ESPEN Congress Lisbon Water and electrolytes. Drug-induced fluid and electrolyte imbalances. R Lourenco

Transcription

1 ESPEN Congress Lisbon 2004 Water and electrolytes Drug-induced fluid and electrolyte imbalances R Lourenco

2 Regina Lourenço Pharmacy Department Center of Nutrition and Metabolism University Hospital Sta. Maria Lisboa, Portugal Drug-induced imbalances

3 Mg 2+ Plasma Ca 2+ P Mg 2+ Intracellular compartment Ca 2+ P Interstitial compartment

4 Drugs Adverse effects Mg 2+ P Ca 2+ Outcomes insignificant / severe Occurence immediate / delayed Patient morbidity / mortality

5 1 Mg 2+ Ca 2+ P

6 Patient Age Drug Chemistry Gender Genetics Excipient Dosage Nutritional status Dietary intake Diagnosis and severity Route Duration of therapy Polymedication

7 2 Mg 2+ Ca 2+ P

8 Ca 2+ Mg2+ P Complexation antibiotics, antacids GI motility antacids (Al 3+ ), antibiotics Disruption on tissue integrity cytotoxics Imbalance phenobarbital / vitamin D Ca 2+ Urinary losses loop diuretics, amphotericin thiazides

9 3

10 Water homeostasis deficit excess Plasma osmolarity thrist Plasma osmolarity Osmoreceptors hypothalamus Posterior pituitary ADH natriuretic factors Water reabsorption ADH Water reabsorption Urine volume reduced Antidiuresis Urine volume increased Diuresis plasma volume plasma osmolarity plasma volume plasma osmolarity

11 Sodium homeostasis deficit Angiotensin II excess Plasma volume Angiotensin I Angiotensinogen Adrenal cortex Aldosterone Plasma volume Natriuretic factors Renin Renin sodium reabsorption sodium reabsorption sodium excretion sodium excretion

12 Water imbalances Dehydration Excessive loss from ECC increased + excretion ECC osmotic pressure rises Cells loose water to ECC by osmosis Cell Diuretics

13 Water imbalances Overhydration Excessive enters the ECC renal reabsorption estrogens, fludrocortisone, minoxidil, nifedipine, NSAIDs ECC osmotic pressure falls Water moves into cells by osmosis Cell capillary permeability interleukin 2

14 Sodium imbalances signs and symptoms nausea, malaise, lethargy, seizures, coma, respiratory arrest Hypernatremia excess of water relative to sodium deficiency of water relative to sodium Hyponatremia signs and symptoms hypertension, dehydration, renal dysfunction

15 Hyponatremia Hypertonic Shift of water from cells to the ECC Normotonic Large volumes of IV isotonic fluids without sodium are retained in ECC Hypotonic Retention of water Renal losses SIADH

16 Hyperglycemia and. Hypertonic hyponatremia Decrease insulin secretion Increase hepatic glucose output Decrease peripheral glucose uptake epinephrine thiazide diazoxide Ca 2+ channels blockers β 2 adrenergic agonist β blockers phenytoin clonidine H 2 receptor blockers morphine epinephrine glucocorticoids β 2 adrenergic agonist epinephrine glucocorticoids diuretics protease inhibitors β 2 adrenergic agonist atypical antipsychotics

17 Hypotonic hyponatremia Renal sodium losses reabsorption of NaCl thiazides diuretics loop / osmotic diuretics thiazides diuretics

18 Hypotonic hyponatremia SIADH - Syndrome of inappropriate secretion of ADH ADH analogues Potentiate renal action of ADH desmopressin oxytocin vasopressin acetaminophen cyclosphosphamide NSAIDs ADH Enhance ADH release psycothropic medications antidepressants, antipsychotics, anxiolytics mood stabilisers, benzodiazepines carbamazepine levodopa vincristine, ifosfamide Unknown mechanism amiodarone clonidine lisinopril

19 Hypernatremia Hypervolemic Normovolemic Hypovolemic excess intake losses + inadequate intake losses penicillins hypertonic bicarbonate chloride lithium amphotericin cidofovir gentamicin verapamil clozapine cyclosphosphamide vinca alkaloids lactulose diuretics loop osmotic

20 4 K +

21 Potassium imbalances influence osmolarity cell membrane polarization signs and symptoms muscular weakness, arrhytmias, cardiac arrest, slow gut motility Hyperkalemia Hypokalemia signs and symptoms arrhytmias, cardiac arrest

22 Hypokalemia GI losses Renal losses Transcellular shifts Extracellular fluid ATP Cytoplasm laxatives diuretics (loop > thiazides) amphotericin B aminoglycosides corticosteroids theophylline intoxication insulin vasoconstrictors bronchodilators inhib.. uterine contraction inhaled beta agonists

23 Hyperkalemia Excessive intake Disturbed cellular uptake Decreased excretion penicillin G potassium potassium supplements beta blockers, lysine, arginine, aminocaproic acid, succinylcholine, digoxin to continue

24 Hyperkalemia Decreased excretion triamterene amiloride trimethoprim pentamidine Blood Cell Tubular lumen ATP Renal blood flow GFR ACEI angiotensin antagonists NSAIDs Aldosterone Secretion ACEI NSAIDs heparin angiotensin antagonists spironolactone CyA tacrolimus CyA tacrolimus

25 Mg 2+ 5 Mg 2+ Mg 2+

26 Magnesium imbalances Co-factor enzymatic / metabolic reactions signs and symptoms nausea, vomiting, sleepiness, weakness, muscle spasms, tremors Hypermagnesemia Mg 2+ signs and symptoms Hypomagnesemia weakness, low blood pressure, impaired breathing

27 Hypomagnesemia Mg2+ GI losses Extracellular shifts Renal losses Mg2+ colestiramine neomycin laxatives foscarnet catecholamines insulin theophylline diuretics (loop > thiazides) amphotericin B aminoglycosides cyclosporine cisplatin, carboplatin

28 Hypermagnesemia Mg2+ renal failure Mg 2+ Antacids Purgatives

29 Ca 2+ 6 Ca 2+ Ca 2+

30 Calcium imbalances signs and symptoms confusion, delirium, depression, hallucinations, tetany, arrhythmias Hypercalcemia Ca 2+ signs and symptoms Hypocalcemia constipation, nausea, abdominal pain, psychological signs, death

31 Calcium homeostasis Calcitonin Stimulates Ca 2+ deposition in bones Reduces Ca 2+ uptake in intestines Reduces Ca 2+ uptake in kidneys High Thyroid Active vitamin D Ca 2+ Low Parathyroid glands Increases Ca 2+ uptake Increases Ca 2+ uptake Stimulates Ca 2+ release PTH

32 Hypocalcemia Ca 2+ absorption Renal losses bone reabsorption complexation foscarnet GI ph antacids (Al 3+ ) 3+ ) tissue dysfunction neomycin, colchicine decreased vitamin D phenobarbital, phenytoin, rifampin, orlistat, cholestyramine furosemide gentamicin glucocorticoids magnesium sulphate calcitonin biphosphonates gallium nitrate mithramycin

33 Hypercalcemia Ca 2+

34 P 7 P P

35 Phosphorus imbalances Energy metabolism signs and symptoms decreased respiratory, cardiovascular, neuromuscular hematological function Hyperphosphatemia P Hypophosphatemia? Drug-induced?

36 Hypophosphatemia P Absorption antacids, sucralfate,, calcium carbonate P Cell catecholamines dextrose Blood Excretion acetozolamide, thiazides, mannitol theophylline glucocorticoids dopamine ifosfamide and cidofovir

37 Mg 2+ Ca 2+ P

38 References McCabe BJ. Prevention of food-drug interactions with special emphasis on older adults. Curr Opin Clin Nutr Metab Care 2004; 7: Chan TYK. Drug-induced syndrome of inappropriate antidiuretic hormone secretion. Causes, diagnosis and management. Drugs Aging 1997; 11: Spigset O et al. Hyponatremia anf the syndrome of inappropriate antidiuretic hormone secretion induced by psychotropic drugs. Drug Safety 1995; 12: Lourenço R. Enteral feeding: drug/nutrient interaction. Clin Nutr 2001; 20(2): Chan LN. Drug-nutrient interactions in transplant recipients. JPEN 2001; 25(3): Greenberg A. Diuretic complications. Am J Med Sci 2000; 319(1): Adrogue H, Madias N. Hyponatremia. N Eng J Med 2000; 342(21): Gennari F. Hypokalemia. N Eng J Med 1998; 339(7): Madhusoodann S, Bogunovic O, Moise D, Brenner R, Markowitz S, Sotelo J. Hyponatremia associated with psychotropic medications. Adv Drug React Toxicol Rev 2000; 21(1-2): Luna B, Feinglos M. Drug-induced hyperglycemia. JAMA 2001; 286(16): Perazella M. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med 2000; 109: