Origin and Metabolism
The drug is obtained by extraction from the dried latex of the opium poppy (Papaver somniferum). Although total synthesis was achieved in 1952, isolation from plant material remains the most economically viable method.
Oral administration is rare: due to intense first-pass hepatic metabolism, bioavailability is low. Parenteral administration yields a significantly faster onset of effect. Morphine itself crosses the blood-brain barrier poorly (unlike its chemically modified derivative, heroin). In the liver, the substance actively conjugates with glucuronic acid. The resulting metabolite, morphine-6-glucuronide, exceeds the parent compound in both potency and duration of analgesic action. Excretion occurs primarily via the kidneys.
Central Pharmacological Effects
The effects are mediated by binding to opioid receptors in the central nervous system. Key manifestations include:
- Analgesia and sedation: pain is relieved, and superficial sleep occurs without memory loss.
- Psychoemotional sphere: patients often experience euphoria (a sense of absolute comfort, suppression of hunger), which serves as a trigger for addiction. In healthy individuals without pain, dysphoria (a feeling of malaise and anxiety) may occur.
- Brainstem reflexes: the drug stimulates oculomotor nerve nuclei, causing persistent miosis. It also stimulates the trigger zone of the vomiting center (provoking nausea, particularly with motion), but paradoxically depresses the vomiting center itself. The cough reflex is suppressed very rapidly.
- Respiration: a vital effect. Morphine decreases the sensitivity of neurons to carbon dioxide. In overdose, breathing becomes shallow and extremely slow, potentially leading to complete respiratory arrest.
- Neuroendocrine regulation: the hypothalamus responds by increasing the production of prolactin, growth hormone (somatotropin), and antidiuretic hormone, while decreasing the secretion of adrenocorticotropic and gonadotropic hormones.
Peripheral Effects on Organs and Tissues
Beyond the nervous system, the drug significantly affects smooth muscle and mediator release:
- Gastrointestinal tract: motor activity of the stomach and intestines decreases, but sphincter tone increases sharply. Spasm of the sphincter of Oddi disrupts bile outflow. Together, these effects lead to pronounced constipation.
- Urinary system: the ureters and urethral sphincter go into spasm, creating a direct risk of acute urinary retention.
- Histamine release: provokes cutaneous vasodilation, urticaria, and increases the risk of bronchospasm, which is particularly dangerous for patients with bronchial asthma.
Tolerance, Dependence, and Indications
With regular use, receptor sensitivity decreases unevenly. The body quickly develops tolerance to analgesia, euphoria, and respiratory depression—allowing dependent individuals to tolerate doses that would be fatal to a non-tolerant person. However, tolerance virtually never develops to miosis and constipation.
Physical dependence manifests as a severe withdrawal syndrome. Initially, lacrimation, rhinorrhea, and piloerection («goosebumps») appear, followed by tachycardia, tremor, vomiting, and severe back and abdominal pain.
In clinical practice, morphine is the drug of choice for severe pain syndromes (oncology, extensive burns, myocardial infarction), for the prevention of traumatic shock, and for managing acute pulmonary edema. Administration is strictly contraindicated in respiratory depression, high intracranial pressure, as well as in children under 2 years of age and pregnant women.