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Flashcards in Pharmacology Deck (114):
1

what is the function of uricosuric drugs?

promote excretion of uric acid into the urine

2

what do diuretics do to urine volume?

increases urine volume

3

in what clinical conditions are diuretics used?

when there is excess interstitial fluid (oedema)

4

oedema results from an imbalance of what?

rate of interstitial fluid formation
rate of interstitial fluid absorption

5

what 2 starling forces when affected cause oedema?

increased capillary pressure
decreased capillary oncotic pressure

6

what is the main starling force which drives water out of the capillary?

capillary pressure

7

what is the main starling force which dries water into the capillary?

capillary oncotic pressure

8

what change in plasma content reduces capillary oncotic pressure?

reduced plasma proteins

9

what 3 main disease states cause oedema due to either increased capillary pressure or decreased oncotic pressure?

-congestive heart failure
-nephrotic syndrome
-herpatic cirrhosis with ascites

10

what is nephrotic syndrome?

a disorder of glomerular filtration which allows protein (mainly albumin) to appear in the filtrate (proteinuria)

11

what is the apperance of urine with protein in it?

frothy

12

when can proteinuria be physiological?

intense periods of exercise

13

what does activation of the RAAS system do to Pc and COP starling forces and therefore what does this do to the oedema?

increases Pc
decreases COP

increases oedema

14

what does protein excretion in the urine do the rate of interstitial fluid formation?

increase rate of interstitial fluid

15

what drug type can be used to stop the cycle of oedema formation in nephrotic syndrome?

diuretics

16

why does congestive heart failure activate the RAS?

reduced cardiac output causes reduced pressure in afferent renal arteriole
activates RAS

17

why does ascites occur in hepatic cirrhosis?

increase capillary pressure in the portal vein
decrease oncotic pressure due to reduced production of albumin

18

why does ascites activate the RAS?

reduced circulating volume causes reduced pressure in the afferent renal arteriole activates RAS

19

what can longstanding hypertension do to the number of nephrons?

decrease

20

what diuretics work in the proximal convoluted tubule?

carbonic anhydrase inhibitors (no longer used)

21

what diuretics work in the thick ascending limb of the loop of henle?

loop diuretics

22

what diuretics work in the distal convoluted tubule?

carbonic anhydrase inhibitors (no longer used)
thiazide diuretics

23

what duretics work in the collecting tubule?

potassium-sparing diuretics

24

how do carbonic anhydrase inhibitor diuretics work?

block Na/H+ exchange transporter in the proximal convoluted tubule

25

how do loop diuretics work?

block Na/K/2Cl triple transporters in the thick ascending limb of the loop of henle

26

how do thiazide diuretics work?

block Na/Cl cotransporter on the distal convoluted tubule

27

how do potassium sparing diuretics work?

block ENaC or bind to aldosterone receptor and so prevent Na/K exchange transporter on the collecting tubule

28

compare thiazide and loop diuretics in terms of strength of diuresis?

thiazides have a milder diuresis

29

what is the main function of potassium-sparing diuretics?

for low serum potassium to prevent potassium excretion

30

what are the 2 important drug transport systems into the renal tubule?

organic anion transporters
organic cation transporters

31

what type of drugs do organic anion transporters transport?

acidic drugs

32

what type of drugs do organic cation transporters transporter?

basic drugs

33

how do organic anions enter the basolateral membrane of the tubular cells?

either diffusion
or via organic anion transporters

34

how do organic anion transporters work?

exchange organic ions for a-ketoglutarate (aKG)

35

how do organic anions enter the tubular fluid across the apical membrane?

either multidrug resistance protein 2 (MDRP2) or organic anion transporter (in exchange for aKG)

36

how do organic cations enter the basolateral membranes of the tubular cells?

either difusion
or via organic cation transporters

37

how do organic cation transporters work?

simple transporter

38

how do organic cations enter the tubular fluid across the apical membrane?

multidrug resistance protein 1 or OC+/H+ antiporter

39

why is gout a side effect of thiazide and loop diuretics?

thiazides and loop diuretics compete with uric acid for transport across the basolateral membrane via organic anion transporter, so lead to increased uric acid in the blood

40

where in the nephron are diuretics excreted into the tubular fluid?

proximal convoluted tubule

41

what site of the Na/K/2Cl triple transporter do loop diuretics bind to?

the Cl site

42

what does increased Na concentration of the filtrate in the distal tubules do to the excretion of K?

increases K excretion

43

why do loop diuretics cause hypokalaemia?

block Na reabsorption so increase Na concentration in the distal tubules, this increases the Na+ exchange for K+ so more K+ is excreted

44

what channels in the distal and collecting tubules does Na pass into? (these are heavily regulated by aldosterone)

ENaC
(epithelial Na channels)

45

how do loop diuretics indirectly effect the blood pressure?

venodilator action

46

why are loop diuretics used in chronic heart failure?

reduce circulating volume

47

why are loop diuretics used in acute chronic kidney failure?

maintain urine output in a vastly reduced kidney blood supply

48

can loop diuretics be used in hyper or hypo-calcaemia in order to bring serum Ca to the normal levels?

hypercalcaemia

49

in what condition can diuretic resitance to loop diuretics occur and why?

nephrotic syndrome
-binds to proteins within the urine and so cant bind to triple cotransporter

50

what do loop diuretics do to serum potassium?

reduce it - hypokalaemia

51

why should you be careful using loop diuretics with digoxin or class III anti-dysrhythmic drugs? (potassium channel blockers)

because hypokalaemia increases toxicity of these drugs

52

loop and thiazide diuretics cause a shift in acid-base balance, what is this shift and why is it cause?

metabolic alkalosis
due to increase Na in the distal tubules so increased H+ (and K) secretion (through Na/H antiporter)

53

what do loop diuretics do to serum calcium and serum magnesium?

decrease serum calcium
decrease serum magnesium

54

what site in the Na/Cl channel on the distal tubule to thiazide diuretics bind to and therefore block?

Cl- site

55

what are the main loop diuretics in use?

furosemide and bumetanide

56

what are the main thiazide diuretics in use?

bendroflumethiazide
hydrochlorothiazide

57

how do thiazide diuretics cause hypokalaemia

block Na reabsorption so increase Na concentration in the distal tubules, this increases the Na+ exchange for K+ so more K+ is excreted

58

what do thiazide diuretics do to serum calcium and serum magnesium?

increases serum calcium
decreases serum magnesium

59

how do thiazide diuretics indirectly contribute to antihypertensive effects?

vasodilatory action

60

what are the main 2 reasons for thiazide diuretic use?

mild heart failure
hypertension

61

why can thiazides be used for renal stone disease (nephrolithiasis)?

decreases Ca excretion and so discourages Ca stone formation

62

which type of diuretic can help increase responsiveness of nephron to ADH? (in nephrogenic diabetes insipidus)

thiazides

63

why must you be cautious about using thiazide diuretics in type 1 or 2 diabetics?

impaired glucose tolerance

64

what are the 2 types of potassium sparing diuretics/

aldosterone antagonists
ENaC inhibitors

65

what type of potassium sparing diuretics are amiloride and tiamterene?

ENaC inhibitors

66

what type of potassium sparing diuretics are spironolactone and eplerenone?

aldosterone antagonists

67

what system can counteract the effect of thiazide and loop diuretics?

RAS
due to reduced BP

68

what is the function of potassium-sparing diuretics when added to a loop or thiazide diuretic?

increases effect of diuretic (by blocking aldosterone)
prevents hypokalaemia

69

what 4 conditions are aldosterone antagonists used in?

-heart failure
-primary hyperaldosteronism (Conn's)
-resistant essential hypertension
-secondary hyperaldosteronism (due to hepatic cirrhosis with ascites)

70

how do osmotic diuretics enter the nephron?

glomerular filtration

71

how do osmotic diuretics work?

increase osmoarity of the filtrate so reduce the reabsorption of water

72

how do osmotic diuretics secondarily decrease Na reabsorption?

cause an increase in volume of filtrate and so there is a decreased Na conc and so a decreased electrochemical gradient for Na to follow

73

when are osmotic diuretics used? (specifically for effect on kidney)

prevention of acute hypovolaemic renal failure by maintaining urine flow

74

how are osmotic diuretics administered?

IV

75

why can osmotic diuretics be used in raised intracranial and raised intraocular pressure?

so polar that the solute cannot enter the eye or brain but increased plasma osmolarity extracts water from these compartments

76

why does osmotic diuresis occur in hyperglycaemia?

glucose transporters (SGLT1 and SGLT2) limits are exceeded so glucose remains in the filtrate, this increased osmolarity decreases reabsorption of water

77

why can patients with cardiovasculat problems experience hypotension due to iodine-based radiocontrast dyes?

the dyes are filtered but not reabsorbed so increase osmolarity of the filtrate, so reduce water reabsorption and increased water is excreted
these patients already have a low cardiac output so reduced volume can send them into hypotension

78

carbonic anhydrase inhibitors shift the pH into what? and why?

metabolic acidosis
due to increase HCO3- excretion

79

even though carbonic anhydrase inhibitors are not used as diuretics any more, what are their 3 clinical uses?

glaucoma/following eye surgery
prophylaxis of altitude sickness
infantile epilepsy

80

how do carbonic anhydrase inhibitors reduce intraocular pressure in glaucoma?

suppress formation of aqueous humour

81

what does alkalinising the urine do to the excretion of weak acids and why?

increases excretion
because alkaline pH favours ionised form of acid which cannot be reabsorped

82

what is neurogenic diabetes insipidus treated with?

desmopressin
(a vasopressin analogue)

83

what benefit does treating diabetes insipidus with desmopressin have over vasopressin?

desmopressin is selective for V2 receptor activity, so doesn't stimulate V1 which would cause increased blood pressure
(vasopressin stimulates V1)

84

what is nephrogenic diabetes indispidus usually caused by?

mutations in V2 receptor gene
(AVPR2)

85

what does lithium do to the action of vasopressin on the kidney?

inhibits
-nephrogenic diabetes inspidus

86

compare diuretics to aquaretics?

diuretics- Na loss with accompanying water loss
aquaretics- water loss with no Na loss

87

what is the function of aquaretics/vaptans?

competitive antagonists of vasopressin receptors (AVPR2) to prevent aquaporin stimulation -->
increased water excretion

88

compare diuretics and aquaretics in terms of what happens to plasma Na con?

diuretics do not change plasma Na conc
aquaretics increase plasma Na conc

89

what drug can be used in the syndrome of inappropriate anti-diuretic hormone secretion?

tolvaptan
(an aquaretic)

90

why is tolvaptan used in the syndrome of inappropriate anti-diuretic hormone syndrome?

causes loss of water to correct hyponatraemia

91

what vasopresin receptor is found in the vascular smooth muscle?

V1a

92

what vasopressin receptor is found in the basolateral membrane of the renal tubular cells?

V2

93

what vasopressin receptor is tolvaptan selective for?

V2

94

where in the nephron is most affected by osmotic diuretics?

proximal tubule

95

where is SGLT1 found?

-in the S2/3 segments of the proximal convoluted tubule of the kidneys
-small intestine

96

where is the SGLT 2 found?

in the S1 segment of the proximal conoluted tubule of the kidneys

97

compare the percentages of glucose reabsorption in the PCT via SGLT1 and SGLT2?

SGLT1 - 10%
SGLT2- 90%

98

reabsorption of glucose via SGLT1 and SGLT2 on the apical is through what mechanism?

secondary active transport

99

reabsorption of glucose on the basolateral membrane is through what mechanism?

facilitated diffusion using GLUT

100

compare SGLT1 and SGLT2 in terms of affinity and capacity for glucose?

SGLT1- high affinity, low capacity
SGLT2- low affinity, high capacity

101

familial renal glucosuria is caused by what?

dysfunction of SGLT2

102

what is the most common side effects of SGLT2 inhibitors?

increased genital bacterial and fungal infections
(due to sugar in urine)

103

are SGLT2 inhibitors dependent or independent of insulin?

independent

104

what are the major prostaglandins synthesised in the kidney?

PGE2
PGI2

105

where in the kidney is PGE2 synthesised?

medulla

106

where in the kidney is PGI2 synthesised?

glomeruli

107

what do PGE2 and PGI2 do to the vascular smooth muscle?

vasodilation

108

PGE2 and PGI2 are synthesised by the kidney in response to which 5 stimuli?

ischamie
mechanical trauma
angiotensin II
ADH
bradykinin

109

when do prostaglandins produced by the kidneys become important?

under conditions of vasoconstriction or decreased arterial blood volume

110

why are prostaglandins produced by the kidneys important in conditions of vasoconstriction or decreased blood volume?

compensatory vasodilation to maintain GFR and urine output

111

which 2 important molecules cause the production of prostaglandins?

COX 1
COX 2

112

why may NSAIDS precipitate acute renal failure (reduced GFR)?

reduce prostaglandin vasodilator affect and so further reduce renal blood flow and GFR

113

what drug combination must you avoid in the kidneys?

ACEI/ARB
and diuretic
and NSAIDs
'triple whammy'

114

what does a triple whammy cause? (ACEI/ARB, diuretic and NSAID)

increased chance of renal failure (due to poor renal perfusion)