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104 theme 3 > drugs which affect the kidney - diuretic gents > Flashcards

drugs which affect the kidney - diuretic gents Flashcards

1
Q

main drugs affecting the kidney

A 
ACE inhibitiors
anticancer drugs
antiviral grugs
aminoglycosides
beta blockers
lithium 
NSAIDs
Radiocontrast media 
vasodilators
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2
Q

acute kidney injury

A 
pre-renal (due to blood loss)
intrinsic (nephrotoxic AKI)
post renal (due to blockage)
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3
Q

what are diuretics

A

any company that causes excretion of an inc vol of urine (both fluids and solutes eg Na)

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4
Q

what are the types of diuretics

A

nature tic inc Na excretion

kaliuretic inc K excretion

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5
Q

what do most diuretics do

A

inc Na and water excretion by kidneys
reduce reabsorption of Na from filtrate and inc water loss is secondary to Na excretion
new aquaretics

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6
Q

what are the two modes of action of diuretics

A

direct action on the cells of the nephron

modification of content of the filtrate

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7
Q

why use diuretics

A

reduce circulating fluid vol

remove excess body fluid (oedema)

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8
Q

what are diuretics used for

A 
hypertension 
chronic heart failure 
liver cirrhosis 
renal disease
premenstrual oedema 
toxic odema 
inc elimination of drugs 
rapid weight loss (abuse)
also 
glaucoma (reduce intra-ocular pressure)
epilepsy (reduces pressure of CSF)
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9
Q

How much water is reabsorbed in the kidney

A 
GFR 180L/day 
PT 70
LofH 20
DT 5
CT 4.5
0.5% excreted (1.5L/day)
urine 99.5 water and 99.4 Na reabsorbed
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10
Q

where do carbonic anhydrase inhibitors work

A

PT

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11
Q

where do osmotic diuretics work

A

PT/Desc LoH

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12
Q

where do loop diuretics work

A

Asc LoH

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13
Q

where do thiazide like diuretics work

A

Early distal tubule

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14
Q

where do potassium sparing diuretics, aldosterone/non aldosterone antagonists

A

late distal tubule

early collecting tubule

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15
Q

where do most diuretics work

A

most are secreted into the PT and then produce their actions from the luminal side of the tubule

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16
Q

what are loop diuretics

A

most effective
aka high ceiling diuretics leading to torrential flow
inhibit Na/K/2Cl transporter (NKCC2) in the thick ascending limb of LoH, reduces reabsorption of Na, K, Cl, rapid and profound diuresis
single dose can inc vol from 200 to 1200 over 3h

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17
Q

clinical uses of loop diuretics

A 
acute pulmonary oedema
chronic HF
liver cirrhosis
resistant hypertension - acute
nephrotic syndrome and AKI - reduce urine prod
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18
Q

unwanted affects of loop diuretics

A 
dehydration 
K loss - low plasma K
metabolic alkalosis (H loss)
hypokalaemia can potentiate cardiac glycosides 
deafness (when used with ah
minoglycosides antibiotics)
19
Q

how do loop diuretics affect Na/K exchange in DT

A

can inc Na delivery to DT, exchanged for K, excreted

K loss contributes to hypokalaemia ass with loop diuretics

20
Q

what are thiazide diuretics

A

cause mod but sustained Na excretion with inc water excretion
moderately powerful - max is lower than loop
well absorbed from GI tract but long action, up to 24h

21
Q

what are the main thiazides

A

bendroflumethiazide - for mild/mod HF
prototype is hydrochlorothiazide
several others
chlortalidone

22
Q

what are the main thiazide like diuretics

A

indapamide

23
Q

clinical uses of thiazide diuretics

A

hypertension
oedema
mild HF

24
Q

unwanted effects of thiazide diuretics

A 
plasma K depletion 
metabolic alkalosis
inc plasma uric acid (gout)
hyperglycaemia 
inc plasma cholesterol (long term use)
male impotence 
indapamide - currently preferred for resistant hypertension due to less unwanted effects
25
Q

what results from hypokalaemia

A

midl - fatigue, drowsiness, muscle weakness

sev - abnormal heart rhythm, muscle paralysis, death

26
Q

what are K sparring diuretics

A 
act on DT to inhibit Na reabsorption but K not sec into DT
aldosterone (eg eplerone, spironolactone)
non aldosterone (eg amiloride, triamterene)
27
Q

what does spironolactone and eplerenone drugs do

A

S metabolised to caner one (active metabolite)
a competitive antagonist of aldosterone (mineralocorticoid) receptor
red Na channel formation and its abs from DT
limited action and mechanism depends on reduction off protein expression in DT cells, sev days to work

28
Q

clinical uses of Spironolactone

A

HF
Oedema
short term
also resistant hypertension, concerns over cancer

29
Q

unwanted effects of spironolactone

A 
hyperkalaemia 
metabolic acidosis 
GI upsets 
gynaecomastia, menstrual dosorder, testicular atrophy
eplerenone less effects
30
Q

how does triamterene and amiloride work

A

weak diuretics - act on DT to inhibit Na reabsorption and dec K excretion
block luminal Na channel where aldosterone prod most effects
little therapeutic use, but can be used in combo with K depleting diuretics as limit loss

31
Q

unwanted effects of triamterene and amiloride

A

hyperkalaemia
metabolic acidosis
GI upset
skin rash

32
Q

why use diuretics in combination

A

to inc diuretic effect
some don’t respond well to one - unknown why
different sites of action -synergistic action - complicated
avoid hypokalaemia
LD/T with K sparing
diuretic preparation with K

33
Q

how to combine diuretics to stop hypokalaemia

A

LD with S
LD with A/Tri
T with S
T with A/Tri

34
Q

what do carbonic anhydrase diuretic inhibitors do

A

azetozolamide
block NaHCO3 reabs in PT
earliest
weak so uncommon now

35
Q

what are carbonic anhydrase diuretic inhibitors used for

A

glaucoma (reduces intraocular pressure)

epilepsy (reduces vol and pressure of CSF)

36
Q

unwanted effects of carbonic anhydrase diuretic inhibitors

A 
metabolic acidosis (HCO3 excretion)
enhances renal stone formation (alkaline urine)
37
Q

what are osmotic diuretics

A

mannitol
non reabsorb able, undergoes glomerular filtration
excreted within 30-60 min
diuresis beings in same time and persists for 4-6hrs

38
Q

clinical uses of osmotic diuretics

A

intercranial pressure (cerebral oedema)
intraocular pressure
orally can cause osmotic diarrhoea to eliminate toxins
useful for acute renal failure

39
Q

unwanted effects of osmotic diuretics

A

presence in blood exerts osmotic pressure inc plasma vol

can’t be used with hypertension

40
Q

how can water act as a diuretic

A

water inc urine vol
cont by ADK
(present in circulation to maintain urine vol)
other substances can alter urine vol
monitor via osmoreceptors (AQP2 receptors) on apical DT/CD

41
Q

Can ADH antagonists be used as a diuretic

A

investigational, inhibit effect of ADH on CD
non selective agents (orally active)
Lithium and demeclocycline also amphotericin

42
Q

unwanted effects of ADH antagonists

A 
toxicity 
diabetes insipidus
renal failure 
Li tremors, mental confusion, cardio toxicity, thyroid dysfunction and leukocytosis 
D not used in liver disease
also Tolvaptan V2R antagonist
43
Q

how does alcohol and smoking affect urine

A

alcohol inhibits ADH so inc urine excretion (tolerance develops rapidly)
nicotine, ether, morphine and barbiturates inc ADH

44
Q

how does coffee effect urine

A

xanthine
weak diuretic effect by inc CO
some vasodilation of G arteriole (inc BF)
rarely used clinically due to gastric irritant effects

104 theme 3 (15 decks)

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