nutrient drug interactions · 2013-09-08 · nutrient drug interactions effects of nutrition on...

ESPEN Congress Brussels 2005

Nutrient Drug InteractionsEffects of Nutrition on Pharmacokinetics

and Pharmacodynamics of Drugs

Rebecca White

Nutrient Drug Interactions

Effects of Nutrition on Pharmacokinetics and

Pharmacodynamics of Drugs

Rebecca WhiteLead Pharmacist; Nutrition & Surgery

Oxford Radcliffe Hospitals, UK

Drug Nutrient Interaction

A pysico-chemical, physiological or pathophysiological process that alters disposition, function or toxicity of a food component or drug

• Absorption

• Distribution

• Metabolism

• Elimination

Absorption

Physiological Changes• Gut transit time• Intraluminal pH• Increased splanchnic blood flow• Decreased portal blood flow• Bile salt production• Competing or interfering with active

transport mechanisms

Absorption

Physico-chemical• Interaction affecting drug and feed physical

properties• Chelation

– Quinolones– Tetracyclines

• Binding to dietary substances– Protein– Fibre/pectin– Al & Mg salts

Distribution

• Malnutrition– Reduced plasma proteins– Increased total body water– Reduced fat stores– Reduced enzyme activity and substrate

availability

• Obesity

Metabolism

• Enzyme induction– High protein/low carbohydrate diet

• Enzyme inhibition– Grapefruit juice– MAOI’s

• Bacterial breakdown– Fibre/Protein source

• Malnutrition

Folate

• Folic acid is involved in DNA synthesis

• Deficiency causes:– Megaloblastic anaemia– Diarrhoea

• Folate metabolism

Dihydrofolate Tetrahydrofolate

Dihydrofolate reductase (DHFR)

Folic Acid

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)

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)

Pyridoxine

• Co-factor for the transaminases and for decarboxylation of amino acids– Isoniazid– Phenelzine– Penicillamine– Oral contraceptive pill– Hydralazine– Phenytoin– Theophylline (Delport et al, 1988)

Elimination

• Increased clearance of electrolytes– Diuretics– Cisplatin– Amphoteracin

• Decreased clearance of electrolytes– Potassium sparing diuretics– Demeclocycline

Summary

• Complex array of interactions• Identification of high risk patients• Prevention/minimisation of interaction• Effective monitoring

ReferencesA.Kappas, K.E.Anderson, A.H.Conney, A.P.Alvares (1976) Influence of dietary protein and

carbohydrate on antipyrine and theophylline metabolism in man. Clin. Pharmacol. Ther. 20:643-53.

T.C.Campbell, J.R.Hayes (1974) Role of nutrition in the drug metabolism enzyme system. Pharmacol Rev 26(3):176

A.G.Goodman, L.S.Gilman (1985) The pharmacological basis of therapeutics. ?th Edition New York McMillan

N.G.Gillespie, G.C.Cotzias, M.A.Bell et al (1973) Diets affecting treatment of parkinsonism with levodopa. J. Am.Dietetic Assoc 62:525

A.Melander,K.Danielson,B.Scherstein,E.Wahlin (1977) Enhancement of the bioavailability of propranolol and metoprolol by food. Clin Pharmacol Ther 22:108

Stockley’s Drug Interactions (2002) 6th Edition, Pharmaceutical Press, LondonK.Krishnaswamy (1978) Drug metabolism and pharmacokinetics in malnutrition. Clin Pharmacokin

3:216-240D.D.Shen, D.L.Azarnoff (1978) Clinical Pharmacokinetics and Methotrexate. Clin Pharmacokinet

3:1-13P.G.Welling (1977) Influence of food and diet on gastrointestinal drug absorption: A review. J

Pharmacokinet Pharmaceut 5:291-333J.F.Adam, J.S.Clark, J.T.Ireland, C.M.Kesson, W.S.Watson (1983) Malabsorption of vitamin B12

and intrinsic factor secretion during biguanide therapy. Diabetologia 24:16-18R.White, A Ashworth (2000) How drug therapy can affect, threaten and compromise nutritional

status. J Hum Nutr Dietet 13:119-129I.A.Bauer (1982) Interference of oral phenytoin absorption by continuous nasogastric feeding.

Neurology 32:570-575