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Mechanisms of drug action

Drugs are able to affect the functioning of living organisms by interrupting the extensive chemical system of communications that regulates the integrated functioning of the cells of the organism. The effects of drugs mimic those of endogenous substances of the body and thus they do not impart new activities to the cells. In order for a drug molecule of a certain molecular configuration to be effective, it must bind with a specific, complementary site that is often located on the membrane of the cell and that is called a receptor. The drug receptor complex thus formed triggers certain biochemical changes within the cell to bring about specific biochemical effects.

Drugs that bind to receptors and actively bring about biochemical changes are called agonists. Drugs that compete with agonists (which can be other drugs or endogenous molecules) but do not in themselves bring about an effect are called antagonists. Regardless of whether a drug is an agonist or an antagonist, it will not exert its influence on target molecules or cells if the receptor configuration is not complementary.

Receptors can be proteins, glycoproteins, or nucleic acids. Receptors can be located at the cell surface, within the cytoplasm, or inside the nucleus. The binding of drugs to receptors is highly specific and can involve a variety of interactions, including hydrophobic interactions, van der Waals forces with ionic, hydrogen, and covalent bonds. The type of interaction and the binding affinity can influence the duration and reversibility of the drug action.

The effects of some drugs do not involve binding with specific receptors because of interactions with molecules or ions, which are not typically defined as receptors. Colligative drug effects are characterized by a lack of requirement for a highly specific chemical structure. Volatile general anesthetic agents with diverse structures are lypophilic and interact with the lipid layer of cell membranes, resulting in depressed excitability. Cathartics, such as magnesium sulfate and sorbitol, act by increasing the osmolarity of intestinal fluids, and, thus changing the distribution of water.

Certain drugs interact with specific ions normally found in the human body. For example, antacids such as aluminum hydroxide, calcium carbonate and magnesium hydroxide act by neutralizing gastric acid.

Systemically active drugs must enter the bloodstream and be transported to the tissues and organs of the body. The drug must pass various cell membrane barriers, escape excessive distribution into sites of loss, and penetrate the site of action. There, the drug molecules must interact with the receptors in order to alter the function of the organ or the body as a whole. Then the drug must be removed from the site of its action and metabolized to a substance form that is easily excreted from the body.

Absorption, metabolism, utilization, and excretion of the drug all depend on its physicochemical properties and the physiological and biochemical properties of the living organism. The drugs can be classified as structurally specific and structurally nonspecific. Structurally specific drugs are those for which pharmacologic activity is determined by the drug's ability to bind to a specific endogenous receptor. Structurally nonspecific drugs are those for which the drug interaction with the cell membrane depends on the physical characteristics of the drug molecule rather than on its chemical structure. Usually, the interaction is based on the nature of the lipids in the cell membrane and the lipophility of the drug.

Another important characteristic of a drug is its bioavailability. Bioavailability is a measurement of the rate and extent to which the active ingredient of the drug becomes available at the site of action. Bioavailability is also considered as a measurement of the rate and extent of systemic absorption of a therapeutically active drug.

II.3. Выпишите из текста А –ing-формы, определите их функции и переведите письменно предложения с ними.

II.4. Найдите в тексте А случаи употребления инфинитива и переведите их на русский язык.

II.5. Найдите в правой колонке синонимы для слов в левой колонке.

to affect similar

to interrupt to change

to mimic location

to trigger value

site to discontinue

within to imitate

to alter to influence

magnitude inside

the same to bring about

II.6. Соедините эти слова в пары антонимов:

new, inside, to continue, to increase, old, active, to interrupt, monopharmacy, outside, irreversible, to decrease, nonspecific, inactive, polypharmacy, an agonist, broad, maximum, an antagonist, reversible, specific, minimum, narrow.

II.7. Прочтите текст А и выделите четыре группы лекарств согласно механизма их действия. Составьте списки ключевых слов для расшифровки понятий an agonist, an antagonist; a specific drug, a nonspecific drug. Напишите 4 дефиниции, расшифровывающие эти понятия.

II.8. Ознакомьтесь со словами к тексту В.

II.9. Прочтите текст В. Найдите в нём два предложения с независимым причастным оборотом и переведите их письменно.

II.10. Ответьте на вопросы по содержанию текста.

1. What does the effect of the drug at the site of its action depend on?

2. What is the common measurement of the drug effect?

3. What is the therapeutic index?

4. When can the drug effect be enhanced?

5. What is synergism? Give an example.

6. What factors contribute to variability of drug effect?

7. Which group of population presents the greatest problem to the pharmacist and why?

8. Why is drug therapy in geriatric patients difficult?

9. What other groups of patients can present difficulties? Give the reasons.

Text В