Drug induced Electrolyte disorder

  1. what is the normal value of sodium?
    135-145 mEq per L
  2. what are 2 etiologies of hyponatremia?
    • 1) due to decrease in sodium
    • 2) due to expansion of fluid volume
  3. what is the prevalence of hyponatremia?
    what kind of patients have this?
    • common in elderly
    • after surgeries
    • in paitents with CHF and cirrhosis (ascites)
  4. what is considered mild hyponatremia?
    lab value, symptoms?
    • 125-134 meq/L
    • usually asymptomatic
  5. what is considered moderate hyponatremia?
    lab value, symptoms?
    • 115-125 meq/L
    • anorexia, nausea, vomiting, muscle weakening, cramping (mostly nonspecific GI symtpoms)
    • may be due to digoxin and etc so check therapeutic ranges for all meds
  6. what is considered a severe hyponatremia?
    lab value, symptoms?
    • <115 meq/L or rapid onset (<48 h)
    • gait disturbances, falls, impaired mental function, tremors, seizures
  7. hyponatremia can be associated with what kind of risks?
    • death or CV events
    • falls and fractures
    • impairment of gait and attention
    • higher mortality
    • poorer outcome in patients with pneumonia
    • mechanical ventilation
  8. what are two water-sodium balance mechanisms?
    • free-water exchange between ICF and ECF
    • arginine vasopressin (AVP or aka ADH (antidiuretic hormone)): maintain osmolality at 280-295 mOsm/kg and BP and volume
  9. what are three different types of hyponatremia?
    • isotonic
    • hypertonic
    • hypotonic
  10. what is isotonic hyponatremia?
    • this has normal osmolality
    • aka pseudo-hyponatremia
    • due to elevated lipids or proteins (hence in hyperlipidemic patients)
    • not likely to occur often
  11. what is hypertonic hyponatremia?
    • osmolality: >295 mOsm/kg
    • presence of effective osmoles (glucose, glycine, mannitol): due to additional solutes
  12. what kind of "hyponatremia" would a diabetic patient present? how do you adjust this?
    • hypertonic hyponatremia because of increased glucose and decreased sodium. however this is NOT a hyponatremia
    • for every 100mg/dL increase of glucose, sodium should be decreased 1.7mEq/L
  13. what is hypotonic hyponatremia?
    • osmolality: <280 mOsm/kg
    • excess water relative to solute in the ECF.
    • decrease in solute = depletion (common in renal problem patients)
    • increase in water = dilution (common in CHF and cirrhosis patients)
  14. how do you differentiate different hyponatremias?
    • important to measure serum osmolality
    • (normal 280-295 mOsm/kg)
  15. what is calculated osmolarity equation? (given during exam)
    how about osmolal gap?
    calculated osmolarity = 2 Na + glucose/18 + BUN/2.8

    osmolal gap = measured - calculated
  16. what is normal glucose level?
    100 mg/dL
  17. what are three kinds of hypotonic hyponatremia?
    • hypovolemic
    • hypervolemic
    • euvolemic
  18. what is hypovolemic hypotonic hyponatremia?
    what are the symptoms?
    • depletional!
    • contraction of ECF fluid due to extra renal losses or diuretic use (THIAZIDE)
    • diarrhea, vomit, excess sweating, burns, thiazide diuretic, adrenal insufficiency
    • assess fluid status
  19. what is hypervolemic hypotonic hyponatremia?
    what are the associated conditions?
    • dilutional or marked expansion
    • increased in ECF fluid with edema
    • CHF, cirrhosis, nephrosis/renal failure
  20. what is euvolemic hypotonic hyponatremia?
    what are the associated conditions?
    • dilutional
    • normal or slightly decreased Na content and increased total body water and ECF volume
    • NO edema
    • primarily polydipsia, low solute intake
    • hypothyroidism, hypocortisolism, syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
  21. what does SIADH stand for? what kind of hyponatremia is it associated with?
    • syndrome of inappropriate secretion of antidiuretic hormone
    • euvolemic hypotonic hyponatremia
  22. what is diuretic induced hyponatremia called?
    when does this develop?
    what ist eh mechanism?
    what kind of diuretic is it associated with? why not the other diuretic?
    • this is ONLY associated with hypovolemic hypotonic hyponatremia (all three "hypo")
    • typically within 2 weeks of therapy initiation (can also occur alter with increase dose or other causes of hyponatremia develop)
    • more Na loss than water: blocks Na reabsorption in distal tubules thus increased Na and water removal. decreased effective circulating volume and ADH is released. increased re-absorption of free water in the collecting duct and stimulate thirst.
    • usually mild but could be severe
    • THIAZIDE: not loop diuretic because when body senses water loss, sodium is reabsorbed back more in distal/proximal tube, not loop. less free water excretion in thiazide
  23. what are some common causes of SIADH?
    • LOSS OF FLUID conditions:
    • thiazide diuretics
    • volume depletion: vomiting, diarrhea, laxative abuse
    • malignant tumor
    • neuropsychiatric
    • pulmonary dysfunction
    • endocrine (hypothyroidism, glucocorticoid deficiency)
    • postoperative
    • alcohol withdrawal
    • renal/adrenal dysfunction
    • volume expansion (cirrhosis, HF, nephritic syndrome)
  24. what is drug induced SIADH associated with?
    what are usual findings?
    what is important to manage?
    • associated with euvolemic hypotonic hyponatremia
    • no peripheral or pulmonary edema
    • osmolarity >100 mOsm/kg, urine Na >20mEq/L
    • rule out other causes first! (not just drug induced)
  25. what are the drugs associated with drug induced SIADH?
    • (euvolemic hypotonic hyponatremia)
    • antipsychotics
    • antidepressants (older SSRI, tricyclic, venlafaxime)
    • anticonvulsants (carbamazepine)
    • narcotic
    • hallucinogenics
    • CV drugs (ACEi (lisinopril, captopril), amiodarone)
    • antineoplastic (esp lung cancer agents)
    • sulfonylurea
  26. what is the mechanism of drug induced SIADH?
    • water intake exceeds the kidney's function to excrete due to AVP release or enhanced renal sensitivity to AVP
    • increased central AVP production
    • increased renal sensitivity to AVP
    • AVP release due to serotonin
  27. what are the risk factors for drug induced SIADH? (list three medications and risks)
    • SSRI: >65yo, concomitant diuretic, elevated potassium, female, baseline serum Na <139 mEq/L, lower BMI
    • carbamazepine: higher dose and duration, elevated serum concentrations
    • vincristine, vinblastine: asian race
  28. what are prevention management for drug-induced SIADH?
    • screen risk factors
    • use lowest dose possible
    • routine monitoring of Na in high risk patients
  29. what are managements for mild-mod drug induced SIADH?
    • d/c offending agent
    • identify underlying cause
    • fluid restriction and maintain negative water balance (<1200 ml/day)
    • monitor urine output and insensible losses
  30. how do you manage acute symptomatic/severe drug induced SIADH? (if severe, could cause seizure)
    • correct no more than 8-12 mEq/L in 24 hours.
    • fluid restriction +/- furosemide
    • sodium chloride +/- furosemide (not helpful in renal failure) (1g of NaCl has 17 mEq Na)
    • NaCl infusion: 0.9% (isotonic), use hypertonic (3%, 5%) with extreme caution
    • for chronic hyponatremia: demeclocycline 600-1200mg in div doses (onset 3-6d, monitor nephrotox) or lithium 900-1200mg qd (slow onset, use if underlying bipolar but otherewise limit)
    • arginine vasopressin receptor (AVP) antagonists for euvolemic or hypervolemic hyponatremia
  31. what are AVP antagonist regimens?
    what are drug interactions?
    when are they used?
    • Conivaptan (Vaprisol) for IV: 20mg IV bolus then 20mg as CI for 24h for up to 4 days, max 40mg qd
    • Tolvaptan (Samsca) for PO: 15mg po qd to max 60mg qd (ask cardiologist, $200/tab)
    • CYP 3A4 interaction
    • use for SIADH, euvolemic and hypervolemic hypOnatremia
    • NOT for hypOvolemic b/c could cause dehydration
  32. When is NaCl infusion regimen used?
    when do you d/c? what is the rate of infusion?
    • for acute symptomatic or severe hypotonic hyponatremia only
    • d/c when Na increases by 10-12 mEq/L or to 120 mEq/L
    • total correction should NOT exceed 8-12 mEq within the first 24 h
    • initial rate is 1-2 mEq/L per hr for several hours then decrease
  33. how much mEq sodium is in 0.9% NaCl?
    154 mEq/L
  34. how do you calculate total body water?
    weight (kg) x body water

    • 0.6 = children and men <70 yo
    • 0.5 = elderly men >70yo, female <70 yo
    • 0.45 = elderly women > 70 yo
  35. how do you calculate infusion rate for NaCl?
    • first:
    • change in Na per L of infusion = (infusion Na content - baseline serum Na) / (total body water + 1L)

    • second:
    • infusion rate = target serum Na increase / change in Na/L of infusion
  36. which is more common? hypo or hypernatremia?
  37. What happens if the change of Na is more than 12mEq/L over 24 hours?
    CNS issues
  38. what is hypernatremia? (definition, lab value)
    what kind of patients will experience this?
    • Na >145 mEq/L
    • a deficit of water in relation to sodium content in the body
    • most common in those with impaired thirst response or in those without access to water (altered mental status, intubated patients, infants, elderly)
  39. what happens to the brain when the body has too much sodium?
    • too much serum sodium causes water to diffuse out of the brain via BBB because water likes to go to concentrated area.
    • thus the brain shrinks.
  40. what are clinical features of hypernatremia?
    • CNS dysfunction
    • infants: hyperpnea, muscle weakness, restlessness, high pitched cry, insomnia, lethargy, coma
    • adults: muscle weakness, confusion, coma
  41. what are three etiologies of hypernatremia?
    • isovolemic
    • hypovolemic
    • hypervolemic
  42. what is hypovolemic hypernatremia?
    what is this related to?
    • water loss > Na loss
    • related to renal, adrenal, GI, lung, skin systems
  43. what is hypervolemic hypernatremia?
    • Na gain > water gain
    • sodium overload, mineralocorticoid excess
  44. what is isovolemic hypernatremia?
    when is this observed?
    loss of water

    • central diabetes insipidus (decreased AVP secretion causes this)
    • nephrogenic diabetes insipidus (decreased renal response to AVP; can be drug induced)
    • osmotic diuresis (urinary Osm <300)
    • skin loss
    • primary polydipsia
    • iatrogenic
  45. nephrogenic diabetes insipidus is associated with what kind of electrolyte imbalance?
    isovolemic hypernatremia
  46. what drugs induce nephrogenic diabetes insipidus hypernatremia?
    • lithium toxicity (check level before d/c)
    • cidofovir
    • foscarnet
    • demeclocycline
    • sodium bicarbonate
    • hypertonic NaCl
    • hypercalcemia, hypokalemia
  47. what is the mechanism of lithium induced nephrogenic diabetes insipidus hypernatremia?
    what is urinary osmolality?
    what are risk factors for this?
    what is lithium therapeutic range?
    • inhibits opening of aquaporins in nephrons and cause polyuria
    • urinary osmolality <250 mOsm/kg
    • chronic kidney disease (CrCl <60), miltiple daily doses, long term tx (>15yo), higher trough serum lithium level
    • 0.8 - 1.2 (1.2 for mania bipolar)
  48. what is the first step to manage hypernatremia?
    • correct underlying cause (including hyperglycemia)
    • withhold lactulose and diuretic
    • treat other electrolyte disturbance
    • moderate lithium
    • correct feeding preparation
  49. how do you manage hypovolemic hypernatremia?
    • calculate water deficit = total body water x [initial serum Na /140) - 1]
    • goal: 0.5 - 1 mEq/L per hr, not to exceed 10 mEq/L per day
    • 0.9% NaCl 200-300 ml/hr until hemodynamically stable then 0.45% NaCl or D5W to correct water deficit
  50. how do you manage central diabetes insipidus hypernatremia (isovolemic)?
    • AVP analogs because AVP secretion is decreased: desmopressin (PO) and DDAVP (intranasal)
    • this is not AVP antagonist (this is for hyponatremia)
  51. how do you manage sodium overload hypernatremia?
    • loop diuretic (furosemide 20-40mg q6h)
    • IV D5W
  52. how do you manage nephrogenic diabetes insipidus hypernatremia (isovolemic)?
    • correct hypercalcemia, hypokalemia (Ca and Na go together and K is opposite)
    • thiazide diuretic + dietary sodium restriction (<2g NaCl daily)
    • indomethacin 50mg TID (adjunct)
    • if lithium induced, amiloride 5-10mg daily
  53. normal range of potassium?
    3.5-5.0 mEq/L
  54. cause/etiology of hypokalemia?
    • due to total body K deficit
    • or when serum K is shifted into the ICF
  55. clinical feature of mild hypokalemia (3-3.5 meq/l)
  56. clinical feature of moderate hypokalemia (2.5-3 meq/L)
    cramping, weakness, malaise, myalgia
  57. clinical feature of severe hypokalemia (<2.5meq/L)
    • ECG ST segmentation depression or flattening, T wave inversion or U wave elevation
    • life threatening cardiac arrhythmia, heart block
  58. what other electrolyte disturbance could happen if hypokalemia? what should you do to fix?
    • hypomagnesemia (<1.7 mg/dL (not meq/l))
    • fix Mg first
  59. what are the etiologies of hypokalemia?
    • inadequate intake
    • magnesium depletion
    • increased excretion - diarrhea, laxative abuse
    • renal losses - diuresis, loop or thiazide diuretics, non-reabsorbable anions (penicillin), high dose glucocorticoids
  60. what are 2 mechanisms of drug induced hypokalemia? give drug examples with each.
    transcellular shift: b2 agonist (albuterol), theophylline, caffeine, insulin overdose

    enhanced fecal elimination: laxative, SPS, sorbitol

    enhanced renal elimination: diuretic, high dose pcn, mineralocorticoids
  61. when do you use IV K supplementation?
    how do you administer?
    • K<2.5 meq/L (severe)
    • presence of cardiac arrhythmias, muscle spasm
    • unable to tolerate PO

    • 10-20 meq K diluted in 100ml NS over 1 h
    • monitor EKG if admin >10meq/h
    • do not exceed 40 meq/l
    • after each 30-40 meq check K 30 min after infusion
  62. K+ should never be given via which way?
    IV push (this is lethal)
  63. when do you give po K+ replacement therapy?
    in milder cases
  64. when K <3.5, every ___ meq/L decrease requires ____ meq supplement.
    1meq/L decrease requires 100-400 meq supplem
  65. hypokalemia due to chroni loop or thiazide diuretic use requires ____ meq orally (in div doses) then prevention.
    40-100 meq
  66. what other electrolyte should you always monitor when hypokalemia?
  67. what is the definition of hyperkalemia?
    K >5.5 meq/L
  68. clinical feature of mild hyperkalemia? (5.5 - 6 meq/L)
    usually asymptomatic
  69. clinical feature of moderate hyperkalemia? (6.1 - 6.9 meq/L)
    heart palpitation
  70. clinical feature of severe hyperkalemia (> 7 meq/L)
    • potentially life threatening
    • cardiac arrhythmia
    • EKG changes (peaked t-wave, widened QRS complex)
  71. what are the 4 etiologies of hyperkalemia?
    • increased K intake
    • impaired K excretion (K sparing diuretic, ACEi, ARB, NSAID, cyclosporine, tacrolimus, Bactrim)
    • tubular un-responsiveness to aldosterone
    • redistribution of K into the extracell space
  72. beta blocker causes __ kalemia.
    beta agonist causes __ kalemia.
    • hyper
    • hypo
  73. for acute management of hyperkalemia, which agents may exhibit immediate effect?
    • calcium gluconate or chloride 1g IV
    • hemodialysis
  74. for acute management of hyperkalemia, which agents may exhibit effect after 30 min ?
    • regular insulin 5-10U iv/sc with dextrose 10~50% 25-100g to avoid hypoglycemia
    • albuterol 10-20mg by inhaler over 10 min (higher dose than 2.5mg for asthma)
  75. if there is metabolic acidosis, what agent can you consider to acutely manage hyperkalemia?
    sodium bicarbonate 50-100 meq
  76. if you were to use loop diuretic 20-40 iv for acute management of hyperkalemia, what should you assess prior?
    fluid status
  77. what is one of the most effective agents to acutely manage hyperkalemia? how fast is the onset
    • kayexalate 15-60g with sorbitol
    • onset in 1 hr
  78. goal of hyperkalemia long term management?
    restrict dietary K intake to ____g/d
    avoid ____
    d/c drugs that interfere with K homeostasis
    agument K+ excretion (use ____, ____)
    if hypoaldosteronism is present, use ____.
    chronic kayexalate (each g of resin removes ___ meq of K)
    • maintain K <6 meq
    • 2-3g
    • K supplement
    • loop, thiazide diuretic
    • fludrocortisone
    • 1 meq of K
  79. if severe hyperkalemia and EKG changes, what would be a reasonable choice of therapy?
    • calcium gluconate (antagonize K damage to heart)
    • kayexalate (removes K)
  80. what is normal Mg? (Careful with the units)
    • 1.7-2.3 mg/dL
    • 1.4 - 1.8 meq/L
  81. definition of hypomagenesmia?
    <1.4 meq/L
  82. clinical features of hypomagnesemia
    • may be present with hypokalemia and hypocalcemia
    • tetny, twitch, tremor, generalized convulsion
    • heart palpitation, cardiac arrhythmia, ECG change
  83. what are two etiology of hypomagnesemia?
    decreased intestinal absorption: small bowel disease, laxative abuse, alcoholism

    increased renal excretion: thiazide, loop diuretic, AG, amphoB, cyclosporin, tacrolimus, cisplatin, pentamidine, foscarnet
  84. how do you manage?
    Mg 1.0-1.4 meq/L without symptoms
    • milk of magnesia 5ml QID
    • Mg antacid 15ml TID
    • Mg Ox tab 400-800 QD
    • these all increase K+ as well
  85. how do you manage?
    Mg <1.0 meq/L without severe symptoms
    • day 1: 1 meq/kg iv inf or div im
    • day 2-5: 0.5 meq/kg/d (iv)
    • Mg sulfate
  86. how do you manage?
    Mg < 1.0meq/L with life threatening symptoms (arrhythmia, seizure)
    • day 1: 2 g Mg sulfate mix with 6ml NS IV push over 1min then 1 meq/kg IV inf over 24 h
    • day 2-5: 0.5 meq/kg/d (iv inf) (same as w/o severe sympt)
  87. Kg in hypomagnesemia IV is based on what kind of weight?
    lean body weight
  88. definition of hypermagnesimia?
  89. clinical features of hypermagenesemia?
    • above 6 is considered serious
    • >6meq/L: loss of deep tendon reflex, EKG change
    • 7-9 meq/L: drowsy, lethargy, somnolence
    • 12 meq/L: resp depression, muscle paralysis, coma
    • 15 meq/L: complete heart block, death
  90. what are the etiologies of hypermagenesmia?
    • decreased renal exc
    • excessive intake
    • drug induced: Mg containing antacid and vitamin, lithium
    • others
  91. how do you manage hypermagnesemia?
    • reduce Mg intake
    • IV calcium: 100-200mg hrly
    • IV furosemide 40mg (do not use if dehydration, hotn or CrCl<30)
    • supportive care
    • dialysis patients (make sure dialysate is Mg-free)
  92. normal range of calcium?
    8.5-10.5 meq/L
  93. definition of hypocalcemia?
    • serum Ca <8.5 meq/L
    • or
    • ionized Ca <4.4 mg/dL
  94. when should you use the formula to adjust Ca level?
    what is the formula?
    • when albmin <4
    • adjusted Ca = 0.8 (4 - albumin) + total measured Ca
  95. clinical features of hypocalcemia?
    • altered mental status, seiure, paresthesia, tetany, hyperreflexia, muscle weak
    • prolonged QT interval, cardiac arrhythmia
  96. 6 etiologies of hypocalcemia
    • result of alterations in the effect of PTH and itamn D on the bone, gut and kidney
    • loss of Ca from circulation: intravascular binding with citrate, lactate, foscarnet, EDTA
    • postoperative hypoparathyroidism
    • magnesium deficiency
    • vitamin D deficiency
    • others - thyroid surgery, sepsis, chemotherapy
  97. what drugs induce hypocalcemia?
    • bisphosphonate
    • cinacalcet
    • calcitonin
    • furosemide
    • ketoconazole
  98. how do you manage hypocalcemia?
    • first look at albumin level and correct
    • treat hypomagnesemia
    • treat hypoparathyroidism, vitamin D deficiency (1,25 dihydroxyvitamin D3 (0.5-3mcg daily), ergocalciferol 50,000 IU daily)
  99. how do you manage asymptomatic hypocalcemia?
    oral elemental calcium 1-3g/d
  100. how do you manage symptomatic hypocalcemia?
    • Ca++ gluconate 1 ampule IV over 10-30min
    • if persistent, rebolus IV and increase maintenance infusion rate
    • check Ca, PO4, Mg q 4-6h
    • monitor EKG
  101. define hypercalcemia
  102. clinical features of hypercalcemia
    • alterned mental status with confusion, lethargy, psychosis, coma
    • hyporeflexia and muscle weakness
    • constipation, shortening of QT interval, pancreatitis
  103. clinical features associated with chronic hypercalcemia
    bone changes, band keratopathy (corneal calcium deposition)
  104. other clinical presentation with hypercalcemia
    • hyperparathyroidism
    • malignancy
    • sarcoidosis
    • vitamin A tox
  105. 4 etiologies of hypercalcemia
    • increased intestinal Ca absorption
    • hypervitaminosis D
    • increased bone resorption
  106. important drug that induces hypercalcemia
    • thiazide
    • (also causes hypokalemia, hypomagnesemia, hypercalcemia)
  107. how do you manage hypercalcemia?
    • d/c offending drug
    • treat even if asymptomatic if >12 mg/dL
    • increase urinary Ca excretion (isotonic saline NS 200-300ml/hr +/- loop diuretic 40-80 mg q1-4h)
  108. how can you diminish bone resorption in hypercalcemia?
    • calcitonin sq/im
    • bisphosphonate: etidronate (Didronel), pamidronate (Acredia), zoledronic acid, ibandronate
  109. how can you manage decreased intestinal Ca absorption in hypercalcemia?
  110. what is the normal level of phosphate?
    2.5 - 3.5 mg/dL
  111. define hypophosphatemia
    <1 - 2 mg/dL (severe if <1)
  112. what are clinical features of hypophsophatemia?
    • CNS manifestation
    • myalgia, bone pain, weakness
    • severe rhabdomyolysis
    • increase alkaline phosphate
    • normal to low PO and Ca
  113. what are drug induced causes of hypophosphatemia?
    • decreased GI absorption (pohsphate binding subtance, glucocorticoid)
    • increased urinary excretion
    • internal redistribution (alcoholism, dextrose solution, re-feeding syndrome)
  114. how do you manage mild to moderate hypophosphatemia without symptoms?
    • oral phosphorus supplementation
    • NeutraPhos
    • Neutra Phos K
    • Fleet Phospho soda
  115. difference between NeutraPhos and NeutraPhosK?
    • Neutra Phos: 7 meq/L each of Na and K, 8mmol PO
    • Neutra Phos K: 12 meq/L of K, 8 mmol PO
  116. how do you manage severe hypophosphatemia?
    • PO <1mg/dL
    • depends on potassium
    • if K >3.5: sodium phosphate over 3h
    • if K <3.5: potassium phosphate over 3h
  117. define hyperphosphatemia
    >4.5 mg/dL
  118. clinical features of hyperphosphatemia
    GI disturbance, lethargy, obstruction urinary tract, seiure, calciphylaxis
  119. drug induced causes of hyperphosphatemia
    • vitamin D
    • bisphosphonate
    • phosphorus containing enema
    • excessive IV or PO of phosphorus
  120. how do you manage hyperphosphatemia?
    • correct and manage hypocalcemia first!
    • goal Ca x PO <55 (precipitation if higher number)
    • goal PO 2.7-4.6 in stage 3/4 CKD
    • goal PO 3.5 - 5.5 in stage 5 CKD

    • phosphate binder (avoid long term therapy)
    • antacids containing calcium
    • lantanum 1.5 - 3g daily in div doses
    • sevelamer 800-1600mg with meals TID
Card Set
Drug induced Electrolyte disorder
Drug induced Electrolyte disorder