The mitochondrial disorder is a general term for a group of disorders that can affect many different organs. There is no specific treatment for these disorders, although the symptoms they cause can be treated with medication, surgery, or diet.

One important goal in treating patients with mitochondrial disorders is to avoid medications that are toxic to mitochondrial function.

A medication can affect many different functions in the mitochondria. The mitochondrial respiratory chain (MRС) consists of five enzyme complexes: IV and uses cytochrome c and coenzyme Q10, which act as electron carriers. Pharmacotherapy-induced MRС dysfunction can result from direct inhibition of one or more of the enzyme complexes or from disconnection of oxidative phosphorylation.

Most of the evidence for effects on the mitochondrial disease organism comes from in vitro or preclinical studies. In addition, because of the wide variety of manifestations of mitochondrial disease in different patients, different results can be reported for the same drug.

Drugs to avoid in patients with mitochondrial disease:


Proposed mechanism

Adverse effects related to mitochondrial toxicity


Inhibits MRC I and III and beta oxidation

Pulmonary toxicity, microvesicular steatosis and liver failure

gentamicin, chloramphenicol, tetracycline

Reduces mt protein synthesis

Deafness, renal failure, myopathy

Anti-cancer medicines: doxorubicin, cisplatin

mtDNA mutation


Antipsychotics: haloperidol, risperidone, clozapine

Inhibits MRC I, increases reactive oxygen species, inhibits oxidative phosphorylation

Extrapyramidal symptoms, metabolic syndrome


Inhibits oxidative phosphorylation and beta oxidation

Causes a Reye-like syndrome

Beta-blockers: metoprolol, propranolol

Inhibits MRC I

Case report of muscle wasting


Inhibits MRC I, weak peroxisome proliferator activated receptor ligand

Myopathy and rhabdomyolysis


Inhibit mt membrane potential, generate reactive oxygen species



Inhibits MRC I and V, interferes with cytochrome c

Gastrointestinal damage


Inhibits MRC I


Isoflurane / halothane / sevoflurane

Inhibits MRC I

Hepatotoxicity, neurotoxicity cardiac effects


Inhibits mt protein synthesis

Polyneuropathy and lactic acidosis

Local anaesthetics: bupivicane, lidocaine

Inhibtis MRC V, increases reactive oxygen species, inhibits oxidative phosphorylation



Inhibits MRC I

Causes lactic acidosis


Inhibits respiratory chain


Non-steroidal anti-inflammatory drugs:
ibuprofen, diclofenac, naproxen

Inhibits oxidative phosphorylation and beta oxidation


Nucleoside reverse transcriptase inhibitors:
zidovudine, didanosine, lamivudine, abacavir

mtDNA depletion which then affects all functions

Encephalomyopathy, anaemia, polyneuropathy, pancreatitis and lactic acidosis

Paracetamol (overdose)




Inhibits mt ATPase

Case report of intestinal pseudo obstruction, may cause hepatotoxicity


Inhibits MRC I, weak, peroxisome proliferator activated receptor ligand

Increases anaerobic glycolysis

Propofol (particularly > 4 mg/kg/h for > 48 hours)

Inhibition of free fatty acid entry to mt, beta oxidation

Propofol infusion syndrome: metabolic acidosis, rhabdomyolysis, heart failure, hepatomegaly, asystole


Inhibits MRC I and V, inhibits oxidative phosphorylation


Simvastatin (other statins have weaker effects)

Inhibits MRC I, reduces coenzyme Q10 levels, weak peroxisome proliferator activated receptor ligand

Causes myopathy, rhabdomyolysis

Sodium valproate

Inhibits oxidative phosphorylation, beta-oxidation

Liver failure, hyperammoninaemia, hypoglycaemia, steatosis and encephalopathy

Tricyclic antidepressants:
amitriptyline, clomipramine

Inhibits MRC

Extrapyramidal symptoms, memory impairmentмт - мітохондрії

*Table in alphabetical order, which is not the same as order of importance of the medicines.

mt = mitochondria