Opioid addiction

Etiology and classification of opioids

Opioid addiction develops upon systematic use of specific psychoactive substances. Initially, these compounds were obtained exclusively from the milky juice of the opium poppy (Papaver somniferum). In modern pathophysiology and pharmacology, all substances capable of causing this type of dependence are divided into three main groups:

Pathogenesis and physiological basis

A key link in the development of opioid addiction is the interaction of exogenous narcotic substances with opioid receptors. It is important to note that the localization of these receptors spans virtually all tissues of the human body, yet the overwhelming majority and primary functional activity are concentrated precisely in nervous tissue.

The physiological basis of this receptor system's function lies in the presence of natural ligands—endogenous opioid peptides. This group of internal regulators produced by the body itself includes enkephalins, endorphins, and dynorphin. In opioid addiction, externally introduced opiates bind to these receptors, severely interfering with normal neurophysiology.

Effects of interaction with the central nervous system

When opiates bind to central nervous system (CNS) receptors, a complex of specific reactions develops. There are three main effects, each with its own neuroanatomical localization:

• Analgesic effect. Manifests as a pronounced decrease in pain sensitivity. This mechanism is mediated via spinal cord neurons, thalamic structures, and the gray matter located in the region of the cerebral aqueduct.
• Sedative effect. Characterized by a general calming action realized with the direct participation of reticular formation neurons and the striatum (striatum).
• Euphoric effect. It plays a key role in the formation of dependence. The mechanism of euphoria development is inextricably linked with powerful activation of limbic system neurons.

Concomitant disorders and pharmacokinetics

Simultaneously with the impact on higher nervous activity, severe concomitant vital activity disorders are observed in opioid addiction:

1. Respiratory depression. This is the most dangerous manifestation, caused by the respiratory center neurons losing their normal sensitivity to the partial pressure of carbon dioxide (pCO₂) in the blood.
2. Nausea and vomiting. This side effect is directly mediated by the impact on neurons of the medulla oblongata.
3. Decreased gastrointestinal (GI) tract functions. There is total suppression of the digestive system's motor and secretory activity, clinically accompanied by pronounced anorexia and persistent constipation.

Pharmacokinetics of opioids Routes of entry of narcotic substances into the body include absorption through the GI tract, penetration through the lungs, or parenteral administration (directly into the bloodstream). After entering the bloodstream, the metabolism stage begins. The main transformation of opioids occurs in the liver, predominantly via conjugation of substances with glucuronic acid. The final stage is elimination: the resulting metabolites are excreted from the body via feces and urine.

Class and exam questions

What else to study on this topic

• Mechanisms of opioid conjugation with glucuronic acid in the liver.
• The role of the gray matter in the area of the cerebral aqueduct in the realization of the analgesic effect.
• Pathogenesis of the suppression of GI motor and secretory activity (anorexia and constipation).
• Interaction of endogenous opioid peptides (enkephalins, endorphins, dynorphin) with receptors under normal conditions.
• Neurophysiology of the decrease in respiratory center sensitivity to pCO₂.

Other topics in «Chapter 18. Drug Addiction. Substance Abuse. Poisoning»

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