drugs which affect the kidney - diuretic gents

Question 1

main drugs affecting the kidney

Answer 1

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

Question 2

acute kidney injury

Answer 2

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

Question 3

what are diuretics

Answer 3

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

Question 4

what are the types of diuretics

Answer 4

nature tic inc Na excretion

kaliuretic inc K excretion

Question 5

what do most diuretics do

Answer 5

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

Question 6

what are the two modes of action of diuretics

Answer 6

direct action on the cells of the nephron

modification of content of the filtrate

Question 7

why use diuretics

Answer 7

reduce circulating fluid vol

remove excess body fluid (oedema)

Question 8

what are diuretics used for

Answer 8

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)

Question 9

How much water is reabsorbed in the kidney

Answer 9

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

Question 10

where do carbonic anhydrase inhibitors work

Answer 10

PT

Question 11

where do osmotic diuretics work

Answer 11

PT/Desc LoH

Question 12

where do loop diuretics work

Answer 12

Asc LoH

Question 13

where do thiazide like diuretics work

Answer 13

Early distal tubule

Question 14

where do potassium sparing diuretics, aldosterone/non aldosterone antagonists

Answer 14

late distal tubule

early collecting tubule

Question 15

where do most diuretics work

Answer 15

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

Question 16

what are loop diuretics

Answer 16

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

Question 17

clinical uses of loop diuretics

Answer 17

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

Question 18

unwanted affects of loop diuretics

Answer 18

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

Question 19

how do loop diuretics affect Na/K exchange in DT

Answer 19

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

K loss contributes to hypokalaemia ass with loop diuretics

Question 20

what are thiazide diuretics

Answer 20

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

Question 21

what are the main thiazides

Answer 21

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

Question 22

what are the main thiazide like diuretics

Answer 22

indapamide

Question 23

clinical uses of thiazide diuretics

Answer 23

hypertension
oedema
mild HF

Question 24

unwanted effects of thiazide diuretics

Answer 24

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

Question 25

what results from hypokalaemia

Answer 25

midl - fatigue, drowsiness, muscle weakness | sev - abnormal heart rhythm, muscle paralysis, death

Question 26

what are K sparring diuretics

Answer 26

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

Question 27

what does spironolactone and eplerenone drugs do

Answer 27

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

Question 28

clinical uses of Spironolactone

Answer 28

HF Oedema short term also resistant hypertension, concerns over cancer

Question 29

unwanted effects of spironolactone

Answer 29

``` hyperkalaemia metabolic acidosis GI upsets gynaecomastia, menstrual dosorder, testicular atrophy eplerenone less effects ```

Question 30

how does triamterene and amiloride work

Answer 30

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

Question 31

unwanted effects of triamterene and amiloride

Answer 31

hyperkalaemia metabolic acidosis GI upset skin rash

Question 32

why use diuretics in combination

Answer 32

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

Question 33

how to combine diuretics to stop hypokalaemia

Answer 33

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

Question 34

what do carbonic anhydrase diuretic inhibitors do

Answer 34

azetozolamide block NaHCO3 reabs in PT earliest weak so uncommon now

Question 35

what are carbonic anhydrase diuretic inhibitors used for

Answer 35

glaucoma (reduces intraocular pressure) | epilepsy (reduces vol and pressure of CSF)

Question 36

unwanted effects of carbonic anhydrase diuretic inhibitors

Answer 36

``` metabolic acidosis (HCO3 excretion) enhances renal stone formation (alkaline urine) ```

Question 37

what are osmotic diuretics

Answer 37

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

Question 38

clinical uses of osmotic diuretics

Answer 38

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

Question 39

unwanted effects of osmotic diuretics

Answer 39

presence in blood exerts osmotic pressure inc plasma vol | can't be used with hypertension

Question 40

how can water act as a diuretic

Answer 40

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

Question 41

Can ADH antagonists be used as a diuretic

Answer 41

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

Question 42

unwanted effects of ADH antagonists

Answer 42

``` 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 ```

Question 43

how does alcohol and smoking affect urine

Answer 43

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

Question 44

how does coffee effect urine

Answer 44

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