Toxicology

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Chapter 40 Toxicology

In the study of toxicology, a solid appreciation of pharmacokinetics and pharmacodynamics (see Chapters 14 to 19) is very important, as the mechanics of the two areas are very much a part of what makes a chemical harmful to a patient. Poisons or toxicants are chemicals that have harmful or adverse effects on living organisms. A chemical can be poisonous under one set of conditions and not under another. For example, potassium is a vital part of body metabolism, but too much will cause atrial fibrillation.

There are two different types of toxic reaction:

1. Irreversible: e.g. mutagenicity (mutation), carcinogenicity (cancer promoting), teratogenicity (congenital malformations) and death.

2. Reversible: providing the initial damage is not overwhelming, such as:

• organ damage, e.g. liver, kidney or skin

• functional damage, e.g. respiratory depression, loss of consciousness or convulsive effect.

When dealing with chemicals, the following must be kept in mind:

• The chemical must get to the effector site (such as a synapse or enzyme receptor site) in a biological system to produce a biological effect.

• Not all chemically induced biological effects are harmful, e.g. the therapeutic effects of herbs.

• The occurrence and intensity of chemical-induced biological effects are dose related.

• Interactions with other chemicals might potentiate the effect of one or more of the active compounds in the drugs, creating a toxic effect in the body.

• The chemical might be altered in the body and the metabolites might cause problems (see Chapter 7 ‘Free radicals’, p. 41).

The Occurrence of Poisons

Virtually all chemicals can be considered toxic under certain conditions, e.g. pure water when inhaled is rapidly absorbed across the lung alveoli to cause lysis of red blood cells. Poisoning is either:

• Acute: this usually manifests as anaphylactic shock e.g. to nuts. Remember that some Chinese herbs are nuts, e.g. Semen/Prunus persicae (peach kernels, Tao Ren) so it might be worth asking patients if they have any known allergies to nuts; they will usually know.

• Chronic: the more usual type of poisoning encountered by herbalists. The chemical builds up over a period of time in the body, particularly anything fat soluble. The symptoms can be far less obvious than for acute poisoning, and in the long term might be lethal or sublethal (e.g. the patient might be ill and tired all the time).

Drug Absorption

The tissues that are most susceptible are those directly in contact with the environment, e.g. skin, mucous membranes of the lungs and gut.

Gut

This is a common route of entry. Different parts of the gut allow different rates of absorption:

• Mouth: rapid absorption. Chemicals in the mouth are in a fairly pure form, not having been diluted or transformed by enzymes or stomach acid. Chemicals entering the body via the mouth will not immediately enter the liver (which is the main detoxifying organ). If you are not sure whether a patient is likely to react to a decoction, ask him or her to take a small amount into their mouth, swill it around, then spit it out.

• Stomach: the change in pH alters the absorption of chemicals (see Chapter 8 ‘Acids and bases’, p. 55). Decreasing pH leads to increased gastric clearance. Gastric movements mix the food material bringing it in close contact with gastric juices:

• Gastric retention increases with decreased motility: the gastric retention will increase if the toxin favours gastric absorption.

• Gastric retention decreases with increased motility: the toxin might be more of a problem in this case if it is better absorbed in the duodenum.

• A fatty diet increases gastric retention time: this is why good movement around the gastrointestinal tract is important so that the normal toxins ingested do not hang around.

• Small intestine: the major site for absorption. The absorption area is large – approximately 250 m², which is the size of a tennis court.

• Large intestine and rectum: rectal absorption bypasses the liver and enters the bloodstream quickly. Thus suppositories can be used in cases where a drug is needed to act fast. However, because they initially bypass the liver, any reaction to the drug will be difficult to counteract.

Respiratory Tract

As much blood passes through the lungs as all the remaining parts of the body together. The lungs are therefore one of the most vascular and effective sites of absorption of the body. This is why it is possible for a patient to have an anaphylactic reaction from inhalation.

Skin

The total skin area of an average human is 2 m²; the skin is a relatively effective barrier to toxins. This is because the toxin has to reach the inner layer – the dermis – before it can diffuse into the bloodstream. The outer layer – the epidermis, through which the toxin must pass – is made up of dead, cornified cells and no active transport takes place. Only lipid-soluble substances will pass through the epidermis. This tends to occur at the sweat glands, sebaceous glands and hair follicles; however, these comprise only 1% of total skin’s surface area.

• Factors Affecting Toxin Absorption through the Skin

• If a toxin is lipid soluble and is contained in a lipid then its absorption is enhanced. Ointments tend to keep the chemical in one area for absorption, so a local as well as a systemic reaction might occur.

• Strong detergents and lipid solvents can remove the surface lipid layer from the skin and make it more susceptible to toxins.

• Damage or injury to the skin, e.g. cut or graze, will cause problems, as the underlying tissue will come into direct contact with toxins present in the environment. This is why Arnica cream must only be applied to unbroken skin.

Distribution and Transport

The Role of Blood

• Only high-molecular-weight materials, e.g. proteins, will be prevented from passing through the blood vessel wall.

• Toxins can travel free in plasma (where they are more of a problem) or bound to plasma proteins or within red and white blood cells (Chapter 16 ‘How do drugs get into cells?’, p. 123).

• The brain, cerebrospinal fluid and developing fetus are separated by a protective layer of cells from the blood (Chapter 16 ‘How do drugs get into cells?’, p. 126). However, the placenta is not a very effective barrier to the entry of toxic chemicals. Many toxins enter the fetus by diffusion, e.g. thalidomide. Herbs containing volatile oils are thought not to be advisable for use during pregnancy as they can easily pass through to the fetus.