Drugs Used For The Treatment Of Hypertension III: Drugs Acting On The Renin-angiotensin-aldosterone System

Question 1

Where is renin produced?

Answer 1

Kidney

Question 2

Where is angiotensinogen produced?

Answer 2

The liver

Question 3

What is the action of renin?

Answer 3

Converts angiotensinogen to angiotensin I

Question 4

Where is ACE found?

Answer 4

Plasma

Question 5

What is the action of ACE?

Answer 5

Converts AT1 to AT2

Question 6

What is the effect of ACE on bradykinin?

Answer 6

ACE inactivates bradykinin

Question 7

What tissues does angiotensin II work on?

Answer 7

Adrenal cortex

Blood vessels

Question 8

What receptors do angiotensin II work on?

Answer 8

AT-1

Angiotensin 2 type 1 receptors

Question 9

What is the action of ACEIs?

Answer 9

Inhibit the conversion of AT1 to AT2

Question 10

What is the action of ATII on the adrenal cortex?

Answer 10

Release of aldosterone

Question 11

Which part of the adrenal cortex is aldosterone released from?

Answer 11

The zone glomerulosa

Question 12

What is the effect of ATII on the blood vessels?

Answer 12

Vasoconstriction

Question 13

What drug inhibits renin?

Answer 13

Aliskiren

Question 14

What accumulates as a result of the action of aliskiren?

Answer 14

Angiotensinogen

Question 15

What does the use of aliskiren prevent the accumulation of?

Answer 15

ATI

Question 16

What does the use of ACEI result in the accumulation of ?

Answer 16

ATI and bradykinin

Question 17

What does the use of ACEI result in the decreased formation of?

Answer 17

ATII

Question 18

What is the receptor for ARBs?

Answer 18

Angiotensin II type 1 receptors

Question 19

What are the effects of aliskiren, ARBs and ACEIs?

Answer 19

Vasodilation

Decreased aldosterone secretion

Question 20

What is the action of aldosterone?

Answer 20

Na+ and water retention

Question 21

Do ARBs interfere with bradykinin degradation?

Answer 21

No

As ACE is not affected when ARBs are used

Question 22

Why are ARBs and ACEIs protective in diabetic nephropathy?

Answer 22

ATII constricts the efferent arterioles of the kidney. If ARBs and ACEs are used there is no ATII action so there is dilation of the efferent arteriole. Therefore filtration pressure and GFR decreases — this decreases the work of the kidney and reduces the risk of proteinuria.

Question 23

What is the action of PG on the afferent arteriole of the kidney?

Answer 23

Vasodilation

Question 24

When is there maximum filtration pressure and maximum GFR?

Answer 24

When PG dilates the afferent arteriole and ATII constricts the efferent arteriole

Question 25

What is the clinical indication of aliskiren?

Answer 25

Mild to moderate hypertension

Question 26

What are the clinical indications of ARBs and ACEIs?

Answer 26

Mild to moderate hypertension Protective of diabetic nephropathy CHF

Question 27

What are the side effects of ACEIs, ARBs and aliskiren?

Answer 27

``` Hyperkalemia Acute renal failure in renal artery stenosis Angioedemia Dry cough (only in ACEIs) Hypotension ```

Question 28

When do we not use aliskiren, ACEIs, ARBs?

Answer 28

Pregnancy Bilateral renal artery stenosis Hypotension

Question 29

Why does aliskiren, ARBs and ACEIs cause hyperkalemia?

Answer 29

Aldosterone promotes K+ wasting, if there is no aldosterone action then no K+ wasting resulting in hyperkalemia

Question 30

Why are ARBs, ACEIs and aliskiren not advised in renal artery stenosis?

Answer 30

In renal artery stenosis there is already a decreased GFR. If you prevent the vasoconstriction of the efferent arteriole via the use of one of these drugs, then the GFR decreases further as the filtration pressure is reduced.

Question 31

What are the enhancers of renin release?

Answer 31

Decreased blood flow or hypotension NaCl excretion SY stimulation via Beta 1 receptors

Question 32

What are the clinical indications for RAAS inhibitors?

Answer 32

``` Hypertension Diabetic nephropathy Metabolic syndrome: insulin sensitivity increases and insulin resistance decreases CHF IHD LVH ```

Question 33

Which drugs do RAAS inhibitors interact with?

Answer 33

K+ sparing diuretics Lithium (can increase Li toxicity) Antidiabetic drugs (hypoglycemic effects may be enhanced) Cytostatics and immunosuppressants (there is a risk of hypersensitivity)

Question 34

Name the ACEIs

Answer 34

``` Captopril Fosinopril Zofenopril Perindopril Enalapril Lisinopril Ramipril ```

Question 35

How are ACEIs administered?

Answer 35

Orally

Question 36

Where are the ACEIs eliminated?

Answer 36

The kidney (apart from fosinopril)

Question 37

Which ACEI is not eliminated in the kidney?

Answer 37

Fosinopril

Question 38

Where is Fosinopril eliminated?

Answer 38

Partly in the liver

Question 39

Which of the ACEIs are pro drugs?

Answer 39

Fosinopril Zofenopril Perindopril Enalapril Ramipril

Question 40

Where and how are the pro-drugs ACEIs activated and how?

Answer 40

Hydrolysis in the liver

Question 41

Where does glucuronidation of ACEIs take place?

Answer 41

The liver

Question 42

What is the bioavailability of ACEIs?

Answer 42

Mild to moderate

Question 43

What is the plasma half life of Captopril?

Answer 43

2h

Question 44

What is the plasma half life of Fosinopril?

Answer 44

4h

Question 45

What is the plasma half life of Zofenopril?

Answer 45

5-6h

Question 46

What is the plasma half life of Perindopril?

Answer 46

9h

Question 47

What is the plasma half life of Enalapril?

Answer 47

11h

Question 48

What is the plasma half life of Lisinopril?

Answer 48

12.5h

Question 49

What is the plasma half life of ramipril?

Answer 49

15h

Question 50

Which ACEI has the longest plasma half life?

Answer 50

Ramipril

Question 51

Which ACEI has the shortest half life?

Answer 51

Captopril

Question 52

What is the mechanism of action of ACEIs?

Answer 52

There is a decrease in ATII which leads to decreased aldosterone secretion. There is decreased Na+ and water retension which reduces pre and after load — decreasing the work of the heart. In addition decreased ATII results in a decrease in peripheral vascular resistance which results in a decrease in BP.

Question 53

Name the ARBs

Answer 53

``` Losartan Eprosartan Valsartan Candesartan Irbesartan Telmisartan ```

Question 54

Which ARB has the largest bioavailability?

Answer 54

Irbesartan

Question 55

Which ARB has the smallest bioavailability?

Answer 55

Eprosartan

Question 56

Which ARB has the longest plasma half life? How long is it?

Answer 56

Telmisartan >20h

Question 57

Which ARBs has the shortest plasma half life? What is it?

Answer 57

Losartan 2-3h

Question 58

Why would you use ARBs over ACEIs?

Answer 58

If the patient has tried ACEIs and developed dry cough or angioedema

Question 59

What are the effects of ARBs?

Answer 59

Arteriolar and venous dilation and block of aldosterone secretion. Decreased BP and Na+ and H20 retention

Question 60

What is the dose of Valsartan?

Answer 60

1 x 80-320mg

Question 61

How is aliskiren administered?

Answer 61

Orally

Question 62

How is aliskiren eliminated?

Answer 62

Without inactivation (mainly)

Question 63

In reference to aliskiren, when is P-glycoprotein involved?

Answer 63

Absorption and biliary excretion

Question 64

What are the drug interactions of aliskiren?

Answer 64

P-glycoproteins inducers (e.g., Rifampicin) decrease the bioavailability P-glycoproteins inhibitors (e.g., ketoconazole, verapamil) enhance the plasma level.

Question 65

What should be avoided when ACEI are prescribed?

Answer 65

Potassium supplements and potassium sparing diuretics

Question 66

Why should potassium sparing diuretics be avoided when using ACEI?

Answer 66

Because it can cause hyperkalemia aldosterone promotes the retention of Na and H20 and the excretion of K. If there is no aldosterone action, then K is not increased therefore there is the risk of hyperkalemia when used with potassium sparing diuretics.

Question 67

What may occur when ACEI are introduced to patients with HF who are already taking high dose diuretics?

Answer 67

Profound first dose hypotension

Question 68

What should be checked before starting ACEI? (or before increasing the dose)

Answer 68

Renal function and electrolytes

Question 69

When should ACEI be completely avoided?

Answer 69

in patients with severe bilateral renal artery stenosis (or severe stenosis of the artery supplying a single functioning kidney).

Question 70

When should ACEI be used with caution?

Answer 70

if the patient may have undiagnosed or clinically silent renovascular disease: this includes patients with peripheral vascular disease or those with severe generalised atherosclerosis.