Aquaretics Flashcards
aquaretic definition
agents affecting the renal conservation of water
aquaretic site of action
collecting ducts
ADH/AVP site of synthesis
paraventricular and supraoptic nuclei of hypothalamus
ADH/AVP stimuli
increase plasma osmolarity >280mOsm/kg decrease ECF pain nausea hypoxia
V1R location
vascular smooth muscle
V1R binding effect
vasoconstriction
V1R mechanism
Gq–>PKC–>IP3 pathway releases Ca2+
V2R location
principal cells of renal CD
V2R binding effect
increase CD permeability to H2O & urea (concentrates urine)
V2R mechanism
Gs–>cAMP–>PKA, which:
- moves aquaporin vesicles to apical membrane
- phosphorylates aquaporin-2
- phosphorylates VRUT (UT1)
aquaporin-1 location
proximal tubule & thin descending limb
aquaporin-2 location
collecting duct
central DI mechanism
inadequate ADH secretion
ADH-sensitive DI
nephrogenic DI mechanism
insufficient response to ADH in kidney
ADH-insensitive DI
central DI etiology
head injury, surgery, or trauma in the pituitary/hypothalamus
tumors
CNS ischemia
AD (chromosome 20) gradual loss of ADH
nephrogenic DI etiology
acquired: obstructive renal disease
drug-induced: lithium, clozapine
genetic: X-linked mutation in V2R
DI mechanism
impaired water reabsorption
AKA too much water excretion
DI symptoms
polyuria
polydipsia
polyuria
excrete large volumes of dilute urine
polydipsia
drink a lot of water b/c increased thirst
how to distinguish (clinically) b/t types of DI
administer V2R agonist
- central DI: increase urine osmolarity (concentrates urine, aka H2O reabsorbs)
- nephrogenic DI: no change
Tx of central DI
synthetic vasopressin peptides
selective V2R agonists: desmopressin
desmopressin MOA
selective V2R agonist
minimal V1R effects
desmopressin ROA
nasally
IV
oral tablet
desmopressin clinical uses
central DI
bleeding disorders (increase factor VIII & vWF via extrarenal V2R)
nocturnal enuresis
Tx of nephrogenic DI
maintain adequate H2O intake
thiazide diuretics
thiazide diuretic MOA in DI
inhibit NCCT in DCT
- mild depletion of ECF H2O&Na+
- compensatory increase in PCT reabsorption
- less volume delivered to DCT
V1R agonists
terlipressin
V1R agonists effect
GI & vascular smooth muscle contraction
V1R agonists clinical uses
post operative ileus
reduce bleeding in
-esophageal varices
-acute hemorrhagic gastritis
terlipressin ROA
IV (restricted use, less side effects than vasopressin)
SIADH mechanism
excessive production of ADH
- impaired H2O excretion (AKA too much reabsorption)
- plasma hypoosmolarity (hyponatremia)
SIADH etiology
drug-induced -psychotropics: SSRI, haloperidol, tricyclic antidepressants -sulfonylureas: chloropropamide -vinca alkaloids: vinblastine, vincristine hypovolemia induced -CHF -liver cirrhosis -nephrotic syndrome
SIADH cutoffs (based on Posm)
Posm = 125-132mM –> asymptomatic
Posm begin treatment
Tx for asymptomatic SIADH
water restriction (IV hypertonic saline)
Tx for symptomatic SIADH
water restriction IV hypertonic saline loop diuretics demeclocycline vaptans
loop diuretics MOA in SIADH
interfere w/kidney concentrating ability
demeclocycline MOA
technically an antibiotic
also antagonizes ADH at V2R
V2R antagonists
tolvaptan
conivaptan
tolvaptan clinical uses
hypervolemic/euvolemic hyponatremia
symptomatic hyponatremia w/CHF, cirrhosis, SIADH
only in hospital
tolvaptan metabolism
CYP3
tolvaptan ADEs
hyperglycemia
GI disturbances
clotting problems
tolvaptan BBW
SLOWLY correct hyponatremia
- monitor serum Na in the hospital
- esp. for susceptible patients
- too rapid can cause osmotic demyelination (and a crap ton of problems with it.. not including those here)
pts susceptible to osmotic demyelination
severe malnutrition
alcoholics
advanced liver disease
conivaptan ROA
IV
conivaptan clinical uses
acute Tx of hyponatremia (in hospital setting)
conivaptan metabolism
CYP3A4
conivaptan ADE
infusion site reaction
probably also everything w/tolvaptan..
conivaptan selectivity
V1a & V2 receptors
