Pharmacology

Question 1

What general effects does a diuretic have on the body?

Answer 1

• Increases urine output
• Inhibits the reabsorption of electrolytes
• Used to enhance excretion of salt and water in conditions where there there is an increase in the volume of interstitial fluid.

Question 2

What is the basic mechanism of a diuretic?

Answer 2

• in the presence of a diuretic, water and salt output is increased
• blood leaving the kidney is haemoconcentrated
• plasma protein concentration is increased and therefore oncotic pressure is increased
• Blood in periphery sucks the fluid from the interstitial fluid.

Question 3

What pressures are involved in Oedema?

Answer 3

1. Capillary oncotic pressure
2. Capillary hydrostatic pressure
3. Interstitial hydrostatic pressure
4. Interstitial oncotic pressure

Question 4

What happens when capillary hydrostatic pressure is increased?

Answer 4

Interstitial fluid increases –> may lead to oedema

Question 5

What happens when interstitial oncotic pressure is reduced?

Answer 5

Fluid moves more easily into interstitium –> may lead to oedema

Question 6

Define nephrotic syndrom

Answer 6

Disorder which causes the kidney to pass too much protein

Question 7

What conditions can cause oedema?

Answer 7

• Nephrotic syndrome
• Congestive heart failure
• Hepatic cirrhosis

Question 8

How does nephrotic syndrome produce oedema?

Answer 8

Decreased plasma protein concentration causes a reduction in the plasma oncotic pressure. Fluid therefore flows into interstitial fluid more easily leading to oedema and a decreased in blood volume and cardiac output. In turn, this activates RAAS leading to formation of angiotensin II causing the release of aldosterone which increases reabsorption of electrolytes and later –> OEDEMA

Question 9

Where are the sites of action of the different types of diuretics?

Answer 9

1. Proximal convoluted tubule = Carbonic anhydrase inhibitors
2. Ascending Limb of the Loop of Henle = Loop Diuretics
3. Distal convoluted tubule = Carbonic anhydrase inhibitors
4. Distal convoluted tubule (Na/Cl- co-transporter) = Thiazide diuretics
5. Collecting ducts (Na/K+ exchanger) = Potassium sparing diuretics

Question 10

Which site of the membrane does most diuretics work at?

Answer 10

Apical membrane

Question 11

How do they enter the filtrate?

Answer 11

1. Glomerular filtration not bound to plasma protein
2. Secretion via transport process in proximal tubule
   - Organic anion transporter
   - Organic cation transporter

Question 12

What type of drugs are associated with Organic anion transporters

Answer 12

Acidic drugs

Question 13

What type of drugs are associated with Organic Cation Transporters

Answer 13

Basic/positive drugs

Question 14

The concentration of a diuretic in the blood is greater than the concentration in the filtrate? True or False

Answer 14

False

Question 15

Organic anion transporter moves substances from the basolateral membrane to the apical membrane, True or False

Answer 15

True

Question 16

How to organic ions enter the cell on the basolateral membrane?

Answer 16

Enter the cell in exchange for a-ktogluterate

Question 17

How does a-ketogluterate enter the cell?

Answer 17

Enters via NaDC channel where sodium enters the cell coupled with a-ketogluterate

Question 18

How does organic anions enter the lumen on the apical membrane?

Answer 18

Multridrug Resistance protein MRP2/4

Question 19

How do organic cations enter via the basolateral membrane?

Answer 19

Organic cation enters the cell via organic cation transporter 2

Question 20

How do organic cations enter the lumen via apical membrane

Answer 20

OC+ enters lumen via MDR1 or OC/H+ antiporters (MATE)

Question 21

Which transporter does Loop Diuretics work on

Answer 21

Triple transporter (Na+/K+/2Cl-)

Question 22

Which part of the Nephron does loop diuretics act upon?

Answer 22

Ascending thick limb of the Loop of Henle

Question 23

What effect does a loop diuretic have upon sodium concentration in the medulla

Answer 23

Sodium is not able to enter the tubular cell on the apical membrane then enter the medulla where it increases the tonicity. Therefore the tonicity of the medulla is reduced, preventing dilution of filtrate in the thick ascending limb. Increases Na+ load delivered to distal regions

Question 24

Does loop diuretics cause a loss of K+?

Answer 24

Yes, increased load of Na+ delivered to the distal regions of the nephron. K+ is exchanged for Na+ and no further opportunity for K+ to be reabsorbed so is excreted in the urine.

Question 25

Adverse effects of Loop diuretics?

Answer 25

• Hypokalaemia
• Metabolic alkalosis –> caused by increased secretion of H+ due to increased load of Na+ at collecting duct/distal tubule
• Hypovolaemia and hypotension corrected by dosage adjustment
• Hyperuricaemia – > uric acid and loop agents compete for organic acid secretory mechanism in proximal tubule - may precipitate a gout attack.