Table of Reported Drugs with Mitochondrial Toxicity

Pharmacologic Category 1. Anticonvulsants Toxin Action Sequesters carnitine; decreases fatty acid oxidation, Krebs, ETC activity and oxidativephosphorylation; complex IV inhibition Causes autonomic dysfunction Symptoms

Valproate (Depakote)

Hepatopathy

2. Psychotropic a. Antidepressants

Amitriptyline (Elavil) Amoxapine Fluoxetine (Prozac) Citalopram (Cipramil) Chlorpromazine (Thorazine) Fluphenazine (Prolixin) Haloperidol (Haldol) Resperidone (Risperdol) Phenobarbital Secobarbital (Seconal) Butalbital (Fiorinal) Amobarbital (Amytal) Pentobarbital (Nembutal)

b. Antipsychotics

c. Barbituates

Reduces mito protein synthesis; dec # and size of mitochondria Inhibits NADH dehydrogenase (complex I)

d. Anxiety meds 4. Cholesterol meds

Alprazolam (Xanax) Diazepam (Valium, Diastat) Statins Bile acids-cholestyramine Ciprofibrate Reduce endogenous coenzyme Q10 Myopathy Inhibits ETC Inhibits complex I

Table of Reported Drugs with Mitochondrial Toxicity

Fenofibrate 5. Analgesic/antiinflammatory ASA (Aspirin) Acetaminophen (Tylenol) Indomethacin (Indocin) Naproxen (Aleve) Diclofenac 6. Antibiotics Tetracycline, minocycline Chloramphenical Aminoglycosides Linezolid (Zyvox) 7. Anti-arrhythmic 8. Steroids 9. Anti-viral Interferon Amiodarone Inhibits beta-oxidation Reduce transmembrane mito potential Impairs mtDNA transcription Impairs mtDNA replication which causes mtDNA depletion; decreases complex I and IV activity Carnitine deficiency; lactic acidosis; lipodystrophy; neuropathy; myopathy; hypatic dysfunction Hearing loss; cardiac toxicity; renal toxicity Reports of deterioration in Kearns-Sayre syndrome Inhibits ETC and uncouples oxidative-phosphorylation Increases oxidative stress Reye syndrome (hepatic failure) Hepatopathy

Inhibit beta-oxidation; inhibit mito protein synthesis Inhibits mito protein synthesis Impair mtDNA translation Hearing loss; cardiac toxicity; renal toxicity Lactic acidosis, optic and peripheral neuropathy

10. Anti-retroviral

Zidovudine

11. Cancer meds

Doxorubicine (Adriamycin) Cis-platinum Tamoxifen Impairs mtDNA transcription

Table of Reported Drugs with Mitochondrial Toxicity

12. Diabetes meds 13. Beta-blockers 14. Immunizations

Metformin

Inhibits oxidative-phosphorylation; enhanced glycolysis Causes oxidative stress No scientific data on oxidativephosphorylation adverse effects

Lactic acidosis Decreased exercise tolerance