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Flashcards in Pharmacology Deck (47)
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1
Q

List the main drugs that act on the kidney

A
Diuretics
Vasopressin agonists/antagonists
SGLT2 inhibitors
Renal failure drugs
pH-altering drugs
2
Q

What effect do diuretics have on volume of urine?

A

Increase urine volume by inhibiting reabsorption of salt which causes decreased reabsorption of water

3
Q

How does oedema arise?

A

Imbalance between rate of formation and absorption of interstitial fluid

4
Q

Which forces are involved in formation of interstitial fluid?

A
Pc = capillary pressure
πp = capillary oncotic pressure
Pi = interstitial fluid pressure
πI = interstitial fluid oncotic pressure
5
Q

Disease states that increase/decrease Pc or increase/decrease πp produce oedema

A

Disease states that increase Pc or decrease πp produce oedema

6
Q

What (simply) happens in nephrotic syndrome?

A

Disorder of glomerular filtration where plasma protein appears in filtrate, resulting in proteinuria

7
Q

Once plasma protein is in the urine, it can’t be reabsorbed. True/False?

A

True

Thus voided in urine; urine appears frothy

8
Q

What effect does the presence of plasma protein in the filtrate have on πp? What is the result of this?

A

Body loses plasma protein in urine so πp decreases; this leads to oedema

9
Q

What effect does decreased πp have on blood volume and cardiac output? What is the result of this?

A

Decreased πp causes decreased blood volume and cardiac output, activating RAAS to cause sodium and water retention

10
Q

What effect does sodium and water retention have on Pc and πp? What is the result of this?

A

Pc increases and πp decreases, causing oedema

when this happens in nephrotic syndrome, you ultimately get worsening oedema

11
Q

List the major sites of diuretic action in the nephron

A

Proximal convoluted tubule
Ascending limb of loop of Henle
Distal convoluted tubule
Collecting tubule

12
Q

Which class of diuretic works in the proximal convoluted tubule? How does it work?

A

Carbonic anhydrase inhibitor

Blocks production of H+, thus inhibiting Na-H+ exchanger (H+ drive sodium reabsorption)

13
Q

Which class of diuretic works in the ascending limb of loop of Henle? How does it work?

A

Loop diuretic

Blocks Na-K-2Cl triple cotransporter

14
Q

Which class of diuretic works in the distal convoluted tubule? How does it work?

A

Thiazide diuretic

Blocks Na-Cl cotransporter

15
Q

Which class of diuretic works in the collecting tubule? How does it work?

A

Potassium-sparing diuretic

Blocks Na-K antiporter

16
Q

Diuretics must be in the filtrate to reach site of action. Why?

A

Site of action is the apical membrane (near the lumen)

17
Q

List the ways diuretic can enter the filtrate

A

Glomerular filtration (if not bound to plasma protein)
Secretion via transport processes in proximal tubule
Organic anion transporter (OAT)
Organic cation transporter (OCT)

18
Q

Which type of drug - acid or alkali - is transported by organic anion transporter (OAT)?

A

Acidic drugs e.g. thiazide, loop diuretics

19
Q

Which type of drug - acid or alkali - is transported by organic cation transporter (OCT)?

A

Basic drugs e.g. triamterene, amiloride

20
Q

How do acidic drugs reach the lumen of the tubule?

A

Enter cell via OAT on basolateral membrane in exchange for alpha-ketoglutarate
Exit cell/enter lumen via MRP2 or via OAT

21
Q

How do basic drugs reach the lumen of the tubule?

A

Enter cell via OCT on basolateral membrane

Exit cell/enter lumen via MRP1 or OC-H+ antiporter

22
Q

What competes with thiazide diuretic for the OAT? What is the consequence of this?

A

Uric acid competes with thiazide diuretic for the OAT

Predisposes to gout

23
Q

Name the main loop diuretics

A

Furosemide

Bumetanide

24
Q

Loop diuretics inhibit the Na-K-Cl triple cotransporter by binding the Cl site. This increases the load of Na in the distal tubules - what effect does this have on K, Ca and Mg levels?

A

Less K, Mg and Ca reabsorbed, resulting in hypokalaemia, hypocalcaemia, hypomagnesia

25
Q

List clinical conditions where loop diuretics are used

A

Acute pulmonary oedema
Chronic heart/kidney failure
Nephrotic syndrome

26
Q

Name the main thiazide diuretics

A

Bendroflumethiazide

Hydrochlorothiazide

27
Q

Thiazide diuretics block the Na-Cl cotransporter by binding the Cl site. This increases Na delivered to the collecting tubule - what effect does this have on K and Cl levels?

A

Less K absorption, resulting in hypokalaemia

Interestingly, for no solid reason, increased Ca absorption

28
Q

List clinical conditions where thiazide diuretics are used

A

Mild heart failure
Hypertension
Renal stone disease

29
Q

Name the main potassium-sparing diuretics

A

Amiloride
Triamterene
Spironolactone
Epleronone

30
Q

How do amiloride and triamterene work?

A

Block apical Na channel to decrease Na reabsorption, ultimately reduce K excretion

31
Q

How do spironolactone and epleronone work?

A

Block aldosterone receptor to decrease Na reabsorption, ultimately reduce K excretion

32
Q

Potassium-sparing diuretics are usually used alone. True/False?

A

False
Usually used in conjunction with loop/thiazide where there is hypokalaema
Used alone, can cause hyperkalaemia

33
Q

Name an osmotic diuretic

A

Mannitol

34
Q

How do osmotic diuretics work?

A

Become trapped in filtrate (cannot be reabsorbed) and exert osmotic pressure to retain water, which in turn retains sodium due to dilution
Net effect: decrease water and sodium reabsorption

35
Q

What is the main indication for using osmotic diuretic?

A

Prevent acute hypovolaemic renal failure

36
Q

Name a carbonic anhydrase inhibitor

A

Acetazolamide

37
Q

What is the effect of carbonic anhydrase inhibitor?

A

Increase excretion of HCO3, Na, K and H20 (alkaline diuresis), resulting in metabolic acidosis

38
Q

How do aquaretics work?

A

Block vasopressin receptors to cause excretion of water without Na loss, resulting in hypernatraemia

39
Q

Name some aquaretics

A

Conivaptan (V1a, V2)

Tolvaptan (V2)

40
Q

Where do SGLT2 inhibitors act?

A

Block SGLT2 in the proximal tubule to prevent glucose reabsorption

41
Q

SGLT1 is present in the intestine only, SGLT2 in the kidney only. True/False?

A

False
SGLT1 = intestine + kidney
SGLT2 = kidney only

42
Q

SGLT2 have low/high affinity for glucose; SGLT1 have low/high affinity for glucose

A

SGLT2 have low affinity for glucose; SGLT1 have high affinity for glucose

43
Q

Name some SGLT2 inhibitors

A

Dapagliflozin

Canagliflozin

44
Q

Which enzymes catalyse the formation of prostaglandins?

A

Cyclo-oxygenases

COX

45
Q

State the major prostaglandins synthesised by the kidney

A

PGE2 (medulla)

PGI2 (glomeruli)

46
Q

What is the effect of prostaglandins on vasculature and GFR?

A

Vasodilation of afferent arteriole

Increase GFR by constricting efferent arteriole

47
Q

How might NSAIDs cause acute renal failure?

A

Inhibit COX, thus inhibit prostaglandin formation, so GFR decreases