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Dose-response relationship

The effect produced by a drug varies with the concentration present at its site of action and usually approaches the maximum value beyond which a further increase in concentration is no more effective. Generally, as the dose of a drug increases, the effect produced will reach a maximum level. A useful measure of the drug effect is the median effective dose, ED₅₀, which is defined as the dose producing a response that is 50% of the maximum obtainable. ED values provide a useful way of comparing the potencies of drugs that produce physiologically similar effects at different concentrations. Sometimes the response is measured in terms of the proportion of individuals in a sample population that show a given all-or nothing response (e.g., loss of reaction to a painful stimulus or appearance of convulsions) rather than a continuously graded response; as such, the ED₅₀ represents the dose that causes 50% of the sample population to respond. Similar measurements can be used as a rough estimate of drug toxicity, the result being expressed as the median lethal dose LD₅₀, which is defined as the dose causing mortality in 50% of a group of animals.

When a drug is used therapeutically it is important to understand the margin of safety that exists between the dose needed for a desired effect and the dose that produces unwanted and possibly dangerous effects. This relationship between the dose of a drug required to produce undesired effect (toxic or lethal) and the dose required to produce the desired therapeutic effect is termed the therapeutic index, and is defined as the ratio TD₅₀: ED₅₀, where TD₅₀ is the median toxic dose, and ED₅₀ is the median effective dose. In general, the narrower the margin of safety, the more likely it is that the drug will produce unwanted effects. The margin of safety is the ratio of the minimum toxic dose for 0.1% of the population (TD_0.1) to the minimum effective dose for 99.9% of the population (ED_99.9).

The drug effect can be enhanced when several drugs are administered concurrently. The effects of polypharmacy can be described in terms of addition, synergism, or potentiation.

Addition occurs when two different drugs with the same effect are given together, which results in a drug effect that is equal in magnitude to the sum of the individual effects of the two drugs. For example, trimethoprim and sulfamethoxazole inhibit different steps in the synthesis of folic acid, resulting in suppressing bacterial growth.

Synergism occurs when two drugs with the same effects are given together, producing a drug effect that is greater in magnitude than the sum of the individual effects of the two drugs. For example, penicillin and gentamicin are synergistic in their anti-pseudomonal activities.

Potentiation occurs when one drug, lacking an effect of its own, increases the effect of another drug that is active. The response to a given dose of a drug is likely to vary when it is given to different people or to the same person on different occasions. This is a serious problem, for it can result in a normally effective dose of a drug being ineffective or toxic in other circumstances. Many factors are known to contribute to this variability, with some important ones being age, genetics, disease states, drug interactions, and drug tolerance. Pediatric drug therapy is the greatest challenge to the pharmacist, because children are so different from adults in pharmacokinetic parameters which change as they mature from birth to adolescence. Drug selection, doses, and dosage intervals change throughout childhood, making drug therapy monitoring essential. Drug therapy in geriatric patients can also be very difficult because of the age-related changes in pharmacokinetics and pharmacodynamics.

II.11. Переведите следующие цепочки слов:

to define – defined – definite – indefinite – definitely – indefinitely – definition

to relate – related – relation – relatively – relationship

synergy – synergist – synergistic – synergism – synergistically

II.12. Назовите номера высказываний, соответствующих содержанию текста В.

1. In general, the larger the drug dose, the higher the drug concentration at the site of action and the greater the effect of the drug up to a maximum effect.

2. Potentiation occurs when two different drugs with the same effect are given together, and the resulting drug effect is equal to the sum effects of the two drugs.

3. The therapeutic index is the same as the median effective dose.

4. The margin of safety is expressed as the median lethal dose.

5. The effect of a drug can vary when given to the same person on different occasions.

6. Drug therapy in geriatric patients presents the greatest problem to a pharmacist.

7. Drug therapy in children is age-related.

II.13. Ознакомьтесь со словами к тексту C.

II.14. Прочтите и переведите текст C.

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