Cardio- Lecture (Steiner) Renin-Angiotensin

Front 1

the renin-angiotensin system is activated by:

Back 1

a fall in arterial renal pressure.

Front 2

Activation of renin-angiotensin system increases not only blood volume (retains Na+) but also:

Back 2

peripheral resistance (arterial vasoconstriction). Both actions are aimed at restoring (increasing) arterial pressure.

Front 3

renin production: regulation

Back 3

1. Macula densa signals

2. Tension within walls of afferent arterioles

3. beta-adrenergic (sympathetic) modulation

Front 4

AT1 medicated effects

Back 4

vasodilation (smooth muscle)

Na+ retention

Front 5

AT1 mediated effects

Na+ retention:

Back 5

1. ↓ Glomerular filtration.

2. ↑ Na+ reabsorption in the proximal tubule and Henle’s loop (direct effect).

3. ↑ Na+ reabsorption in the late distal tubule and collecting duct (indirect effect). (via aldosterone)

Front 6

decreased renal blood flow leads to:

Back 6

decreased glomerular filtration

Front 7

renin-angiotensin and hypertension

Back 7

20% of patients with essential hypertension have elevated plasma renin activity.

Inhibition of the renin-angiotensin system can lower blood pressure not only in those hypertensive patients that have elevated renin activity, but also in those that have normal renin activity.

Front 8

ACE inhibitors

examples

Back 8

Captopril is an inhibitor itself not a prodrug-

(prodrug) Enalapril ( ester ) if you hydrolyze it, you get enalaprilat- which can’t be absorbed in GI tract

Front 9

ACE inhibitors

adverse effects

Back 9

Important note: In general, ACE inhibitors are very well tolerated

Hypotension

Hyperkalemia

Fetal defects

Dry cough & angioedema

Front 10

ACE inhibitors

hypotension:

Back 10

This adverse effect results from patients hyper-responsiveness to the drug’s therapeutic action.

Risk is higher in patients with high plasma renin activity.

Renin activity can be particularly high in patients taking diuretics or under salt-restriction, since the blood pressure-reducing effects of these therapies are a stimulus for renin secretion.

Front 11

ACE inhibitor adverse effects

hyperkalemia: increased plasma K+

Back 11

Adverse effect could be potentiated by potassium-sparing diuretics or potassium supplements.

Front 12

ACE inhibitor adverse effects

fetal defects

Back 12

ACE inhibitors also affect fetal AII level.

The fetus may develops hypotension, anuria, and renal failure.

Malformations and fetal death might also occur.

need angiotensin II for blood vessel formation (angiogenesis)

Front 13

ACE inhibitors are NOT to be taken during pregnancy

Back 13

true!!

Front 14

ACE inhibitors adverse effects

dry cough and angioedema

Back 14

see notes or slide 45

Front 15

AT1 receptor blocker

example:

Back 15

losartan

absorbed in GI tract
prodrugs are common

Front 16

AT1 receptor blockers are competitive antagonists

Back 16

true

Front 17

AT1 receptor blockers vs ACE I

Back 17

1) AT1 rec. blockers do not affect bradykinin and are less likely to cause cough or angioedema.

2) AT1 rec. blockers inhibits the action of AII derived from ACE and alternative pathways, whereas ACE inhibitors inhibit only the production of ACE-derived AII.

3) AT1 rec. blockers inhibits the action of AII on AT1 rec. only, whereas ACE inhibitors may also inhibit some beneficial actions of AII on AT2 rec.

Front 18

AT1 receptor blockers

adverse effects

Back 18

Hypotension (like ACE inhibitors)

Hyperkalemia (like ACE inhibitors)

Fetal defects (like ACE inhibitors)

Front 19

A hypertensive patient cannot continue taking the diuretic amiloride, because he has been diagnosed with hyperkalemia. Which of the following drugs would you recommend to treat the patient’s hypertension?

Back 19

not: spironalactone, captopril, enalapril

which one?

Front 20

Which of the following adverse effects are equally likely to occur with ACE inhibitors and AT1 receptor blockers?

Back 20

fetal defects

Front 21

Which adverse effect of Captopril can be potentiated by Spironolactone?

Back 21

hyperkalemia