Diuretics I Flashcards
Which ion transporter do the most effective diuretics and natriuretics work upon?
NKCC2 in the TAL
Broad mechanism of action for osmotic diuretics?
- ) Freely filtered by glomerulus
- ) No reabsorption from urine
- ) Must be pharmacologically-inert
Natriuresis vs diuresis:
Natriuresis: sodium excretion causing urination, large amounts of sodium in the urine
Diuresis: urination due to excretion of water, dilute urine
Administration of osmotic diuretics:
IV only, oral use laxative
Natriuretics:
Aldosterone antagonists
Diuretics
Aldosterone antagonists:
Spironolactone
Eplerenone
Three general diuretic categories:
Potassium sparing
Thiazide diuretics
Loop diuretics
Potassium sparing diuretics:
Amiloride
Triamterene
Thiazide diuretics:
Hydrochlorothiazide
Loop diuretics:
Furosemide
Torsemide
What occurs with inhibition of carbonic anhydrase?
You get reduced plasma bicarbonate levels
With reduced bicarbonate levels in the plasma what do you get?
It is replaced by chloride leading to hypercholoremic acidosis
What is refractoriness?
Natriuresis being reduced by bicarbonate depletion
Carbonic anhydrase inhibitor:
Acetazolamide (it’s a sulfonamide)
What competes with uric acid for secretion and can lead to inhibition of uric acid secretion?
Diuretics
Penicillins
Low-dose aspirin
Thiazide diuretic affect on calcium?
Reduce urinary calcium excretion
Reduce renal calculus formation
Positive calcium balance
Loop diuretic effect on calcium?
Increased urinary calcium excretion
Support renal calculus formation
Negative calcium balance
What occurs with sodium delivery into the DCT?
Any intervention increasing sodium delivery to DCT stimulates potassium excretion (Na in K out to lumen)
What is the active substrate for renin in plasma?
Alpha-2-globulin angiotensinogen
What increases plasma angiotensinogen levels?
Glucocorticoids
Estrogens
Alternative pathway for angiotensin I conversion?
Angiotensin I -> Angiotensin 1-9 via ACE II -> Angiotensin 1-7 via ACE
What receptor does angiotensin I work on?
ATR-1
What receptors does angiotensin II work on?
ATR-1
ATR-2
What receptors does angiotensin III work on?
ATR-1
ATR-2
What receptor does angiotensin 1-7 work on?
MAS receptor
Action of ATR-1 when stimulated?
Vasoconstriction
Pro-inflammatory
Pro-mitotic
Action of ATR-2 and MAS receptors when stimulated?
Oppose:
Vasoconstriction
Pro-inflammatory
Pro-mitotic
Aldosterone action on kidneys:
Sodium reabsorption
Sodium potassium exchange in DCT
Sodium hydrogen exchange in DCT
Aldosterone action on CNS:
Increased BP
Aldosterone action on heart:
Cardiac hypertrophy
ACE inhibitor SE:
Hyperkalemia Fetal death 2/3 trimester Teratogenic 1st trimester Decreased proteinuria in diabetics ANGIOEDEMA
Angiotensin receptor antagonists SE:
Hyperkalemia
Fetal death 2/3 trimester
Teratogenic 1st trimester
Decreased proteinuria in diabetics
What causes angioedema?
Inactivation of ACE which is responsible for the breakdown of bradykinin to inactive bradykinin
What does bradykinin cause?
NO formation
Hypotension
Prostacyclin formation
Angioedema
How do you treat angioedema?
As anaphylaxis
ACE has polymorphisms in different patients, how is this done?
Insertion deletion variants for intron 16
What are the three ways can ACE have polymorphisms in intron 16?
- ) Insertion/insertion (I/I)
- ) Insertion/deletion (I/D)
- ) Deletion/deletion (D/D)
What do each of the three ACE polymorphisms cause?
I/I= normal A-II levels I/D= mild increase in A-II levels D/D= large increase in A-II levels
How do potassium sparing diuretics work?
By inhibiting sodium input channel aka sodium reabsorption (Na in/K out to lumen)
What effect do potassium sparing diuretics have on bicarbonate levels?
Reduces NHE therefore increasing bicarbonate ion excretion in urine
Which drug alkalizes urine?
Acetazolamide
Which drugs do you treat hypertension with?
Renin inhibitors
ACE inhibitors
AT-1 receptor blockers
Thiazide diuretics
Which drugs mobilize edema?
Loop diuretics
Thiazide diuretics
Which drugs cause diuresis (flow only)?
Loop diuretics
Mannitol
Which drugs treat altitude sickness?
Acetazolamide
Which drugs treat hypercalcemia?
Loop diuretics
Which drugs treat osteoporosis?
Thiazide diuretics
Which drugs combinations are for acute exacerbation of edema?
IV hydrochlorothiazide
IV acetazolamide
Oral thiazide/thiazide like drugs
Who is at risk for renal carcinoma?
Patients taking thiazide and loop diuretics chronically; ACE inhibitors
OTC diuretics:
Ammonium chloride
Caffeine
Ammonium chloride mechanism:
Metabolized to urea + chloride ion
Sodium passively follows chloride ion excretion
Caffeine mechanism:
Blocks adenosine receptor mediated sodium reabsorption (inhibition of sodium reabsorption)
What do uricosurics do?
Block tubular diuretic secretion