1: Drugs acting on the kidney 1 & 2 Flashcards Preview

Renal Week 4 2017/18 > 1: Drugs acting on the kidney 1 & 2 > Flashcards

Flashcards in 1: Drugs acting on the kidney 1 & 2 Deck (58)
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1
Q

What is a diuretic?

A

Prevents reabsorption of electrolytes (usually sodium) causing diuresis (because water follows sodium)

2
Q

What is ADH?

What is its other name?

A

Anti-diuretic hormone

Acts on V2 receptors (G-protein coupled) to increase water reabsorption

Vasopressin

3
Q

How do SGLT2 inhibitors work?

What symptom do they cause?

A

Inhibit combined glucose-sodium transporter

Glycosuria

4
Q

What are uricosuric drugs?

A

Stimulate excretion of uric acid into tubules

5
Q

Diuretics (increase / decrease) urine flow.

A

increase urine flow

6
Q

What is

a) hydrostatic
b) osmotic/oncotic pressure?

A

hydrostatic pressure - pressure of the fluid in a tube pushing outwards

oncotic pressure - negatively charged plasma proteins in the blood pulls fluid from the interstitium

so oncotic pressure opposes hydrostatic pressure

7
Q

What change in forces causes oedema?

A

Increase in capillary hydrostatic pressure

and/or

Decrease in capillary oncotic pressure

8
Q

How does nephrotic syndrome cause oedema in the short and long-term?

A

Proteinuria

Less protein in the blood

So less oncotic pressure pulling fluid back into the capillaries

So more fluid in the interstitium

(Also: blood volume & pressure drop, RAAS increases BP and BV (aldosterone), capillary hydrostatic pressure increases and oncotic pressure decreases because there’s even less protein in blood = even more fluid in the interstitium)

OEDEMA

9
Q

How does CCF cause oedema?

A

Reduced cardiac output

Renal hypoperfusion

RAAS

BV, BP increases

So hydrostatic pressure increases and oncotic pressure decreases (dilution)

OEDEMA

10
Q

How does cirrhosis cause oedema?

What is abdominal oedema called?

A

Portal hypertension increases hydrostatic pressure

Liver can’t produce albumin, so oncotic pressure decreases

Plus RAAS activates because blood volume decreases…

OEDEMA

(Ascites)

11
Q

Where in the nephron is sodium reabsorbed?

A

Proximal tubules (passively, along with Cl-)

Ascending limb (triple transporter)

Distal tubules (Na+/Cl- co-transporter)

Collecting tubules (Na+/K+ exchange)

12
Q

How is sodium reabsorbed in the

a) proximal tubules
b) ascending limb
c) distal tubules
d) collecting ducts?

A

a) Passively

b) Triple transporter

c) Na/Cl co-transport

d) Na/K exchange

13
Q

Which drugs block sodium reabsorption in the

a) proximal tubules
b) ascending limb
c) distal tubules
d) collecting ducts?

A

a) Carbonic anhydrase inhibitors (minor)

b) Loop diuretics (block triple transporter)

c) Thiazide & thiazide-like diuretics (block Na/Cl co-transporter)

d) Potassium-sparing diuretics (e.g spironolactone)

14
Q

As sodium reabsorption is paired to potassium secretion in the collecting ducts, what happens to [K+] if you give a patient

a) thiazide diuretics
b) loop diuretics
c) spironolactone

A

a) Decreases
b) Decreases
c) Spared, actually increases as a result

15
Q

What percentage of sodium is reabsorbed by the glomeruli?

A

99%

diuretics still cause massive changes in sodium conc. in the urine

16
Q

By which two routes could diuretics enter the urine?

Why is one far more common than the other?

A

1. Filtration at glomerulus

2. Secretion from peritubular capillaries into proximal tubules

Drug is usually bound to protein so it can’t be filtered

17
Q

What are

a) positive
b) negative ions called?

A

a) Cations

b) Anions

18
Q

What transporters carry

a) acidic diuretics like thiazides and loop drugs
b) basic diuretics?

A

a) Organic ANION transporters

b) Organ CATION transporters

because acids are negatively charged and bases are positively charged

19
Q

What two types of transporter cause secretion of diuretics into the proximal tubules?

A

OATs

OCTs

depending on if they’re acidic or basic

20
Q

Why aren’t diuretics toxic?

A

Transporters make sure [diuretic]urine > [diuretic]blood

21
Q

Which membranes do transporters have to get diuretics through to secrete them into the proximal tubules?

A

Capillary membrane

Basolateral membrane

Apical membrane

22
Q

Which transporter moves acidic diuretics across membranes towards the proximal tubule?

A

OAT

23
Q

Which transporter moves alkaline diuretics across membranes towards the proximal tubule?

A

OCTs

24
Q

Which other transporter may move acidic diuretics across the apical membrane of tubular cells?

A

MRP2

multi-drug-resistance protein

25
Q

What effect do loop diuretics have?

How?

A

Torrential diuresis

Block Na/K/2Cl triple transporter

Medulla’s osmolarity doesn’t increase because it’s not getting Na, K and Cl

So corticomedullary conc. gradient is abolished

So water isn’t reabsorbed in Loop of Henle

26
Q

By which route is magnesium and calcium absorbed into the interstitium around the ascending limb?

Why?

A

Paracellular

Electrochemical gradient - Na+, K+ (but leaks back) and 2 Cl- move into interstitium via triple transporter, so medulla is NEGATIVE

So Mg2+ and Ca2+ are attracted to it

27
Q

The reabsorption of which ions is directly blocked by loop diuretics?

A

Ca2+, Mg2+

because loop diuretics abolish electrochemical gradient between tubules and medullary interstitium

and these ions aren’t reabsorbed anywhere else

28
Q

Apart from Ca2+ and Mg2+, what other ion will patients on loop diuretics be deficient in?

A

K+

more Na+ reabsorption in collecting ducts, so more K+ secretion

look over this

29
Q

Why can loop diuretics be used to treat pulmonary oedema?

A

Drains fluid pretty much

30
Q

How do loop diuretics enter the proximal tubules?

A

Transport by OATs

because they’re acidic

31
Q

Which diseases are loop diuretics used to treat?

A

Pulmonary oedema (IV)

CCF

Cirrhosis with ascites

Kidney failure and nephrotic syndrome

Resistant hypertension

Hypercalcaemia

32
Q

Loop diuretics are sometimes used to treat ___ but may cause ___.

(hyper/hypokalaemia, hyper/hypocalcaemia)

A

used to treat hypercalcaemia

may cause hypokalaemia

33
Q

How is hypokalaemia caused by loop diuretics treated?

A

Potassium-sparing diuretic

K+ supplements

34
Q

Which cardio drugs may loop diuretics interact with?

A

Digoxin

Class III arrythmia drugs

35
Q

What acid-base imbalance can loop diuretics cause?

Why?

A

Metabolic alkalosis

More Na+ gets to collecting ducts, so more K+ is secreted (paired)

And K+ / H+ secretion is also paired

may be seen with hypokalaemia

36
Q

To summarise, what are fluid, electrolyte and acid-base imbalances caused by loop diuretics?

A

Hypovolaemia

Hypokaelamia, hypocalcaemia, hypomagnesaemia, hyperuricaemia (causing GOUT)

Metabolic alkalosis

37
Q

Why do thiazide and loop diuretics become less effective over time?

A

Transporters they act on are UPREGULATED with prolonged use

38
Q

What channel do thiazide diuretics block?

Where are they found in the nephron?

A

Na+/Cl- co-transporter

Distal tubules

39
Q

Where in particular do loop diuretics and thiazide diuretics bind on their respective targets?

A

Cl- site

40
Q

What effect do thiazide diuretics have on

a) K+
b) Ca2+?

A

a) Decrease in K+ - more Na+ makes it to collecting ducts to be reabsorbed, so more K+ is secreted

b) Increase in Ca2+ - opposite of loop diuretics, reason isn’t important

41
Q

What effects do loop diuretics and thiazide diuretics have on calcium concentration?

A

Loop diuretics cause a DECREASE

Thiazide diuretics cause an INCREASE

42
Q

How big a diuresis do thiazide diuretics cause compared to loop diuretics?

A

Mild diuresis

43
Q

What cardio diseases are treated with thiazide diuretics?

A

Mild heart failure (revise)

Hypertension

44
Q

Which disease, causing renal colic, are thiazide diuretics used to treat?

Why?

A

Renal stones

Reduce Ca2+ excretion (increased reabsorption), reducing stone formation

45
Q

What is the effect of thiazide diuretics on

a) calcium
b) magnesium?

A

a) Increases blood conc.

b) Decreases blood conc. as in loop diuretics

46
Q

To summarise, what are fluid, electrolyte and acid-base imbalances caused by thiazide diuretics?

A

Hypovolaemia

Hypokalaemia, Hypercalcaemia, hypomagnesiaemia, hyperuricaemia

Metabolic alkalosis

47
Q

Which hormones increase

a) sodium
b) water

reabsorption in the distal tubules and collecting ducts?

How do they do this?

A

a) Aldosterone - increase no. of Na/K/ATPase channels (more sodium reabsorbed, more potassium secreted)

b) ADH - increase no. of aquaporins (more water in)

48
Q

In the distal tubules and collecting ducts, Na+ ___ is paired to K+ ___.

A

Na+ reabsorption

K+ secretion

49
Q

The more ___ which arrives at the distal tubules and collecting ducts, the more ___ which is secreted.

A

More Na+ (as in diuretics, which block reabsorption in ascending limb and distal tubules), more Na+ reabsorption, more K+ secretion

50
Q

Why does more Na+ reabsorption cause more K+ secretion?

A

More Na+ reabsorption means tubular fluid is more negative

So more K+ passes through K+ channels into tubules (positive ion)

51
Q

What are some examples of potassium-sparing diuretics?

A

Amiloride and Triamterene

Spironolactone and Eplerenone

52
Q

How do

a) amiloride and triamterene

b) spironolactone and eplerenone work?

A

a) Block Na+ reabsorption in distal tubule and collecting ducts

b) Block Na+ channels (apical) AND Na/K/ATPase (less Na+ in, less K+ out as well)

53
Q

Spironolactone and eplerenone compete with which hormone?

A

Aldosterone

54
Q

What electrolyte imbalance does an aldosterone antagonist cause if used alone?

A

Hyperkalaemia

55
Q

Where do aldosterone antagonists bind to block K+ secretion?

A

Cytoplasmic receptors

56
Q

What must aldosterone antagonists be given with?

A

Thiazide or loop diuretics

to prevent hyperkalaemia

57
Q

What cardio diseases are aldosterone antagonists used to treat?

A

Heart failure

Resistant hypertension

58
Q

Which endocrine disease are aldosterone antagonists used to treat?

A

Hyperaldosteronism