5.23: Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or paralyzing parasympathetic ganglia, leading to increased blood pressure and an accelerated heart rate. It can also stimulate epinephrine release from the adrenal medulla. Nicotine has a biphasic effect on the adrenal medulla, with small doses causing catecholamine release and large doses preventing its release.
Nicotine has significant central nervous system [CNS] stimulation effects. Low doses act as analgesics, higher doses cause tremors, and toxic doses result in convulsions. Nicotine directly affects the medulla oblongata, leading to respiratory depression, diaphragm and intercostal muscle paralysis, and peripheral blockade. It induces vomiting through central and peripheral actions. Chronic exposure to nicotine increases nicotinic receptor density, contributing to dependence and tolerance. Nicotine enhances gut tone and motility through parasympathetic cholinergic and ganglionic activation. Initially, bronchial and salivary secretions increase, followed by inhibition. Nicotine can be absorbed through the skin, buccal membrane, and respiratory tract, with limited absorption in the stomach but more efficient absorption in the intestines. Metabolism primarily occurs in the liver, with partial metabolism in the lungs and kidneys. The kidneys eliminate nicotine and its metabolites.
In clinical practice, nicotine is indicated for short-term replacement therapy in individuals abstaining from tobacco. Adverse effects of nicotine include salivation, abdominal pain, diarrhea, dizziness, headache, hearing difficulty, mental confusion, weakness, breathing difficulties with a weakening pulse, blood sugar irregularities, and convulsions. Severe cases can lead to respiratory failure and potentially death.
