CVS Drugs

Question 1

Give two examples of ACEi ?

Answer 1

Lisinopril

Ramipril

Question 2

Describe the MoA of ACEi

Answer 2

ACE inhibitors act by binding to ACE and therefore decrease production of AngII.
Normal effects of AngII:
- activates sympathetic NS –> vasoconstriction
- acts on adrenal medulla to release aldosterone. Aldosterone acts on basolateral membrane of DCT and CT –> taken up into the principal cell where it causes nuclear transcription of ENaC. ENaC then displayed on apical membrane and results in increased Na+ uptake and therefore H20 retention.
- acts on posterior pituitary to release ADH –> increases AQP2 channels in apical membrane of CD –> increased water reuptake.
- acts directly on the kidney –> constriction of afferent arteriole, increases activity of NHE and NaK ATPase in PCT to increase Na+ reabsorption
- stimulates thirst centre

Therefore by inhibiting ACE:

• can cause decrease in BP
• can decrease glomerular pressure as ACEi induces glomerular efferent arteriolar vasodilatation and therefore reduces renal filtration pressure(this actually may be damaging especially in case of renal artery stenosis)

Question 3

What are the indications for use of ACEi?

Answer 3

1. First line treatment for HTN in white patients under 55 years old. 2nd line for all HTN patients with CCB.
2. HF - reduces mortality and improves symptoms

Question 4

What are the contraindications and cautions for ACEi use?

Answer 4

Cardiac: severe aortic stenosis (risk of hypotension), postural hypotension (Especially first dose)
Renal and electrolyte: risk of renal impairment!!! And hyperkalaemia!!
Bilateral renal artery stenosis is contraindicated.
Should not really be used in conjunction with NSAIDs as these act on afferent arterioles –> constriction.

Question 5

Why should ACEi be given with caution in patients with renovascular disease?

Answer 5

ACEi cause efferent arteriole vasodilation and consequently reduces renal filtration pressures
Any additional reduction in pre-glomerular pressures may lead to significant reduced renal filtration and result in renal failure
Caution therefore required with hypovolemia and diuretic use, renal artery stenosis (bilateral renal artery stenosis contraindicated) and concomitant NSAID use (reduced PG mediated afferent arteriolar constriction)
When there is bilateral renal artery stenosis - the effective renal bf is not significantly reduced but maintained at the cost of increasing the efferent arteriolar constrictor tone. This helps maintain intraglomerular pressure.
When ACEi use - efferent arteriolar tone is removed -> triggers intraglomerular pressure to drop suddenly and filtration pressure reduces.

Question 6

ADRs of ACEis?

Answer 6

Angioedema - due to accumulation of bradykinin
Dry cough - due to accumulation of bradykinin as ACE is a kininase and without it –> increased bradykinin
Renal failure - due to efferent arteriolar dilation –> decreases renal perfusion pressure
Hyperkalaemia
Orthostatic hypotension

Question 7

How do ACEis cause hyperkalaemia?

Answer 7

As AngII acts directly on the kidney to cause Na+ reabsorption via aldosterone and thus K+ excretion, without AngII effects –> less K+ excretion and more K+ retention –> hyperkalaemia

Aldosterone –> increased ENaC which creates negative lumen which allows loss of K+ in urine. Also, increased Na+K+ ATPase needed which also promotes K+ loss

Question 8

Give an example of an Angiotension Receptor Blocker?

Answer 8

Losartan

Candersartan

Question 9

Why is the first dose of an ACEi given at night?

Answer 9

To avoid symptomatic postural hypotension

Question 10

What is the drug treatment of HTN?

Answer 10

Step 1: if <55 and white: ACEi / ARB. If >55 or black give CCB
Step 2: ACEi (or ARB) + CCB
Step 3: ACEi/ARB + CCB + Thiazide diuretic

Question 11

What type of diuretic is most commonly used in the treatment of HTN?

Answer 11

Thiazide diuretic

Question 12

Give two examples of a thiazide diuretic?

Answer 12

Indapamide

Bendroflumethiazide

Question 13

What are the indications for use of thiazide diuretics?

Answer 13

HTN
Oedema (use with loop diuretic)
Prevent of renal calculi (ca2+ reabsorption increased therefore decresed in urine)

Question 14

Contraindications of thiazide diuretics?

Answer 14

Gout (as causes hyperuricaemia)
Long standing hypokalaemia or hyponatraemia
Hypercalcaemia

Question 15

What are some ADRs of thiazide diuretics?

Answer 15

Postural hypotension (especially when used in conjunction with ACEi or ARB)
Hypomagnesiumaemia, hyponatraemia, hypokalaemia
Hypercalcaemia
Hyperuraemia –> gout

Question 16

Interaction between NSAIDs and thiazides?

Answer 16

NSAIDs decrease diuretic effect

Question 17

What class of Calcium channel blockers are used in hypertension? Give two examples.

Answer 17

Dihydropyridines
E.g. Nifedipine and amlodopine

Dihydropyridines better for HTN as more selective for SM receptors

Question 18

What is the MoA for CCBs?

Answer 18

CCBs block L-type Calcium channels (present in cardiac and SM tissue) which results in decreased influx of Ca2+ –> relaxation of muscle i.e. Vasodilation.
Acts in SM to vasodilate
In heart : negative inotrophy (force of contraction) and chrontropy (HR)

Question 19

ADRs of amlodopine/nifedipine?

Answer 19

Amlodopine is a dihydropyridine - acts selective of L-type Calcium Channels in SM
Vasodilatory effects: palpitations, flushing,
Peripheral oedema - common
Orthostatic hypertension

Question 20

Give two examples of loop diuretics?

Answer 20

Indapamide and Furosemide

Question 21

How do loop diuretics work?

Answer 21

Act on TAL on LoH and inhibit Na+ K+ 2 Cl- cotransporter. Therefore decreased Na+ reuptake. Water follows.
Significant effect on diuresis.

Question 22

When should loop diuretics be used?

Answer 22

Heart failure (decrease preload and afterload)
Acute pulmonary oedema (IV furosemide for quick fix)
Oedema due to other causes: nephrotic syndrome, renal failure, cirrhosis

Question 23

Common ADRs of furosemide?

Answer 23

Hyponatraemia, hypocalcaemia, hypokalaemia
Ototoxicity (usually reversible)
Hyperuricaema –> gout
N+V

Question 24

What risk is associated with taking ACEi/ARBs with loop diuretics or thiazide diuretics?

Answer 24

1st dose hypotension

Question 25

Why should NSAIDs be avoided when taking loop diuretics?

Answer 25

NSAIDs inhibit PG production which therefore inhibits diuretic effect which partially relies on stimulating PG production for its vaso/venodilatory effects

Question 26

Give two examples of potassium sparing diuretics and state how each works.

Answer 26

Amiloride - directly blocks ENaC. Inhibits uptake of Na+.

Spironolactone - Aldosterone antagonist.Inhibits aldosterone binding –> decreased transcription of ENaC –> decreased Na+ reabsorption. No change to luminal charge therefore results in no loss of K+.

Both act in late DCT/CD

Question 27

ADRs of spironolactone?

Answer 27

Has anti-androgen effects (antagonism of DHT i.e. Testosterone at its binding site): irregular menstruation, painful gynaecomastia, impotence, hirsuitism
Hyperkalaemia

Question 28

Indications for use of spironolactone?

Answer 28

Liver cirrhosis: ascites
HF - congestive
Nephrotic syndrome
Primary hyperaldosteronism

Question 29

When is mannitol used and how does it work?

Answer 29

Mannitol works on the PCT

IV mannitol used to treat cerebral oedema

Question 30

Why must you give spironolactone for ascites related to liver cirrhosis?

Answer 30

Hypokalaemia can precipitate hepatic encephalopathy!

Spironolactone is potassium sparing whereas most other diuretics cause hypokalaemia