Origin and Physicochemical Properties
The drug is a phenanthrene derivative and accounts for about 10% of the total mass of opium. Although complete chemical synthesis was achieved back in 1952, Morphinum is still obtained on an industrial scale through extraction from plant raw materials due to economic feasibility.
Chemically, it is a weak base (capable of accepting a proton). Its pKa is 7.9, which is very close to the physiological pH of blood.
Pharmacodynamics and Mechanism of Action
The mechanism of action is based on the stimulation of opioid receptors. Exogenously administered morphine mimics the effects of endogenous opioid peptides (specifically, enkephalins).
The central effects of the drug are multifaceted:
- Psychotropic action: induction of euphoria (altering the emotional perception of pain, eliminating fear and tension). This is associated with the stimulation of receptors in the mesolimbic and mesocortical systems.
- Effects on the brainstem: stimulation of the trigger zone of the vomiting center clinically manifests as nausea and vomiting. Excitation of the oculomotor nerve nuclei leads to pupillary constriction (miosis)—this is a crucial diagnostic sign. There is also a decrease in the excitability of the respiratory center.
- Cardiovascular system: in the context of differential diagnosis, morphine is characterized by bradycardia.
Pharmacokinetics and Metabolism
Biotransformation of the drug proceeds via two main pathways:
- Microsomal oxidation: involving endoplasmic reticulum enzymes (primarily the cytochrome P-450 system), N-oxidation and dealkylation of the molecule occur.
- Conjugation (biosynthetic reactions): the drug reacts with an endogenous substrate—glucuronic acid (glucuronidation)—forming esters, thioesters, or amides.
Clinically important interaction: morphine acts as an P-glycoprotein inducer. It increases the activity of this transporter protein, which accelerates the elimination of other drugs (P-glycoprotein substrates) and reduces their therapeutic efficacy.
Acute Poisoning and Management
Overdose is accompanied by profound respiratory depression and marked miosis. Treatment relies on two main directions:
1. Detoxification (removal of the toxin):
- Gastric lavage with 0.05% potassium permanganate solution (causes chemical oxidation of morphine) or an activated charcoal suspension in warm water (toxin adsorption).
- Bowel cleansing: administration of a saline laxative strictly after gastric lavage.
2. Restoration of vital functions:
- Administration of a specific pharmacological antagonist—naloxone (an opioid receptor blocker) intramuscularly or intravenously.
- In case of severe respiratory depression, resuscitation measures are indicated, including mechanical ventilation.
Prescribing Guidelines and Dosage
The drug has a high abuse potential (causes drug dependence), so its dispensing is strictly regulated.
- Oral: prescribed in powders, tablets, or drops at 0.01–0.02 g. The maximum single dose (MSD) orally is 0.02 g.
- Parenteral: administered subcutaneously (SC) as 1 mL of a 1% solution. The maximum daily dose (MDD) for subcutaneous administration is 0.05 g.