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5.23:

Fármacos que Atuam em Gânglios Autônomos: Estimulantes

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Pharmacology
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JoVE Core Pharmacology
Drugs Acting on Autonomic Ganglia: Stimulants

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Recall that the nAChRs are classified as NM and NN receptors. Agents that specifically stimulate the NN receptors are called ganglionic stimulants. Being lipid soluble, these agents are absorbed readily via the mucosal membrane. They possess CNS stimulant properties. At lower doses, they exhibit analgesic effects, while higher doses can induce tremors. Toxic doses can lead to convulsions. Additionally, their impact on the medulla oblongata results in respiratory muscle paralysis, causing labored breathing. They also trigger the CTZ  within the brain, which induces vomiting. They stimulate the adrenal medulla to release adrenaline, which in turn causes sympathetic stimulation and induction of tachycardia, ultimately leading to increased blood pressure. Ganglionic stimulants undergo metabolism in the liver and are eliminated via the kidneys. Adverse effects associated with them include dizziness, tremors, fluctuations in blood sugar level, convulsions, development of tolerance, and withdrawal symptoms.

5.23:

Fármacos que Atuam em Gânglios Autônomos: Estimulantes

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.