Pharm: Diuretics

Front 1

increase output of urine

Back 1

diuresis

Front 2

increase renal na excretion

Back 2

natriuresis

Front 3

clinical use of diuretics

Back 3

HTN - primary use
- forms basis of tx regimen
mobilization of edema fluid (ie heart failure, liver disease, renal disease)
prevention of renal failure (attempt to maintain urine flow)

Front 4

what is defining characteristic of diuretic drugs

and what do they do

Back 4

their site of action in the nephron

- almost all exert thier effects at luminar surface of renal tubular cells (they are ion transport inhibitors)

function: they compromise normal operation of the kideny to promote excretion of water --> hypovolemia, acid-base imbalance, loss of electrolytes *****************

Front 5

how can you minimize AE of diuretcis

Back 5

SHORT ACTING

time doses allow kidney to readjust ECF to compensate for undesired alterations

Front 6

what are some examples of diuretic LIKE agents

where do they act?

Back 6

methylxanthines (caffeine, theophylline), cardiac glycosides (digoxin), sympathomimetic amines (dopamine)

act at level of glomerulus to increase volume of blood filtered (increase cardiac output --> renal bloodflow)




digoxin STRENGTHENS HEART!

Front 7

what do kidneys do?

Back 7

cleans the ECF! and composision (not INTRAcellular)

maintain pH

excrete metabolic waste (urea, N2) and foreign substances (drugs, toxins)


summary:
filtration
reabsorption (opposite direction of active secretion)
active secretion

Front 8

what is filtration

Back 8

it occurs at glomerular evel
1st step in urine formation
filters small molecules (electrolytes, glucose, amino acids, na, k , cl, hco3)
large filtration capacity
nonselective - cannot regulate COMPOSITION of urine

Front 9

where is Na absorbed

Back 9

65% in PCT
20% in THICK ascending limb of loop of henle
10% in early DCT
1-5% in collective duct and late DCT

Front 10

what is reabsorption

Back 10

>99% of filtrate
conserves valuable portions while allowing wastes to be excreted
reabsorption of solutes (ch, na, k) - in active transport
H2O flows passively
PRIMARY ACTION OF DIURETICS --> INTERFERE WITH REABSORPTION
Na, K predominant solutes in filtrate

Front 11

what is active secretion

Back 11

transports compounds from plasma into lumen of nephron

located in PCT --> organic acids (S2) - uric acid, antibiotics ; ; ; ; organic bases (S1 and 2) - creatinine, choline, procainamide

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function of PCT

Back 12

high resorptive capacity (99%)
65% of filtered Na and Cl is reabsorbed (and also HCO3, K, glucose, amino acids)
H2O passively follows
solutes and H2O reabsorbed to = extent (urine is ISOTONIC - 300 mOsm/L)

Front 13

function of loop of henle

DESC limb

Back 13

thin segment
freely permeable to H2O
as tubular urine moves down loop thru hypertonic medulla, H2O is drawn from loop into interstitial space (tryingt o make medulla ISOtonic) --> role: decr. volume of urine and increase con'n

Front 14

function of loop of henle

ASC limb

Back 14

THICK segment - NOT permeable to H2O

30% of filtered Na and Cl reabsorbed (actively)

H20 remains in loop as Na and Cl reabsorbed - tonicity returns to original (regarded as diluting segment) - utilizes Na/K/2Cl cotransport system which is selectively blocked by diuretics ; the action of hte transporter leads to excess K accumulation within the cell ; results in back diffusion of K into tubular lumen --> lumen + electrical potential

driving force for reabsorption of Mg and Ca via paracellular pathway


at this point 95% of Na has been absorbed!

and this is an ESSENTIAL site of diuretic action

Front 15

function of DCT

Back 15

< 10% of filtered NaCL reabsorbed

H2O follows passively

Na and Cl neutral cotransport

Ca+ actively reabsorbed via apical Ca channel and basolateral Na/Ca exchanger RREGULATED BY PTH (different from other steps)

Front 16

function of collecting tubule

Back 16

2-5% of NaCl reabsorption (usually less) ; responsible for determining final conc'n of Na in urine ; Na/K exchange (aldosterone incr. activity of apical membrane channels and basolateral Na/K ATPase)

major site of K excretion
impermeable to H2O in absce of ADH - dilute urine produced

only site in nephron where membrane H2O permeability can be REGULATED ; ADH incr. permeability to H2O!

ADH regulates H2O reabsorption!! important

Front 17

action of diuretics

Back 17

block Na (and Cl) reabsorption

create osmotic pressure within nephron that prevents passive reabsorption of H2O

cause H2O and solutes to be retained within the nephron thereby promoting their excretion

incr. in urine flow that a diuretic produces is diretly related to the amount of Na and Cl reabsorption that the drug blocks

inhibition of specific membrane transport proteins at luminal surface of renal tubular epithelial cells

osmotic effect to prevent water reabsorption in water - permeable segments

enzyme inhibition

interfere with hormone receptors in renal epithelial cells

Front 18

drugs whose site of action is early in the nephron will have the opportunity to...

Back 18

block the GREATEST amount of solute reabsorbed - produce greatest diuresis

180L / filtrate / day = almost ALL absorbed

for each 1% of solute reabsorption BLOCKED, urine output incr. by 1.8L

3% blockade = 5.4 L urine / day = 12lb WEIGHTLOSS!

small blockade can have profound effects

Front 19

compare efficacy and potency of loop diuretics vs the thiazides

Back 19

LOOPS ARE SIGNIFICANTLY MORE POTENT --> THEY INCR NaCl EXCRETION TO ABOUT 25% AS COMPARED TO ABOUT 5% WITH THIAZIDES