Acid-Base Disorders

(1)

Professor of Medicine, Department of Medicine, Chief, Division of Nephrology and Hypertension, Rutgers New Jersey Medical School, Newark, NJ, USA

Keywords

Metabolic acidosisMetabolic alkalosisRespiratory acidosis

In previous chapters, we discussed various systemic and drug-induced causes of acid-base disorders. Since drug-induced acid-base disorders are rather common in daily clinical practice, this chapter summarizes the iatrogenic causes of the four primary acid-base disorders. The pathophysiology of systemic and drug-induced primary acid-base disorders is discussed in their respective chapters.

Metabolic Acidosis

Drugs that cause metabolic acidosis fall into three groups:

1.

Drugs that generate endogenous acid (Table 15.1)
2.

Drugs that cause loss of HCO₃ ⁻ from GI tract or kidney (Table 15.2)
3.

Drugs that impair renal tubular function (Tables 15.3, 15.4, and 15.5)

Table 15.1

Common drugs that generate acids with high AG

Drug	Major acid generated	Mechanism
Metformin	Lactic acid	Inhibition of mitochondrial oxidative phosphorylation (mitochondrial dysfunction)
Antiretroviral agents (didanosine, zidovudine, stavudine, zalcitabine, tenofovir, abacavir)	Lactic acid	Mitochondrial dysfunction
Linezolid	Lactic acid	Mitochondrial dysfunction
Propofol	Lactic acid	Mitochondrial dysfunction
Cyanide poisoning	Lactic acid	Mitochondrial dysfunction, hypoxia
Propylene glycol	Lactic acid	Metabolic product
Salicylate	Lactic acid, ketoacid	Mitochondrial dysfunction causing increased lipolysis with ketoacid formation
Ethanol	Ketoacid	Decreased insulin and increased lipolysis, leading to ketoacid formation
Methanol	Formic acid	Metabolic product
Ethylene glycol	Oxalic acid	Metabolic product
Diethylene glycol	2-hydroxy-ethoxyacetic acid	Metabolic product
Toluene	Hippuric acid	Metabolic product
Acetaminophen, netilmicin, flucloxacillin, vigabatrin, paracetamol	Pyroglutamic acid	Dysfunction of γ-glutamyl cycle with reduced glutathione levels
Intravenous diazepam and lorazepam	D-lactic acidosis	Due to propylene glycol used as a solvent
Na/glucose cotransporter 2-inhibitors (dapagliflozin, canagliflozin, empagliflozin)	Ketoacid	Decreased insulin and increased lipolysis, leading to ketoacid formation

Table 15.2

Drugs that cause loss of HCO₃ ⁻ from GI tract or kidney with normal AG

Drug	Source of loss	Mechanism
Acetazolamide	Kidney	Inhibition of carbonic anhydrase (CA) in proximal tubule
Topiramate	Kidney	Inhibition of carbonic anhydrase (CA) in proximal tubule
Cholestyramine	GI tract	Adsorption of HCO₃ in exchange for Cl⁻, causing hyperchloremic metabolic acidosis
Sevelamer HCl	GI tract	Addition of Cl⁻, resulting in hyperchloremic metabolic acidosis
Calcium chloride	GI tract	Loss of HCO₃ ⁻ and gain of Cl⁻

Table 15.3

Drugs that cause proximal RTA with hypokalemia

Drugs	Mechanism
Acetazolamide, topiramate	Inhibition of carbonic anhydrase in proximal tubule and loss of HCO₃ ⁻
Ifosfamide	Proximal tubule toxicity, cell apoptosis and loss of HCO₃ ⁻ (Fanconi syndrome)
Cisplatin, carboplatin, oxaplatin	Proximal tubule toxicity and loss of HCO₃ ⁻ (Fanconi syndrome)
Outdated tetracyclines, aminoglycosides	Interfere with mitochondrial function and proximal tubule toxicity (Fanconi syndrome). Gentamicin reduced the conversion of ADP to ATP, thereby reducing the activity of Na/K-ATPase
Valproic acid	Mitochondrial dysfunction
Adefovir, cidofovir, tenofovir	Mitochondrial dysfunction and Fanconi syndrome