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
PENG 2006 R.White
Drug Effects on Nutrient Metabolism
PENG 2006 R.White
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
PENG 2006 R.White
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)
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