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):
1

What is a diuretic?

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

2

What is ADH?

What is its other name?

Anti-diuretic hormone

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

Vasopressin

3

How do SGLT2 inhibitors work?

What symptom do they cause?

Inhibit combined glucose-sodium transporter

Glycosuria

4

What are uricosuric drugs?

Stimulate excretion of uric acid into tubules

5

Diuretics (increase / decrease) urine flow.

increase urine flow

6

What is

a) hydrostatic

b) osmotic/oncotic pressure?

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

What change in forces causes oedema?

Increase in capillary hydrostatic pressure

and/or

Decrease in capillary oncotic pressure

8

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

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

How does CCF cause oedema?

Reduced cardiac output

Renal hypoperfusion

RAAS 

BV, BP increases

So hydrostatic pressure increases and oncotic pressure decreases (dilution)

OEDEMA

10

How does cirrhosis cause oedema?

What is abdominal oedema called?

Portal hypertension increases hydrostatic pressure

Liver can't produce albumin, so oncotic pressure decreases

Plus RAAS activates because blood volume decreases...

OEDEMA

(Ascites)

11

Where in the nephron is sodium reabsorbed?

Proximal tubules (passively, along with Cl-)

Ascending limb (triple transporter)

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

Collecting tubules (Na+/K+ exchange)

12

How is sodium reabsorbed in the

a) proximal tubules

b) ascending limb

c) distal tubules

d) collecting ducts?

a) Passively

b) Triple transporter

c) Na/Cl co-transport

d) Na/K exchange

13

Which drugs block sodium reabsorption in the

a) proximal tubules

b) ascending limb

c) distal tubules

d) collecting ducts?

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

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) Decreases

b) Decreases

c) Spared, actually increases as a result

15

What percentage of sodium is reabsorbed by the glomeruli?

99%

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

16

By which two routes could diuretics enter the urine?

Why is one far more common than the other?

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

What are

a) positive

b) negative ions called?

a) Cations

b) Anions

18

What transporters carry

a) acidic diuretics like thiazides and loop drugs

b) basic diuretics?

a) Organic ANION transporters

b) Organ CATION transporters

because acids are negatively charged and bases are positively charged

19

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

OATs

OCTs

depending on if they're acidic or basic

20

Why aren't diuretics toxic?

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

21

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

Capillary membrane

Basolateral membrane

Apical membrane

22

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

OAT

23

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

OCTs

24

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

MRP2

multi-drug-resistance protein

25

What effect do loop diuretics have?

How?

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

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

Why?

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

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

Ca2+, Mg2+

because loop diuretics abolish electrochemical gradient between tubules and medullary interstitium

and these ions aren't reabsorbed anywhere else

28

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

K

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

look over this

29

Why can loop diuretics be used to treat pulmonary oedema?

Drains fluid pretty much

30

How do loop diuretics enter the proximal tubules?

Transport by OATs

because they're acidic

31

Which diseases are loop diuretics used to treat?

Pulmonary oedema (IV)

CCF

Cirrhosis with ascites

Kidney failure and nephrotic syndrome

Resistant hypertension

Hypercalcaemia

32

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

(hyper/hypokalaemia, hyper/hypocalcaemia)

used to treat hypercalcaemia

may cause hypokalaemia

33

How is hypokalaemia caused by loop diuretics treated?

Potassium-sparing diuretic

Ksupplements

34

Which cardio drugs may loop diuretics interact with?

Digoxin

Class III arrythmia drugs

35

What acid-base imbalance can loop diuretics cause?

Why?

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

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

Hypovolaemia

Hypokaelamia, hypocalcaemia, hypomagnesaemia, hyperuricaemia (causing GOUT)

Metabolic alkalosis

37

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

Transporters they act on are UPREGULATED with prolonged use

38

What channel do thiazide diuretics block?

Where are they found in the nephron?

Na+/Cl- co-transporter

Distal tubules

39

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

Cl- site

40

What effect do thiazide diuretics have on

a) K+

b) Ca2+?

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

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

Loop diuretics cause a DECREASE

Thiazide diuretics cause an INCREASE

42

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

Mild diuresis

43

What cardio diseases are treated with thiazide diuretics?

Mild heart failure (revise)

Hypertension

44

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

Why?

Renal stones

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

45

What is the effect of thiazide diuretics on

a) calcium

b) magnesium?

a) Increases blood conc.

b) Decreases blood conc. as in loop diuretics

46

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

Hypovolaemia

Hypokalaemia, Hypercalcaemia, hypomagnesiaemia, hyperuricaemia

Metabolic alkalosis

47

Which hormones increase

a) sodium

b) water

reabsorption in the distal tubules and collecting ducts?

How do they do this?

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

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

Na+ reabsorption

K+ secretion

49

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

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

50

Why does more Nareabsorption cause more K+ secretion?

More Nareabsorption means tubular fluid is more negative

So more Kpasses through Kchannels into tubules (positive ion)

51

What are some examples of potassium-sparing diuretics?

Amiloride and Triamterene

Spironolactone and Eplerenone

52

How do

a) amiloride and triamterene

b) spironolactone and eplerenone work?

a) Block Nareabsorption in distal tubule and collecting ducts

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

53

Spironolactone and eplerenone compete with which hormone?

Aldosterone

54

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

Hyperkalaemia

55

Where do aldosterone antagonists bind to block K+ secretion?

Cytoplasmic receptors

56

What must aldosterone antagonists be given with?

Thiazide or loop diuretics

to prevent hyperkalaemia

57

What cardio diseases are aldosterone antagonists used to treat?

Heart failure

Resistant hypertension

58

Which endocrine disease are aldosterone antagonists used to treat?

Hyperaldosteronism