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5. LOCAL AND SYSTEMIC EFFECTS OF THE DRUGS. DIRECT AND REFLEX EFFECTS. LOCALIZATION AND MECHANISM OF ACTION. DRUG «TARGETS». REVERSIBLE AND IRREVERSIBLE ACTIONS. SELECTIVE ACTION

Drug effect that occurs at the site of its application is called local. For example, coating drugs cover the mucous membrane preventing irritation of the afferent nerve endings. In local anesthesia, application of a local anesthetic onto the mucous membrane leads to the blockade of sensory nerves endings only at the site of the drug application. However, truly selective local action is observed extremely rarely since most substances are either partially absorbed or have a reflex effect.

The effect of a drug that develops after it is absorbed and carried to the tissues by the blood flow, is called systemic (resorptive1). Systemic effect depends on the routes of administration of drugs and their ability to penetrate through biologic barriers.

Local and systemic effects of drugs can be either direct or reflex. The first occurs at the site of contact of the drug with the tissue. Reflex effect is produced when substances influence exteroor interoceptors causing changes in the status of either corresponding nerve centers or effector organs. For example, application of mustard plasters to treat respiratory illnesses reflexively improves their trophism (essentially mustard oil stimulates skin exteroceptors). Lobeline, administered intravenously, stimulates carotid glomerular chemoceptors and increases volume and frequency of respirations via reflex stimulation of the respiration center.

The main purpose of pharmacodynamics is to find out where and how the drug acts to cause its effects. Due to improvements in methodology these questions are answered not only on systemic or organ level, but also on cellular, subcellular, molecular and submolecular ones. Thus, for neurotropic drugs it is possible to distinguish the structures of the nervous system and the synapses that have the highest sensitivity to these compounds. One can localize tissue enzymes, cells and subcellular formations, activity of which changes most substantially due to substances affecting metabolism. In all cases the search is for biologic «targets» - the substrates with which the drug interacts.

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