The Liver

• One of the most metabolically active areas in the body.

• The main site of detoxification in the body.

• The detoxification process has two phases: phase I (involves an enzyme complex called cytochrome p450) and phase II.

• This processing, which allows chemicals to be made water soluble and excreted from the body, can make it difficult to achieve a sufficient concentration of remedy in the body.

• Liver disease causes great problems because harmful substances are not prepared for removal from the body.

The First-Pass Mechanism

All orally administered remedies (apart from the very small amounts absorbed through the mucous membranes in the mouth) pass through the liver before they reach the tissues. Some drugs (such as nitroglycerin) are almost completely removed by the liver at the first pass (i.e. on the first go). Others take a little longer because they are not completely removed by this system (due to the enterohepatic cycle or they are just more difficult to remove). Other drugs rely on this system to activate their components, as the liver will change the chemistry of the drug.

The more resistant a drug is to the first-pass mechanism, the longer its half-life (i.e. the time it takes for a remedy to halve its dosage in the body). It is difficult to say how herbal remedies are affected by the first-pass mechanism because the constituents and their interactions are so complex. However, some elements of the first-pass mechanism will be involved in the metabolism of herbal remedies.

Liver Enzyme Induction and Inhibition

Enzymes can be encouraged to speed up or slow down. For example, cytochrome p450 (the enzyme involved in phase I in the liver), of which there are several variations, can be particularly affected.

• Enzyme Induction

Many substances already present in the body, or that can be introduced (e.g. nicotine, caffeine, alcohol, dioxin, oranges, tangerines and excess protein from high-protein diets) will speed up the metabolism. Chemicals such as hormones will also increase the activity of enzymes.

Hypericum (St John’s wort) increases the rate of action of cytochrome p450.

• Enzyme Inhibition

Certain flavonoids and furanocoumarins (see Chapter 21 ‘Phenols’, p. 156) inhibit cytochrome p450. Naringenin (found in grapefruits) is a well-known flavonoid that inhibits cytochrome p450; bergapten and quercitin also have this effect. Such inhibition can be a greater problem than enzyme induction, as an unusual rise of a drug or remedy in the system beyond its therapeutic limit can be harmful to the body.

Note: water-soluble chemicals tend to be less toxic than lipid-soluble chemicals because they can be so easily removed via the kidneys. Lipid-soluble compounds, if not dealt with by the detoxification pathways in the liver, tend to be stored in fatty tissues and released at a time when fat stores are utilized, for example if the patient fasts. This is why fasting can make patients ill.

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