A large number of drugs, including antibiotics, aspirin, NSAIDS,
antidepressants, statins, cannabis, amphetamines, cocaine, heroin,
morphine, and antidepressants may impair mitochondrial oxidative
phosphorylation (1-14). It is very likely that the effects of many of
theses substances are additive when administered together, the most
serious damage likely to be inflicted not only by individual substances
taken in abnormally large amounts but also by the mixing of different
substances taken in normal amounts (15). Different doses have different
effects. In the case of alcohol, the most extensively studied, a binge may
induce massive mitochondrial damage (16). Chronic consumption in moderate
amounts, on the other hand, may increase the efficiency of oxidative
phosphorylation (17) and abstinence may reverse the mitochondrial damage
done (18).
An impairment of mitochondrial oxidative phosphorylation appears to
be the cause of most organ dysfunctions and failures in the acutely ill
(19,20) and probably in the chronically ill (21-28). It is very likely,
therefore, that many of the medications that are being administered for
the management of chronic illnesses and taken for recreational purposes
increase the risk of developing organ dysfunctions and failures in acute
illnesses and the risk of developing chronic illnesses such as
neurodegenerative disorders and chronic heart failure.
1. Fosslien E. Mitochondrial medicine--molecular pathology of
defective oxidative phosphorylation. Ann Clin Lab Sci. 2001 Jan;31(1):25-
67. Review
2. Yamanouchi H, Imataka G. Mitochondrial diseases due to drug toxicity
Nippon Rinsho. 2002 Apr;60 Suppl 4:473-7. Review.
3. Szewczyk A, Wojtczak L. Mitochondria as a pharmacological target.
Pharmacol Rev. 2002 Mar;54(1):101-27. Review.
4. Cormier A, Morin C, Zini R, Tillement JP, Lagrue G. In vitro effects of
nicotine on mitochondrial respiration and superoxide anion generation.
Brain Res. 2001 May 4;900(1):72-9.
5. Berson A, Fau D, Fornacciari R, Degove-Goddard P, Sutton A, Descatoire
V, Haouzi D, Letteron P, Moreau A, Feldmann G, Pessayre D. Mechanisms for
experimental buprenorphine hepatotoxicity: major role of mitochondrial
dysfunction versus metabolic activation. J Hepatol. 2001 Feb;34(2):261-9.
6. Boess F, Ndikum-Moffor FM, Boelsterli UA, Roberts SM. Effects of
cocaine and its oxidative metabolites on mitochondrial respiration and
generation of reactive oxygen species. Biochem Pharmacol. 2000 Sep
1;60(5):615-23.
7. Muscari C, Bastagli L, Ventura C, Bernardi P, Caldarera CM. Reduction
of the rate of mitochondrial respiration in the rat heart perfused with
opioids and naloxone Cardiologia. 1988 Apr;33(4):353-7.
8. Das NP, Ratty AK. Studies on the effects of the narcotic alkaloids,
cocaine, morphine, and codeine on nonenzymatic lipid peroxidation in rat
brain mitochondria. Biochem Med Metab Biol. 1987 Apr;37(2):258-64.
9. Chari-Briton A. Proceedings: Swelling of rat liver mitochondria
induced by delta1-tetrahydrocannabinol. Isr J Med Sci. 1975
Nov;11(11):1189.
10. Bailey SM, Cunningham CC. Contribution of mitochondria to oxidative
stress associated with alcoholic liver disease. Free Radic Biol Med. 2002
Jan 1;32(1):11-6. Review.
11. Cunningham CC, Bailey SM. Ethanol consumption and liver mitochondria
function.
Biol Signals Recept. 2001 May-Aug;10(3-4):271-82. Review
12. Goodlett CR, Horn KH. Mechanisms of alcohol-induced damage to the
developing nervous system.
Alcohol Res Health. 2001;25(3):175-84. Review.
13. Burrows KB, Gudelsky G, Yamamoto BK. Rapid and transient inhibition
of mitochondrial function following methamphetamine or 3,4-
methylenedioxymethamphetamine administration. Eur J Pharmacol. 2000 Jun
9;398(1):11-8.
15. Fiddian-Green RG. The real danger is in the mixing?
bmj.com/cgi/eletters/325/7367/736/c#26113, 7 Oct 2002
16. Mansouri A, Gaou I, De Kerguenec C, Amsellem S, Haouzi D, Berson A,
Moreau A, Feldmann G, Letteron P, Pessayre D, Fromenty B. An alcoholic
binge causes massive degradation of hepatic mitochondrial DNA in mice.
Gastroenterology. 1999 Jul;117(1):181-90.
17. Piquet MA, Nogueira V, Devin A, Sibille B, Filippi C, Fontaine E,
Roulet M, Rigoulet M, Leverve XM. Chronic ethanol ingestion increases
efficiency of oxidative phosphorylation in rat liver mitochondria. FEBS
Lett. 2000 Feb 25;468(2-3):239-42.
18. Addolorato G, Capristo E, Greco AV, Caputo F, Stefanini GF,
Gasbarrini G. Three months of abstinence from alcohol normalizes energy
expenditure and substrate oxidation in alcoholics: a longitudinal study.
Am J Gastroenterol. 1998 Dec;93(12):2476-81.
Rapid Response:
Do medications make patients better or worse?
A large number of drugs, including antibiotics, aspirin, NSAIDS,
antidepressants, statins, cannabis, amphetamines, cocaine, heroin,
morphine, and antidepressants may impair mitochondrial oxidative
phosphorylation (1-14). It is very likely that the effects of many of
theses substances are additive when administered together, the most
serious damage likely to be inflicted not only by individual substances
taken in abnormally large amounts but also by the mixing of different
substances taken in normal amounts (15). Different doses have different
effects. In the case of alcohol, the most extensively studied, a binge may
induce massive mitochondrial damage (16). Chronic consumption in moderate
amounts, on the other hand, may increase the efficiency of oxidative
phosphorylation (17) and abstinence may reverse the mitochondrial damage
done (18).
An impairment of mitochondrial oxidative phosphorylation appears to
be the cause of most organ dysfunctions and failures in the acutely ill
(19,20) and probably in the chronically ill (21-28). It is very likely,
therefore, that many of the medications that are being administered for
the management of chronic illnesses and taken for recreational purposes
increase the risk of developing organ dysfunctions and failures in acute
illnesses and the risk of developing chronic illnesses such as
neurodegenerative disorders and chronic heart failure.
1. Fosslien E. Mitochondrial medicine--molecular pathology of
defective oxidative phosphorylation. Ann Clin Lab Sci. 2001 Jan;31(1):25-
67. Review
2. Yamanouchi H, Imataka G. Mitochondrial diseases due to drug toxicity
Nippon Rinsho. 2002 Apr;60 Suppl 4:473-7. Review.
3. Szewczyk A, Wojtczak L. Mitochondria as a pharmacological target.
Pharmacol Rev. 2002 Mar;54(1):101-27. Review.
4. Cormier A, Morin C, Zini R, Tillement JP, Lagrue G. In vitro effects of
nicotine on mitochondrial respiration and superoxide anion generation.
Brain Res. 2001 May 4;900(1):72-9.
5. Berson A, Fau D, Fornacciari R, Degove-Goddard P, Sutton A, Descatoire
V, Haouzi D, Letteron P, Moreau A, Feldmann G, Pessayre D. Mechanisms for
experimental buprenorphine hepatotoxicity: major role of mitochondrial
dysfunction versus metabolic activation. J Hepatol. 2001 Feb;34(2):261-9.
6. Boess F, Ndikum-Moffor FM, Boelsterli UA, Roberts SM. Effects of
cocaine and its oxidative metabolites on mitochondrial respiration and
generation of reactive oxygen species. Biochem Pharmacol. 2000 Sep
1;60(5):615-23.
7. Muscari C, Bastagli L, Ventura C, Bernardi P, Caldarera CM. Reduction
of the rate of mitochondrial respiration in the rat heart perfused with
opioids and naloxone Cardiologia. 1988 Apr;33(4):353-7.
8. Das NP, Ratty AK. Studies on the effects of the narcotic alkaloids,
cocaine, morphine, and codeine on nonenzymatic lipid peroxidation in rat
brain mitochondria. Biochem Med Metab Biol. 1987 Apr;37(2):258-64.
9. Chari-Briton A. Proceedings: Swelling of rat liver mitochondria
induced by delta1-tetrahydrocannabinol. Isr J Med Sci. 1975
Nov;11(11):1189.
10. Bailey SM, Cunningham CC. Contribution of mitochondria to oxidative
stress associated with alcoholic liver disease. Free Radic Biol Med. 2002
Jan 1;32(1):11-6. Review.
11. Cunningham CC, Bailey SM. Ethanol consumption and liver mitochondria
function.
Biol Signals Recept. 2001 May-Aug;10(3-4):271-82. Review
12. Goodlett CR, Horn KH. Mechanisms of alcohol-induced damage to the
developing nervous system.
Alcohol Res Health. 2001;25(3):175-84. Review.
13. Burrows KB, Gudelsky G, Yamamoto BK. Rapid and transient inhibition
of mitochondrial function following methamphetamine or 3,4-
methylenedioxymethamphetamine administration. Eur J Pharmacol. 2000 Jun
9;398(1):11-8.
14. Fiddian-Green RG. Concerns about prescribing antidepressants
bmj.com/cgi/eletters/325/7366/701#25874, 28 Sep 2002
15. Fiddian-Green RG. The real danger is in the mixing?
bmj.com/cgi/eletters/325/7367/736/c#26113, 7 Oct 2002
16. Mansouri A, Gaou I, De Kerguenec C, Amsellem S, Haouzi D, Berson A,
Moreau A, Feldmann G, Letteron P, Pessayre D, Fromenty B. An alcoholic
binge causes massive degradation of hepatic mitochondrial DNA in mice.
Gastroenterology. 1999 Jul;117(1):181-90.
17. Piquet MA, Nogueira V, Devin A, Sibille B, Filippi C, Fontaine E,
Roulet M, Rigoulet M, Leverve XM. Chronic ethanol ingestion increases
efficiency of oxidative phosphorylation in rat liver mitochondria. FEBS
Lett. 2000 Feb 25;468(2-3):239-42.
18. Addolorato G, Capristo E, Greco AV, Caputo F, Stefanini GF,
Gasbarrini G. Three months of abstinence from alcohol normalizes energy
expenditure and substrate oxidation in alcoholics: a longitudinal study.
Am J Gastroenterol. 1998 Dec;93(12):2476-81.
19. Fiddian-Green RG. Gastric intramucosal pH, tissue oxygenation and
acid-base balance. Br J Anaesth. 1995 May;74(5):591-606. Review.
20. Fiddian-Green RG. Monitoring of tissue pH: the critical measurement.
Chest. 1999 Dec;116(6):1839-41.
21. Fiddian-Green RG. Haemodynamic and/or tonometric monitoring in
cardiac surgery.
Br J Anaesth. 2000 Jan;84(1):128.
22. Iatrogenic diseases with a common cause?
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7370/913#26512, 25 Oct 2002
23. Depression: a metabolic perspective.
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7370/934#26529, 26 Oct 2002
24. Beta blockers and the risk of neurodegenerative disorders
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7369/873#26451, 22 Oct 2002
25. Coenzyme Q vs levodopa for Parkinson's
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7369/851#26420, 21 Oct 2002
26. Headaches and cerebral tissue oxygenation
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7369/881#26368, 18 Oct 2002
27. Might statins cause Parkinsons?
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7369/851#26356, 18 Oct 2002
28. Fiddian-Green RG. Iatrogenic diseases with a common cause?
bmj.com, 25 Oct 2002
Competing interests:
None declared
Competing interests: No competing interests