PENG 2006 R.White

Drug Nutrient Interactions

Pharmacological, Physical and

Pharmacokinetic

Rebecca WhiteLead Pharmacist; Surgery, GI & Nutrition

John Radcliffe Hospital, Oxford

PENG 2006 R.White

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

PENG 2006 R.White

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

PENG 2006 R.White

Side Effects of Drugs Influence on Nutrient Intake

• Reduced Gastric Emptying– Paralysing Agents, Anticholinergics,

Opiates

• Increased Gastric Emptying– Metoclopramide, Erythromycin, Cisapride

• Anorexia

• Taste disturbance

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Drug Effects on Nutrient Metabolism

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Folate

• Folic acid is involved in DNA synthesis

• Deficiency causes:– Megaloblastic anaemia– Diarrhoea

• Folate metabolism

Dihydrofolate

Folic Acid

Tetrahydrofolate

Dihydrofolate reductase (DHFR)

PENG 2006 R.White

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)

PENG 2006 R.White

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)

PENG 2006 R.White

Pyridoxine

• Co-factor for the transaminases and for decarboxylation of amino acids

• Deficiency causes:– Peripheral neuropathy– Dermatitis and rough skin– Irritability– Hypochromic anaemia– Glossitis

PENG 2006 R.White

Pyridoxine Deficiency

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

PENG 2006 R.White

Effect of Nutrition on Drug Pharmacokinetics

• Malnutrition– Low plasma proteins

• Altered protein binding• Increased volume of distribution

– Reduced hepatic enzyme function

• Nutrition composition

PENG 2006 R.White

Drug Administration

via Feeding Tubes

PENG 2006 R.White

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?

PENG 2006 R.White

Choice of formulation

• Solution

• Syrup

• Suspension

• Soluble tablet

• Effervescent tablet

• Dispersible tablet

PENG 2006 R.White

PENG 2006 R.White

Factors Affecting Drug & Formulation

• Tube Blockage

• GI side effects

• Pharmacokinetics

PENG 2006 R.White

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

PENG 2006 R.White

PENG 2006 R.White

PENG 2006 R.White

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

PENG 2006 R.White

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)

PENG 2006 R.White

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

PENG 2006 R.White

• 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

Drug Interactions

PENG 2006 R.White

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

PENG 2006 R.White

Clinical Monitoring

• Very little information relating to clinical significance of interactions

• No data for most drugs

• Clear monitoring parameters

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Information Available

Available from www.bapen.org.uk

PENG 2006 R.White

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

PENG 2006 R.White

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)