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 absorptionFor 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

Ethanol

Griseofulvin

Metoprolol

Phytoin

Proproxyphene

Dicumarol

Morphine

Theophylline

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