Aquaretics

Question 1

aquaretic definition

Answer 1

agents affecting the renal conservation of water

Question 2

aquaretic site of action

Answer 2

collecting ducts

Question 3

ADH/AVP site of synthesis

Answer 3

paraventricular and supraoptic nuclei of hypothalamus

Question 4

ADH/AVP stimuli

Answer 4

increase plasma osmolarity >280mOsm/kg
decrease ECF
pain
nausea
hypoxia

Question 5

V1R location

Answer 5

vascular smooth muscle

Question 6

V1R binding effect

Answer 6

vasoconstriction

Question 7

V1R mechanism

Answer 7

Gq–>PKC–>IP3 pathway releases Ca2+

Question 8

V2R location

Answer 8

principal cells of renal CD

Question 9

V2R binding effect

Answer 9

increase CD permeability to H2O & urea (concentrates urine)

Question 10

V2R mechanism

Answer 10

Gs–>cAMP–>PKA, which:

• moves aquaporin vesicles to apical membrane
• phosphorylates aquaporin-2
• phosphorylates VRUT (UT1)

Question 11

aquaporin-1 location

Answer 11

proximal tubule & thin descending limb

Question 12

aquaporin-2 location

Answer 12

collecting duct

Question 13

central DI mechanism

Answer 13

inadequate ADH secretion

ADH-sensitive DI

Question 14

nephrogenic DI mechanism

Answer 14

insufficient response to ADH in kidney

ADH-insensitive DI

Question 15

central DI etiology

Answer 15

head injury, surgery, or trauma in the pituitary/hypothalamus
tumors
CNS ischemia
AD (chromosome 20) gradual loss of ADH

Question 16

nephrogenic DI etiology

Answer 16

acquired: obstructive renal disease
drug-induced: lithium, clozapine
genetic: X-linked mutation in V2R

Question 17

DI mechanism

Answer 17

impaired water reabsorption

AKA too much water excretion

Question 18

DI symptoms

Answer 18

polyuria

polydipsia

Question 19

polyuria

Answer 19

excrete large volumes of dilute urine

Question 20

polydipsia

Answer 20

drink a lot of water b/c increased thirst

Question 21

how to distinguish (clinically) b/t types of DI

Answer 21

administer V2R agonist

• central DI: increase urine osmolarity (concentrates urine, aka H2O reabsorbs)
• nephrogenic DI: no change

Question 22

Tx of central DI

Answer 22

synthetic vasopressin peptides

selective V2R agonists: desmopressin

Question 23

desmopressin MOA

Answer 23

selective V2R agonist

minimal V1R effects

Question 24

desmopressin ROA

Answer 24

nasally
IV
oral tablet

Question 25

desmopressin clinical uses

Answer 25

central DI bleeding disorders (increase factor VIII & vWF via extrarenal V2R) nocturnal enuresis

Question 26

Tx of nephrogenic DI

Answer 26

maintain adequate H2O intake | thiazide diuretics

Question 27

thiazide diuretic MOA in DI

Answer 27

inhibit NCCT in DCT - mild depletion of ECF H2O&Na+ - compensatory increase in PCT reabsorption - less volume delivered to DCT

Question 28

V1R agonists

Answer 28

terlipressin

Question 29

V1R agonists effect

Answer 29

GI & vascular smooth muscle contraction

Question 30

V1R agonists clinical uses

Answer 30

post operative ileus reduce bleeding in -esophageal varices -acute hemorrhagic gastritis

Question 31

terlipressin ROA

Answer 31

IV (restricted use, less side effects than vasopressin)

Question 32

SIADH mechanism

Answer 32

excessive production of ADH - impaired H2O excretion (AKA too much reabsorption) - plasma hypoosmolarity (hyponatremia)

Question 33

SIADH etiology

Answer 33

``` drug-induced -psychotropics: SSRI, haloperidol, tricyclic antidepressants -sulfonylureas: chloropropamide -vinca alkaloids: vinblastine, vincristine hypovolemia induced -CHF -liver cirrhosis -nephrotic syndrome ```

Question 34

SIADH cutoffs (based on Posm)

Answer 34

Posm = 125-132mM --> asymptomatic | Posm begin treatment

Question 35

Tx for asymptomatic SIADH

Answer 35

``` water restriction (IV hypertonic saline) ```

Question 36

Tx for symptomatic SIADH

Answer 36

``` water restriction IV hypertonic saline loop diuretics demeclocycline vaptans ```

Question 37

loop diuretics MOA in SIADH

Answer 37

interfere w/kidney concentrating ability

Question 38

demeclocycline MOA

Answer 38

technically an antibiotic | also antagonizes ADH at V2R

Question 39

V2R antagonists

Answer 39

tolvaptan | conivaptan

Question 40

tolvaptan clinical uses

Answer 40

hypervolemic/euvolemic hyponatremia symptomatic hyponatremia w/CHF, cirrhosis, SIADH only in hospital

Question 41

tolvaptan metabolism

Answer 41

CYP3

Question 42

tolvaptan ADEs

Answer 42

hyperglycemia GI disturbances clotting problems

Question 43

tolvaptan BBW

Answer 43

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)

Question 44

pts susceptible to osmotic demyelination

Answer 44

severe malnutrition alcoholics advanced liver disease

Question 45

conivaptan ROA

Answer 45

IV

Question 46

conivaptan clinical uses

Answer 46

acute Tx of hyponatremia (in hospital setting)

Question 47

conivaptan metabolism

Answer 47

CYP3A4

Question 48

conivaptan ADE

Answer 48

infusion site reaction | probably also everything w/tolvaptan..

Question 49

conivaptan selectivity

Answer 49

V1a & V2 receptors