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Year 2 - Renal (DP) > Pharmacology > Flashcards

Flashcards in Pharmacology Deck (105)
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1

How do diuretics increase urine flow?

Inhibit electrolyte reabsorption:
- Mainly Na+ in nephron
-> So reduced water reabsorption

2

What causes oedema?

Imbalance between:
- Rate of ISF formation
AND
- Rate of ISF absorption

3

What is ISF formation proportional to?

(Pc - Pi) - (πp - πi)
Where:
- Pc is capillary hydrostatic pressure
- Pi is ISF hydrostatic pressure
- πp is capillary oncotic pressure
- πi is ISF oncotic pressure

4

What is the main constituent of πp?

Plasma proteins (Mainly albumin)

5

How does Nephrotic syndrome cause oedema?

Reduces πp

6

How does CHF cause oedema?

Increases Pc

7

How does hepatic cirrhosis cause ascites (intraperitoneal oedema)?

Reduced hepatic blood flow
-> Increased portal system pressure
-> Increased Pc -> Ascites
Reduced albumin production -> Decreased πp

8

How does increased ISF formation lead to further oedema?

1. Blood volume and cardiac output reduced
2. RAAS Activation (as there is renal hypoperfusion)
3. Sodium and water retention
4. Increased blood volume
5. Increased Pc and further decreased πp

9

What sort of oedema does CHF cause?

Pulmonary (+/- peripheral)

10

What drugs block Na+ reabsorption in the PCT?

Carbonic anhydrase inhibitors

11

What drugs block Na+ reabsorption in the Loop of Henle?

Loop diuretics

12

What drugs block Na+ reabsorption in the DCT?

Thiazide diuretics

13

What drugs block Na+ reabsorption in the collecting duct?

Potassium-sparing diuretics

14

Where do most diuretics act, the apical membrane or the basolateral membrane?

Apical

15

What drugs are transported into the filtrate by Organic Anion Transporters (OATs)?

Acidic drugs:
- Thiazides
- Loop diuretics

16

What drugs are transported into the filtrate by Organic Cation Transporters (OATs)?

Basic drugs:
- Triamterene
- Amiloride

17

In regards to OATs, how do organic anions enter the cell at the basolateral membrane?

Diffusion
Exchange for α-ketoglutarate

18

How is the [α-ketoglutarate]i kept high?

Transported into cell via a Na+-dicarboxylate transporter:
- Na+ from Na+/K ATPase

19

How do organic anions enter the lumen at the apical membrane?

Via the Multidrug Resistant Protein 2 (MRP2)
And via OAT4 (in exchange for α-ketoglutarate)

20

Why do thiazides predispose to gout?

Uric acid competes with thiazides at MRP2:
- Increases [Uric acid]p -> Gout

21

How do organic cations move across the basolateral membrane?

Diffusion (if uncharged)
OR
Organic Cation Transporters

22

How do organic cations enter the lumen at the apical membrane?

Via MRP1
OR
Organic Cation+/H+ antiporters (OCTN)

23

What transporter do Loop diuretics block in the thick ascending loop of the Loop of Henle? How do they do this?

The Na+/K+/Cl- co-transporter:

24

Put the following steps of the pharmacophysiology of how loop diuretics work:
- Filtrate is less dilute in thick ascending limb of Loop of Henle
- Increased calcium and magnesium excretion
- Reduced tonicity of medullary ISF
- Diuretic binds to Cl- site on NKCC2
- Increased Na+ load in DCT and CD
- Potassium loss

1. Diuretic binds to Cl- site on NKCC2 in TAL of Henle
2. Reduced tonicity of medullary ISF
3. Filtrate is less dilute in thick ascending limb of Loop of Henle
4. Increased Na+ load in DCT and CD
5. Potassium loss
6. Increased calcium and magnesium excretion

25

What percentage of filtered Na+ is excreted on the use of IV loop diuretics?

15-25%

26

Loop diuretics have an indirect vasodilator action which makes them useful in pulmonary oedema. What are the possible mechanisms by how this works?

Increase levels of vasodilating prostaglandins?
Reduce response to Angiotensin II and NA?
Open K+ channels in resistance vessels?
-> Hyperpolarisation
-> Reduced Calcium influx -> Relaxation

27

Loop diuretics are strongly bound to plasma proteins, how does this affect their transport into the nephron lumen?

They rely heavily on OATs

28

True or false; Loop diuretics are poorly absorbed from the GI tract?

False

29

Which of the following is not a major use of loop diuretics:
- Acute pulmonary oedema (IV)
- CHF
- Chronic kidney failure
- Ankle oedema
- Hepatic cirrhosis with ascites
- Nephrotic syndrome

Ankle oedema

30

Why do loop diuretics have a reduced effect in nephrotic syndrome?

There is protein in the tubules so the diuretics bind to them