ACEI (amboss and UW)

Question 1

ACEI agents?

Answer 1

captopril, enalapril, lisinopril, ramipril, benazepril

Question 2

ACEI indicatons?

Answer 2

Arterial hypertension

Diabetes mellitus (type I and type II)

HF with reduced ejection fraction

History of MI

Nondiabetic chronic kidney disease with proteinuria

Scleroderma-associated hypertensive crisis (even if creatinine is elevated)

Question 3

Why ACEI used in DM?

Answer 3

Nephroprotective indications, such as: Arterial hypertension, Microalbuminuria and proteinuria (especially ≥ 300 mg/g)

Coronary heart disease

Question 4

ACE inhibitors and ARBs are generally recommended in hypertensive diabetic patients to reduce the risk of cardiovascular events, but they are strongly recommended in diabetic patients with concurrent hypertension and an elevated urinary albumin-to-creatinine ratio (as an indicator for microalbuminuria).

Answer 4

.

Question 5

Why ACEI used in CHD?

Answer 5

To reduce the risk of cardiovascular events.

Question 6

There is minimal evidence to support primary prevention of moderately increased albuminuria in normotensive and normoalbuminuric type I and type II diabetes. Annual screening to identify persistently increased albuminuria is recommended instead. Treatment with a RAAS inhibitor may be considered if albuminuria persists to delay progression towards severely increased albuminuria, especially in patients with type I diabetes, and cardiovascular events

Answer 6

.

Question 7

ACEI has similar effect of what drug?

Answer 7

Amyl nitrite is a vasodilator that mimics the effects of ACE inhibitors on the heart.

Question 8

Why ACEI used in MI?

Answer 8

The ability of ACE inhibitors to attenuate ventricular dilatation (remodeling) after an MI is responsible for its survival benefit. Patients will still derive benefit from ACE inhibitors or ARBs if they are not administered immediately after the event.

Question 9

ACEI mechanism?

Answer 9

Mechanism of action: inhibition of ACE → ↓ conversion of angiotensin I to angiotensin II

Question 10

ACEI effect on GFR?

Answer 10

Dilation of efferent arteriole → ↑ renal plasma flow → ↓ GFR → ↓ filtration fraction

Question 11

ACEI effect on blood pressure? 2

Answer 11

↓ Vasoconstriction → ↓ blood pressure

↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → ↓ blood pressure

Question 12

ACEI on renin secretion?

Answer 12

↑ Renin secretion (due to lack of feedback inhibition) → ↑ angiotensin I

Question 13

ACEI and bradykinin?

Answer 13

↓ Breakdown of bradykinin → ↑ production of arachidonic acid metabolites → ↑ vasodilation → ↓ blood pressure

Question 14

ACEI on proteinuria and proteinuric CKD?

Answer 14

↓ Proteinuria and ↓ progression of proteinuric chronic kidney disease: ↓ intraglomerular hydrostatic pressure attenuates thickening and sclerosis of the GBM

Question 15

ACEI on preload and afterload?

Answer 15

↓ Preload and afterload → ↓ cardiac remodeling after acute myocardial infarction or in chronic hypertensive disease

Question 16

Increase in bradykinin concentration, which can lead to? 2

Answer 16

Dry cough (can be treated by discontinuing ACE inhibitor, consider switching to ARB)

Bradykinin-mediated angioedema due to increased vascular permeability and vasodilation

Question 17

Why dry cough in bradykinin?

Answer 17

The mechanism is not fully understood. However, protussive and proinflammatory effects from local accumulation of bradykinin (and other mediators) in the lung are considered most likely.

Question 18

Adverse of ACEI?

Answer 18

Hypotension

↓ GFR (with ↑ creatinine): can cause AKI in patients with preexisting renal hypoperfusion (e.g., renal artery stenosis, hypovolemia, heart failure)

Hyperkalemia!!!!

Proteinuria

Pemphigus vulgaris (unknown mechanism)

Teratogenicity: renal malformations

Leukopenia

Rash

Taste changes

Question 19

Early DN effect on glomerular filtration pressure?

Answer 19

Elevated glomerular filtration pressure

+ATII further increases glomerular pressure by selective vasoconstriction of the efferent arteriole

Question 20

Blockage of what decr. glomerular filtration pressure?

Answer 20

blockage of ATII, since it increases glomerular pressure by selective vasoconstriction of the efferent arteriole –> lowered glomerular pressure

Question 21

ACEI use with caution in what condition? and why?

Answer 21

In bilateral renal artery stenosis. It leads to decr. renal blood flow –> decr. GFR THEREFORE –> ACTIVATION OF RAAS –> RELEASE OF ATII –> constr. of efferent –> maintain GFR.

ACEI - drop in systemic BP and dilation of efferent.

Drop in BP is no longer high enough to overcome the stenosis –> renal blood flow drops. Due to dilation of efferent –> reduction of intraglomerular filtration pressure -> decr GFR and filtration fraction.

Question 22

Patients with bilateral and use ACEI are at what risk?

Answer 22

Acute renal failure

Question 23

What pressure is reduced in renal artery stenosis?

Answer 23

Reduced hydrostatic pressure –> stimulation of ATII –> vasoconstriction –> incr. BP –> incr. renal perfusion

Question 24

In unilateral stenosis normally functioning kidney compensates impaired kidney function.

Answer 24

.

Question 25

Why in RAS is normal urinalysis?

Answer 25

because glomeruli and tubules functions normally --> no hematuria, proteinuria or casts --> urinalysis is unremarkable

Question 26

Angiotensin-receptor blocker (ARBs, sartans). Agents?

Answer 26

valsartan, candesartan, losartan, irbesartan

Question 27

Angiotensin-receptor blocker (ARBs, sartans). Indications?

Answer 27

same as ACE inhibitors, mostly used as second-line treatment if ACE inhibitors are not tolerated

Question 28

Direct renin inhibitors. Agents?

Answer 28

Aliskiren

Question 29

Direct renin inhibitors. | Indications?

Answer 29

Arterial hypertension if both ACE inhibitors and ARBs are not tolerated

Question 30

Angiotensin-receptor blocker (ARBs, sartans). Mechanism?

Answer 30

Inhibition of angiotensin II receptor type 1 (AT1 receptor)

Question 31

Angiotensin-receptor blocker (ARBs, sartans). Effect?

Answer 31

↓ Vasoconstriction → ↓ blood pressure ↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → ↓ blood pressure ↑ Renin secretion (compensatory) → ↑ angiotensin I → ↑ angiotensin II Other effect: ↓ Proteinuria and ↓ progression of proteinuric kidney disease ↓ Cardiac remodeling after acute myocardial infarction or chronic hypertensive disease No bradykinin elevation (opposed to ACE inhibitors)

Question 32

ACEI vs ATII inhibitors on bradykinin?

Answer 32

ACEI - bradykinin levation --> angioedema; ATII inhibitors --> no bradykinin elevation --> no angioedema

Question 33

Direct renin inhibitors. Mechanism?

Answer 33

direct inhibition of renin → ↓ conversion of angiotensinogen into angiotensin I → ↓ angiotensin I and angiotensin II → ↓ angiotensin II → ↓ vasoconstriction

Question 34

Direct renin inhibitors. Effect?

Answer 34

↓ Blood pressure ↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → further ↓ blood pressure

Question 35

ARBS and Direct renin inhibitors adverse?

Answer 35

``` Angioedema Hypotension Hyperkalemia ↓ GFR (with ↑ creatinine) Teratogenicity Rash Diarrhea (direct inhibt) Leukopenia (ARBS) ```

Question 36

What kind of kidney injury may occur in patients takins RAAS inhibitors and NSAIDs?

Answer 36

Acute kidney injury is a potential side effect of all types of RAAS inhibitors, especially in patients with preexisting kidney disease or in combination with NSAIDs

Question 37

Contraindications for ACE inhibitors and ARBs. Absolute?

Answer 37

Hypersensitivity C1 esterase inhibitor deficiency (due to predisposition to angioedema) Pregnancy: risk of harm to the fetus (e.g., renal impairment, renal malformations, oligohydramnios, placental insufficiency) Breastfeeding

Question 38

Contraindications for ACE inhibitors and ARBs. Relative?

Answer 38

Aortic stenosis Renal dysfunction, consider altering dose if GFR < 60 mL/min Bilateral renal artery stenosis or a solitary kidney: GFR is already decreased and further reduction may lead to acute kidney injury.

Question 39

Contraindications for ACE inhibitors and ARBs. Why mitral stenosis is relative contraindication?

Answer 39

These patients may not be able to further increase their stroke volume to compensate for the peripheral vasodilation caused by ACE inhibitors. Severe hypotension may occur.

Question 40

Contraindications for ACE inhibitors and ARBs. Why relative contraindication is Bilateral renal artery stenosis or a solitary kidney?

Answer 40

Even patients with advanced renal dysfunction may benefit from treatment with ACE inhibitors, although there might be an initial drop in GFR and increase in creatinine (tolerable up to 30%). Therefore, regular GFR monitoring is required in patients with chronic kidney disease.

Question 41

Contraindications for direct renin inhibitors?

Answer 41

Hypersensitivity Pregnancy Current treatment with ACE inhibitors or ARBs

Question 42

Interactions. ACE inhibitors and ARBs + other antihypertensive drugs?

Answer 42

Other antihypertensive drugs → ↑ hypotensive effect

Question 43

Interactions. ACE inhibitors and ARBs + NSAIDs?

Answer 43

NSAIDs → ↓ antihypertensive effect

Question 44

Interactions. ACE inhibitors and ARBs + K sparring diuretics?

Answer 44

Potassium-sparing diuretics or other drugs that increase potassium level: ↑ hyperkalemia

Question 45

Interactions. ACE inhibitors and ARBs + allopurinol?

Answer 45

Allopurinol: ↑ risk of immunological reactions or leukopenia (not yet fully understood mechanism)

Question 46

Interactions. ACE inhibitors and ARBs. | ↑ Level of lithium due to ↓ renal elimination

Answer 46

.

Question 47

Interactions. Direct renin inhibitors + ACEI/ARBS?

Answer 47

ACE inhibitors or ARBs → ↑ hyperkalemia DO NOT COMBINE RENIN INHIBITORS + ACEI/ARBS

Question 48

Interactions. Direct renin inhibitors + P-glycoprotein inhibitors?

Answer 48

P-glycoprotein inhibitors (e.g., ketoconazole, verapamil, clarithromycin, erythromycin, amiodarone): ↑ aliskiren level

Question 49

When starting an ACE inhibitor or an ARB, monitor what? 3

Answer 49

Blood pressure, potassium, and creatinine

Question 50

Combine ACE inhibitors or ARBs with thiazide diuretics to .......

Answer 50

offset the risks of hyperkalemia and hypokalemia

Question 51

Starting with low doses (preferably in a controlled setting) is recommended to avoid ........

Answer 51

Starting with low doses (preferably in a controlled setting) is recommended to avoid severe hypotension

Question 52

Drops in blood pressure reduce.........

Answer 52

Drops in blood pressure reduce renal perfusion

Question 53

What mmHg drop in RENAL ARTERY activates juxtaglomerular apparatus?

Answer 53

If the pressure in the RENAL ARTERY falls by more than 10–15 mmHg, proteolytic renin is released from the juxtaglomerular apparatus

Question 54

How RAAS increase BP?

Answer 54

2 ways: vasoconstriction and stimulation of the release of aldosterone, which increases the retention of water and sodium