Drug Food Int

DRUG-FOOD & HERBAL INTERACTIONS HASHMI FURQAN

• FOOD can increase, decrease or not affect the absorption of drugs • Food may influence bioavailability of drugs from modified-release dosage form For example: opening of capsule of enteric coated Omeprazole beads & giving it in a acidic food such as orange juice  eases administration of the drug maintaining the enteric coating until the drug reaches the basic pH of the duodenum

• Complexation & Adsorption affecting the extent of absorption For example: Quinolones & di- or tri-valent containing elements • Food can be metabolized by the same hepatic enzymes causing enzyme induction or inhibition  toxic or subtherapeutic levels For example: grapefruit inhibits CYP3A4  increased level of substrate drugs such as Midazolam. Nimodipine, Nifedipine, Lovastatin, CBZ, Verapamil • Food can pharmacodynamically antagonize the effects of some drugs  For example: Spinach & broccoli provide dietary source of vitamin-K  antagonizes the effect of warfarin garlic can cause additive antiplatelet effect in combination with warfarin, heparin & low mol. wt. heparin (LMWH)  increased risk of bleeding

Foods can contain pharmacologically active compounds  Interact with drugs meant to inhibit endogenous compounds For Example: MAOIs prevent normal metabolism of catecholamines. Also inhibit the metabolism of tyramine from tyramine-containing foods such as red wine & cheese (increased levels of tyramine cause hypertensive crisis)

Affect of food on drug bioavailability Reduced or Delayed

Increased

No effect

NSAIDs Naproxen, naproxen sodium, aspirin, acetoaminophen Antibiotics Tetracyclin & penicillins

Griseofulvin Metoprolol Phytoin Proproxyphene Dicumarol Morphine

Theophylline

Ethanol

Metronidazole

HERBAL-DRUG INTERACTIONS • Herbal preparations contain combinations of herbs or a single herb • Some herbal preparations represent a single herb containing a variety of alkaloids or constituents that may exhibit a variety of pharmacological activities

Some herbs contain a No. of different pharmacologically active constituents For example: St John’s wort  6 different constituents i.e. Hyperforin, Biapigenin, Hypericin, Quericitin, Chlorogenic acid, & Pseudohypericin • Each constituent has its own action, metabolism, binding & pharmacological action • Predominant effect or interaction depends on the relative potency of each constituent The constituents of St john wort have inhibitory effects on CYP450 isozymes 3A4, 2C9, 1A2, 2D6 & 2D9 It appears overall to be an inducer of CYP3A4

Many herbal drugs interact at the same transport, metabolism & receptor sites as traditional prescription drugs

• Traditional Chinese medicines may contain combination of herbs • Some products have been found to contain some unlisted legend drugs • Some herbals may contain some contaminants such as heavy metals

• •

Pharmacodynamic or pharmacokinetic interactions Drugs with narrow therapeutic window are at greater risk for drug-herbal interactions

For example  important herbal-drug interaction occurs in patients taking warfarin •

Coenzyme Q10 has a chemical structure related to vitamin K. combination of CoQ10 and warfarin antagonizes warfarin’s effects  inadequate anticoagulation

•

Ginger and garlic also increase bleeding in pts taking warfarin by directly inhibiting platelets & causing increased risk of bleeding

•

Wheat grass contains high levels of vit-K which directly antagonize the warfarin  inadequate anticoagulation

Potency of herbal product Potency of herbal product is influenced by a variety of factors • The stage of growth during which herb was harvested • Drying time • Solvents used for the extraction of herbs • Shelf life & storage conditions of the herbal extract