Wr report 2/00 (eng)

alcohol. The disulfiram reaction manifests nutritional status. Some modification in itself by headaches, nausea, vomiting, chest interactions could increase or decrease drug action and/or contribute to dietary deficiencies associations will minimize or avoid such is of particular importance in the management of patients receiving medications. The chronic use of drugs requires close monitoring of Drug-Nutrient Interactions of Clinical Relevance
José A. Morais, MD, FRCPC, Assistant Professor of Medicine, McGill University
Table 1: Mechanisms of Drug-Nutrient Interactions
Division of Geriatric Medicine, McGill University Health Centre
prolonged use of medications for the treatmentof chronic conditions and in patients with aborderline nutritional status, e.g. frail elderly persons and patients with inflammatory bowel Introduction
vitamin D. The metabolism of vitamin D in the reduced9, contributing to a higher free plasma
May induce vitamin or mineral deficiencies disease. Polypharmacy is also recognized as liver is altered by the anticonvulsant phenytoin, drug concentration of drugs that are highly being a risk factor for nutrient depletion and is developed to treat many medical conditions leading to decreased calcium absorption and bound to plasma proteins (>90%): lithium, often seen in the elderly14. Table 2 illustrates
and to improve patients’ quality of life.
osteomalacia3. Warfarin, an oral anticoagulant
digoxin, valproate, phenytoin, warfarin, NSAIDS clinically relevant drug-nutrient interactions.
Historically, these active ingredients were that is a vitamin K antagonist, contributes to and ASA . This physiological change allows The choice of the drugs was elicited by the osteoporosis due to the lack of vitamin K more of the drug to diffuse out of the vascular Dietary habits or nutritional deficiencies may alter drug action or toxicity occurring foods1; some of them are still being
stimulation on new bone formation4.
compartment and to reach the drug receptor drug-nutrient interactions seen in clinical sold by the growing market of health-food Acetylsalicylic acid (ASA) overuse is associated practice, especially among elderly persons.
stores. Not surprisingly, drugs share the same with folic acid deficiency, as is methrotrexate by Nutritional status may alter drug distribution & metabolism concentration, the plasma clearance is also inhibition of the dihydrofolate reductase accelerated with decreased therapeutic effect enzyme. Examples of increased nutrient losses interactions responsible for adverse drug are potassium, magnesium and zinc depletion borderline high therapeutic concentrations reactions, known as drug-nutrient interactions.
by diuretics, increased renal calcium excretion biotransformation reactions in the liver are because of severe anorexia with or without The interactions between drugs and nutrients induced by glucocorticoids and iron losses in reduced with malnutrition, especially those nausea and vomiting. This condition is called occur in both directions, i.e., drugs may alter the gastrointestinal tract by NSAIDs.
involving phase II reactions by cytochrome “digitalis cachexia”. The centrally mediated Table 2: Examples of Clinical Relevant Drug-Nutrient Interactions
the nutritional status and dietary habits, or P450 isoenzymes10. Medications that are
effect of SSRIs on appetite suppression is also nutritional deficiencies may alter drug action or Effects of Diet on Drug Bioavailability
eliminated by hepatic metabolism will have Mechanism
Nutrient Affected
toxicity (Table 1). The knowledge of these their half-lives increased with higher risks of malabsorption can be a consequence of the interactions may help health professionals toxicity. This is the case with many drugs, chronic use of colchicine to treat gout because obtain the maximum effect of a drug and avoid gastrointestinal tract. Absorption can be including TAD, neuroleptics, antiarrythmics, etc.
this drug can create a structural defect in the unnecessary side effects that would diminish delayed by the effect of the meal in slowing The opposite effect of a high protein content intestinal mucosa. As already stated, specific and severe mineral depletion is seen with bioavailability. While food usually reduces or isoenzymes, as is the effect of vegetables of the diuretics for potassium, sodium, magnesium, Drugs and General Nutritional Status
delays drug absorption, some drugs’ absorption Brassica family (cabbage, brussels sprouts) will Drugs may alter nutritional status because is promoted with food. This is the case with result in a decreased therapeutic effect of many thiazides). The chronic use of NSAIDs or ASA they can increase or decrease food intake.
medications. Recently, the inhibition of the to treat arthritis is responsible for iron Drugs, such as neuroleptics, benzodiazepines, hydrochlorothiazide and metoprolol. The meal deficiency anemia, induced by blood loss in the tricyclic antidepressants (TAD), can directly content also has an effect on absorption, as attracted attention because of the increased gastrointestinal tract. Specific folate deficiency stimulate the appetite centre in the central with the once-a-day preparation of theophylline therapeutic effect seen with most calcium nervous system leading to weight gain, whereas that is increased by a high-fat meal5. The
channel antagonists (felodipine, nifedipine, opposite effect of a high-fat meal is seen for serotonin-reuptake inhibitors (SSRIs) do the zidovudine, an antiretroviral agent. A high- concentration of other drugs metabolized by opposite2. Weight gain has been observed with
protein meal will also diminish the absorption hypercholesterolemia through binding of bile sulfonylurea drugs used to treat diabetes cholesterol-lowering agents of the statins mellitus (e.g., glyburide). This weight gain is a acids for absorption6. Bioavailability can be
employed to control seizure disorders can alter result of increased insulin secretion by the family, cisapride, midazolam, triazolam and affected by the fiber content of the meal that pancreas. Appetite alterations can also be cyclosporin11.
binds to the drug and decreases its absorption, mechanisms, including inhibition of hepatic SSRIs: Selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline, fluoxamine NSAIDs: Nonsteroidal antiinflammatory drugs, e.g., ibuprofen, indomethacin, naproxen changes in taste perception, as in the case of Incompatibility of Drugs and Nutrients
osteomalacia. The effect of anticonvulsants on lithium, metronidazole and metformin. Any mechanism that decreases the absorption of bone density can be affected by calcium and drug that is responsible for the appearance of drugs is chelation, which consists of the interaction with clear detrimental effects due to gastrointestinal symptoms will contribute to vitamin D supplements. Glucocorticoids are incompatibility of certain drugs and nutrients12.
The Whitehall-Robins Report is a Whitehall-Robins publication that focuses on current issues on the role of vitamins decreased appetite and induce protein-energy drugs with systemic manifestations that are insoluble non-absorbable product. This is the This is the case for the irreversible monoamine and minerals in health promotion and disease prevention. Complimentary copies are distributed to Canadian health malnutrition. Examples of this are dyspepsia, employed in many serious medical conditions.
care professionals active or with a special interest in nutrition. Each issue is written and/or reviewed by independent caused by nonsteroidal antiinflammatory drugs Unfortunately, they also contribute to an array tranylcypromine) with food containing tyramine health care professionals with expertise in the chosen topic. (NSAIDs), constipation induced by narcotics and nausea from theophylline or digitalis electrolyte abnormalities (hypernatremia and effectiveness is compromised when concurrently If you have any comments about the Whitehall-Robins ingested with calcium supplements or dairy accumulates in the body when inhibitors are nitrogen balance, responsible for loss of lean Report or would like to be added to the mailing list, products7.
given to treat depressive mood disorders. Drugs and Mineral and Vitamin Deficiencies
It reaches toxic levels that are responsible for prevented in part with diet counseling and use Nutritional Status Affecting Drug Metabolism
headaches, nausea, vomiting, palpitations, The Editor: The Whitehall-Robins Report, 2000-February. May be reproduced without 5975 Whittle Road, Mississauga, ON L4Z 3M6 permission provided source is recognized.
absorption, by altering their metabolism or by alter drug distribution and metabolism. Drug cerebrovascular accidents. Similar reactions Conclusions
distribution is affected because protein-energy are observed with isoniazid-treated patients REFERENCES 1. Camp J. Magic, Myth and Medicine. New York, Taplinger Publishing Co., 1974. 2. Stock MJ. Sibutramine: a review of the pharmacology of a novel anti-obesity agent. Int J Obes Relat Metab Disord 1997;21(suppl):S25-
medications that increase stomach pH will malnutrition is associated with low body fat 29. 3. Ray JG, Adachi JR. Anticonvulsants and bone disease: a systematic overview of their association and possible preventive strategies. Can J Clin Pharmacol 1998;4:217-223. 4. Heaney RP. Nutritional factors in osteoporosis. Annu
decrease iron absorption by decreasing the rate depots and loss of lean body mass8. This
histamine such as sardinella, skipjack or tuna13.
Rev Nutr 1993;13:287-316. 5. Karim A, Burns T, Janky D, Hurwitz A. Food induced changes in theophylline absorption from controlled release formulations. II. Importance of meal composition and dosing time relative to meal intake
of conversion of ferric iron to its absorbable implies that the volume of distribution for The disulfiram-like reaction is another example in assessing changes in absorption. Clin Pharmcol Ther 1985;38:642-647. 6. Goldin BR, Goldman P. The metabolism of L-dopa: the role of the intestinal microflora. Fed Proc 1973;32:798. 7. The Medical Letter. Ethididronate for
postmenopausal osteoporosis. Vol. 14, No. 19 (M.L. 833), January 11,1991. 8. Shizgal HM. Nutritional assessment with body composition measurements. JPEN 1987;11(suppl):S42-47. 9. Ashton M, Bolme P, Zerihum G, Holmberg K,
ferrous form. Mineral oil, if taken in the water-soluble drugs (digitalis, cimetidine) is of this category of interactions observed when Paalzow LK. Disposition of salicylic acid in malnourished Ethiopian children after single oral dose. Clin Pharmacokinet 1993;25(suppl):S483-494. 10. Mandl J, Banhegyi G, Kalapos MP, Garzo T. Increased oxidation and decreased
postprandial period will reduce absorption of reduced in malnutrition with increased risks of metronidazole, nitrofurantoin, griseofulvin or conjugation of drugs in the liver caused by starvation. Altered metabolism of certain aromatic compounds and acetone. Chemico-Biological Interactions 1995;96:87-101. 11. Bailey DG, Malcom J, Arnold O, Spence JD. Grapefruit juice-
fat-soluble vitamins, including carotenes and side effects. Serum binding proteins are also chlorpropamide are taken in association with drug interactions. Brit J Clin Pharmacol 1998;46:101-110. 12. Roe DA. Interactions between drugs and nutrients. Med Clin N Amer 1979;63:985-1007. 13. Uragoda CG. Histamine poisoning in tuberculous patients after ingestion of
tuna fish. Ann Rev Resp Dis 1980;121:157-160. 14. Steward RB, Cooper JW. Polypharmacy in the aged. Drugs & Aging 1994;9:73-80.
Contains 50% recycled paper including 20% post-consumer fibre alcohol. The disulfiram reaction manifests nutritional status. Some modification in itself by headaches, nausea, vomiting, chest interactions could increase or decrease drug action and/or contribute to dietary deficiencies associations will minimize or avoid such is of particular importance in the management of patients receiving medications. The chronic use of drugs requires close monitoring of Drug-Nutrient Interactions of Clinical Relevance
José A. Morais, MD, FRCPC, Assistant Professor of Medicine, McGill University
Table 1: Mechanisms of Drug-Nutrient Interactions
Division of Geriatric Medicine, McGill University Health Centre
prolonged use of medications for the treatmentof chronic conditions and in patients with aborderline nutritional status, e.g. frail elderly persons and patients with inflammatory bowel Introduction
vitamin D. The metabolism of vitamin D in the reduced9, contributing to a higher free plasma
May induce vitamin or mineral deficiencies disease. Polypharmacy is also recognized as liver is altered by the anticonvulsant phenytoin, drug concentration of drugs that are highly being a risk factor for nutrient depletion and is developed to treat many medical conditions leading to decreased calcium absorption and bound to plasma proteins (>90%): lithium, often seen in the elderly14. Table 2 illustrates
and to improve patients’ quality of life.
osteomalacia3. Warfarin, an oral anticoagulant
digoxin, valproate, phenytoin, warfarin, NSAIDS clinically relevant drug-nutrient interactions.
Historically, these active ingredients were that is a vitamin K antagonist, contributes to and ASA . This physiological change allows The choice of the drugs was elicited by the osteoporosis due to the lack of vitamin K more of the drug to diffuse out of the vascular Dietary habits or nutritional deficiencies may alter drug action or toxicity occurring foods1; some of them are still being
stimulation on new bone formation4.
compartment and to reach the drug receptor drug-nutrient interactions seen in clinical sold by the growing market of health-food Acetylsalicylic acid (ASA) overuse is associated practice, especially among elderly persons.
stores. Not surprisingly, drugs share the same with folic acid deficiency, as is methrotrexate by Nutritional status may alter drug distribution & metabolism concentration, the plasma clearance is also inhibition of the dihydrofolate reductase accelerated with decreased therapeutic effect enzyme. Examples of increased nutrient losses interactions responsible for adverse drug are potassium, magnesium and zinc depletion borderline high therapeutic concentrations reactions, known as drug-nutrient interactions.
by diuretics, increased renal calcium excretion biotransformation reactions in the liver are because of severe anorexia with or without The interactions between drugs and nutrients induced by glucocorticoids and iron losses in reduced with malnutrition, especially those nausea and vomiting. This condition is called occur in both directions, i.e., drugs may alter the gastrointestinal tract by NSAIDs.
involving phase II reactions by cytochrome “digitalis cachexia”. The centrally mediated Table 2: Examples of Clinical Relevant Drug-Nutrient Interactions
the nutritional status and dietary habits, or P450 isoenzymes10. Medications that are
effect of SSRIs on appetite suppression is also nutritional deficiencies may alter drug action or Effects of Diet on Drug Bioavailability
eliminated by hepatic metabolism will have Mechanism
Nutrient Affected
toxicity (Table 1). The knowledge of these their half-lives increased with higher risks of malabsorption can be a consequence of the interactions may help health professionals toxicity. This is the case with many drugs, chronic use of colchicine to treat gout because obtain the maximum effect of a drug and avoid gastrointestinal tract. Absorption can be including TAD, neuroleptics, antiarrythmics, etc.
this drug can create a structural defect in the unnecessary side effects that would diminish delayed by the effect of the meal in slowing The opposite effect of a high protein content intestinal mucosa. As already stated, specific and severe mineral depletion is seen with bioavailability. While food usually reduces or isoenzymes, as is the effect of vegetables of the diuretics for potassium, sodium, magnesium, Drugs and General Nutritional Status
delays drug absorption, some drugs’ absorption Brassica family (cabbage, brussels sprouts) will Drugs may alter nutritional status because is promoted with food. This is the case with result in a decreased therapeutic effect of many thiazides). The chronic use of NSAIDs or ASA they can increase or decrease food intake.
medications. Recently, the inhibition of the to treat arthritis is responsible for iron Drugs, such as neuroleptics, benzodiazepines, hydrochlorothiazide and metoprolol. The meal deficiency anemia, induced by blood loss in the tricyclic antidepressants (TAD), can directly content also has an effect on absorption, as attracted attention because of the increased gastrointestinal tract. Specific folate deficiency stimulate the appetite centre in the central with the once-a-day preparation of theophylline therapeutic effect seen with most calcium nervous system leading to weight gain, whereas that is increased by a high-fat meal5. The
channel antagonists (felodipine, nifedipine, opposite effect of a high-fat meal is seen for serotonin-reuptake inhibitors (SSRIs) do the zidovudine, an antiretroviral agent. A high- concentration of other drugs metabolized by opposite2. Weight gain has been observed with
protein meal will also diminish the absorption hypercholesterolemia through binding of bile sulfonylurea drugs used to treat diabetes cholesterol-lowering agents of the statins mellitus (e.g., glyburide). This weight gain is a acids for absorption6. Bioavailability can be
employed to control seizure disorders can alter result of increased insulin secretion by the family, cisapride, midazolam, triazolam and affected by the fiber content of the meal that pancreas. Appetite alterations can also be cyclosporin11.
binds to the drug and decreases its absorption, mechanisms, including inhibition of hepatic SSRIs: Selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline, fluoxamine NSAIDs: Nonsteroidal antiinflammatory drugs, e.g., ibuprofen, indomethacin, naproxen changes in taste perception, as in the case of Incompatibility of Drugs and Nutrients
osteomalacia. The effect of anticonvulsants on lithium, metronidazole and metformin. Any mechanism that decreases the absorption of bone density can be affected by calcium and drug that is responsible for the appearance of drugs is chelation, which consists of the interaction with clear detrimental effects due to gastrointestinal symptoms will contribute to vitamin D supplements. Glucocorticoids are incompatibility of certain drugs and nutrients12.
The Whitehall-Robins Report is a Whitehall-Robins publication that focuses on current issues on the role of vitamins decreased appetite and induce protein-energy drugs with systemic manifestations that are insoluble non-absorbable product. This is the This is the case for the irreversible monoamine and minerals in health promotion and disease prevention. Complimentary copies are distributed to Canadian health malnutrition. Examples of this are dyspepsia, employed in many serious medical conditions.
care professionals active or with a special interest in nutrition. Each issue is written and/or reviewed by independent caused by nonsteroidal antiinflammatory drugs Unfortunately, they also contribute to an array tranylcypromine) with food containing tyramine health care professionals with expertise in the chosen topic. (NSAIDs), constipation induced by narcotics and nausea from theophylline or digitalis electrolyte abnormalities (hypernatremia and effectiveness is compromised when concurrently If you have any comments about the Whitehall-Robins ingested with calcium supplements or dairy accumulates in the body when inhibitors are nitrogen balance, responsible for loss of lean Report or would like to be added to the mailing list, products7.
given to treat depressive mood disorders. Drugs and Mineral and Vitamin Deficiencies
It reaches toxic levels that are responsible for prevented in part with diet counseling and use Nutritional Status Affecting Drug Metabolism
headaches, nausea, vomiting, palpitations, The Editor: The Whitehall-Robins Report, 2000-February. May be reproduced without 5975 Whittle Road, Mississauga, ON L4Z 3M6 permission provided source is recognized.
absorption, by altering their metabolism or by alter drug distribution and metabolism. Drug cerebrovascular accidents. Similar reactions Conclusions
distribution is affected because protein-energy are observed with isoniazid-treated patients REFERENCES 1. Camp J. Magic, Myth and Medicine. New York, Taplinger Publishing Co., 1974. 2. Stock MJ. Sibutramine: a review of the pharmacology of a novel anti-obesity agent. Int J Obes Relat Metab Disord 1997;21(suppl):S25-
medications that increase stomach pH will malnutrition is associated with low body fat 29. 3. Ray JG, Adachi JR. Anticonvulsants and bone disease: a systematic overview of their association and possible preventive strategies. Can J Clin Pharmacol 1998;4:217-223. 4. Heaney RP. Nutritional factors in osteoporosis. Annu
decrease iron absorption by decreasing the rate depots and loss of lean body mass8. This
histamine such as sardinella, skipjack or tuna13.
Rev Nutr 1993;13:287-316. 5. Karim A, Burns T, Janky D, Hurwitz A. Food induced changes in theophylline absorption from controlled release formulations. II. Importance of meal composition and dosing time relative to meal intake
of conversion of ferric iron to its absorbable implies that the volume of distribution for The disulfiram-like reaction is another example in assessing changes in absorption. Clin Pharmcol Ther 1985;38:642-647. 6. Goldin BR, Goldman P. The metabolism of L-dopa: the role of the intestinal microflora. Fed Proc 1973;32:798. 7. The Medical Letter. Ethididronate for
postmenopausal osteoporosis. Vol. 14, No. 19 (M.L. 833), January 11,1991. 8. Shizgal HM. Nutritional assessment with body composition measurements. JPEN 1987;11(suppl):S42-47. 9. Ashton M, Bolme P, Zerihum G, Holmberg K,
ferrous form. Mineral oil, if taken in the water-soluble drugs (digitalis, cimetidine) is of this category of interactions observed when Paalzow LK. Disposition of salicylic acid in malnourished Ethiopian children after single oral dose. Clin Pharmacokinet 1993;25(suppl):S483-494. 10. Mandl J, Banhegyi G, Kalapos MP, Garzo T. Increased oxidation and decreased
postprandial period will reduce absorption of reduced in malnutrition with increased risks of metronidazole, nitrofurantoin, griseofulvin or conjugation of drugs in the liver caused by starvation. Altered metabolism of certain aromatic compounds and acetone. Chemico-Biological Interactions 1995;96:87-101. 11. Bailey DG, Malcom J, Arnold O, Spence JD. Grapefruit juice-
fat-soluble vitamins, including carotenes and side effects. Serum binding proteins are also chlorpropamide are taken in association with drug interactions. Brit J Clin Pharmacol 1998;46:101-110. 12. Roe DA. Interactions between drugs and nutrients. Med Clin N Amer 1979;63:985-1007. 13. Uragoda CG. Histamine poisoning in tuberculous patients after ingestion of
tuna fish. Ann Rev Resp Dis 1980;121:157-160. 14. Steward RB, Cooper JW. Polypharmacy in the aged. Drugs & Aging 1994;9:73-80.
Contains 50% recycled paper including 20% post-consumer fibre

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