ACE Inhibitors & Angiotensin Antagonists

Question 1

How do ARBs impact the urate transporter?

Answer 1

• it BLOCKS the urate transporter

- uricosuric effect (increased uric acid excretion, reduces gout risk)

Question 2

ACE INHIBITOR CONTRAINDICATIONS

Answer 2

• PREGNANCY
• typically not used in pts with Scr > 2.5 (high doses in pts w/ renal insufficiency may = neutropenia)
• typically not good in BLACKS

Question 3

Breakdown of ARB impact

Answer 3

blocks AT1 –> blocks release of norepi –> decreases sympathetic action

Question 4

Renin released due to

Answer 4

1. Drop in BP
2. Low NaCl in the distal tubule of the kidney
3. . Activation of specific receptors in JG cells

Question 5

angiotensin II stimulates the adrenal cortex which

Answer 5

• releases aldosterone

- increases BP

Question 6

BLOCKED BRADYKININ CAUSES

Answer 6

• PGE2/PGI2 = vasodilation = increased vascular permeability
• bronchoconstriction = COUGH
• natriuresis

Question 7

ARB examples

Answer 7

• losartan (cozaar)

- valsartan (diovan)

Question 8

angiotensin II can modulate baroreceptor reflex which

Answer 8

increases BP WITHOUT reflex bradycardia

Question 9

Angiotensin II Receptor Type 1 (AT1) Blockers end in

Answer 9

-sartans

Question 10

angiotensin II causes

Answer 10

widespread vasoconstriction

Question 11

Liver releases

Answer 11

angiotensinogen

Question 12

angiotensin II activates thirst center (pituitary gland) which

Answer 12

• causes release of antidiuretic hormone (ADH, vasopressin)
• drink more –> increase volume
• increases BP

Question 13

ADVERSE EFFECTS OF ARBS

Answer 13

• hypotension
• hyperkalemia («< ACE-Is)
• teratogenic potential (2nd + 3rd trimester)

Question 14

Selectively block effects of ANG II does 3 things

Answer 14

1. reduce BP
   * **SANS: inhibit stimulation of NE system (fast pressor effects)
   * **RAAS: reduce secretion of aldosterone (slow pressor effect)
   * **prevent cardiac hypertrophy
2. reduce renal vasoconstriction
3. no effects on bradykinin system (cough and angioedema less prevalent)

Question 15

ACE inhibitor examples

Answer 15

• lisinopril (zestril)
• enalapril (vasotec)
• captopril (capote)

Question 16

enalapril (vasotec)

Answer 16

• prodrug (has ester that needs to be cleaved)

- similar to lisinopril

Question 17

why ace-inhibitors not good in Blacks

Answer 17

• due to low circulating renin

- but use to treat DN and heart failure

Question 18

ADH causes

Answer 18

aquaporins to move to the collecting duct plasma membrane, which increases water reabsorption

Question 19

AT1 Receptor is blocked by

Answer 19

ARBs

Question 20

WHEN BLOCK ACE-I

Answer 20

-INCREASES CONCENTRATION OF BRADYKININ

Question 21

SANS definition

Answer 21

sympathetic autonomic nervous system

Question 22

Angiotensin Receptor 1 (AT1) coupled to _____ and causes (3 things)

Answer 22

Gq GPCR (but also Gi);

1. vasoconstriction of smooth muscles
   * **PLC –> Ca increase
   * **activation of Ca channels
   * **reduce NO synthesis
2. Increases BP
   * **increase aldosterone production (adrenal medulla)
3. Cardiac hypertrophy

Question 23

angiotensin II causes constriction of smooth muscle cells which

Answer 23

increases BP

Question 24

captopril (capote)

Answer 24

• useful for supine HTN-orthostatic hypotension
• short acting (t1/2= < 3 h)
• side effect = rash

Question 25

angiotensin II does (5 things)

Answer 25

1. stimulates the adrenal cortex 2. causes constriction of smooth muscle cells 3. activates thirst center (pituitary gland) 4. can modulate baroreceptor reflex 5. causes cardiovascular hypertrophy

Question 26

ACE inhibitors end in

Answer 26

-pril

Question 27

inhibition of renin (direct and indirect) contraindications

Answer 27

- PREGNANCY and nursing mothers - use with ARBs or ACEIs in pts with kidney impairment or diabetes because of kidney impairment risk, low BP and high K+ in blood

Question 28

RAAS definition

Answer 28

renin-angiotensin-aldosterone system

Question 29

CLINICAL USES OF ARBS

Answer 29

- HTN - Congestive heart failure - diabetic nephropathy - stroke prophylaxis

Question 30

ACE INHIBITOR CLINICAL USES

Answer 30

- HTN - Heart failure with reduced ejection fraction (left ventricular systolic dysfunction) - MI (dampened SNS response) - slows down progression of diabetic nephropathy

Question 31

HOW DO ACE INHIBITORS SLOW DOWN PROGRESSION OF DIABETIC NEPHROPATHY

Answer 31

- act on efferent arteriole of the kidney - this reduces pressure in the glomerulus - diminishes proteinuria

Question 32

lisinopril (zestril)

Answer 32

- most commonly used - well tolerated - t1/2 = 12h - not a pro-drug (available mixed with HCTZ - Zestoretic)

Question 33

Kidney releases

Answer 33

renin

Question 34

The release of renin

Answer 34

increases BP

Question 35

direct inhibition of renin by

Answer 35

- aliskiren (Tekturna) * **10 years old * **used alone or in combination to treat HTN * **benefit: may decrease carotid arterial stiffness vs HCTZ

Question 36

Indirect inhibition of renin

Answer 36

impacts beta 1 blockers (blocks B1-AR mediated release)

Question 37

Mechanism

Answer 37

- enzyme reaction (kidney - renin, liver - angiotensinogen) - angiotensin I - enzyme reaction (ACE in pulmonary blood) - angiotensin II - stimulation of adrenal cortex to secrete aldosterone

Question 38

ACE-I ADVERSE EFFECTS

Answer 38

- first dose hypotension (fainting, orthostatic hypotension) - hyperkalemia (via aldosterone effect) - acute renal failure - dry cough - angioedema

Question 39

Most relevant diuretics

Answer 39

- thiazides - K sparing (aldosterone) - loop diuretics

Question 40

Renin is released by ____________ cells in the _______

Answer 40

juxtaglomerular; kidney

Question 41

angiotensin-converting enzyme located in

Answer 41

pulmonary blood

Question 42

ACE-I drug-drug interactions

Answer 42

- food/antacids reduce bioavailability - NSAIDs may reduce effectiveness (renal) - K+ supplements - may increase plasma levels of digoxin and lithium

Question 43

aldosterone stimulates

Answer 43

Na uptake on the apical cell membrane in the distal convoluted tubule and collecting ducts

Question 44

angiotensin II causes cardiovascular hypertrophy which

Answer 44

- increases contraction | - increases BP