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Unformatted text preview: NUTRIENT- DRUG NUTRIENTINTERACTIONS INTERACTIONS DR. V. Jagadeesan Former Deputy Director ( Sr . Gr . ) Food and Drug Toxicology Research Institute National Institute of Nutrition Hyderabad 1. McCabe BJ, Frankel EH &Wolfe ,JJ: Handbook of Food­Drug Interactions 2. Boullata JI, ArmentiVT &Malone . M : Handbook of Drug – Nutrient Interactions 1 CATEGORIES Drugs affecting nutritional status Drug Food incompatibilities Drug –alcohol interactions 2 Most drug –nutrient interactions involve food interfering with drugs rather than drugs interfering with nutrient status . 3 EXAMPLES • Effectiveness of warfarin , an anticoagulant is reduced when Vitamin K –rich foods are consumed . • Children with seizure disorders may come to suffer from rickets , secondary to drug interference with vitamin D and Ca status • It may also cause B6, B12, or riboflavin deficiencies Symptoms of drug interference with nutrient status may be very slow or gradual – almost going unnoticed . 4 CONTD …. Drug influences on nutrient status are less obvious because nutrient deficiencies symptoms are not specific and may be attributed to primary disease effects . More likely in individuals with nutrient inadequacy. Some drug metabolism requires micronutrients and therapy with these drugs places a greater demand on adequate intake . Without adequate nutrition , drug clearance may also be slowed . NIN Studies are to the contrary. 5 CLINICAL DRUG TRIALS For efficacy and safety of a drug are usually done on a short term basis only with a small no . of subjects ( approx. 30­80 )and often in a fasting state. Assessments of nutritional status is not done usually, unless the exptl drug or drug combination is considered a nutrient per se , such as vitamin E and selenium supplements as a combination in cancer treatment With no baseline nutritional data, small and gradual changes in nutritional status is unlikely to be detected , until the drug is there for a long time in the market . 6 POINTER Using formula feeding adequate in all nutrients or carrying out drug trials in healthy volunteers does not reflect ground realities . 7 MECHANISMS BY WHICH DRUG GROUPS MECHANISMS CAN INDUCE NUTRIENT DEPLETION METABOLICALLY AND PHYSIOLOGICALLY METABOLICALLY Mechanism Malabsorption Nutrient Folate B12 A Beta carotene Drug Groups Anticonvulsants Anti inflammatories (Sulfasalzine,Azufidine) Bile acid sequestrants Biguanides Antihyperlipidemics Clofibrate Salicylates Aluminium Preparations Competitive Binding Folate Thiamine Antacids Potassium Magnesium Phosphates Folate B6 B12 Inhibition of coenzyme biosynthesis B6 antagonists Antituberculars (perithiamine), antineoplastics (Cytarabine), folate antagonists 8 Methotraxate, nitrous oxide MECHANISMS BY WHICH DRUG GROUPS MECHANISMS CAN INDUCE NUTRIENT DEPLETION METABOLICALLY AND PHYSIOLOGICALLY METABOLICALLY Mechanism Selective action on apoor holoenzyme Hyperexcretion by kidneys Nutrient B6 Drug Groups Contraceptive steroids, hypotensives(hydralazine, serpasil ) Glucocorticoids Antiarthritics (Indomethacin ) Diuretics (Lasix ) B6 and folate antagonists Anticonvulsants (phenytoin,PB) H2 Inhibitors (Cimetidine) 9 Ascorbic acid Potassium Aminoacids Magnesium Zinc FolateB6 D K Non heme iron B12 Increased turnover especially in children Changes pH in GIT MAJOR DRUG –INDUCED MAJOR MALNUTRITION MALNUTRITION Drugs may induce nutrient deficiencies in several unusual circumstances. Deficiencies that are rarely seen due to inadequate diets ( pyridoxine deficiency ) Slow and gradual storage deficiencies Unusual and complex nutrient deficiencies such as Vitamin D or folate in anti convulsant therapy Either single or multivitamin deficiencies . Mineral imbalances secondary to increased urinary excretion 10 e.g, Reasons : Marginal intake or marginal synthesis Physiological stress increased nutrient requirement s secondary to a particular disease state,. Last, but not the least , decreased absorption of nutrients 11 NUTRIENTS COMMONLY NUTRIENTS AFFECTED BY DRUGS AFFECTED B12 , because its digestion , absorption and utilisation can be impacted at several points and by multiple drugs and conditions B vitamins, in general secondary to initial low body stores leading to early depletion Iron and other nutrients important in red cell production Calcium and Vitamin D important to maintenance of healthy bones in adults and avoidance of rickets in children 12 FOLATE AND PYRIDOXINE FOLATE ANTAGONISTS ANTAGONISTS DRUGS THAT WORK BY INTERFERING WITH METABOLIC PATHWAYS DEPENDENT ON FOLATE AND B6 AS COENZYMES Major attention has recently been placed on drug induced deficiencies of folate, thiamine and protein . The multiple mechanisms by which folate and pyridoxine status can be impacted are as follows : 13 FOLATE AND PYRIDOXINE FOLATE ANTAGONISTS ANTAGONISTS GENERAL CLASSIFICATION PYRIDOXINE ANTAGONISTS MAY REQUIRE B6 SUPPLEMENTATION OR RICH FOOD SOURCES Antiarthritics Antineoplastics Antituberculins Hypotensives Antiparkinsonism GENERIC NAME PRODUCT NAME Penicillamine Cytarabine Isoniazid Hydralazine Levodopa Cupramine Cytosar INH Serpasil Lardopa, Sinemet 14 FOLATE AND PYRIDOXINE FOLATE ANTAGONISTS ANTAGONISTS GENERAL CLASSIFICATION FOLATE ANTAGONISTS MAY REQUIRESUPPLEMENTATIO N OR SPECIAL FORTIFIED FOODS Anti Neoplastics Anti inflammatories Antituberculars Alcohol Immunosuppresants GENERIC NAME PRODUCT NAME Methotrexate Sulfasalzine Pyrimathamine Ethyl alcohol Azatioprine Mexate Azulidine Daraprim Imuran 15 ADDL INFORMATION Lack of dietary folate or drugs interfering with folate or both can lower Vitamin B12 status The widespread use of certain cardiovascular drugs leads to poor thiamine status 16 CLINICAL SYMPTOMS Most common symptoms associated with drug influences on nutritional status may well be commonly occurring symptoms like dry mouth, nausea, vomiting , constipation or diarrhea that discourage the intake of food . These are indirect influences of the drug which enhances the disease state , but not the effect of the drug itself. It is therefore important to identify the use of drugs that may interfere with nutrient status when monitoring nutrient status . A diet history needs to be recorded especially during chronic usage of drugs . 17 ALCOHOL INTAKE ALCOHOL Acute or chronic alcohol intake may lead to lower or elevated drug levels lower or elevated plasma levels of glucose depletion of vitamins and minerals A potent depressant substance 18 PHYSICAL EXAMINATION FOR PHYSICAL DRUG INDUCED MALNUTRITION DRUG MALABSORPTION Use of laxatives (Dulcolex or mineral oil ) decrease GI time Gastric antacid products(Al,Mg hydroxides) change of pH to decrease absorption of folate. transit Drugs for Git disorders like ulcerative colitis. decrease hydrolysis of dietary folate poly glutamate , contributing to dietary folate deficiency 19 ANEMIA B12 def.—Pernicious Anemia folate antagonists – Secondary B12 def Single mineral nutrient supple. Like Iron may cause imbance –competition for other minerals causing relative def. Ex. Zn supplements cause copper def . 20 NEUROPATHIES Drug induced imbalances in B6 or B12 can cause neuropathies Other B­ vitamin deficiencies especially B2 can affect B6 status and lead to clinical signs like stomatitis, cheilosis , glossitis, irritability, depression and confusion 21 DRUGS AND CONDITIONS THAT MAY INTERFERE DRUGS WITH RIBOFLAVIN ABSORPTION OR METABOLISM: ENCOURAGE MILK PRODUCTS OR SUPPLEMENT USE ENCOURAGE DRUG CLASS ODR CONDITION Anticonvulsants Antimalarial Anti neoplastic Bile acid sequesterants Psychotropic Adrenal Insuff. Diarrheal Dis. Thyroid Disorder 22 GENERIC NAME PB(long term ) Quinacrine Adriamycin Cholestyramine ( severe diarrhea) Chlorpromazine BRAND NAME Luminol Questran Thorazine OTHER CONDITIONS Bone Diseases Anti tuberculars, (osteomalasia in adults & Anticonvulsants rickets in Children ) antilipedemics Interference in the uptake of Vitamin D, vitamin K GIT diseases Almost all drugs Anorexia, dry mouth, nausea, vomiting Chronic diseases Drugs given for cancer, obstructive pulmonary disease 23 SIDE EFFECTS AND IMPACT ON SIDE DIETARY INTAKE BY DRUGS DIETARY Adequate intakes of energy and protein are necessary for the optimal usage of drugs Therapeutic drugs for treatment of diseases may cause nutrient def. states that need to be minimised or corrected Another general guideline is to take medications with appropriate fluid to prevent or minimise side effects , including damage to mucosal linings of GIT . 24 CHRONIC DRUG THERAPY AND NUTRIENT CHRONIC SUPPLEMENTATION IN THE ELDERLY SUPPLEMENTATION DRUG Antacids Aspirin Chloretetracycline Colestipol Estrogens/Progestins Hydralazine hydrochloride Phenothiazones Phenytoin Rifampin Sulfasalzine Tetracycline SUPPLEMENT(S) Folic acid, B12 ( if necessary ) Folic acid, iron , vitamin C Ca, Vitamin C, riboflavin Vit.A,D,E,K, Folic acid, Ca. B6, folicacid B6 B2 Folic acid , D, K, Ca. B6, niacin, vitamin D Folic acid Ca, riboflavin, vitamin D 25 Thank You ! 26 ...
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This note was uploaded on 10/07/2010 for the course DBT 456 taught by Professor Ss during the Spring '10 term at Indian Institute of Technology, Guwahati.

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