Pharmacology 1

Question 1

What is oedema due to?

Answer 1

increase in hydrostatic capillary pressure or a decrease in osmotic capillary pressure of plasma resulting in an increase of interstitial fluid

Question 2

What does an increase in interstitial fluid result in?

Answer 2

decrease in BP and hypovolaemia - which activates RAAS which leads to sodium and water retention

Question 3

What drugs act in the proximal convoluted tubule?

Answer 3

carbonic anhydrase inhibitors - block Na/H exchange

Question 4

What drugs act in the early distal convoluted tubule?

Answer 4

carbonic anhydrase inhibitors

thiazide diuretics - block Na/Cl

Question 5

What drugs act in the thick ascending limb of loop of henle?

Answer 5

loop diuretics - Na/K/2Cl transporter

Question 6

What drugs act in the collecting tubule and duct?

Answer 6

potassium sparing diuretics - block Na/K exchange

Question 7

What is the action of carbonic anhydrase inhibitors?

Answer 7

depress HCO3 reabsorption by inhibiting catalysis of Co2 hydration and dehydration which increases HCO3, Na and H secretion

Question 8

How long do carbonic anhydrases act for?

Answer 8

self limiting so only a short period

Question 9

Where do most diuretics act?

Answer 9

apical membrane - so must enter the filtrate

Question 10

What are the two mechanisms that diuretics can enter the filtrate?

Answer 10

glomerular filtration - if not bound to plasma protein

secretion via organic anion transports (OATs) or organic cation transports (OCTs)

Question 11

Describe the characteristics of OATs?

Answer 11

for acidic drugs

Question 12

What is the action of OATs at the basolateral membrane?

Answer 12

organic anions enter the cell against a concentration gradient in exchange for a-ketoglutarate via OAT4
a-KG enters the cell against a concentration gradient via NaDC3

Question 13

What is the action of OATs at the apical membrane?

Answer 13

OAs are actively pumped out of the cell to the lumen via multidrag resistance protein 2 and 4 (MRP2/4) and BCRP through primary active transport

Question 14

What are the characteristics of OCTs?

Answer 14

for basic drugs

Question 15

What is the action of OCTs at the basolateral membrane?

Answer 15

organic cations enter the cell mainly by OCT2 - driven by the negative potential of cell interior and against a concentration gradient

Question 16

What is the action of OCTs at the apical membrane?

Answer 16

OCs enter the lumen via MATES in a rate limiting manner and by MDR1 in an active transport manner

Question 17

Give two examples of loop diuretics?

Answer 17

furosemide and bumetanide

Question 18

What is the action of loop diuretics?

Answer 18

binds to the Cl site of the Na/K/2Cl transporter in the ascending limb of henle
causes impaired Ca/Mg reabsorption as K movement creates a positive charge which drives Ca/Mg reabsorption
there is also an increased Na load delivered to distal regions of the nephrons which causes K loss

Question 19

What are the general features of loop diuretics?

Answer 19

cause 15-25% of filtered Na to be excreted
also possess a venodilator affect due to the increased formation of vasodilation prostaglandins and opening of K channels in resistance vessels
absorbed from the GI tract
strongly bind to plasma proteins

Question 20

By what mechanism do loop diuretics enter the nephron?

Answer 20

OAT

Question 21

What are the side effects of loop diuretics?

Answer 21

hyonatremia
hypotension
can precipitate gout attack - hyperuricaemia 
metabolic alkalosis
hypomagnesium
hypovolaemia
hypokalaemia
deafnesss

Question 22

When are loop diuretics contraindicated?

Answer 22

hypovolaemia

dehydration

Question 23

What is Bartter Syndrome?

Answer 23

autosomal recessive

salt and water wasting

Question 24

Name a thiazide diuretic?

Answer 24

bendroflumethiazide

Question 25

Where do thiazide diuretics act?

Answer 25

distal convuluted tubule

Question 26

What is the action of thiazide diuretics?

Answer 26

Inhibit NaCl reabsorption by binding to the Cl site on the Na/Cl symptorter - causing the excreteion of Cl and Na, and therefore H20 It also increases Na load delivered to collecting tubule which stimulates Na exchange with K and H, increasing K and H secretion

Question 27

How do thiazide diuretics enter the nephron?

Answer 27

OAT

Question 28

What are the characteristics of thiazide diuretics?

Answer 28

well absorbed from GI tract cause 5% of Na to be excreted has a vasodilator action

Question 29

What are thiazide diuretics contraindicated in?

Answer 29

hypokalaemia | hyponatraemia and gout - less so

Question 30

What are the side effects of thiazide diuretics?

Answer 30

``` hypokalaemia metabolic alkalosis hypovoleamia hypotension hypomagnesium hyperuricaemia - can precipitate gout impaired glucose tolerance in diabetics erectile dysfunction ```

Question 31

What is the role of aldosterone?

Answer 31

aldosterone acts via cytoplasmic receptors to: 1. increase synthesis of a protien that activates ENaC channels 2. increases ENaC expression 3. increases abundance of Na/K/ATPase 4. rapidly increase expression of ENaC via SgK1

Question 32

What secretes K into the collecting tubule?

Answer 32

ROMK and BK

Question 33

How does Na reabsorption result in K secretion?

Answer 33

Na reabsorption results in charge separation that makes the lumen more negative and depolarises the lumen vs basolateral membrane increased driving force of K across the lumenal membrane leads to enhanced secretion of K, SgK1 increases K channel (ROMK) number in apical membrane K is washed away by urinary flow rate that indirectly activates ROMK channels

Question 34

Name four potassium sparing diuretics?

Answer 34

amiloride triamterene spironolactone eplernane

Question 35

What is the action of amiloride and triamterene?

Answer 35

block the apical Na channels in the collecting tubules, decreasing Na permeability enter the nephron via OCTs in the proximal tubule Increases Na, Cl and H20 excretion decreases K excretion triamterene is well absorbed from GI tract Amiloride is poorly absorbed

Question 36

What is the action of spironolactone and eplernane?

Answer 36

antagonise aldosterone at cytoplasmic aldosterone receptors - compete with it gain access to the cytoplasm via the basolateral membrane increase Na excretion decrease K excretion well absorbed from GI tract

Question 37

What are the side effects of potassium sparing diuretics?

Answer 37

if given alone can cause hyperkalaemia

Question 38

When are potassium sparing diuretics contraindicated?

Answer 38

severe renal impairment hyperkalaemia addisons - aldosterone is already low