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Psychotherapeutic Medications
Phenothiazines


Depletions
Coenzyme Q10
Mechanism

Cardiac toxicity is a potential side effect of phenothiazine treatment (Deglin et al. 1977; McGee and Alexander 1979). In vitro, phenothiazines inhibited CoQ10-NADH-oxidase and CoQ10-succinate dehydrogenase, two enzymes that are important for cardiac function because they donate electrons to CoQ10 in the mitochondria (Kishi et al. 1980). Inhibiting these enzymes disrupts mitochondrial function and may play a role in the development of cardiotoxic side effects associated with phenothiazines.


Significance of Depletion

Although CoQ10 is manufactured by the body, deficiencies occur in some physiological and pathological conditions (Artuch et al. 1999). CoQ10 deficiency may be related to certain conditions such as gingivitis (Nakamura et al. 1974); breast cancer (Jolliet et al. 1998); congestive heart failure (Munkholm et al. 1999); angina pectoris (Kamikawa et al. 1985); acute myocardial infarction (Singh et al. 1998); mitochondrial encephalomyopathies (Chan et al. 1998); hypertension, and cardiac function (Singh et al. 1999). In addition, CoQ10 depletion may contribute to aging and photoaging (Hoppe et al. 1999). Low levels of CoQ10 may also compromise immune function (Folkers et al. 1993) and play a role in male infertility (Overvad et al. 1999).


Replacement Therapy

Daily doses as high as 200 mg for periods of 6 to 12 months or 100 mg for up to 6 years have not been associated with reports of serious adverse effects in clinical studies (Overvad et al. 1999). The addition of low concentrations of CoQ10 reverses phenothiazine-induced inhibition of CoQ10-NADH-oxidase and CoQ10-succinate dehydrogenase (Chiba 1984; Kishi et al. 1980). CoQ10 treatment may prevent some of the cardiac side effects associated with phenothiazine treatment. More research is needed to confirm these effects.


Vitamin B2 (Riboflavin)
Mechanism

Chlorpromazine promotes riboflavin excretion in animal and human studies (Pinto and Rivlin 1987). This could deplete riboflavin levels in nutritionally compromised patients. This effect has not been reported with promethazine.


Significance of Depletion

Riboflavin deficiency usually occurs as a result of deficiencies in dietary protein and is associated with other B vitamin deficiencies (Covington 1999). Depleted levels of riboflavin affect carbohydrate and amino acid metabolism by interfering with enzyme systems involved in the production of ATP. Lack of an adequate supply of riboflavin disturbs several physiological and biochemical processes and results in retarded growth in infants and children (Covington 1999; Powers 1999). Symptoms include corneal vascularization, glossitis, cheilosis, seborrheic dermatitis, and impaired wound healing (Covington 1999).


Replacement Therapy

Doses of 5 to 25 mg/day are recommended for the treatment of riboflavin deficiency (Covington 1999). For replacement therapy, doses should be based upon the patient's individual needs, considering the clinical presentation, serum riboflavin levels, age, gender, dietary habits, and medication regimen.


Editorial Note

This information is intended to serve as a concise reference for healthcare professionals to identify substances that may be depleted by many commonly prescribed medications. Depletion of these substances depends upon a number of factors including medical history, lifestyle, dietary habits, and duration of treatment with a particular medication. The signs and symptoms associated with deficiency may be nonspecific and could be indicative of clinical conditions other than deficiency. The material presented in these monographs should not in any event be construed as specific instructions for individual patients.


References

Artuch R, Colome C, Vilaseca MA, et al. [Ubiquinone: metabolism and functions. Ubiquinone deficiency and its implications in mitochondrial encephalopathies. Treatment with ubiquinone]. Rev Neurol. 1999;29(1):59-63.

Chan A, Reichmann H, Kogel A, et al. Metabolic changes in patients with mitochondrial myopathies and effects of coenzyme Q10 therapy. J Neurol. 1998;245(10):681-685.

Chiba M. A protective action of coenzyme Q10 on chlorpromazine-induced cell damage in the cultured rat myocardial cells. Jpn Heart J. 1984;25(1):127-137.

Covington T, ed. Nonprescription Drug Therapy Guiding Patient Self-Care. St Louis, MO: Facts and Comparisons; 1999:467-545.

Deglin SM, Deglin JM, Chung EK. Drug-induced cardiovascular diseases. Drugs. 1977;14(1):29-40.

Folkers K, Morita M, McRee J Jr. The activities of coenzyme Q10 and vitamin B6 for immune responses. Biochem Biophys Res Commun. 1993;1:88-92.

Hoppe U, Bergemann J, Diembeck W, et al. Coenzyme Q10, a cutaneous antioxidant and energizer. Biofactors. 1999;9(2-4):371-378.

Jolliet P, Simon N, Barre J, et al. Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther. 1998;36(9):506-509.

Kamikawa T, Kobayashi A, Yamashita T, et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol. 1985;56(4):247-251.

Kishi T, Makino K, Okamoto T, et al. Inhibition of myocardial respiration by psychotherapeutic drugs and prevention by coenzyme Q. Biomedical and Clinical Aspects of Coenzyme Q. Yamamura Y, et al, eds. Elsevier/North-Holland Biomedical Press: Amsterdam. 1980;2:139-154.

McGee JL, Alexander MR. Phenothiazine analgesia-fact or fantasy? Am J Hosp Pharm. 1979;36(5):633-640.

Munkholm H, Hansen HH, Rasmussen K. Coenzyme Q10 treatment in serious heart failure. Biofactors. 1999;9(2-4):285-289.

Nakamura R, Littarru GP, Folkers R, et al. Study of CoQ10-enzymes in gingiva from patients with periodontal disease and evidence for a deficiency of coenzyme Q10. Proc Natl Acad Sci USA. 1974;71(4):1456-1460.

Overvad K, Diamant B, Holm L, Holmer G, Mortensen SA, Stender S. Coenzyme Q10 in health and disease. Eur J Clin Nutr. 1999;53:764-770.

Pinto JT, Rivlin RS. Drugs that promote renal excretion of riboflavin. Drug Nutr Interact. 1987;5(3):143-151.

Powers HJ. Current knowledge concerning optimum nutritional status of riboflavin, niacin and pyridoxine. Proc Nutr Soc. 1999;58(2):435-440.

Singh RB, Niaz MA, Rastogi SS, et al. Effect of hydrosoluble coenzyme Q10 on blood pressure and insulin resistance in hypertensive patients with coronary heart disease. J Hum Hypertens. 1999;13(3):203-208.

Singh RB, Wander GS, Rastogi A, et al. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther. 1998;12(4):347-353.


Copyright © 2000 Integrative Medicine Communications

This publication contains information relating to general principles of medical care that should not in any event be construed as specific instructions for individual patients. The publisher does not accept any responsibility for the accuracy of the information or the consequences arising from the application, use, or misuse of any of the information contained herein, including any injury and/or damage to any person or property as a matter of product liability, negligence, or otherwise. No warranty, expressed or implied, is made in regard to the contents of this material. No claims or endorsements are made for any drugs or compounds currently marketed or in investigative use. The reader is advised to check product information (including package inserts) for changes and new information regarding dosage, precautions, warnings, interactions, and contraindications before administering any drug, herb, or supplement discussed herein.