Lecture 7 Aces, ARBS, and aliskiren

Question 1

ACE converts ______ to _____ and also converts _____ to _____

Answer 1

Ang 1 to Ang 2; bradykinin to inactive metabolites

Question 2

Angiotensin II causes an increase in BP in two major ways:

Answer 2

constrict vascular smooth muscle –>vasoconstriction;

increases aldosterone production –> increase Na and H2O reabsorption

Question 3

Angiotensin III is biologically _____ and causes an increase in _____

Answer 3

active; aldosterone

Question 4

Pro-renin bound to the pro-renin receptor causes what?

Answer 4

end organ damage

Question 5

3 ways to activate renin release:

1. decrease in _____ sensed by the _____ ____
2. Decrease in ____ sensed by the ____ ____ ____
3. increase in ______ _____ caused by ____ receptors

Answer 5

decrease in bp sensed by Juxtaglomerular cells;

2. decrease in NaCl resorption at macula densa
3. increase in sympathetic tone B1 receptors

Question 6

decreased NaCl resorption at the macula densa causes ____ release, which causes a release of renin from what?

Answer 6

prostaglandin; Juxtaglomerular cells

Question 7

Where does angiotensinogen primarily come from? What about ACE?

Answer 7

liver;

lungs

Question 8

what is the name of the receptor that Angiotensinogen II binds to? What kind of receptor is it>

Answer 8

angiotensin II type 1 (AT1) receptors;

GPCR

Question 9

AT1 receptors are located in _____, the brain, adrenal, _____, and ____

Answer 9

blood vessels, kidney, heart

Question 10

Ang II causes a rapid pressor response by…

1. direct ____
2. enhanced release of ______ and decreased ____ reuptake
3. increased ______ discharge

Answer 10

1. vasoconstriction
2. NE, NE
3. Sympathetic

Question 11

Ang II causes a slow pressor response by…

1. Directly increases ____ reabsorption in the ____ tubule.
2. Release of _____ from the adrenal cortex
3. Direct renal ______

Answer 11

1. Na+, PCT
2. Aldosterone
3. Vasoconstriction

Question 12

Ang II also causes _____ and _____ ______ and remodeling by increased expression of proto-oncogenes and production of _____ factors

Answer 12

vascular, cardiac hypertrophy; growth

Question 13

The sulfhydryl containing ACE inhibitor is _____.

Answer 13

captopril

Question 14

ACE inhibitors act by _____ binding to what part of the receptor?

Answer 14

competitively, active site

Question 15

In addition to inhibiting conversion of Ang I to Ang II, ACE inhibitors also inhibit conversion of bradykinin to _____. This allows buildup of bradykinin which causes ____ and ____ blood pressure

Answer 15

inactive metabolites; vasodilation, decrease

Question 16

What class of drugs intereferes with bradykinin mediated vasodilation

Answer 16

NSAIDS

Question 17

Captopril has a ____ half life and absorption is ____ by food. Side effects include altered _____ and also a _____, due to the sulfhydryl group

Answer 17

short, decreased;

taste (metallic), rash

Question 18

The main _____ containing ACE inhibitor is enalopril. Others include benazepril and ramipril.

Answer 18

dicarboxyl

Question 19

Enalopril is a _____. It requires _____ to form its active form. It has a _____ half life

Answer 19

pro-drug, hydrolysis, long

Question 20

_____ is a dicarboxyl containing ACE inhibitor that is not a pro-drug.

Answer 20

lisinopril

Question 21

______ is phosphinate-containing ACE inhibitor.

Answer 21

fosinopril

Question 22

Fosinopril is a prodrug that requires cleavage by ____ esterases. It has extensive ____ metabolism and thus can be given to patients with _____ problems

Answer 22

hepatic, hepatic;

renal

Question 23

In addition to HTN, ACE-Inhibitors are also used in _____, _____, and ____ _____

Answer 23

Heart Failure, MI, diabetic nephropathy

Question 24

side effects of ACE Inhibitors: remember ______

Answer 24

CATCHH

Question 25

CATCHH side effects of ACE inhibitors:
C = _____, due to _______
A =
T =

Answer 25

cough, bradykinin effects;
angioedema
Teratogen

Question 26

CATCHH side effects of ACE inhibitors:

C = ______, indicating ______
H = ______, due to decreased _____
H =

Answer 26

creatinine, acute renal failure;

hyperkalemia, aldosterone

hypotension

Question 27

ACE inhibitors may increase plasma levels of _____ and ____. Also avoid with K+ supplements

Answer 27

digoxin, lithium

Question 28

What do ARBS end in?

Answer 28

-sartan

Question 29

what is the effect of ARBs on bradykinin? why is this important

Answer 29

no effect (ie no increase), so no cough

Question 30

doe ARBs provide a more or less incomplete inhibition of Ang II relative to ACE inhibitors?

Answer 30

more complete

Question 31

In addition to the same uses as ACE inhibitors, ARBs are also used in ____ prophylaxis

Answer 31

stroke

Question 32

Aliskiren is a ______ inhibitor. It can be used alone to treat ____.

Answer 32

Renin;

HTN

Question 33

Main side effect of aliskiren = _____. What is it contraindicated in?

Answer 33

diarrhea;

nursing/pregnant mothers ( as opposed to fathers)