Drugs for Hyponatremia and Hypernatremia (Wolff)

Question 1

What is the “rough estimate” equation for determining plasma osmolality and what is the actual equation to determine plasma osmolality?

Answer 1

RE: 2 x [plasma Na]

Real: 2[plasma Na] + [plasma Glucose]/18 + [plasma BUN]/2.8

Question 2

What is the difference between Hypotonic, Hypertonic, and Isotonic solutions and their effects on the cell volume?

Answer 2

Hypo - cause cells to SWELL (inc. cell volume)

Hyper - cause cells to SHRINK (dec. cell volume)

Iso - do not change the volume of the cell

Question 3

How do these Intravenous Solutions affect ECF and ICF volumes?

1. isotonic (0.9%) NaCl
2. 0.45% NaCl
3. 3% or 5% NaCl
4. 5% albumin
5. 5% dextrose

Answer 3

1. NORMAL SALINE –> inc. ECF volume ONLY
2. expands both ICF and ECF volume (ECF majority)
3. expands ECF volume while shrinking ICF volume
4. expand plasma volume compartment
5. DWF - expands TOTAL BODY WATER (distilled H2O)
   
   • glucose metabolized by CO2, leaving H2O behind

Question 4

What is the definition of Hypernatremia and Hyponatremia?

What is the normal value of plasma osmolality in the body?

Answer 4

Hyper = plasma {Na} > 145 mEq/L

Hypo = plasma [Na] < 135 mEq/L
- most COMMON electrolyte abnormality encountered in clinical practice

Normal plasma osmolality = 285-295 mOsm/kg

Question 5

Hyponatremia Symptoms Mnemonic

SALT LOSS

Answer 5

S - stupor/coma
A - anorexia, nausea, vomiting
L - lethargy
T - tendon reflex DEC

L - limp muscles (WEAKNESS)
O - orthostatic HYPOtension
S - seizures
S - stomach cramp

Question 6

What is the treatment for Hyponatremic pts with:

1. No or minimal symptoms (headache, irritable)
2. Moderate symptoms (nausea, confusion, disoriented)
3. Severe symptoms (vomit, seizure, coma)

Answer 6

1. fluid restriction, but vaptans can be given under certain circumstances (can’t tolerate fluid restriction)
2. vaptan or hypertonic NaCl, followed by fluid restriction
3. hypertonic NaCl, followed by fluid restriction or vaptans

Question 7

Conivaptan (Vaptan)

What is its MOA, what is it used to treat (2), how is it administered, and what are 3 toxicities of use?

Answer 7

MOA: block ADH (AVP) receptor in the collecting duct, blocking Aquaporin 2 channel insertion into lumen principle cell wall (promotes excretion of free water)

• inc. urine output and plasma osmolarity
• dec. urine osmolarity
• used for euvolemic and hypervolemic hyponatremia pts that are hospitalized, symptomatic, or not fluid restricted
• given IV and is a substrate of CYP3A4

T: orthostatic hypotension, thirst, osmotic demyelination if too rapid of correction (coma/death)

Question 8

Tolvaptan

What is it, where is it used, and how long must it be used for and why?

Answer 8

• vaptan that is a selective V2 receptor antagonist administered ORALLY
  
  • can be used to slow progression of adult polycystic kidney disease
• used ONLY in a hospital where plasma sodium can be monitored closely
• must use for LESS than 30 days; any longer inc. risk of fatal HEPATOTOXICITY

Question 9

Hypernatremia Symptoms Mnemonic

TRIP

Answer 9

T - twitching, tremors, hyperreflexia
R - restlessness, irritability, confusion
I - intense thirst, dry mouth, dec. urine output
P - pulmonary and peripheral edema

Question 10

How should a hypovolemic hypernatremic pt be treated?

Answer 10

• pt has both a sodium deficit in addition to a water deficit, so use ISOTONIC saline

Question 11

How should pts with euvolemic or hypervolemic hypernatremia be treated?

Answer 11

• use hypotonic IV solutions, such as D5W, half-normal saline, or quarter-normal saline

Question 12

What is the calculation for Water Deficit?

Answer 12

0.6% body weight (kg) x (1-[140/Na])

Question 13

Desmopressin (DDAVP)

What is its MOA, what are 4 things it is used to treat, and what are 2 major toxicities of use?

Answer 13

MOA: synthetic AVP (ADH) analogue that is a selective V2 agonist (renal) and inc. cAMP lvls in collecting duct principle cells, inc. water permeability

• dec. urine volume, inc. urine osmolarity
• inc. plasma lvls of von Willebrand Factor

Tx: central diabetes insipidus, primary nocturnal enuresis, Hemophilia A and von Willebrand disease

T: hyponatremia (fluid retention) and hypotension (occurs with rapid IV infusion)

Question 14

What is Diabetes Insipidus and what is the difference between Central and Nephrogenic?

Answer 14

DI = excessive passing of water through the urine (intense thirst and heavy urination)

Central: LACK of ADH due to trauma, tumors, surgery

• can be treated with exogenous ADH agonists
• Tx: dDAVP

Nephrogenic: renal tubules unresponsive to ADH

• can be treated with adequate water intake
• can use thiazide diuretics in some cases (NOT if caused by Lithium)

Question 15

What is the most common cause of Nephrogenic DI?

Why should thiazides NOT be used to treat Nephrogenic DI that is caused by Lithium?

How would Li-induced Nephrogenic Diabetes Insipidus be treated?

Answer 15

LITHIUM THERAPY

• Li reabsorption takes place in the proximal tubule, so Thiazide therapy would inc. the amount of Li being reabsorbed there –> causing lithium toxicity

Tx: amiloride (blocks influx of Li into CCD cells)