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Nutrition and Drugs Identifying the Issues

Drug Nutrient Interactions Pharmacological, Physical and Pharmacokinetic Rebecca White Lead Pharmacist; Surgery, GI & Nutrition John Radcliffe Hospital, Oxford. Nutrition and Drugs Identifying the Issues. Drug effects on nutritional intake Drug effects on nutrient metabolism

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Nutrition and Drugs Identifying the Issues

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  1. Drug Nutrient InteractionsPharmacological, Physical and PharmacokineticRebecca WhiteLead Pharmacist; Surgery, GI & NutritionJohn Radcliffe Hospital, Oxford

  2. Nutrition and DrugsIdentifying the Issues • Drug effects on nutritional intake • Drug effects on nutrient metabolism • Nutrient effects on drug metabolism • Drug administration via enteral feeding tubes • Practical administration • Equipment, formulation choice • Physical Interactions • Pharmacokinetics interactions • Legal considerations

  3. Drug administration via enteral feeding tubes… …a multidisciplinary problem The Dietitian…wants to ensure the patient is receiving the full volume of feed prescribed The Pharmacist…wants to make sure the drugs are administered safely and at effective doses The Doctor…wants the drug to work and doesn’t want to have to replace the tube The Nurse…has to administer the medicine and feed without harming the patient or themselves The Patient…needs their feed and their medication and may need to be independent

  4. Side Effects of Drugs Influence on Nutrient Intake • Reduced Gastric Emptying • Paralysing Agents, Anticholinergics, Opiates • Increased Gastric Emptying • Metoclopramide, Erythromycin, Cisapride • Anorexia • Taste disturbance

  5. Drug Effects on Nutrient Metabolism

  6. Folate • Folic acid is involved in DNA synthesis • Deficiency causes: • Megaloblastic anaemia • Diarrhoea • Folate metabolism Dihydrofolate reductase (DHFR) Tetrahydrofolate Folic Acid Dihydrofolate

  7. Folate Deficiency • DHFR Inhibitors • Methotrexate • Trimetrexate • Pentamidine • Proguanil • Pyrimethamine • Trimethoprim • Triamterene • Impaired Absorption or • Utilisation • Alcohol • Metformin • Nitrofurantoin • O.C.P • Phenobarbitone • Phenytoin (Carl, 1992) • Primidone • Sulphasalazine (Pironi, 1988)

  8. Thiamine (Vitamin B1) • Deficiency causes Beri Beri • Lactic acidosis, cardiovascular, cerebral and peripheral neurological impairment • Drugs associated with thiamine deficiency • Frusemide (Seligmann et al, 1991)

  9. Pyridoxine • Co-factor for the transaminases and for decarboxylation of amino acids • Deficiency causes: • Peripheral neuropathy • Dermatitis and rough skin • Irritability • Hypochromic anaemia • Glossitis

  10. Pyridoxine Deficiency • Isoniazid • Phenelzine • Penicillamine • Oral contraceptive pill • Hydralazine • Phenytoin • Theophylline (Delport et al, 1988)

  11. Effect of Nutrition on Drug Pharmacokinetics • Malnutrition • Low plasma proteins • Altered protein binding • Increased volume of distribution • Reduced hepatic enzyme function • Nutrition composition

  12. Drug Administration via Feeding Tubes

  13. Before administering a drug via a feeding tube…...things to consider • Is this drug needed at all? • Can I administer it via any other route? • Does it come in a suitable formulation for administering down a tube? • If not, can I crush the tablet/open capsule? • Does it interact with the enteral feed? • Is the drug absorbed from where it is being delivered to?

  14. Choice of formulation • Solution • Syrup • Suspension • Soluble tablet • Effervescent tablet • Dispersible tablet

  15. Factors Affecting Drug & Formulation • Tube Blockage • GI side effects • Pharmacokinetics

  16. Tube Blockage • Bore size of Tube • Feed related • Inadequate flushing • Warm water flushes • Pancreatic enzyme locking (Sriram, 1997) • Drug related • Medication significant cause of tube blockage (Marcuard & Stegall, 1990) • Inappropriate formulations • Physical Interactions • Sucralfate (Aggozzine et al, 1983) • Aluminium binds to protein to form insoluble complex (bezoar). • High electrolyte containing solutions

  17. GI Side effects • GI Side effects (Edes, 1990) • Not all liquids are suitable • Osmolality (Dickerson & Melnik, 1988) • pH • Viscosity • Sorbitol Content (Greenwood, 1989) • Kay-Cee-L liquid • Baclofen liquid

  18. Pharmacokinetics • Changing between formulations of the same drug • Bioavailability • Dosing Frequency • Exit point of feeding tube • Site of absorption of drug • Significant for Phenytoin (Rodman et al, 1998) and Ketoconazole (Adams, 1994)

  19. Drug Interactions • Phenytoin (Bauer, 1982; Summers & Grant,1989) • Enteral feed reduces drug absorption by 75% • Theophylline (Gal &Layson, 1986) • Interaction poorly defined and very variable • Warfarin (Petretich, 1990) • Binds to protein in enteral feed. Be aware of variable vitamin K intake

  20. Drug Interactions • Ciprofloxacin (Mueller et al, 1994) • Binds to divalent ions. Absorption reduced by 30%. Peak levels reduced by up to 50% • Tetracyclines • Absorption reduced by 70-80% in the presence of milk or dairy products • Stop feed 1 hour before and after feed? • Rifampicin • Absorption reduced by food • Give during break in feed to maximise absorption

  21. Practical Solutions • Simplify drug choice to once daily preparations with long half lives • Document feeding and drug regimen accurately • Avoid frequent changes in feeding regimen and drug regimen • Stabilise regimen at earliest opportunity

  22. Clinical Monitoring • Very little information relating to clinical significance of interactions • No data for most drugs • Clear monitoring parameters

  23. Information Available Available from www.bapen.org.uk

  24. Summary • Broad range of complex interactions • Range of clinical outcomes • Requires multidisciplinary input • Correct identification of issues • Use of correct formulation • Practical application of pharmaceutical and clinical skills

  25. References • White.R, Ashworth.A. (2000) How drug therapy can affect, threaten and compromise nutritional status. Journal of Human Nutrition and Dietetics 13(2):119-129 • Adams.D (1994) Administration of drugs through a jejunostomy tube. Br.J. Int.Care 4:10-17 • Thompson.F.C, Naysmith.M.R, Lindsay.A (2000) Managing drug therapy in patients receiving enteral and parenteral nutrition. Hospital Pharmacist 7(6):155-164 • Boullata.J.I, Armenti.V.T (2004) Handbook of drug-nutrient interactions. Humana Press, NJ, USA • www.NPSA.nhs.uk • www.BAPEN.org.uk • BPNG Handbook of Drug Administration via Enteral Feeding Tubes (2006), Pharmaceutical Press, (in press)

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