Antihypertensives II

Question 1

what is an example of a low -ceiling thiazide diuretic?

Answer 1

Hydrochlorothiazide

Question 2

what is an example of high-ceiling loop diuretic?

Answer 2

Furosemide

Question 3

What is an example of potassium-sparing diuretic (aldosterone antagonist)?

Answer 3

Spironolactone

Question 4

What are the functions of diuretics?

Answer 4

Diuretics act on
various sites in the
nephron to cause
diuresis (increase in
urine production)
+
Affect reabsorption
and/or excretion of
Na, K+, Mg2+,Ca2+, Cl, HCO3-

Question 5

site of action of thiazide diuretics

Answer 5

Early Distal Convoluted Tubule

Question 6

MOA of thiazide diuretics

Answer 6

Inhibit the Na-Cl symporter, therefore increases sodium, potassium, magnesium excretion and decreases Calcium exceretion

Question 7

What is the antihypertensive MOA of thiazide diuretics

Answer 7

Initially, thiazide diuretics
decrease blood volume and thereby decrease cardiac output. Over time, the drugs decrease peripheral vascular resistance (PVR), an action that may be
secondary to a reduction in the sodium content of smooth muscle cells.

Question 8

Indications of thiazide diuretics?

Answer 8

Initial Tx of mild to moderate HPT

Thiazide diuretics are also used in combination with other types of antihypertensive agents, because they have additive or synergistic effects on blood pressure, and a diuretic may prevent the compensatory fluid retention evoked by another agent.

Question 9

Why is an angiotensin inhibitor or CCB more preferable that a thiazide diuretic?

Answer 9

They may be preferable because of the superior ability of these agents to control blood pressure for the entire day, and because they tend to cause fewer adverse effects.

Question 10

A combination of which drugs effectively controls blood pressure while reducing the risk of stroke and myocardial infarction in hypertensive patients?

Answer 10

Combination of indapamide and an angiotensin inhibitor

Question 11

Thiazide diuretics are ____________________ compounds

Answer 11

Sulphonamide

Question 12

Excretion of of thiazide diuretics?

Answer 12

Partially metabolised before excretion in the urine
* Actively secreted into the nephron by proximal tubular cells, travel
through nephron lumen to reach site of action (distal convoluted
tubule)

Question 13

Thiazide diuretics offer protection against which medical condition? How?

Answer 13

Appear to offer protection against osteoporosis (decrease urinary
excretion of calcium)

Question 14

Electrolyte-associated adverse effects of thiazide diuretics

Answer 14

• Dose-dependent (12.5mg versus 25 mg)
• Electrolyte (hypokalaemia, hypomagnesaemia, hyponatraemia,
  hypochloraemic alkalosis)

Question 15

Metabolic-associated adverse effects of diuretics

Answer 15

Metabolic abnormalities: elevated glucose, uric acid and lipid levels
* Decreased insulin sensitivity and insulin secretion (hypokalaemia)
* Hyperuricaemia = decreased uric acid secretion from proximal tubule (precipitate gout)

Question 16

Contraindications of hydrochlorothiazide (4)

Answer 16

Gout
* Pregnancy
* Severe liver impairment
* Kidney impairment (eGFR <30ml/min)

Question 17

Caution of thiazide diuretics

Answer 17

Caution in patient with family history of skin cancer – counsel on sun
avoidance and sun protection

Question 18

MOA of loop diuretics

Answer 18

Inhibits symporter that transports Na, K, 2Cl- back into tubular cells

Reduces back diffusion of K+ and increase excretion of Mg2+ and Ca2+

Question 19

Where do loop diuretics work?

Answer 19

In the thick ascending limb of loop of Henle

Question 20

Why are loop diuretics more potent?

Answer 20

Exert a more powerful natriuretic effect than other diuretics, because
they inhibit the reabsorption of a greater percentage of sodium
* High-ceiling diuretics – dose dependent effect

Question 21

Indications of loop diuretics

Answer 21

Oedema, pulmonary oedema
* Oedema secondary to heart failure, liver cirrhosis, etc.
* Reserved for use in hypertension for patient with poor renal function
(CrCL<30ml/min)

Hypercalcemia

Question 22

In people with normal renal function, agent is more effective in lowering Bp between loop diuretics and thiazide diuretics?

Answer 22

• Despite greater natriuretic effect than thiazides, usually less effective that thiazides to control blood pressure in patients with normal renal
  function.

Therefore answer is thiazide diuretics

Question 23

ROA and excretion of loop diuretics

Answer 23

Route of administration: oral or IV
Partly metabolised before excreted in the urine

Question 24

adverse effects of loop diuretics

Answer 24

*Hypokalaemia, hypomagnesaemia, hypocalcaemia, hyponatraemia,

• Hyperuricaemia (gout), hypochloraemic alkalosis
• Dehydration, hypotension, hypovolaemia
• Endocrine abnormalities like thiazides
• Hearing loss
• Hypersensitivity (sulphonamide structure)

Question 25

How is sodium normally transported through through the Principal cells in the collecting duct?

Answer 25

Sodium enters the principal cells through sodium channels. Sodium is then transferred into the interstitial fluid by the sodium pump, while potassium is pumped in the opposite direction and then moves through potassium channels into the tubular fluid.

Question 26

How does Aldosterone the process of sodium transport in the kidneys?

Answer 26

Aldosterone stimulates these processes by increasing the synthesis of messenger RNA that encodes for sodium channel and sodium pump proteins

Question 27

The potassium-sparing diuretics exert their effects via two mechanisms. Explain these mechanisms

Answer 27

amiloride and triamterene inhibit the entrance of sodium into the principal cells, whereas spironolactone blocks the mineralocorticoid (aldosterone) receptor and thereby inhibits sodium reabsorption and potassium secretion.

Question 28

MOA of spironolactone

Answer 28

Structural analogue of aldosterone, blocks aldosterone binding to the mineralocorticoid (aldosterone) receptor in epithelial cells of the distal tubule and collecting duct.

Question 29

What is the normal function of mineralocorticoid receptors?

Answer 29

Mineralocorticoid receptors (when stimulated) interact with DNA to promote expression of genes for sodium channels and the sodium pump that enable sodium reabsorption and reduce renal potassium excretion – i.e. sodium excretion and decreased potassium excretion

Question 30

Indications for spironolactone (4)

Answer 30

* Prevent hypokaleamia * Primary hyperaldosteronism * Reduce mortality in people with heart failure * Antiandrogenic effects: polycystic ovary disease and hirsutism in women

Question 31

Adverse effects of spironolactone (2)

Answer 31

Antiandrogenic effects: Gynecomastia & impotence in men * Hyperkalaemia

Question 32

Contraindications of Spironolactone

Answer 32

* Kidney impairment (eGFR <30ml/min) * Pregnancy