♣ DOC in all stages
♣ Improved morbidity and mortality
♣ One of the first drugs you will prescribe chronically for a pt in HF will be an ace inhibitor

Question 22

Ace inhibitors indications for MI

Answer 22

♣ Should be started immediately after MI
♣ Because of prevention of cardiac remodeling, helping to reduce preload and afterload which reduces work of heart and oxygen demand of heart.

Question 23

Ace inhibitors indications for DM nephropathy

Answer 23

If patient has HTN and diabetes ace inhibitors are good drugs to use because patients with diabetes are susceptible to HTN and nephropathy

Question 24

all drugs that are Ace inhibitors are “pro drugs” except for what 2?

Answer 24

except lisinopril and captopril

Question 25

Pro-drugs (except lisinopril and captopril) require activation by hydrolysis by _____ enzymes

Answer 25

hepatic

Question 26

most ACE inhibitors have renal elimination, what things should you monitor?

Answer 26

MONITOR BUN/ CREATINE/ GFR

Question 27

ACE inhibitors ADRs

Answer 27

1. Hypotension 2. Acute renal failure: especially in renal artery stenosis******* 3. Hyperkalemia 4. Cough 5. Angioedema/wheezing 6. Pregnancy: CI during pregnancy and should stop ASAP if taking 7. Rash 8. Extremely rare: dysgeusia (loss of taste), neutropenia, glycosuria, anemia, hepatotoxicity (these are more for FYI) 9. January 2013: ACEIs linked to hallucinations in elderly (d/c if pt c/o of this) 10. November 2013: Case report links ACEIs with oral allergy (things they consume) syndrome

Question 28

ACE inhibitor ADR of hypotension causes a rapid, steep fall in BP. this can occur after initial doses in patients with elevated __________.

Answer 28

plasma renin activity

Question 29

ACE inhibitors are renal protective but also can cause renal damage, main time it causes damage is when someone has underlying ____ problems.

Answer 29

renal vascular

Question 30

If you ever see a sharp spike in BP response after starting an ACE or an ARB, that’s a good indication that patient has what?

Answer 30

renal artery stenosis

Question 31

To monitor the ADR of acute renal failure when using ACE inhibitors, what 2 things should you be watching out for?

Answer 31

♣ sudden increase in BP when you start an ACE, because it should fall. ♣ Monitor labs and see creatinine going up then that is also an indication

Question 32

in regards to the hyperkalemia ADR when using ACE inhibitors, what things should you be cautious about?

Answer 32

renal insufficiency, DM, K-sparing diuretics, BBs, NSAIDs

Question 33

When using ACE inhibitors one ADR is cough, what is this believed to be due to?

Answer 33

due to bradykinin and substance P 5-20% of patients described as dry cough

Question 34

bradykinin and substance P release are thought to be the cause of what 2 ADRs of ACE inhibitors?

Answer 34

Angioedema/wheezing cough

Question 35

angiodema/wheezing ADR of ACE inhibitors is more likely to happen in what race of patients?

Answer 35

black patients

Question 36

should you use an ace inhibitor in pregnancy?

Answer 36

NO

Question 37

WHY is ACE inhibitors CI in pregnancy?

Answer 37

o Fetal hypotension, anuria and renal failure o Fetal malformations and death o All drugs that work through renin-angiotensin system are CI in pregnancy because it can cause birth defects and issues with blood supply to developing fetus.

Question 38

January 2013, a study released showed ACEIs linked to hallucinations in ____ patients

Answer 38

elderly

Question 39

In November 2013: Case report links ACEIs with ______.

Answer 39

oral allergy (things they consume) syndrome

Question 40

What are some extremely rare ADRs of ACEIs?

Answer 40

dysgeusia (loss of taste), neutropenia, glycosuria, anemia, hepatotoxicity

Question 41

patients may develop a ______ rash as an ADR when taking ACEIs

Answer 41

maculopapular may be temporary or could resolve with antihistamine

Question 42

If a patient is peeing protein, then there is something wrong with their _____.

Answer 42

glomerulus

Question 43

______ is the leading cause of renal disease

Answer 43

Diabetes mellitus

Question 44

In patients with type 1 diabetes mellitus and diabetic nephropathy, what drug (ACEI) prevents or delays the progression of renal disease?

Answer 44

captopril

Question 45

Renoprotection in type 1 diabetes, as defined by changes in albumin excretion, is also observed in patients using what ACEI?

Answer 45

lisinopril

Question 46

The renoprotective effects of ACE inhibitors in type 1 diabetes are in part independent of ______ reduction.

Answer 46

blood pressure

Question 47

______ may also decrease retinopathy progression in type 1 diabetics and attenuate the progression of renal insufficiency in patients with a variety of nondiabetic nephropathies.

Answer 47

ACE inhibitors

Question 48

there Several mechanisms in the renal protection afforded by ACE inhibitors, what are they?

Answer 48

1. Increased glomerular capillary pressure induces glomerular injury, and ACE inhibitors reduce this parameter both by decreasing arterial blood pressure and by dilating renal efferent arterioles 2. ACE inhibitors increase the permeability selectivity of the filtering membrane, thereby diminishing exposure of the mesangium (supportive cells) to proteinaceous factors that may stimulate mesangial cell proliferation and matrix production, two processes that contribute to expansion of the mesangium in diabetic nephropathy 3. Because angiotensin-II is a growth factor, reductions in the intrarenal levels of angiotensin-II may further attenuate mesangial cell growth and matrix production

Question 49

- If you dilate afferent arteriole and constrict efferent arteriole it will_____ GFR.

Answer 49

increase

Question 50

nitric oxide, ANP, dopamine can dilate the _____ arterial

Answer 50

afferent

Question 51

Angiotensin II is a vasoconstrictor, it will cause constriction in efferent arteriole and at ____(low or high) doses it can cause afferent constriction.

Answer 51

high

Question 52

afferent vasoconstriction _____ GFR

Answer 52

decrease

Question 53

afferent vasodilation _____ GFR

Answer 53

increases

Question 54

efferent vasoconstriction _____ GFR

Answer 54

increases

Question 55

efferent vasodilation _____ GFR

Answer 55

decreases

Question 56

ACEIs and ARBS cause efferent _____.

Answer 56

vasodilation. | this decreases GFR

Question 57

ANP, NE, and low levels of angiotensin II causes efferent _____.

Answer 57

vasoconstriction | this increases GFR

Question 58

NSAIDs and high levels of angiotensin II causes afferent _____.

Answer 58

vasoconstriction | decreases GFR

Question 59

ANP, Prostaglandins, DA, Kinins, and NO causes afferent ______.

Answer 59

vasodilation | increases GFR

Question 60

the use of ANP, Prostaglandins, DA, Kinins, and NO does what to GFR?

Answer 60

increases GFR

Question 61

NSAIDs and high levels of angiotensin II does what to GFR?

Answer 61

decreases GFR

Question 62

ANP, NE, and low levels of angiotensin II does what to GFR?

Answer 62

INCREASES GFR

Question 63

ACEIs and ARBS does what to GFR?

Answer 63

decreases GFR

Question 64

- ACE/ARB will lower efferent arteriole pressure because it ____.

Answer 64

dilates

Question 65

Angiotensin II causes constriction of the efferent arteriole. This helps to maintain adequate glomerular filtration when renal perfusion pressure is___.

Answer 65

low

Question 66

Negative Renal Effects of ACEIs (2)

Answer 66

1. Angiotensin II causes constriction of the efferent arteriole 2. Can induce acute renal insufficiency in patients with: o bilateral renal artery stenosis o Stenosis of the artery to a single remaining kidney o Heart failure o Volume depletion owing to diarrhea or diuretics

Question 67

when using ACEIs, you should be careful of DDIs with what 2 drugs?

Answer 67

- Potassium-sparing diuretics and potassium supplementation: increase risk of hyperkalemia - NSAIDs: decrease hypotensive effects, increase risk for renal impairment

Question 68

Angiotensin-Receptor Blockers (ARBs) | all end in ______.

Answer 68

SARTAN

Question 69

out of all the ARBs,_____has more benefits, it’s once a day and is generic

Answer 69

Losartan

Question 70

ARBs: MOA | they are Competitive antagonists of the __________receptors

Answer 70

angiotensin II

Question 71

ARBs do NOT affect _______ levels so any ACE produced can degrade this vasodilator

Answer 71

bradykinin

Question 72

When using ARBs, You don’t get as much bradykinin (like with ACEIs) so you shouldn’t get as much ________. (2 ADRs of ACEIs)

Answer 72

cough or angioedema

Question 73

are ARBs therapeutically identical to ACEIs?

Answer 73

- Technically are NOT therapeutically identical to ACEIs

Question 74

ARBs Can be used in patients who cannot tolerate ACEIs (due to cough)- especially in patients with ___ and _____.

Answer 74

Heart failure | MI

Question 75

ARBs uses on the cardiovascular system

Answer 75

o HTN: first-line option or add-on o HF: typically used if ACEI not tolerated o MI: typically used if ACEI not tolerated o DM Nephropathy: typically used if ACEI not tolerated

Question 76

All ARBs are ___ active

Answer 76

orally

Question 77

ARBs require _____ dosing

Answer 77

once-daily

Question 78

______ (first in class) is only agent in class with extensive hepatic metabolism

Answer 78

Losartan

Question 79

If pt has underlying liver disease, what ARB should be used?

Answer 79

Losartan

Question 80

If pt has underlying liver disease then Loasartan might be best option, but it does help with other medical conditions like ___.

Answer 80

gout

Question 81

ARBs ADRs are similar toe ACEs except no ____

Answer 81

COUGH

Question 82

should you use ARBs in pregnant patients?

Answer 82

NO

Question 83

what is the drug name that is a renin inhibitor?

Answer 83

Aliskiren (Tekturna)

Question 84

what is Aliskiren (Tekturna) MOA?

Answer 84

direct inhibition of renin

Question 85

What is Aliskiren (Tekturna) be used to treat?

Answer 85

HTN -Not first line, typically used after pt has failed an ACE and an ARB

Question 86

when taking Aliskiren, you should Avoid use with ______, unless prescribed by specialist

Answer 86

ACEIs and ARBs

Question 87

when taking Aliskiren, what can decrease absorption of the drug?

Answer 87

High-fat meal decreases absorption but in general can be taken without regards to meals

Question 88

Aliskiren is Metabolized via ___ system

Answer 88

CYP450

Question 89

Aliskiren: ADRs

Answer 89

- Similar to ACEIs and ARBs - Diarrhea with higher doses - Hyperkalemia (especially with other drugs that can cause this) - Cough - Angioedema - Pregnancy: Category D (as with ACEIs and ARBs)

Question 90

what is Aliskiren BBW?

Answer 90

BBW: can cause injury or death to fetus

Question 91

If using ACEI/ARB plus other drug that stresses kidney, risk of ___increases

Answer 91

ADR o Due to decreased efferent pressure o Examples: NSAIDs, corticosteroids, diuretics o MONITOR RENAL FUNCTION: BUN/Cr

Question 92

All ARBs, ACEIs, renin inhibitors should be used with caution in patient with _____.

Answer 92

severe renal impairment