Micronutrient-Drug Interactions

Transcription

1 Micronutrient-Drug Interactions Wahida Karmally, Dr.PH,RD,CDE,CLS,FNLA Associate Research Scientist Director of Nutrition Irving Institute for Clinical and Translational Research Columbia University, NY Clinical lipid Update 2013

2 Conflict of Interest Member: American Pistachio Growers Research Advisory Committee Member: Sesame Workshop: "Healthy Habits for Life" initiative

3 Objectives 1. To review micronutrient drug interactions. 2. To increase awareness of micronutrientdrug interactions for patient safety and wellness

4 3 Main Types of Drug Interactions 1. Drugs with food and beverages 2. Drugs with dietary supplements 3. Drugs with other drugs

5 Nutrient Drug Interactions Nutrient Drug Interaction is a consequence of physical, chemical or pathophysiologic relationship between a drug and nutrient. Interactions can occur between a drug and a nutrient, multiple nutrients, dietary pattern or specific foods. An interaction is clinically significant if it alters the therapeutic drug response and /or compromise nutritional status

6 Nutrient Drug Interactions The interaction can therefore alter the therapeutic response. These interactions can result in decreased bioavailability of drug causing treatment failure or increased bioavailability causing toxicity and adverse effects. The patient s nutritional status and dietary components with pharmacological activity can affect drug metabolism thereby altering action and function.

7 Nutrient Drug Interactions Drugs can play a significant role in developing nutrient deficiencies. Drug induced micronutrient depletion may be responsible for the unexplained symptoms that affect medication compliance (zinc and ACE inhibitors and ARAII) Many micronutrients are potentially vulnerable to the effects of prescribed medicines when consumption is regular and sustained

8 Nutrient Drug Interactions Vitamins and trace elements are essential to the body Micronutrients are required for intermediary metabolism in varying amounts usually <1 gram/day to as low as a few micrograms/day.

9 Nutrient Drug Interactions Medications, can affect nutrients by: Decreasing food intake Decreasing nutrient absorption Slowing down nutrient production Interfering with nutrient metabolism Increasing nutrient excretion

10 Common Interactions Alcohol Can cause side effects to become more pronounced Can increase or decrease the effectiveness of certain drugs Acetaminophen serious liver damage can occur with >3 alcoholic beverages/day NSAID s can cause stomach bleeding with >3 alcoholic beverages/ day

11 Nutrient Drug Interactions Fruits, vegetables, herbs and teas contain a large variety of micronutrients and phytochemicals that have been associated with health benefits. These however consist of complex phytochemicals that can inhibit or induce the activity of cytochrome (CYP) P450 family of enzymes

12 Clinical Significance of the Interaction The clinical significance of any particular interaction depends on the seriousness of the dose-related drug toxicity and the extent to which the systemic drug concentration increases. The latter relies on multiple factors that include the innate oral bioavailability of the interacting drug, the circumstances under which the grapefruit or other citrus fruit is consumed and the vulnerability of the patient to the interaction. Bailey et al.cmaj DOI: /cmaj

13 Grapefruit Juice Grapefruit & grapefruit juice contain a compound that interferes with the way a digestive enzyme works Medications can pass more readily into the blood stream, causing higher than intended levels of drugs.

14 Grapefruit Drug Interaction Grapefruit juice has a significant effect on the intestinal CYP system and on drug bioavailability. The major flavonoids in grapefruit : naringen, naringenin, quercetin, kaemferol (Furanocoumarins ) are the cause of the interactions Dietary supplements containing flavonoids and other phytochemicals may be a cause of concern in terms of interactions and drug toxicity.

15 Citrus Fruits Containing Furanocoumarins Grapefruit Seville oranges Limes Pomelos Pomegranate does not contain furanocoumarins but shares certain chemical properties with grapefruit suggesting a potential drug interaction

16 Grapefruit Drug Interaction Grapefruit juice does not need to be taken simultaneously with the medication in order to produce the interaction. The bioavailability of drugs can be doubled by grapefruit juice even several hours after ingestion ACTION : Grapefruit and grapefruit juice shall not be included as patient menu selections

17 Selected Drugs that Interact with Grapefruit and other Fruits Containing Furanocoumarins Antilipemic Agents Cardiovascular agents Atorvastatin, Felodipine Amiodarone Lovastatin Nifedipine Apixaban Simvastatin Quinidine Clopidogrel Verapamil Eplerenone Ticagrelor Dronedarone Rivaroxaban Quinidine Alternatives with the same therapeutic indication that have no or minor interaction Pravastatin, Amlodipine Sotalol Rosuvastatin, Acetylsalicyclic acid Spironolactone Fluvastatin Warfarin

18 Chocolate The caffeine in chocolate can cause the effects of stimulant medications (including methyl phenidate) to be intensified. Opposite effects with sedatives can cause their intended effects to be decreased. One ounce of dark chocolate can contain up to 35gm of caffeine, enough to potentially cause a problem.

19 Chocolate Chocolate also contains tyramine, a chemical that controls blood pressure. If taking MAOI s to treat depression, tyramine can cause a dangerous increase in blood pressure, potentially leading to a stroke.

20 Licorice (glycyrrhizic acid) increases sodium resorption, water retention and increases blood pressure

21 Dying for Cup of Tea BMJ Case Rep Oct 19;2012. pii: bcr doi: /bcr Kormann R, Languille E, Amiot HM, Hertig A. SourceUrgences Néphrologiques et Transplantation Rénale, APHP, Hôpital Tenon, Paris, France. Abstract We report the case of a 70 year old woman who developed lifethreatening arrhythmia as a result of acute and severe hypokalaemia, which she developed after consuming large quantities of a liquorice rich herb tea. She had no previous heart condition. We also discuss the legislative discrepancy in both the USA and in Europe, whereby consumers are warned about the risk of chronic hypertension whenever they buy a product containing liquorice, yet the risk of hypokalaemia may not be mentioned at all

22 Plast Reconstr Surg Jan;131(1): doi: /PRS.0b013e318272f1bb. Herbal products that may contribute to hypertension. Jalili J, Askeroglu U, Alleyne B, Guyuron B. Source Department of Plastic Surgery, Case Western Reserve University, Cleveland, Ohio, USA The herbal products that may cause hypertension include arnica, bitter orange,blue cohosh, dong quai, ephedra, ginkgo, ginseng, guarana, licorice, pennyroyal oil, Scotch broom, senna, southern bayberry, St. John's wort, and yohimbine.

23 The 10 most common natural products used by adults. Percentages based on the 2007 National Health Interview Survey (NHIS) Zelig R, and Rigassio Radler D Nutr Clin Pract 2012;27: Copyright by The American Society for Parenteral and Enteral Nutrition

24 Drugs with Dietary Supplements St. Johns Wort Inducer of liver enzymes reduces the concentration of medications in the blood. Can reduce blood levels of lanoxin, mevacor, lovastatin and sildenafil (Viagra) Vitamin E Taken with Coumadin can increase anti clotting activity and may cause an increased risk of bleeding.

25 Drugs with Dietary Supplements Ginseng Can interfere with the bleeding effects of Coumadin, and enhance the bleeding effects of Heparin, aspirin, & NSAID s Gingko Biloba Can decrease the effectiveness of anticonvulsants therapy in patients taking medications to control seizures.

26 Role of Herbal Medicines and Dietary Supplements Supplement Commonly Reported use Interactions, Side Effects or Cautions Fish Oil Glucosamine / Chondroitin Used to lower BP and/or TG; prevent heart disease and stroke Used to reduce pain from osteoarthritis In large doses may increase the risk of bleeding May increase the effects of warfarin and thus risk of bleeding; may raise blood sugar in patients with diabetes Echinacea Flaxseed and/or fiber (psyllium) Ginseng Used for the prevention of the cold, flu and other infections Used to lower cholesterol, or as a laxative Used to increase sense of well being and improving overall health Generally viewed as safe High fiber content may lower absorption of important medications or other supplements May lower blood glucose levels and should be taken with caution in combination with other herbal products Garlic Coenzyme Q10 Green Tea Cranberry Used by individuals with high cholesterol, heart disease and high blood pressure Used to lower blood pressure and treat other cardiac conditions Used to prevent cancers, lower cholesterol and promote weight loss Used to prevent and/or treat urinary tract infections Garlic has the ability to thin the blood should be taken with caution with blood thinning or blood clotting drugs May lower blood pressure should be taken with caution by patients on BP lowering meds. May also increase blood clotting. Contains small amounts of vitamin K, which may make anticoagulant medications less effective. Cranberry contains salicylic acid, which can increase the effect of anticoagulants. Zelig R. & Rigassio Radler D. Nutr Clin Pract. 2012;27:

27 The most common herbals known to interfere with the action of Warfarin or Coumadin include the following: Increases Bleeding Risks Fenugreek Feverfew Garlic (capsules) Ginger (capsules) Ginkgo Biloba Green tea Omega 3 fatty acids Vitamin E Increases Clot Risk Ginseng St. John s Wort Coenzyme Q10

28 Drug/ Drug Type Antibiotics (ciprofloxacin, tetracycline) MAOI Inhibitors Tricyclic Antidepressants (amitriptyline) Anticonvulsants (phenytoin) Lithium H 2 Receptor Antagonists and PPIs Some Calcium Channel Blockers and some HMG Coenzyme A Reductase Inhibitors (simvastatin) Nutrient Interaction Form complexes with Ca, Mg, Zn, Fe supplements, and Al in antacids prevents absorption of nutrient and drug. Avoid taking with dairy products; can cause mild deficiency of Vit K Pressor agents Blood Pressure (Tyramine, Dopamine, Histamine, Phenylethylamine) found in aged cheese/meats, fermented foods: soy sauce, tempeh, miso, etc High fiber diet decreases absorption Increased metabolism of Vitamin D, K, and folic acid (concern of osteoporosis with long term use) Stable sodium intake necessary to prevent toxicity Reduce absorption of B12, vitamin C, Fe Grapefruit/ grapefruit juice/ pomelos, and tangelos prevent metabolism of these drugs, causing toxic levels to build up in the blood Statins: Also avoid Niacin, St. John s Wort, and Red Yeast Rice

29 Warfarin Antihypertensive/diuretics i. Loop Diuretics (furosemide) ii. Thiazides iii. Potassium Sparing Corticosteroids/ steroids Iron Supplements Antiosteoporosis drugs (alendronate, risedronate, ibandronate) Metformin Foods rich in vitamin K such as dark leafy green vegetables, and liver. St. John's Wort, or Avocado may counteract; Onions, garlic, quinine, papaya, and mango may enhance action of drug. i. losses of K, Mg, Na, Cl, Ca ii. calcium absorption; losses of K, Mg,Zn iii. K absorption; losses of Na, Cl, Ca insulin sensitivity Long term: need for: K, Ca, P, Vit A,C,D, protein, and folate Absorption by 50% if taken with food. Best on empty stomach (if w/ food: avoid bran, eggs, fiber supplements, high phytate foods, tea, coffee, dairy products, and calcium supplements) Not absorbed when taken with food. Absorption reduced by 60% if taken with coffee or OJ Decreases absorption of Vitamin B12 and Folic Acid

30 Isoniazid Antihyperlipemic cholestyramine, colestipol Changes B6 metabolism; B6 supplementation Decreases absorption of fat soluble vitamins A,D,E and K Angiotensin conversion enzyme inhibitors (ACEI), Angiotensin II receptpr antagonists (ARAII) Statins Decreases serum zinc CoQ10 intramuscular levels decreased Low levels of 25 hydroxyvitamin D

31 POLICY/PURPOSE: In patients who are prescribed specific drugs with known drug nutrient interactions will receive nutrition intervention in order to avert the potential for such interaction. APPLICABILITY: All in patients who are prescribed identified drugs. PROCEDURE: 1. The Nutrition Advisory board recommends that drugs with clinically significant drug nutrient interactions be recognized and reviews procedures to assure that patients receive proper intervention to avert these interactions. 2. The Department of Nursing, Department of Food & Nutrition and Department of Pharmacy implements the Drug Nutrient Interaction Policy and Procedure: NYPRESBYTERIAN HOSPITAL

32 A) MEDICATIONS THAT REQUIRE DIET MODIFICATION: The following medication/nutrient groups have been determined to be significant in the in-patient setting. The following procedures are designed to avert these interactions. I) Monoamine Oxidase Inhibitors (MAOIs) Upon order entry of this class of drugs, a screen will appear requesting the pharmacist to contact Food & Nutrition regarding appropriate diet. At the Westchester Division, order entry of this class of drugs is recorded by the pharmacy. ACTION: The pharmacist will call Food and Nutrition to communicate that an order for a MAO inhibitor (or other medication that requires a tyramine restricted diet) has been received for a specified patient. At Westchester Division, the list of patients receiving MAOIs is printed in the Department of Food & Nutrition. ACTION: Food and Nutrition will automatically institute a Tyramine Restricted Diet, contact the prescriber, if necessary, to assure that an appropriate diet order is written and will notify Nursing. ACTION: The clinical dietitian/nutritionist will initiate diet education, when necessary, and will document this in the medical record on the Interdisciplinary Patient and Family Education form.

33 II)Warfarin (Coumadin ): Upon admission, patients prescribed Warfarin prior to admission will be screened to determine need for additional drug-nutrient education; during admission patients newly started on Warfarin will receive nutrition assessment and/or education. ACTION: Nursing will screen patients upon admission thus alerting the clinical dietitian/nutritionists of those patients who request additional education on the drug-nutrient interactions associated with Warfarin. ACTION: Food & nutrition will receive daily reports of patients newly started on Warfarin. These patients will receive nutrition assessment and/or education.

34 II)Lithium Salts: Upon order entry of this class of drugs, a screen will appear requesting the pharmacist to contact Food & Nutrition regarding appropriate diet and/or consult. At the Westchester Division, order entry of this class of drugs is recorded by the pharmacy. ACTION: The pharmacist will call Food & Nutrition to communicate that an order for lithium has been received for a specified patient. At the Westchester Division, the list of patients receiving lithium is printed in the Department of Food & Nutrition. ACTION: Food & Nutrition will evaluate if the sodium content of the diet ordered for the patient is consistent with the patients usual dietary intake of sodium. ACTION: Food & Nutrition will contact the prescriber if the diet order contains a different amount of sodium than the patient s usual sodium intake. ACTION: The dietitian will initiate appropriate education to assure that a diet containing a consistent level of sodium is followed and will document this in the medical record on the Interdisciplinary Patient and Family Education form.

35 Nutrient Drug Interactions The scientific data on nutrient drug interactions are limited particularly for synergistic effects of polypharmacy on micronutrient metabolism. Patients need to be screened for micronutrient deficiencies with reference to their diets, medications prescribed and lifestyle habits.