L12 Hypertension 3

Question 1

What is the mechanism of action of thiazide diuretics?

Answer 1

Thiazides are week anions secreted by the proximal convoluted tubule into tubular fluid.
They inhibit the reuptake of sodium chloride into the luminal membrane of the early segment of the distal tubule, thus increasing excretion of sodium ions, chloride ions, water, potassium and hydrogen.
Low doses have a vasodilator effect.
Blood volume, venous return and cardiac output are all decreased.
also causes hypokalaemia and metabolic alkalosis through exchange of Na with K and H.
Also decrease peripheral vascular resistance by modulating activity of K channels in arterioles. Membrane becomes hyper polarised, thus opposing smooth muscle calcium entry and therefore contraction.

Question 2

What are the indications for use of thiazides?

Answer 2

Moderate hypertension (first line of treatment if over 65, and with new onset diabetes).
Oedema associated with heart failure
nephrogenic diabetes insipidus
prevention of renal calculi associated with hypercalciuria

Question 3

How do thiazide diuretics act on renal calculi?

Answer 3

Increase renal reabsorption of calcium and thus prevent calcium stone formation in the urine.

Question 4

What are the side effects of thiazides?

Answer 4

dizziness, weakness, muscle cramps, orthostatic hypotension, hypercalcaemia.
Hypokalemia.
Metabolic alkalosis (increased H secretion)
Hyperglycaemia
Increase in TC, LDL and TG. decrease in HDL
Erectile dysfunction
Hyperuricaemia: increased serum uric acid levels may precipitate gout

Question 5

In which patients is the development of hypokalaemia most hazardous?

Answer 5

Those undergoing digoxin therapy (increases plasma concentration of digoxin).
Those with chronic arrhythmias
those with acute MI

Question 6

What is the treatment for hypokalaemia?

Answer 6

Potassium supplements or potassium-sparing diuretics.

can also combine a thiazide with an ACE inhibitor or angiotensin II receptor antagonist.

Question 7

Which drugs should not be given with thiazides and why?

Answer 7

Bile acid binding resins reduce the absorption of anionic drugs. Thiazides are anionic drugs.
Thiazide should be taken at least 1 hour before, or 4-6 hours after the resin.

Question 8

Why is it more effective to add a drug from another class to thiazide treatment, rather than increasing the dose of thiazide?

Answer 8

Thiazides have a flat dose response curve for reducing blood pressure, meaning that when the dose is increased beyond a threshold there is little further antihypertensive effect, but metabolic effects continue to increase.
Adding an ACE inhibitor will result in additive antihypertensive effects, without additive side effects.

Question 9

What is the mechanism of action of potassium-sparing diuretics?

Answer 9

Inhibit sodium channels in the luminal membrane of distal tubule, preventing reabsorption of sodium. this increases sodium, Cl and water excretion, and decreases potassium excretion.

Question 10

Give 2 examples of potassium sparing diuretics.

Answer 10

Amiloride and triamterene.

Question 11

Why are potassium-sparing diuretics preferred over potassium supplements?

Answer 11

Convenience: need to use 3-8 K supplement tabs daily

Better tolerance: KCl supplement causes ulceration of GI tract.

Question 12

In which products are amiloride and trimterene available in?

Answer 12

Amiloride is available alone or in combination with hydrochlorothiazide.
Triamterene is only available in combination with hydrochlorothiazide.

Question 13

Describe drug interactions of thiazides.

Answer 13

May have add-on effect with drugs that cause hypokalaemia and those that increase blood glucose.
NSAIDs decrease antihypertensive effect (not including low dose aspirin).
Risk of severe hypotension if combined with ACE inhibitor at first dose. Also increases risk of renal impairment.
Bile acid binding resins prevent the absorption of thiazides. Need to stagger dosing.

Question 14

What is the “triple whammy”?

Answer 14

Risk of renal failure when a diuretic, NSAID and ACE inhibitor/ATII antagonist are combined.
NSAIDs reduce renal blood flow
ACEI and ATIIB reduce renal perfusion
Diuretics decrease blood volume and decrease renal blood flow. This causes activation of RAAS to increase renin and ATII, however ineffective if ACE inhibitor is present.

Question 15

Why are beta blockers no longer a first line treatment for uncomplicated hypertension?

Answer 15

Assosciated with decreased stroke protection and increased risk of diabetes.

Question 16

What is the mechanism of action of beta blockers?

Answer 16

Competitively block beta receptors, resulting in decreased HR, contractility, cardiac output
Reduce central release of adrenergic substances
Inhibit peripheral release of NA
decrease renin release from the kidneys

Question 17

What are the side effects of beta blockers?

Answer 17

Heart failure
Bradycardia
Bronchospasm (due to blockage of beta-2 bronchodilation)
Alteration of glucose and lipid metabolism
CNS effects with lipid soluble drugs (propanolol and metoprolol). Atenolol and bisprolol have low lipid solubility
Erectile dysfunction
fatigue

Question 18

In which patients is beta-blocker treatment contraindicated?

Answer 18

heart failure: may precipitate or worsen heart failure in patients with existing cardiac dysfunction.
Heart block
asthma
peripheral vascular disease and raynauds syndrome
Hyperlipidaemia
diabetes
hyperthyroidism
anaphylaxis

Question 19

Define Raynaud’s disease and Raynaud’s phenomenon.

Answer 19

Disease: primary vascular disorder most often affecting women, marked by attacks of Raynaud’s phenomenon.
Phenomenon: intermittent bilateral attacks of ischaemia of fingers, toes, ears, nose, marked by severe pallor with parasthesia and pain. brought on my cold or emotional stimuli, and relieved with heat.

Question 20

Describe the effects and benefits of beta-1 selective drugs.

Answer 20

May produce less bronchospasm, less peripheral vasoconstriction and less alteration of glucose and lipid metabolism.
Selectivity decreases as dose is increased.
Includes atenolol and metoprolol

Question 21

Describe the effects and benefits of beta blockers with intrinsic sympathomimetic activity.

Answer 21

able to stimulate and block beta receptors by competing with NA. May cause less bradycardia, less coldness of extremities and less alteration of lipid profiles. May however be less effective in the treatment of angina and MI.
Eg oxprenolol and pindolol.

Question 22

Describe the effects and benefits of beta blockers with mixed beta blocking and alpha-1 blocking

Answer 22

Provide additional arteriolar vasodilating action. Have been shown to improve ventricular function and to reduce overall mortality in patients with chronic heart failure. Eg Labetalol and carvedilol

Question 23

Describe the effects and benefits of less lipid soluble beta blockers

Answer 23

May be less likely to enter CNS and cause fewer sleep disturbances and nightmares. Eg atenalol.

Question 24

When might beta blockers with predominant hepatic elimination be preferred?

Answer 24

in patients with renal impairment.

Question 25

Why shouldn’t beta blockers be combined with verapamil?

Answer 25

Both drugs cause bradycardia, and so combination may cause heart block and hypotension.

Question 26

What are some counselling points for beta blockers?

Answer 26

Do not stop taking this medication abruptly, as this may exacerbate angina, precipitate rebound hypertension, MI or arrhythmias.
Dosage should be reduced gradually over at least 2 weeks.

Question 27

Which class of antihypertensives might offer additional benefit in patients with renal calculi?

Answer 27

Thiazides. Also lower urinary excretion of calcium.