kaplan flashcards
think of :
sites of action
electrolyte balances/results of diaretics
:)
What is absorbed at the PCT? (proximal convoluted tubule)
60% Na+
and two anions to maintain electroneutrality:
>95% HCO3-
45% Cl-
Which diuretics work at the PCT?
- CA anhydrase inhibitors
2. Osmotic diuretics (work along the entire tubule, but proximal tubule is most efficient part of the nephron)
What is absorbed at the TAL? (thick ascending loop)
25% Na+
Which diuretic work at the TAL?
- Loop diuretics: block salt reabsorption in the loop of Henle
How does ADH work?
Works in early collecting duct to retain free water
if the receptors work well, it will place aquaporin channels and water will be retained because of the concentration gradient that was enstated in the medulla by salt re-absorption
What is hepato-renal syndrome?
liver through urea cycle detoxifies ammonia to produce the milder form which is urea ;
this means that when the liver fails then so will the kidney; without urea there would be no way to concentrate the urine through the action of ADH
How much Na is retained at the DCT? (distal convoluted tububle)
10% Na
PTC dependend CA2+ re-absorption
Where do thiazide diuretics work?
DCT (distal convoluted tubule)
Where does aldosterone work?
at the early collecting duct
How much Na+ is reabsorbed at the collecting duct?
<5% Na+ re-absorption
Which drugs work on the early collecting duct?
K+ sparing diuretics
Aldosterone antagonists
How does the kidney adapt when given a diuretic?
adapt or die:
if a drug was to block Na re-absorption proximally, then the kidney would adapt to increase Na+ re-absorption distal to the medication;
this in turn would result in better Na retention by aldosterone but at the expense of K+ and H+
as the diuretics result in hypovolemia (water follows Na?)
hypokalemia( due to aldosterone action distal to the drug’s site of action)
alkalosis (through loss of H+)
unless the drug is a K+ sparking diuretic there should be hypokalemia with diuretics
What are names of some osmotic diuretics?
mannitol, glycerin, isosorbide, urea
What is the moa, uses, and side effects of mannitol?
IV; inhibits water reabsorption throughout the tubule because it’s filtered freely but not reabsorbed; traps water in the tubule and increases urine volume
decreases fluid load in :
glaucoma acute attack
decrease ICP
reopen kidney function in toxic acute tubular necrosis (rhabdomyosis) ; increase excretion of toxins in the kidney
side effect: acute hypovolemia
When thinking of the other diuretics…
they don’t increase diuresis, but rather increase Na+ excretion
How do carbonic anhydrase inhibitors work?
prevent reabsorption of Na+ in the PCT
a little bit of physiology: Na+ is exchanged for for H+ on the luminal side by Na/H antiport; from the luminal side soidum will only come into the PCT cell if it has a proton to be exchanged with; this proton is coming from the intracellular CA; this H is release in the PCT; it will not change the pH because the H is immediately recycled with the actual HCO3 which has been freely filtered just like the other salts; it needs to become carbonic acid through the enzyme CA on the extracellular side (luminal side) to make it CO2 and H2O which is freely permeable between membranes; that same CO2 and H2O are the substrates for intracellular CA which produces the H needed for Na exchange and the HCO3 which goes back into the blood as a buffer
What is the mechanism of acetazolamide?
CA inhibitor; will prevent the proton from being made and without the proton, then NA cannot enter the PCT and will built inside the lumen -> diuretic since it enhances sodium excretion and water follows
What happens to the HCO3- when using acetazolamide?
since the H+ cannot be released into the lumen, the HCO3 depended on the H+ to be reabsorbed so you will loose HCO3- along with Na+
consequence: huge change in pH causing metabolic acidosis
What are the names of carbonic anhydrase inhibitors?
acetazolamide, dorzolamide
Summarize the action of CA inhibitors. do it…do it now…
4 things
- decrease H+ formation inside the cell
- decrease H+/Na+ antiport
- increase Na+ and HCO3- in the lumen
- increase diuresis
What are the medical uses of CA inhibitors?
What are some side effects?
glaucoma, acute mountain sickness and metabolic alkalosis
side effects: metabolic acidosis, hypovolemia, hypokalemia, hypercholoremia(think of Na and Cl cotransporters distal to the drug’s site of action)…compensation , sulfonamide HS
*causes hypokalemia yet acidosis…whaaattttt!!…..it makes sense though *
Explain the mechanism of using acetazolamide in acute mountain sickness
when you go into altitude, you have a decrease in atm pressure, decrease in alveolar oxygen resulting in hypoxemia
respiratory centers cause hyperventilation due to low oxygen; hyperventilation causes a decrease in PCO2 causing respiratory alkalosis
also: pulmonary vasoconstriction in the lung to divert the blood to better ventilated areas; this increases hydrostatic pressure in capillaries resulting in edema,
acetazolamide will drain the edema and will treat the alkalosis
What is classic of a CA inhibitor drug?
Hyperchloremic acidosis
Where do loop diuretics work?
Thick ascending loop of Henle; work on the NKCC2 pump
What is the issue with the excess potassium?
Potassium enters the cell through the interstitium and through the lumen
K+ leaks out into the lumen, this causes a positive potential in the lumen and causes Mg2+ and Ca2+ to enter back into the blood intercellularily preventing ion wasting
What happens when you block the NKCC2 pump with the loop diuretics?
sodium excretion, loss of the positive potential across the membrane ; causes all ions to be lost
all negative ions will follow the positive charge
HYPO of every ion in the body
What are the names of loop diuretics?
ethacrynic acid, furosemide, bumetanide, torsemide
What is the mechanism of action of loop diuretics?
inhibition of the NKCC2:
- decrease intracellular K+ in TAL
- decrease positive potential across the membrane
- decrease reabsorption of Mg2+ and Ca2+
- increase diuresis (increased Na+ excretion)
What are some uses of loop diuretics?
- drug of choice in acute pulmonary edema in heart failure
- renal failure, anion overdose ,hypercalcemic states
- anti hypertensive
they also vasodilate by increasing PGLs ; NSAIDs block PGLs can interfere the anti hypertensive effect of loop diuretics
What are the side effects of loop diuretics?
- sulfonamide HS
- hypokalemia and alkalosis( not loosing HCO3)
- hypocalcemia, hypomagnesemia
- hyperurecemia
- ototoxicity
What do sulfur containing drugs have cross allergenicity with?
- CA inhibitors
- all loop diuretics except ethacrynic acid
- thiazides
- sulfa antibiotics
- celecoxib
What is the site of action of the thiazides?
DCT (distal convoluted tubule) involving the symport transport of Na and Cl
<10% of Na is reabsorbed
What is the mechanism of thiazides?
Blocks Na/Cl cotransport across the luminal side into the DCT cell; this causes low [Na] in the cell which increases the concentration gradient between the DCT cell and the interstitium; Na moves across more quickly into the cell from the interstitium while Ca (in the presence of adequate PTH) moves from the lumen into the DCT cell and finally into the blood
What is the main result of thiazide diuretics?
hypercalcemia
What are some examples of thiazides?
hydrochlorothiazide, indapamide, metolazone
What is the mechanism of thiazides?
- inhibits the Na/Cl pump on the luminal side
- increases diuresis
- decreases level of intracellular Na
- Ca2+ gets more easily reabsorbed
What are the medical uses of thiazide diuretics?
hypertension, edema of the CHF
nephrolithiasis
nephrogenic diabetes insipidus
Explain the mechanism of how thiazide diuretics work in nephrogenic diabetes insipidus.
In nephrogenic diabetes insipidus the ADH receptors do not work. By using thiazide diuretics you are forcing Na to stay in the lumen, which decreases the amount of free water in the lumen. When aldosterone is upregulated to reabsorb sodium, water will now follow since there is more sodium in the lumen.
What are the side effects of thiazides?
sulfonamide HS hypokalemia and alkalosis hypercalcemia hyperurecemia hyperglycemia , hyperlipidemia avoid in patients with diabetes mellitus
Where do the K+ sparing diuretics work?
they block the aldosterone receptor preventing sodium and water retention that the expense of K+
and block entry of Na from the lumal side into the cortical collecting tubule (CCT)
What are examples of K+ sparing diuretics?
block aldosterone receptor aka aldosterone antagonists: spironolactone, eplerenone
prevent Na reabsorption: amiloride, triamterene
What are the uses and side effects of spironolactone?
hyperaldosteronism (elevated in CHF); used to correct hypokalemia in acetazolamide, loop diuretics, and thiazides; antiandrogenic effect -> stems from the fact that as a steroid receptor antagonist it is not selective and also blocks androgens (can be a benefit or a side effect)
side effects: hyperkalemia and acidosis
What are the uses and side effects of amiloride and triamterene?
used with K+ wasting diuretics, have nothing to do with aldosterone,
hyperkalemia and acidosis
Which drug is more selective of aldosterone receptors?
eplerenone; devoid of anti androgenic effect
Urinary electrolytes: up in Na up in K up in HCO3 blood pH=acidic
acetazolamide: inhibition of CA
Urinary electrolytes: upup in Na up in K up in Mg up in Ca2+ up in Cl- blood pH: alkalosis
loop diuretics: ethacrynic acid, furosemide, torsemide
inhibition of NKCC2 in TAL
Urinary electrolytes: up in Na up in K up in Cl down in Ca blood pH: alkalosis
hydrochlorothiazide, indapamide, metolazone: inhibits Na/Cl cotransporter in DCT
Urinary electrolytes:
small up in Na
down in K
blood pH: acidosis
amiloride, triampterene, spironolactone, eplerenone
K+ sparing diuretics
