Pharmacology Flashcards
(114 cards)
1
Q
what is the function of uricosuric drugs?
A
promote excretion of uric acid into the urine
2
Q
what do diuretics do to urine volume?
A
increases urine volume
3
Q
in what clinical conditions are diuretics used?
A
when there is excess interstitial fluid (oedema)
4
Q
oedema results from an imbalance of what?
A
rate of interstitial fluid formation
rate of interstitial fluid absorption
5
Q
what 2 starling forces when affected cause oedema?
A
increased capillary pressure
decreased capillary oncotic pressure
6
Q
what is the main starling force which drives water out of the capillary?
A
capillary pressure
7
Q
what is the main starling force which dries water into the capillary?
A
capillary oncotic pressure
8
Q
what change in plasma content reduces capillary oncotic pressure?
A
reduced plasma proteins
9
Q
what 3 main disease states cause oedema due to either increased capillary pressure or decreased oncotic pressure?
A
- congestive heart failure
- nephrotic syndrome
- herpatic cirrhosis with ascites
10
Q
what is nephrotic syndrome?
A
a disorder of glomerular filtration which allows protein (mainly albumin) to appear in the filtrate (proteinuria)
11
Q
what is the apperance of urine with protein in it?
A
frothy
12
Q
when can proteinuria be physiological?
A
intense periods of exercise
13
Q
what does activation of the RAAS system do to Pc and COP starling forces and therefore what does this do to the oedema?
A
increases Pc
decreases COP
increases oedema
14
Q
what does protein excretion in the urine do the rate of interstitial fluid formation?
A
increase rate of interstitial fluid
15
Q
what drug type can be used to stop the cycle of oedema formation in nephrotic syndrome?
A
diuretics
16
Q
why does congestive heart failure activate the RAS?
A
reduced cardiac output causes reduced pressure in afferent renal arteriole
activates RAS
17
Q
why does ascites occur in hepatic cirrhosis?
A
increase capillary pressure in the portal vein
decrease oncotic pressure due to reduced production of albumin
18
Q
why does ascites activate the RAS?
A
reduced circulating volume causes reduced pressure in the afferent renal arteriole activates RAS
19
Q
what can longstanding hypertension do to the number of nephrons?
A
decrease
20
Q
what diuretics work in the proximal convoluted tubule?
A
carbonic anhydrase inhibitors (no longer used)
21
Q
what diuretics work in the thick ascending limb of the loop of henle?
A
loop diuretics
22
Q
what diuretics work in the distal convoluted tubule?
A
carbonic anhydrase inhibitors (no longer used)
thiazide diuretics
23
Q
what duretics work in the collecting tubule?
A
potassium-sparing diuretics
24
Q
how do carbonic anhydrase inhibitor diuretics work?
A
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)
