Pharmacologically-induced metabolic acidosis: a review.
Metabolic acidosis may occasionally develop in the course of treatment with drugs used in everyday clinical practice, as well as with the exposure to certain chemicals. Drug-induced metabolic acidosis, although usually mild, may well be life-threatening, as in cases of lactic acidosis complicating antiretroviral therapy or treatment with biguanides. Therefore, a detailed medical history, with special attention to the recent use of culprit medications, is essential in patients with acid-base derangements. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on the acid-base status. In this review, we evaluate relevant literature with regard to metabolic acidosis associated with specific drug treatment, and discuss the clinical setting and underlying pathophysiological mechanisms. These mechanisms involve renal inability to excrete the dietary H+ load (including types I and IV renal tubular acidoses), metabolic acidosis owing to increased H+ load (including lactic acidosis, ketoacidosis, ingestion of various substances, administration of hyperalimentation solutions and massive rhabdomyolysis) and metabolic acidosis due to HCO3- loss (including gastrointestinal loss and type II renal tubular acidosis). Determinations of arterial blood gases, the serum anion gap and, in some circumstances, the serum osmolar gap are helpful in delineating the pathogenesis of the acid-base disorder. In all cases of drug-related metabolic acidosis, discontinuation of the culprit medications and avoidance of readministration is advised.
Liamis
George
G
Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
Milionis
Haralampos J
HJ
Elisaf
Moses
M
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000138:Acidosis / Q000139:chemically induced*; D000140:Acidosis, Lactic / Q000139:chemically induced; D000141:Acidosis, Renal Tubular / Q000139:chemically induced; D001639:Bicarbonates / Q000378:metabolism; D016883:Diabetic Ketoacidosis / Q000139:chemically induced; D006801:Humans
D001639:Bicarbonates
Ann Pharmacother. 2005 Mar;39(3):424-6
15701764
J Am Optom Assoc. 1991 Dec;62(12):934-7
1814986
N Engl J Med. 1976 Feb 12;294(7):361-5
1674
Am J Nephrol. 1988;8(3):245-8
3071139
N Engl J Med. 1961 Apr 27;264:848-52
13740726
Ren Fail. 1989;11(2-3):117-24
2623197
Am J Psychiatry. 2004 Sep;161(9):1709-11
15337666
Trans Am Clin Climatol Assoc. 2000;111:122-33; discussion 133-4
10881337
Neurosurgery. 1995 Aug;37(2):363-9; discussion 369-71
7477798
Pharmacotherapy. 2009 May;29(5):554-61
19397463
Am J Kidney Dis. 2007 Sep;50(3):463-7
17720526
Ann Emerg Med. 1984 Oct;13(10):956-9
6476520
Postgrad Med. 2009 Jul;121(4):162-8
19641282
Clin Nephrol. 2009 Mar;71(3):326-8
19281746
Am J Med. 2001 Dec 15;111(9):716-23
11747852
Chest. 2005 Sep;128(3):1674-81
16162774
Nephrol Dial Transplant. 1995;10(4):543-5
7624000
Am J Med. 1991 Aug;91(2):119-28
1867237
J Nephrol. 2006 Mar-Apr;19 Suppl 9:S41-5
16736440
Toxicol Appl Pharmacol. 1972 Jan;21(1):102-11
4553872
Basic Clin Pharmacol Toxicol. 2009 Jan;104(1):22-6
19152550
Clin Ter. 2008 Mar-Apr;159(2):87-9
18463766
J Clin Psychiatry. 2004 Jun;65(6):857-63
15291665
Emerg Med J. 2008 Sep;25(9):613
18723724
Pflugers Arch. 1989 Jan;413(3):280-6
2717375
Rev Infect Dis. 1982 Mar-Apr;4(2):426-8
6981160
Clin Chem. 1998 Feb;44(2):336-40
9474033
Clin Chem. 1998 Jul;44(7):1497-503
9665429
J Nephrol. 2006 Mar-Apr;19 Suppl 9:S62-9
16736443
Pediatr Nephrol. 2008 Apr;23(4):611-8
18204866
Clin Infect Dis. 2006 Feb 1;42(3):434-5
16392096
Lancet. 1996 Aug 31;348(9027):578-80
8774570
Intern Med. 2008;47(2):113-7
18195501
Arch Dis Child. 1970 Apr;45(240):264-8
5419996
Sex Transm Infect. 2003 Aug;79(4):340-3
12902594
J Med Toxicol. 2007 Jun;3(2):52-5
18072160
Am J Med. 1987 Aug;83(2):236-42
3303926
Ann Intern Med. 1979 Mar;90(3):338-40
426401
Intensive Care Med. 1995 Aug;21(8):641-4
8522667
J Clin Pharmacol. 1989 Apr;29(4):348-53
2498399
N Engl J Med. 1977 Sep 15;297(11):576-83
18672
Lancet. 2001 Feb 24;357(9256):606-7
11558490
Anesthesiology. 2007 Jun;106(6):1134-8
17525588
Am J Ther. 2007 Jul-Aug;14(4):403-5
17667216
J Clin Psychiatry. 2005 Apr;66(4):504-14
15816794
JAMA. 1981 Aug 28;246(9):970-3
7253181
Arch Intern Med. 1985 Jul;145(7):1306-7
4015282
Crit Care. 2003 Jun;7(3):R41-5
12793889
Clin Pharmacol Ther. 2002 Oct;72(4):461-4
12386648
Ann Emerg Med. 2002 Aug;40(2):259-60
12140510
Am J Kidney Dis. 1996 Mar;27(3):431-4
8604715
Ann Intern Med. 1978 Mar;88(3):352-4
24402
Crit Care. 2008;12(6):R149
19036140
Toxicol Appl Pharmacol. 1979 Jun 30;49(2):377-84
40324
Kidney Int. 1985 Feb;27(2):472-83
2581012
Med Sci Sports Exerc. 2008 Mar;40(3):477-85
18379210
Clin Endocrinol Metab. 1984 Jul;13(2):333-49
6488577
J Clin Endocrinol Metab. 2008 May;93(5):1541-52
18270259
Chest. 2002 Jul;122(1):385-6
12114394
Lancet. 1989 Jun 24;1(8652):1452-3
2567460
Clin Infect Dis. 2005 Jun 15;40(12):e113-6
15909253
Am J Med. 1988 Jan;84(1):145-52
3337119
N Engl J Med. 1980 Oct 9;303(15):854-8
6774247
Int J Clin Pract. 2009 Oct;63(10):1516-25
19769708
Antimicrob Agents Chemother. 2002 Mar;46(3):716-23
11850253
J Neurosurg Anesthesiol. 2009 Apr;21(2):112-9
19295389
Am J Emerg Med. 1991 Jul;9(4):363-5
2054009
Am J Kidney Dis. 2005 Jul;46(1):143-6
15983968
Crit Care Med. 2007 May;35(5):1264-70
17334252
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD002967
16437448
Am J Med. 1969 Jan;46(1):154-62
4951424
South Med J. 1991 Apr;84(4):496-7
2014436
Am J Physiol. 1987 Sep;253(3 Pt 1):E271-6
3631257
Clin Infect Dis. 2002 Mar 15;34(6):838-46
11850865
N Engl J Med. 2009 Jul 2;361(1):62-72
19571284
Diabet Med. 2006 Apr;23(4):432-5
16620273
Pharmacotherapy. 2008 Sep;28(9):1198-202
18752391
Intern Med. 2004 Aug;43(8):750-4
15468980
Blood. 1981 Jan;57(1):182-5
6160887
Diabetes Care. 2006 Apr;29(4):950-1
16567854
Ann Intern Med. 1995 Jun 1;122(11):839-42
7741368
Clin Chem. 1990 Jan;36(1):173-4
2297927
Anesth Analg. 2002 Jun;94(6):1583-5, table of contents
12032031
Pediatr Emerg Care. 2008 Dec;24(12):842-4
19092563
Am J Kidney Dis. 2005 May;45(5):804-17
15861345
Int J Artif Organs. 2005 Mar;28(3):222-8
15818544
Nat Rev Nephrol. 2009 May;5(5):270-6
19384328
Am J Obstet Gynecol. 1983 May 1;146(1):1-5
6846409
Toxicol Appl Pharmacol. 2008 Dec 1;233(2):203-10
18817800
Arch Intern Med. 1964 Aug;114:232-5
14160116
Int Arch Med. 2008 Apr 15;1(1):3
18471314
South Med J. 2006 Mar;99(3):257-73
16553100
Paediatr Anaesth. 1998;8(6):491-9
9836214
J Infect. 2006 Feb;52(2):92-6
15907341
Crit Care Med. 1998 Nov;26(11):1807-10
9824071
Nephrology (Carlton). 2007 Feb;12(1):3-7
17295653
Transplantation. 2007 Nov 15;84(9):1151-7
17998871
Pharmacotherapy. 2003 Sep;23(9):1190-4
14524651
J Med Case Rep. 2007 Oct 31;1:126
17974034
CNS Drugs. 2005;19 Suppl 1:1-93
15998156
Pediatr Blood Cancer. 2007 Apr;48(4):447-52
16628552
Pharmacotherapy. 2007 May;27(5):771-4
17461714
Nat Clin Pract Nephrol. 2006 Jan;2(1):4-5
16932379
Biol Trace Elem Res. 2008 Aug;124(2):164-72
18575818
Clin Endocrinol Metab. 1983 Jul;12(2):391-411
6347452
Schizophr Res. 2003 Jul 1;62(1-2):77-88
12765747
Drug Saf. 2007;30(7):589-99
17604410
Kidney Int. 1986 Mar;29(3):752-74
3702227
J Med Chem. 2008 Apr 10;51(7):1981-90
18338841
Neth J Med. 2008 May;66(5):185-90
18490795
Infection. 2008 Aug;36(4):387-8
18642110
Miner Electrolyte Metab. 1994;20(5):274-81
7700215
Am Fam Physician. 1998 Feb 15;57(4):749-52
9490997
Am J Med. 1979 Nov;67(5):905-8
507101
Ann Intern Med. 1982 Jan;96(1):122
6459048
Crit Care Med. 1990 Mar;18(3):275-7
2302951
Arch Intern Med. 1985 Oct;145(10):1815-7
4037942
Am J Kidney Dis. 1993 Aug;22(2):333-6
8352262
Clin Infect Dis. 2003 May 15;36(10):1324-8
12746780
J Trauma. 2005 Feb;58(2):238-43
15706182
Br J Ophthalmol. 2006 Feb;90(2):247-8
16424547
Neth J Med. 2008 Sep;66(8):354-7
18809985
N Engl J Med. 1999 Mar 11;340(10):764-71
10072411
Kidney Blood Press Res. 2006;29(5):280-93
17035713
Arch Intern Med. 1981 Feb 23;141(3 Spec No):364-9
7469627
J Lab Clin Med. 2005 Dec;146(6):317-20
16310513
Respirology. 2006 Mar;11(2):182-7
16548904
Am J Kidney Dis. 2005 Jun;45(6):978-93
15957126
Handb Exp Pharmacol. 2008;(182):227-52
18175094
Drugs Today (Barc). 2008 Apr;44(4):303-14
18536788
Semin Liver Dis. 1998;18(4):313-29
9875551
Intensive Care Med. 2003 Sep;29(9):1417-25
12904852
Am J Physiol. 1980 Aug;239(2):F135-42
7406043
J Clin Anesth. 2008 Jun;20(4):290-3
18617128
CJEM. 2006 Mar;8(2):78
17175866
Clin Toxicol (Phila). 2008 Feb;46(2):164-6
18259965
N Engl J Med. 1986 Dec 18;315(25):1591-5
3785323
Am J Med. 1980 Mar;68(3):414-8
7361809
J Emerg Med. 2010 May;38(4):494-6
19232874
Gynecol Obstet Invest. 2008;66(2):138-41
18483459
J Inherit Metab Dis. 1989;12(2):120-30
2502672
Ann Intern Med. 1996 Feb 1;124(3):316-20
8554227
Arch Intern Med. 1965 Dec;116(6):853-6
5848218
J Clin Pharmacol. 1992 Jun;32(6):536-8
1634640
Intensive Care Med. 1988;14(3):221-6
3132492
Clin Lab Med. 2006 Mar;26(1):31-48, vii
16567224
Perit Dial Int. 2007 Nov-Dec;27(6):697-701
17984434
Eur J Intern Med. 2005 Feb;16(1):3-11
15733814
AIDS. 2002 Jul 5;16(10):1341-9
12131210
J Lab Clin Med. 2000 Nov;136(5):379-89
11079465
Pharmacology. 2003 Mar;67(3):118-20
12571406
Br J Psychiatry. 1986 Nov;149:650-1
3101931
Clin Transplant. 1998 Oct;12(5):465-71
9787958
N Engl J Med. 1996 Feb 29;334(9):574-9
8569826
Ann Pharmacother. 2008 Oct;42(10):1502-6
18698010
Kidney Int Suppl. 2005 Jul;(96):S15-23
15954945
Biochem J. 2000 Jun 15;348 Pt 3:607-14
10839993
Eur Psychiatry. 2005 Dec;20 Suppl 4:S349-57
16459250
Ann Intern Med. 1980 Feb;92(2 Pt 1):227-37
6766289
Am J Physiol. 1983 Nov;245(5 Pt 1):F601-5
6638181
Am J Emerg Med. 1989 Jul;7(4):417-8
2567599
Clin J Am Soc Nephrol. 2008 Sep;3(5):1324-31
18596116
Nat Clin Pract Nephrol. 2007 Sep;3(9):515-20
17717564
Am J Kidney Dis. 1987 Nov;10(5):329-45
3314489
Infection. 2007 Jun;35(4):278-81
17646908
Intensive Care Med. 2009 Aug;35(8):1377-82
19367388
Aust N Z J Med. 1979 Dec;9(6):694-6
294928
J Clin Pathol. 2004 Sep;57(9):989-90
15333664
Kidney Int. 1975 Nov;8(5):279-83
536
Chest. 2003 Mar;123(3):897-922
12628894
Ann Emerg Med. 2007 Nov;50(5):587-90
17418450
Indian Pediatr. 1993 Aug;30(8):1025-6
8125574
Am J Med. 1967 Mar;42(3):435-40
6018860
Adv Exp Med Biol. 1987;212:129-34
3618353
N Engl J Med. 2002 Mar 14;346(11):811-20
11893792
Kidney Int. 2003 Sep;64(3):777-87
12911526
Curr Opin Anaesthesiol. 2006 Aug;19(4):404-10
16829722
AIDS. 2008 Jul 11;22(11):1374-6
18580619
Clin Toxicol (Phila). 2008 Nov;46(9):858-60
18608252
J Clin Invest. 1971 Jan;50(1):166-74
5101293
J Am Soc Nephrol. 1991 Feb;1(8):1019-27
1912400
Clin J Am Soc Nephrol. 2006 May;1(3):441-7
17699243
J Nephrol. 2006 Mar-Apr;19 Suppl 9:S70-5
16736444
Pharmacotherapy. 2002 Jul;22(7):841-52
12126218
Med Pediatr Oncol. 1999 Mar;32(3):177-82
10064184
Crit Care Med. 2000 May;28(5):1631-4
10834725
Expert Opin Drug Saf. 2005 Nov;4(6):1097-109
16255667
N Engl J Med. 1985 Oct 3;313(14):890-1
4033719