Mechanism of action and systemic effects
Nicotinic agonists stimulate neuronal-type nicotinic acetylcholine receptors. Since this receptor group is localized in both sympathetic and parasympathetic ganglia simultaneously, the ultimate pharmacological response of organs is of a mixed nature.
- Cardiovascular system: Sympathomimetic effects predominate. Activation of sympathetic ganglia, release of catecholamines (adrenaline and noradrenaline) by the adrenal glands, and stimulation of the vasomotor center via the carotid bodies lead to vasoconstriction, tachycardia, and increased blood pressure. However, transient bradycardia (resulting from parasympathetic ganglion stimulation) may be observed at the very onset of action.
- Gastrointestinal tract: Parasympathomimetic effects dominate. Stimulation of intramural ganglia increases intestinal tone and dramatically enhances peristalsis.
- Exocrine glands: Secretory activity is increased, although high (toxic) doses produce an inhibitory effect.
Pharmacology of nicotine
Nicotine is the main alkaloid found in tobacco leaves (Nicotiana tabacum). Chemically, it is a tertiary amine (containing pyridine and pyrrolidine rings) with high lipophilicity, allowing it to easily cross the blood-brain barrier.
Effects on the CNS: Releases dopamine and other biogenic amines, producing subjective pleasurable sensations and marked psychological dependence. The effect on the respiratory center is dose-dependent: small amounts stimulate respiration, while large amounts cause depression up to complete arrest (paralysis). Additionally, high doses provoke tremors, seizures, and stimulate the trigger zone of the vomiting center.
Pharmacokinetics: Rapidly absorbed through the respiratory mucosa and intact skin. Metabolized by the liver and excreted by the kidneys (both unchanged and as metabolites). The half-life is only 1.5–2 hours, and tolerance to the substance develops rapidly.
Poisoning: Acute intoxication (via skin or mucosal contact) causes hypersalivation, vomiting, diarrhea, transition from bradycardia to tachycardia, elevated blood pressure, dyspnea, and seizures. Death results from paralysis of the respiratory center; the primary intervention is mechanical ventilation. Chronic poisoning from smoking leads to bronchitis, lung cancer, and cardiovascular pathologies.
Lobeline and cytisine: clinical use
Unlike nicotine, the alkaloids lobeline (from the plant Lobelia inflata) and cytisine (from plants of the genera *Cytisus* and *Thermopsis*) have found application in medical practice.
- Smoking cessation aid: Administered as tablets (e.g., Lobesil and Tabex), they bind to receptors, acting as replacement therapy. This helps reduce distressing withdrawal symptoms.
- Reflex respiratory stimulation: When administered intravenously as solutions (e.g., Cytiton), they stimulate the receptors of the sinocarotid zone, which reflexively stimulates the respiratory center in the medulla oblongata. This effect is short-lived—from 2 to 5 minutes. Indications are rare: neonatal asphyxia (if mechanical ventilation is unavailable) and carbon monoxide poisoning.
Important clinical limitation: These drugs are effective only when reflex excitability of the medulla oblongata is preserved. They are completely ineffective in poisonings caused by hypnotics or general anesthetics, as the reflex arc is blocked in these cases.
To understand the effect of lobeline on blood pressure, remember the principle "one step back, two steps forward" (biphasic effect): first, vagal center stimulation lowers blood pressure, and then sympathetic ganglion and adrenal stimulation persistently raises it. In contrast, cytisine goes "forward only"—producing an exclusively pressor effect.
Class and exam questions
Why does nicotine cause strong dependence?
It is highly lipophilic, easily crosses the blood-brain barrier, and stimulates dopamine release in the CNS, causing pleasurable sensations. When administration ceases, a severe withdrawal syndrome and psychological dependence develop.
Can cytisine be used to stimulate respiration in barbiturate poisoning?
No. In poisoning with CNS depressants (hypnotics, general anesthetics), the reflex arc is blocked, so reflex stimulants will not work.
What is the immediate cause of death in acute nicotine poisoning?
Death results from paralysis of the respiratory center. The only effective life-saving measure in this situation is the immediate transfer of the patient to mechanical ventilation.
What else to study on this topic
- Chemical structure: differences between tertiary amines (nicotine, lobeline) and secondary amines (cytisine)
- Toxicokinetics of nicotine and features of tolerance development
- Symptoms of acute lobeline and cytisine overdose
- Contraindications to respiratory stimulants (arterial hypertension, atherosclerosis, pulmonary edema)
- Pharmacotherapy replacement for smoking cessation (patches, gums)
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