L11 Hypertension 2

Question 1

When is renin secreted?

Answer 1

In response to a fall in sodium concentration of the fluid in the distal tubule.
In response to a fall in renal perfusion pressure.

Question 2

How is glomerular filtration pressure maintained?

Answer 2

By activation of AT1 receptors in the efferent arteriole.

Question 3

What are the 3 mechanisms by which renin secretion is controlled?

Answer 3

1. renal vascular receptors detect decrease in blood pressure
2. macula dense cells of the distal tubule sense decreased sodium chloride in filtrate, stimulating renin release.
3. noradrenaline acts directly on beta1-adrenoreceptors on juxtoglomerular cells to stimulate renin secretion (i.e. action on sympathetic nervous system).

Question 4

What is the result of AT1 receptor stimulation?

Answer 4

1. increased sympathetic tone and NA release
2. vasoconstriction
3. aldosterone release from adrenal cortex –> sodium reabsorption –> water reabsorption.

Question 5

What is the result of AT2 receptor stimulation?

Answer 5

1. vasodilation

2. cellular growth and differentiation

Question 6

Give examples of ACE inhibitors, and combination products.

Answer 6

Ace inhibitors end in -pril.
Eg catopril, enlapril, peridopril.
Many are available in combination with a diuretic (e.g. hydrochlorothiazide) or a Ca channel blocker.

Question 7

What are the 3 drug classes that act on the RAAS?

Answer 7

ACE inhibitors
angiotensin receptor antagonists
beta blockers

Question 8

What is the mechanism of action of ACE inhibitors?

Answer 8

block the conversion of angiotensin 1 to angiotensin 2, and block the degradation of bradykinin.

Question 9

What is the role of bradykinin?

Answer 9

potent vasodilator.

Question 10

What are the indications for use of ACE inhibitors?

Answer 10

First line of treatment for hypertension in patients with chronic kidney disease, diabetes with albuminuria, heart failure and left ventricular dysfunction following MI.

Question 11

Give 4 important practice points for initiation of ACE inhibitor treatment.

Answer 11

1. potassium supplements and potassium sparing diuretics should be stopped.
2. any diuretic should be temporarily stopped for 24 hours to avoid potentiation of 1st dose effect.
3. therapy should be started at low dose
4. renal function should be checked before starting treatment.

Question 12

What are the two major side effects of ACE inhibitors?

Answer 12

1. First dose effect: very steep fall in blood pressure may occur with first dose, resulting in dizziness and fainting. Patients on diuretics or vasodilators are more likely to have this effect due to volume depletion.
2. hyperkalaemia: reduced potassium excretion as a result of decreased aldosterone production.

Question 13

Which patients are at risk of hyperkalaemia?

Answer 13

those on K sups
patients on K sparing diuretics such as amiloride, triamterene, spironolactone.
those with renal dysfunction
diabetics

Question 14

What are the general side effects of ACE inhibitors?

Answer 14

dry cough caused by vasodilation of lung BVs, followed by oedema and then coughing.
Oedema
taste disturbances: metallic or salty taste, disappears after 5-6 months.
Angiodema: potentially fatal. difficulty breathing or swelling of face, mouth, larynx, hands and feet.

Question 15

how should angiodema (as an affect of ACE inhibitors) be treated?

Answer 15

Discontinuation of drug and use of antihistamine and/or adrenaline/steroids and airway management.

Question 16

What are the contraindications for use of ACE inhibitors?

Answer 16

pregnancy: may cause foetal renal dysfunction in 2nd-3rd trimester
Renal artery stenosis: may lead to renal failure
Chronic renal disease: renal impairement increases the risk of hyperkalaemia and may effect drug excretion

Question 17

Why should you not use ACE inhibitors in renal artery stenosis?

Answer 17

In renal artery stenosis, angiotensin II is required to constrict postglomerular arterioles and maintain adequate glomerular filtration.

Question 18

What is the mechanism of action of angiotensin II receptor antagonists (sartans)?

Answer 18

AT1 receptors are blocked in the blood vessels –> blocks vasoconstriction
receptors blocked in adrenal cortex –> blocks aldosterone release and subsequent sodium reabsorption

Question 19

Side effects of sartans?

Answer 19

Common: dizziness, headache and hyperkalaemia
Infrequent: first dose orthostatic hypotension
Rare: cough

Question 20

Describe the use of sartans in type 2 diabetes.

Answer 20

losartan and irbesartan are marketed to reduce the progression of renal disease in patients who have type 2 diabetes, hypertension and proteinuria.

Question 21

What drug interactions occur with ACE inhibitors and sartans?

Answer 21

Diuretics: concurrent use –> increased risk of 1st dose hypotension. should withhold diuretic for 24 hours on initiation of ace inhibitor. Use a lower dose and take first dose at night when lying down.
K and K sparing diuretics: increased risk of hyperkalaemia
Lithium: may cause lithium toxicity.
NSAIDs: may reduce antihypertensive response and increase the risk of hyperkalaemia.