Chapter 9 Clinical: Food-Drug Interactions

Importance of Awareness Drug–nutrient interactions: specific changes to pharmacokinetics of a drug caused by nutrient(s) or changes to the kinetics of nutrient(s) caused by a drug Food–drug interactions: broader term that also includes effects of medication on nutritional status e.g. a drug causing a vitamin deficiency Food–drug interactions can Alter the intended response to medication Cause drug toxicity Alter nutritional status

Benefits of Minimizing Drug Interactions Medications achieve intended effects Patients do not discontinue drugs Minimize need for additional medication Avoid adverse side effects Preserve optimal nutritional status Avoid accidents and injuries Minimize disease complications Reduce cost of health care services Meet licensing agency requirements

Pharmacologic Aspects Pharmacodynamics: physiologic and biochemical effects of a drug or combination of drugs Pharmacokinetics: movement of a drug through the body by absorption, distribution, metabolism, and excretion Process: Absorption: from site of administration to the bloodstream Distribution: from blood to other regions of the body Bound vs. unbound fraction: only unbound fraction can effect target organ Biotransformation: metabolism- the major organ is the liver Cytochrome P-450 enzyme system: An important enzyme system in the liver that facilitates drug metabolism Excretion: elimination of drugs and their metabolites

Risk Factors for Food–Drug Interactions Polypharmacy: taking many drugs Chronic disease Older patients Malnutrition – affects albumin levels Cancer and AIDS GI tract alterations- nausea, vomiting, diarrhea, anorexia Body composition- accumulation of fat-soluble drugs Fetus, infant, pregnant woman- drugs not tested on unborn- pregnant women need to avoid many drugs

Effects of Food on Drug Therapy 1. Drug absorption Bioavailability Meds delivered via IV are 100% bioavailable but decreases when consumed orally because of incomplete absorption and metabolism (due to e.g. fiber, fat, and other food components). If food in the stomach is a major issue, the drug will come with directions on meal timing. GI pH: Any situations that results in a change in gastric pH such as achlorhydria or hypochlorhydria can reduce drug absorption. E.g. failure of ketoconazole to clear candida in patients with HIV when patient also on acid-reducing agent for GERD

Effects of Food on Drug Therapy 2. Drug distribution Albumin is the most important drug-binding protein in the blood. Low serum albumin levels (poor intake for any reason) eventually means there are fewer drug binding sites leading to more unbound drug circulating through the body. Treatment: lower dosing of some medications 3. Drug metabolism Enzyme systems in the GI tract and liver account for much of the drug metabolism in the body. Food can both inhibit or, enhance drug metabolism by changing the activity of these enzyme systems E.g. a substance found in grapefruit and grapefruit juice can inhibit the intestinal metabolism of some drugs and VERY IMPORTANTLY, grapefruit and grapefruit juice inhibits the cytochrome P- 450 which is responsible for the metabolism of many oral drugs including statins prescribed for high serum cholesterol. Normal metabolism cannot be completed so more unmetabolized drug remains in systemic circulation resulting in potential toxicity. Patients must avoid grapefruit altogether (not enough to separate from drug administration)

Effects of Food on Drug Therapy 4. Drug excretion Some food and nutrients can alter the reabsorption of drugs from the renal tubules The drug lithium is resorbed by the kidneys as part of normal metabolism; when lithium is resorbed, so too is Na. When a patient consumed too much Na, the kidneys work to eventually excrete this sodium, unfortunately lithium follows suite and is also excreted. Patient who consume too much Na, therefore excrete a lot of Na, excrete too much lithium thus decreasing it’s therapeutic effects.

Effects of Drugs on Food and Nutrition 1.Nutrient absorption Chelation: Can occur between medications and mineral – reducing the amount of mineral available. Adsorption: Some antihyperlipidemic bile acid sequesterants cause fat-soluble vitamin malabsorption Transit time: Some drugs speed up transit time so not enough digestion can occur GI environment: pH Damage intestinal mucosa: These drugs have the greatest effect on nutrient absorption. Damaging the villi and microvilli inhobits the brush-border enzymes and intestinal transport systems the body uses to get nutrients from the GI tract to circulation (NSAIDS!)

Effects of Drugs on Food and Nutrition 2. Nutrient metabolism A drug may increase speed of metabolism Vitamin antagonism: because of a drug a vitamin cannot be converted to its active form. E.g. anticonvulsants (phenobarbotol) increase metabolism of vits D, K and B9 (folic acid) 3. Nutrient excretion Interfere with nutrient resorption Increase or decrease excretion

Effects of Drugs on Nutritional Status Side effects Oral, taste, and smell Dysgeusia (taste distortion) and hypogeusia (reduced ability to taste) Metallic or salty taste Antineoplastic drugs (for tumors): mucositis (inflammation of mucosal lining of GI tract) Xerostomia (dry mouth) GI effects Irritation and ulceration Nausea and vomiting Constipation or diarrhea Destruction of intestinal bacteria Fat malabsorption

Effects of Drugs on Nutritional Status (cont’d) Appetite changes Undesired weight changes Nutritional imbalance Growth retardation in children Appetite suppressants Stimulant drugs and hypertension CNS side effects Appetite stimulants: undesirable and desirable

Excipients and Food–Drug Interactions Excipients: inactive ingredients added as buffers, binders, fillers, diluents, flavorings, dyes, preservatives, suspending agents, or coatings Allergies and enzyme deficiencies Lactose Gluten sensitivity Nutritionally significant amounts of excipient nutrients

Medical Nutrition Therapy for Food–Drug Interactions Prospective: all medical nutrition therapy offered when the patient first starts a drug Retrospective: evaluation of symptoms to determine if medical problems might be the result of food–drug interactions Diet history: include OTC, alcohol, supplements, and herbals Warnings and recommendations