Food and Drug Interactions PDF Lecture Notes

9/23/24 Food and Drug Interactions LECTURE 4 – FALL 2024 1 1 Food-Drug Interactions v Medications can affect or be affected by food v Each p...

9/23/24 Food and Drug Interactions LECTURE 4 – FALL 2024 1 1 Food-Drug Interactions v Medications can affect or be affected by food v Each patient must be individually assessed for potential food-drug interactions o Effect of food on medication action o Effect of medication on nutritional status o All medications must be reviewed for potential interactions v Medications in the same pharmaceutical class generally exhibit similar effects 2 2 1  9/23/24 Effect of Food/Nutrients on Medication Absorption v Food in stomach o Could → ↓ rate of absorption or extent of drug absorption o Examples o High-fat or high-fiber meals could delay gastric emptying; typically delay in drug absorption not clinically significant as long as extent of absorption is not affected, but could be clinically significant with antibiotics or analgesics o Occurrence of chelation reactions between medications and divalent or trivalent cations (Fe, Ca, Mg, Zn) → reduced drug absorption o Fluoroquinolone antibiotics (ex: Cipro) and tetracycline form insoluble complexes with calcium in dairy products or calcium fortified foods → prevents or reduces absorption of drug and nutrients o On the other hand: Ceftin (antibiotic) and Invirase (antiretroviral drug) have enhanced absorption with presence of food; prescribed to be taken after meal to reduce dose required to reach effective level 3 3 Effect of Food/Nutrients on Medication Metabolism v Food can alter the metabolism of drugs o Example: grapefruit (juice, segments, extract) inhibit the cytochrome P- 450 3A4 enzyme system responsible for metabolism of many orally administered drugs: simvastatin (Zocor), lovastatin, cyclosporine, carbamazepine (anticonvulsant), +many others § This ↓ in metabolism → increase in medication that reaches systemic circulation → ↑ pharmacologic effect and possible toxicity § Effects of grapefruit on cytochrome P-450 last up to 72 hours o Example: competition between food & drugs may → ↓ first pass metabolism of certain drugs (propranolol, metoprolol) § Competing for the same metabolizing enzymes § Reduction in first pass metabolism → ↑ serum level of the drug Can → toxic effect if dose titration occurs in fasting state 4 4 2  9/23/24 Effect of Food/Nutrients on Medication Excretion v Alteration of renal excretion → altered blood levels of certain drugs o Example: Lithium is reabsorbed in the kidney at the same site as Na § Excess sodium intake → ↑sodium excretion and lithium excretion → produces lower lithium levels, possible therapeutic failure § If concurrently hyponatremic while taking lithium → ↑ lithium re- absorption due to similar molecular structure to Na → toxicity risk 5 5 Effect of Medication on Nutrient Excretion v Drug → increased or decreased urinary excretion of nutrients o Example: Loop diuretic (Lasix) → ↑ excretion of Na, K, Cl, Mg, Ca § K supplement routinely prescribed with loop diuretics § Ca and Mg supplementation should also be considered, especially with long-term use of loop diuretics § Requires close monitoring of electrolyte levels o Example: Thiazide diuretics (hydrochlorothiazide HCTZ) → ↑ excretion of K and Mg BUT ↓ excretion of Ca (↑ renal reabsorption of Ca) o Example: Potassium-sparing diuretics (spironolactone, Aldactone) → ↑ excretion Na, Cl, and Ca, but not K (K-sparing) § Can reach dangerous K blood levels if taken with K supplement o Example: Antihypertensive angiotensin-converting enzyme (ACE) inhibitors (blood pressure, Vasotec) → ↓ excretion of K o Example: Corticosteroids (prednisone) → ↓ sodium excretion (sodium & water retention) and ↑ excretion of K and Ca § Ca and Vitamin D supplements with long-term use to prevent osteoporosis 6 6 3  9/23/24 Effect of Medication on Nutrient Absorption v Drug → ↓ absorption of drug, nutrient or both o Example: tetracycline and ciproflaxin (antibiotics) chelate with cations, such as calcium found in supplements or dairy products § Also true Fe, Mg, Zn (mineral supplements or multivitamin-mineral) § Reduce amount of mineral available for absorption § Minerals should be taken at least 2-6 hours apart from drug o Example: Prolonged use of H2-receptor antagonists (Pepcid, Zantac) or proton pump inhibitors (Prilosec, Nexium); anti-ulcer, anti-GERD; antacids § Alters gastric acidity (increased gastric pH) → ↓ absorption of B12 § PPI → ↓ Ca absorption → ↑ osteoporosis risk o Example: Medications can damage gut mucosa → ↓nutrient absorption § Alters ability for GI tract to absorb mineral (Fe, Ca) § Antineoplastic medication (methotrexate), non-steroidal anti- inflammatory drug (NSAIDs), long-term antibiotic use 7 7 Effect of Medication on Nutrient Metabolism v Drug increases metabolism of nutrients → ↑ nutrient requirement and possibly deficiency o Example: Phenytoin (Dilantin, anticonvulsant) and phenobarbital (barbiturate, CNS depressant; seizures) → induce hepatic enzymes, increased metabolism of folic acid, vitamins D and K § Macrocytic anemia; Osteoporosis § Supplementation often provided with these medications v Drug may cause vitamin antagonism; blocking conversion of vitamin to active form o Example: Isoniazid (anti-tuberculosis drug) → blocks conversion of pyridoxine (vitamin B6) to its active form (B6 involved with nerve function) § Risk for deficiency and peripheral neuropathy § Vitamin B6 supplement typically given with isoniazid 8 8 4  9/23/24 Enhancement of Medication Action v Foods or additives can ↑ the effects or toxicity of a drug o Examples § ↑ caffeine intake → ↑ adverse effects of Ritalin § → nervousness, tremor, insomnia § Tyramine in food → ↑toxic effect of monoamine oxidase inhibitors (MAOI) § tyramine deaminated by MAO (monoamine oxidase) § MAOI prevents breakdown of tyramine (vasoconstrictor, raises blood pressure) → hypertensive crisis → death § antidepressant: Isocarboxazid (Marplan), Phenelzine (Nardil), Selegiline (Emsam), Tranylcypromine (Parnate) § ex food high in tyramine: aged cheeses, cured meats, pickled or fermented food, soybeans, soy or teriyaki sauce, tofu and tempeh, miso, brewer’s yeast or sourdough bread, alcohol 9 9 Antagonism of Medication Action v Nutrient, food substance, diet → ↓ in the desired action of the drug or counteracts the effect of the drug o Example: Warfarin (coumadin, anti-coagulant) § action is opposed by Vitamin K § balance must be maintained between dose of medication and vitamin K intake (consistent vitamin K intake) § leafy green vegetables mainly § caution also with: onions, garlic, ginger, papaya, vitamin E supplement; may enhance anti-coagulant effect of warfarin o Example: Echinacea (immuno-stimulatory) § → ↓ immunosuppressant effect of cyclosporine o Example: Caffeine (CNS stimulatory properties) § → ↓ anti-anxiety effect of benzodiazapines (Ativan) 10 10 5  9/23/24 Effects of Medication on Nutritional Status v Side Effects / Gastrointestinal Effects: o Impair salivary flow → dry mouth, ↑ caries, stomatitis, glossitis o In saliva → bitter taste (for as long as drug remains in body) o Suppression of natural oral bacteria → oral candidiasis o Cause dysgeusia, abnormal sense of taste o Damage to cells that rapidly turnover → stomatitis, glossitis, oral ulceration, esophagitis o Induce dry mouth, throat, mucositis → dysphagia o Irritate stomach mucosa → n/v, bleeding, ulceration (Aspirin, Advil) o Slow intestinal peristalsis → constipation o Destroy intestinal bacteria → (colitis) secondary inflammation due to bacterial overgrowth 11 11 Effects of Medication on Nutritional Status v Appetite Changes o Suppression of appetite § Ex: CNS stimulants used to treat ADHD (Adderall, Ritalin) § Ex: medications with CNS side effects (drowsiness, dizziness, tremor, confusion, headache, weakness, peripheral neuropathy) can interfere with ability or desire to eat, especially in elderly or chronically ill § Common with anti-infective drugs (antibiotics, antifungals), antineoplastics, bronchodilators (albuterol), stimulant drugs o Increased appetite (c/o feeling ravenous); often results in weight gain § Ex: antidepressants (Elavil), antipsychotic drugs (clozapine) § Ex: corticosteroids associated with dose dependent weight gain appetite stimulation +sodium/water retention § Drugs used as appetite stimulants: Megace, Marinol (dronabinol, marijuana derivative), Remeron (antidepressant) 12 12 6  9/23/24 Effects of Medication on Nutritional Status v Metabolic Effects o Affect glucose metabolism → hypoglycemia, hyperglycemia, diabetes § Stimulate glucose production, impair glucose uptake, inhibit insulin secretion, decrease insulin sensitivity, increase insulin clearance § Example: Antipsychotics (Zyprexa) → hyperglycemia § Example: Corticosteroids → gluconeogenesis, insulin resistance, inhibit glucose uptake → hyperglycemia o Lipid abnormalities (↑cholesterol, ↑triglycerides) § Example: Antipsychotics (Zyprexa, Risperdal) 13 13 Counseling Guidelines v Patient Counseling should include o Pertinent medication information (name, indications, duration of therapy) o When and how to take the medication (ie with meals) o Food and beverages to avoid or limit o Expected side effects; potential nutritional problems o Dietary changes that may alter drug action o Advice on alcohol ingestion o Potential interactions between medication and supplements o Importance of following a prescribed diet o Nutritional information – consult a Registered Dietitian o Medication information – consult a Registered Pharmacist 14 14 7  9/23/24 Some Prevalent Interactions v Diuretics o Loop: Furosemide (lasix): losses of K+, Mg+, Ca+ o Thiazides (HCTZ): losses of K+, Mg+, increased Ca+ re-absorption o Potassium Sparing (spirulactone): K+ sparing v Steroids o Prednisone, Dexamethasone, many others o Hyperglycemia, fluid retention, increased BP, weight gain o Altered protein metabolism, GI ulceration/hemorrhage o Long term: Osteoporosis 15 15 Some Prevalent Interactions v Antibiotics (Tetracycline/Ciprofloxin) o Decreased absorption with dairy products, Ca, Fe, Zn, Mg v Anticoagulants o Warfarin [Coumadin] and Vitamin K; consistent intake § Note: not needed with Lovenox/Heparin v Grapefruit inhibits metabolism of certain medications o Examples: Lovastatin, Simvastatin, Cyclosporine v MAOI (monoamine oxidase inhibitors) o Prevents breakdown of tyramine o Avoid tyramine (aged cheese, fermented foods, …) 16 16 8