12.2: CNS Depressants: Alcohol and Nicotine

Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol ingestion triggers life-threatening withdrawal symptoms, known as delirium tremens (DTs) (tachycardia, sweating, tremors, anxiety, hallucinations, and convulsions), necessitating immediate medical intervention and long-term addiction treatment. For treating alcohol dependence, medications like disulfiram create aversive reactions to deter further drinking, while naltrexone reduces cravings. Acamprosate, combined with psychotherapy, helps decrease cravings through NMDA-mediated glutamatergic effects.

Nicotine, a widely used CNS stimulant found in tobacco, leads to euphoria, improved attention, and cognition at low doses. However, it causes ganglionic blockade at high doses, raising concerns about health risks. So, nicotine has a dose-dependent dual action as both CNS stimulant and depressant. Nicotine's addictive potential is high, with withdrawal symptoms such as irritability, sleep problems, and difficulty concentrating. To combat nicotine addiction, therapies like nicotine replacement therapy (NRT), cytisine, varenicline, bupropion, and behavioral approaches have proven effective. The rapid absorption of nicotine through various routes, including smoking and skin contact, contributes to its addictive nature. Both alcohol and nicotine addiction require detoxification to manage withdrawal symptoms and for long-term treatment. Cross-tolerance between alcohol and sedatives like benzodiazepines exacerbates the dangers of concurrent use. Alcoholism's adverse effects extend beyond addiction, including depression, memory impairment, liver disease, and gastrointestinal problems. Comprehensive evaluation, hydration, and pharmacotherapy, often with benzodiazepines, constitute the initial steps in alcohol detoxification.

CNS depressants like alcohol and nicotine mediate their actions via ionotropic receptors by distinct mechanisms.

Ethanol, primarily found in alcoholic beverages, acts as a GABA agonist and inhibits glutamate's excitatory actions, causing impaired motor control and sedation.

Chronic ethanol use can lead to tolerance and physical dependence, resulting in withdrawal symptoms like anxiety, tremors, and seizures.

Alcohol dependence is treated with detoxification and pharmacotherapy, using drugs like benzodiazepines. Further, disulfiram creates unpleasant reactions to alcohol consumption and mitigates cravings.

Additionally, naltrexone, a competitive, long-acting opioid antagonist, and acamprosate, an NMDA regulator, also help reduce alcohol cravings.

Nicotine, found in tobacco, acts as a CNS stimulant and a depressant. It stimulates the nicotinic acetylcholine receptors in the CNS, leading to dopamine release. This creates feelings of relaxation and pleasure.

Nicotine withdrawal can cause irritability, restlessness, and cravings.

To assist nicotine deaddiction, varenicline, a partial nicotinic receptor agonist, alleviates withdrawal symptoms.