Food and drug interactions and their impact on your health

Grapefruit juice and fruit
Grapefruit juice and fruit

I am going to write about food and drug interactions and their impact on your health.

What are food-drug interactions

The presence, constitution, and scheduling of food may influence the absorption of multiple of the immunosuppressive medications. Since the avoidance of food consumption at the time of drug administration is not always experiential, many physicians advise that patients be consistent and take their medications in the same mode, that is with or without food.

A number of active chemical compounds in grapefruit, known as furanocoumarins, are powerful inhibitors of the cytochrome P-450 3A4 enzyme. It’s important for you to know that grapefruit or grapefruit juice can produce an augmentation in systemic exposure to immunosuppressive drugs such as tacrolimus or cyclosporine used to preclude and treat allograft rejection. It is paramount to teach patients about the interaction between grapefruit and/or grapefruit juice and their immunosuppressive medications. If you are taking cyclosporine or tacrolimus you should be counseled to completely avoid grapefruit and/or grapefruit juice. If you refuse to avoid consumption of grapefruit and/or grapefruit juice, more frequent testing of blood cyclosporine or tacrolimus levels is required.

Consumption of large acute or chronic doses of alcohol inhibit transaminases which play a major role in the breakdown of drugs. Drug-food interactions are known to diminish therapeutic effects of the medication and to cause strong unfavorable drug reactions. Inhibition of histaminase and monoamine oxidase by isoniazid ( a drug used in the treatment of tuberculosis) can produce notable drug-food interactions. Food significantly reduces isoniazid bioavailability (the percentage or amount of the medication that enters the body via absorption from the gut into the circulation and is able to exert an active effect). Moreover, isoniazid is probably best known as a significant inhibitor of drug metabolism affecting such drugs as phenytoin, carbamazepine, theophylline, warfarin, selected benzodiazepines, vitamin D and acetaminophen. You must be aware of signs of toxicity resulting from these drugs while you’re taking isoniazid. Isoniazid exerts a biphasic end result of inhibition-induction on one cytochrome P450 isoenzyme, CYP2E1, which partly elucidates the interaction with acetaminophen and augmented risk of liver damage.

Hepatotoxicity
Hepatotoxicity

The greater number of clinically important food-drug interactions are created by food-induced alterations in the bioavailability of the medication. Food-drug interactions may unwittingly decrease or augment the drug effect. The most salient food-drug interactions are those linked with a high risk of treatment failure resulting from a notably diminished bioavailability in the fed condition. These interactions are commonly caused by chelation with ingredients in food. Moreover, gastric acid secretion, a physiological response to ingested food, may decrease or increase the bioavailability of certain medications. It’s important for you to know that Coenzyme Q-10 (a very well-known and popular food supplement consumed by humans) impedes intestinal efflux transporter P-glycoprotein and as a consequence food-drug interactions occur.

The interactions between medications and organic products are attributed to the same pharmacodynamic ( an individual’s body’s therapeutic response is to a drug; this is usually determined by the medication’s activity and affinity at its location of action, which is frequently a receptor) and pharmacokinetic ( refers to movement of the drug through your body; pharmacokinetics of a drug includes its absorption, distribution, metabolism, and excretion, all of which influence the drug’s response by changing the drug’s concentration at its site of activity) parameters as drug-drug interactions. A number of fruits and berries have been demonstrated to contain compounds that alter drug-metabolizing enzymes. Grapefruit, star fruit, Sevillian orange and pomelo contain compounds that inhibit cytochrome P450 3A4, which is the most salient enzyme in the metabolism of drugs.

Amid all the fruit juices, grapefruit juice highly interacts with practically all types of medications. Active bioflavonoids and furanocoumarins present in grapefruit juice are likewise inhibitors of organic anion transporting polypeptide ( a membrane transport protein that deals with the transport of primarily organic anions across the cell membrane) and when ingested together, can diminish the oral bioavailability of the organic anion transporting polypeptide substrate, fexofenadine (an antihistamine). A number of flavonoids present in grapefruit juice are recognized as esterase inhibitors, of which naringenin and kaempferol are demonstrated to bring about pharmacokinetic drug interaction with most of the calcium channel blockers, lovastatin, and enalapril due to their ability of esterase inhibition.

A number of vegetables such as broccoli, kale, Brussels sprouts, spinach, parsley, and others contain high concentrations of vitamin K and consumption of sizable quantities or making sudden modifications in the amounts consumed of these vegetables, interferes with the safety and efficacy of warfarin. The hypoprothrombinemic sequela of warfarin may be reduced and thromboembolic adverse events may occur if warfarin is consumed with leafy green vegetables.

Spinach
Spinach

Monoamine oxidase inhibitors (MAOIs) are efficacious in the treatment-resistant depression. They are under-utilized by many physicians predominantly due to their interaction with tyramine-containing foods (red vine, matured cheese, ripped bananas, yogurt, salami and shrimp paste) causing hypertensive crisis in individuals taking monoamine oxidase inhibitors. Since monoamine oxidase inhibitors are efficacious in the treatment-resistant depression, transdermal preparations may serve as a beneficial therapeutic option and exclude the drug-food interaction.

Most common drug-drug interactions

  • It is important to know that there are many interactions between calcineurin inhibitors such as tacrolimus and/or cyclosporine and commonly used drugs.
  • Since tacrolimus and cyclosporine are substances on which cytochrome P-450 3A4/5 enzymes act, any medication that is broken down by these enzymes or that alters metabolism by these enzymes can likely interact with calcineurin inhibitors. Examples of interacting medications include but not limited to: amiodarone, ritonavir, fluconazole, atazanavir, erythromycin, verapamil, diltiazem, St. John’s wort, rifabutin, nafcillin, phenobarbital, carbamazepine, gentamycin, colchicine, nonsteroidal anti-inflammatory drugs, ACE inhibitors, spironolactone, triamterene, atorvastatin, quinidine, etc. If you cannot avoid taking a potent inhibitor/inducer of CYP3A4/5 enzyme, then medication levels and toxicities must be carefully observed. There is limited information available regarding exact dose modifications when inhibitors of CYP3A4/5 are administered together with tacrolimus or cyclosporine.
Uses of cyclosporine
Uses of cyclosporine
  • If you are a clinician you can take advantage of cytochrome medication interaction to decrease the dose of the calcineurin inhibitor or augment the medication concentration. The outcome of ketoconazole and diltiazem on cyclosporine metabolism has led to their use in transplant recipients as a way of reducing the total cyclosporine dose and, therefore, the expenditure of cyclosporine therapy.
  • Medications that act on gastrointestinal emptying such as prokinetic agents, for example, metoclopramide, used to treat gastroesophageal reflux disease by enhancing muscle action in the gastrointestinal tract, may unfavorably influence the absorption of calcineurin inhibitors. Laxatives can diminish oral tacrolimus and cyclosporine intestinal absorption by hastening their transit through the intestine, whereas narcotics may extend the duration of transit time in the intestine, augmenting the time for absorption.
  • If you concomitantly administer tacrolimus or cyclosporine with other potentially nephrotoxic medications such as the nonsteroidal anti-inflammatory drugs, augmented toxicity may occur, and therefore, such treatment combinations should be avoided. Also, you should be aware of the fact that calcineurin inhibitors may induce or worsen hyperkalemia, and therefore, serum potassium levels should be observed closely in those individuals who are concomitantly taking medications that may augment potassium, such as spironolactone, amiloride, and triamterene.
  • Bivalent cations may affect the absorption of tacrolimus. Concomitant administration of tacrolimus and magnesium/aluminum hydroxide, in a single dose crossover study in healthy volunteers, produced a 21% rise in the mean tacrolimus area under the curve and a 10% diminution in the mean tacrolimus Cmax in comparison to tacrolimus administration alone. In another study, patients did not need tacrolimus dose adjusting when magnesium/aluminum hydroxide was co-prescribed with tacrolimus. If you want to diminish these potential drug to drug interactions, magnesium and aluminum-containing medications should not be administered within 2 hours of tacrolimus, and tacrolimus drug concentrations should be closely observed.
  • Cyclosporine is an inhibitor and substrate of P-glycoprotein. In vitro data indicates that tacrolimus in neither an inhibitor nor a substrate of P-glycoprotein. Cyclosporine can augment the effectiveness of some chemotherapeutic drugs via inhibition of P-glycoprotein and diminish the efflux of chemotherapeutic drug out of the tumor cell. In addition, carvedilol inhibits P-glycoprotein and may augment the serum concentrations of cyclosporine.

Genetic factors and drug response

It’s important to know that genetic polymorphisms for numerous drug metabolizing enzymes and drug receptors have been established and apparently contribute to interpatient variability in drug response. There are 4 conventional mechanisms by which genetic factors can affect the response to a drug:

  • Effect on the pharmacokinetics of a drug, which may include drug’s absorption, distribution, metabolism and/or excretion.
  • Effects on pharmacodynamics, the therapeutic response of a receptor to the drug.
  • Effect on idiosyncratic reactions, for example, augmented frequency of allergic reactions in patients with certain genotypes.
  • Effect on the pathogenesis of the disease, which may cause the disease to be more or less responsive to a specific treatment.
  • Pharmacogenetic testing
    Pharmacogenetic testing

Pharmacogenetic testing is available in certain areas along with some classes of drugs and may empower physicians to realize why patients respond differently to various drugs and to construct better decisions about treatment. The target of individualized treatment based upon pharmacogenetic testing has yet to be accomplished. The US Food and Drug Administration guidelines as to the use of genetic markers to monitor therapy for an array of drugs is not on a large scale with a few significant exceptions:

  • Use of the anti-HER2 monoclonal antibody trastuzumab is confined to breast cancers that overexpress HER2.
  • Use of Ivacaftor for treatment of patients with cystic fibrosis who have G551D mutation. Ivacaftor is an orally available CFTR (cystic fibrosis transmembrane regulator) modulator that is specific for the G551D mutation; it revitalizes the function of the CFTR protein in individuals who possess this mutation. All patients with cystic fibrosis should undergo genotyping to find out whether they possess the G551D mutation.
  • Guidelines from expert panels who advocate the use of an anti-HIV drug abacavir only in individuals who have tested negative for HLA-B*5701 (see the effect on idiosyncratic reactions above).
  • Numerous clinicians recommend screening patients for mutations in the thiopurine methyltransferase gene that causes thiopurine methyltransferase deficiency.

Many roadblocks exist to the direct utilization of pharmacogenomics advances in education to drug treatment in the context of clinical care setting, which will need to be conquered before individualized drug therapy becomes a routine fundamental part of mainstream medicine.

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