Etiology and Classification of Opioids
Opioid dependence develops upon systematic use of specific psychoactive substances. Originally, these compounds were derived exclusively from the milky latex 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:
| Opioid Group | Characteristics and Main Representatives |
|---|---|
| Natural Opiates | Alkaloids contained in plant raw materials. These include morphine, codeine (3-methylmorphine), and pantopon. |
| Semisynthetic Opioids | Derivatives synthesized from the morphine molecule. These include hydromorphone, diacetylmorphine (heroin), and oxycodone. |
| Synthetic Opioids | Artificially created analogs with a similar mechanism of action, such as pethidine (meperidine) or fentanyl derivatives. |
Pathogenesis and Physiological Basis
A key link in the development of opioid dependence is the interaction of exogenous narcotics with opioid receptors. Notably, these receptors are distributed across virtually all human tissues, but the vast majority and primary functional activity are concentrated within nervous tissue.
The physiological basis of this receptor system relies on natural ligands—endogenous opioid peptides. This group of internal regulators produced by the body includes enkephalins, endorphins, and dynorphins. In opioid dependence, exogenously administered opioids bind to these receptors, profoundly disrupting normal neurophysiology.
Central Nervous System (CNS) Effects
When opioids bind to central nervous system (CNS) receptors, a complex of specific reactions develops. There are three main effects, each with a distinct neuroanatomic localization:
- Analgesic Effect. Manifests as a marked reduction in pain sensitivity. This mechanism is mediated via spinal cord neurons, thalamic structures, and the periaqueductal gray matter surrounding the cerebral aqueduct (Sylvian aqueduct).
- Sedative Effect. Characterized by a general calming action, mediated directly by neurons of the reticular formation and the striatum.
- Euphoric Effect. This plays a critical role in the development of dependence. The mechanism of euphoria is inextricably linked to powerful activation of the limbic system neurons.
Comorbid Complications and Pharmacokinetics
Alongside alterations in higher nervous activity, opioid dependence presents severe systemic complications:
- Respiratory Depression. This is the most dangerous manifestation, caused by respiratory center neurons losing their normal sensitivity to the partial pressure of carbon dioxide (pCO₂) in the blood.
- Nausea and Vomiting. This side effect is directly mediated by stimulation of the area postrema and neurons in the medulla oblongata.
- Gastrointestinal (GI) Tract Suppression. There is a total inhibition of the motor and secretory activity of the digestive system, clinically accompanied by marked anorexia and persistent constipation.
Pharmacokinetics of Opioids Routes of administration include absorption through the GI tract, pulmonary inhalation, or parenteral injection (directly into the bloodstream). Following entry into the systemic circulation, metabolism begins. The primary transformation of opioids occurs in the liver, predominantly through conjugation with glucuronic acid. The final stage is elimination: the resulting metabolites are excreted via feces and urine.