CHAPTER 9 - Sedatives, Hypnotics, and Inhalants PDF

CHAPTER 9 - Sedatives, Hypnotics, and Inhalants The text you've provided offers a comprehensive overview of sedative and hypnotic drugs, detailing their historical background, mechanisms of action, effects, medical uses, potential for dependence, and withdrawal management. Below, I've extracted key...

CHAPTER 9 - Sedatives, Hypnotics, and Inhalants The text you've provided offers a comprehensive overview of sedative and hypnotic drugs, detailing their historical background, mechanisms of action, effects, medical uses, potential for dependence, and withdrawal management. Below, I've extracted key points and organized them to aid in understanding: Overview of Sedatives and Hypnotics: - **Definitions**: - **Sedatives**: Drugs that relieve anxiety and cause relaxation. - **Hypnotics**: Drugs that induce drowsiness and sleep. - **Common Classes**: - **Barbiturates**: Used for anesthesia and epilepsy treatment. - **Benzodiazepines (BZDs)**: Commonly used for anxiety relief and muscle relaxation. Historical Context: - **Early Use**: Kava and valerian root have been traditional remedies for anxiety and sleep. - **Chloral Hydrate**: The first synthetic hypnotic, synthesized in 1832. - **Barbiturates**: First synthesized in 1864; became widely prescribed and used for various medical purposes. - **Benzodiazepines**: Discovered in 1955, viewed as safer alternatives to barbiturates. Mechanisms of Action: - **GABA Receptors**: Both barbiturates and BZDs work on GABA receptors but through different mechanisms. - **Benzodiazepines**: Enhance GABA's effects by increasing chloride channel openings. - **Barbiturates**: Bind to multiple sites on the GABA receptor and can increase channel opening duration even without GABA present. Acute Effects: - **Physiological**: - Moderate doses can cause sedation, relaxation, and muscle relaxation. - High doses can lead to unconsciousness or respiratory depression. - **Psychological**: - Mood changes, disinhibition, impaired thinking and memory. Withdrawal and Dependence: - **Barbiturates**: Higher potential for tolerance, dependence, and abuse. Withdrawal symptoms can include severe conditions like seizures and hallucinations. - **Benzodiazepines**: Less addictive than barbiturates but can still lead to dependence and withdrawal symptoms such as anxiety and tremors. Medical Uses: - **Common Indications**: - Anxiety disorders - Insomnia - Seizure disorders - Alcohol withdrawal - **Therapeutic Considerations**: BZDs are preferred due to their safety profile compared to barbiturates. Safety and Side Effects: - **General Side Effects**: Drowsiness, confusion, dizziness, decreased libido, and impaired coordination. - **Serious Risks**: Respiratory depression in overdose situations, particularly dangerous when combined with other CNS depressants. Long-term Use Concerns: - **Cognitive Effects**: Long-term BZD users may experience cognitive impairments. It's difficult to determine whether this is due to the drug or the underlying conditions the drug was prescribed for. - **Risks to Pregnant Women**: Use during pregnancy can lead to withdrawal symptoms in newborns as well as potential congenital malformations. Drug Interactions: - **Synergistic Effects**: Combination with alcohol or other depressants can dangerously enhance respiratory depression. - **Metabolism**: Both barbiturates and BZDs are metabolized through liver enzymes, leading to possible interactions with other medications. Treatment and Management: - **Withdrawal Management**: Should be medically supervised; gradual tapering or switching to longer-acting sedatives may be employed. - **Psychotherapy**: Cognitive-behavioral therapy is often used to address the underlying issues of dependence. 1. Sedatives reduce anxiety and increase relaxation; benzodiazepines reduce anxiety and work as a muscle relaxant; hypnotics induce drowsiness and sleep; and barbiturates treat seizures and work as an anesthetic. 2. Barbiturates were once widely used for sleep; however due to safety concerns, they were phased out for this purpose and replaced with the safer benzodiazepines, which were also popular for treating stress. 3. Why, given the sheer number of drugs in the sedative/hypnotic categories, is the search for CNS depressants that alleviate stress and anxiety still ongoing? Drugs in these categories were all, at one time, thought to be safe and non-addictive; however, they were later discovered to have significant dangers, and cause tolerance, dependence, and withdrawal. 4. Which of these is in the correct order in terms of best clinical uses of barbiturates from long-acting to intermediate/short-acting to ultra-short-acting? epilepsy management → pre-anesthetic sedative → emergency (rapid) surgical anesthetic 5. Benzodiazepines can have a half-life ranging from 1–3 up to 200 hours. 6. Barbiturates tend to work faster than benzodiazepines because barbiturates are absorbed in the stomach, whereas benzodiazepines are absorbed in the small intestine. 7. Sedative/hypnotics work as GABA agonists, while barbiturates and benzodiazepines work at the GABA receptor but have a more specific mechanism of action involving GABAA. 8. BZDs exert different primary effects depending on which subtype of GABAA receptor they bind to. For instance, BZDs that bind to alpha1 subunits are effective hypnotics, and those with a higher affinity for alpha2 or alpha3 subunits are better anxiolytics. 9. Which of the statements below is the best description of the dose-dependent effects of barbiturates and BZDs? Lower doses lead to relaxation and decreased anxiety; medium/high doses may lead to euphoria and sedation/sleep; higher doses can lead to unconsciousness, respiratory depression, coma, and death. 10. The effects sedatives have on mood range widely. All the following are known mood effects except mania. 11. Rohypnol is one BZD which is especially effective at impairing memory formation and causing blackouts; it is best known for its use as a date rape drug. 12. One risk of prenatal exposure to BZDs in the third trimester of pregnancy is that the baby may go through a lengthy withdrawal period starting shortly after delivery. 13. One of the reasons that barbiturates are so dangerous is that their lethal dose is not significantly higher than their effective dose. 14. BZDs are safer compounds than barbiturates, but they are not risk-free. In 2013, BZDs were involved in about 30 per cent of all fatal overdoses of prescription drugs in the United States. 15. What is the link between the recent rise in BZD overdose mortality rates and opioids? This rise occurred at the same time that opioid prescriptions were on the rise and opioids are involved in about three-quarters of the overdose deaths involving BZDs. 16. Compared to tolerance to barbiturates, tolerance to BZDs is not as fast or complete and BZDs do not increase the activity of liver enzymes that metabolize it. 17. All the following are common symptoms of withdrawal from sedatives except constipation 18. Withdrawal from high doses of barbiturates is especially dangerous and may result in all the following except violent outbursts. 1. GHB may take the form of a(n) natural substance found in food, a(n) synthetic drug used for therapeutic and recreational purposes, and a(n) neurotransmitter. 2. At low doses, GHB binds almost exclusively to GHB receptors, which stimulates the release of excitatory glutamate. As the dose of GHB increases, more GHB binds to and activates GABAB receptors. 3. High doses of GHB can put the user into a(n) comatose state relatively quickly; however, it is not uncommon to awaken spontaneously and abruptly from this state. This is one example of how the effects of GHB appear as a(n) paradoxical mix of sedative and stimulatory properties. 4. Which of the following uses is GHB approved for in the Canada? treating narcolepsy 5. Propofol has a fast onset of action as well as a quick recovery time. Not only does propofol reduce awareness, it also leaves the patient with no memory of the experience; for this reason, it is sometimes called milk of amnesia. 1. What sets inhalants apart from the other drugs covered in this chapter? They are found in commonly used household cleaning products. 2. Glues, aerosols, and solvents are all types of volatile inhalants. Ether and nitrous oxide are anesthetic inhalants, and the nitrite group includes amyl nitrite and butyl nitrite. 3. Huffing the fumes of inhalants produces effects most similar to alcohol and anesthetics. 4. Which of the following is not an effect associated with using very high doses of inhalants? Blood oxygenation 5. Compared to the damage seen in cocaine abusers, long-term inhalant abusers are more likely to have brain abnormalities, have more extensive brain damage, and have more memory, cognitive, and behavioural impairments. 6. In terms of cognitive function, it has been found that inhalant abusers performed significantly worse than cocaine abusers on tests of all of the following except for neuroticism Inhalants - Inhalants produce depressant effects and can be found in everyday products. - They include volatile solvents (glues, paints, fuels), anesthetics (chloroform, ether, nitrous oxide), and nitrites. - High doses can lead to effects similar to sedative/hypnotics. History of Inhalants - Ancient Greeks used trance-inducing gases, possibly ethylene, at the Temple of Apollo. - People have historically inhaled fumes from various substances to alter consciousness. - Ether and nitrous oxide were popular recreational inhalants in the mid-20th century. Ether - Discovered by Spanish alchemist Raymundus Lullius in 1275. - Synthesis of diethyl ether developed by Valerius Cordus in 1540, noted for analgesic properties. - Ether used successfully in surgery by William Morton in 1846 but is not used in modern surgeries due to side effects (nausea, flammability). Nitrous Oxide - Discovered by Joseph Priestley in 1772. - Horace Wells demonstrated its use in dental anesthesia in 1845, though initial attempts met with complications. - Not strong enough for major surgery, but used for anxiety and pain relief in dentistry. Glue Sniffing - First print reference to glue sniffing appeared in 1959, highlighting the dangers. - Surge in glue sniffing cases followed media attention; first peer-reviewed article appeared in JAMA in 1962. - The New York Times began an anti-inhalant campaign in 1971. Prevalence of Inhalant Use - Common in younger demographics; often a first introduction to drug use, especially in grades 7 and 8. - Lifetime use reported by approximately 1.3% of Canadians age 15 and older. - Higher prevalence among disadvantaged youth and Indigenous communities. - Use declines with age; lowest among older adolescents. Sources and Forms of Inhalants - Over 1,400 household products can serve as inhalants; categorized as volatile substances, anesthetics, and nitrites. Volatile Substances - Liquid at room temperature and produce fumes for inhalation. - Among the most toxic recreational substances. - Effects include euphoria, dizziness, impaired judgment. - Examples include adhesives (glue), aerosols (spray paint), cleaning agents (degreasers), fuels (butane), and solvents (nail polish remover). Anaesthetic Inhalants: Ether and Nitrous Oxide - Ether: Colorless, flammable liquid; previously a general anesthetic; irritates airways and causes side effects with high doses. - Nitrous oxide: Colorless gas, also known as ‘laughing gas’; euphoria-inducing, primarily available for dental use. Nitrites - Volatile, flammable liquids with fruity odor; include amyl nitrite and butyl nitrite (known as “poppers”). - Amyl nitrite used medically for chest pain or as an antidote for cyanide poisoning; recreational use peaked in the 1970s and 1980s for sexual enhancement. - Sale of poppers prohibited in Canada in 2013. Pharmacokinetics and Mechanism of Action of Inhalants - Inhalation methods include sniffing from bags or rags and direct inhalation from containers. - Effects resemble alcohol and anesthetics, peaking within minutes and lasting 15-30 minutes. - Diverse group with varied mechanisms; commonly thought to interact with GABAergic systems. - Toluene may enhance GABA inhibition and inhibit NMDA receptors; further research needed to clarify mechanisms for inhalants overall. Acute Effects of Inhalants - Similar to alcohol intoxication and high doses of sedative/hypnotics. - Initial effects may include euphoria, disinhibition, dizziness, lightheadedness. - Followed by drowsiness, disorientation, headache. - Heavier doses can cause slurred speech, poor coordination, lethargy, nausea, vomiting, double vision, ringing in the ears, delusions, hallucinations. - Very high doses can lead to unconsciousness, respiratory suppression, coma, and death. Dangers from Inhalants - High doses, method of administration, behavioral effects, and toxic properties pose risks. - Users often expose themselves to concentrations 50–100 times greater than safe levels. - Hypoxia and asphyxiation risks from inhaling less oxygen. - Abrupt cooling from pressurized gases can cause frostbite. - Inhalants are highly flammable; about 25% of inhalant-related deaths are due to accidental burns. - Impaired judgment and coordination can lead to recklessness and accidents. - Toxic effects include vomiting (risk of choking while unconscious), kidney damage, liver damage, anemia, seizures, cardiovascular problems, respiratory suppression, and death. - Death often results from cardiac arrhythmia, hypoxia, accidents, or suicide. - Approximately 20% of inhalant-related deaths occur in first-time users. - Inhalants increase heart sensitivity to adrenaline, leading to fatal arrhythmias, a condition known as sudden sniffing death syndrome. Acute Effects of Nitrous Oxide - Produces mild euphoria, giddiness, drowsiness, and pain reduction. - Users may experience brief loss of consciousness and feelings of flying. - Safe in clinical settings, but risks increase when used recreationally. - Dangers include severe hypoxia if inhaled without oxygen, physical tissue damage from expanding gas, neurotoxicity when combined with NMDA antagonists (e.g., alcohol, dextromethorphan, PCP). - Long-term use can lead to vitamin B12 deficiency, damaging the bone marrow and nervous system, impairing memory and mental functioning. Acute Effects of Amyl Nitrite - Causes vasodilation, leading to sudden blood pressure drop, increased heart rate, warmth, and skin flushing. - Users may feel mildly euphoric or dizzy and may experience visual disturbances (bright yellow spots). - Increased blood flow to genitals and dilation of the anal sphincter may occur. - After inhalation, users may feel nauseated, have vision problems, and experience headaches. - Low toxicity when inhaled, but can interfere with oxygen transport if swallowed or injected. Chronic Effects of Inhalants - Long-term effects are poorly documented as inhalant abuse tends to be sporadic. - Tolerance may develop, leading to withdrawal symptoms (nausea, tremors, irritability, anxiety, sleep disturbances). - Repeated use can lead to rashes around the nose and mouth, nosebleeds, weight loss, depression, hostility, paranoia, and organ damage (liver, kidneys, lungs, bone marrow, brain). - Many inhalants are carcinogenic. - Chronic abuse linked to brain damage and cognitive impairments, ranging from mild to severe dementia. - Studies show inhalant abusers have greater brain abnormalities and cognitive impairment compared to cocaine users. - Affected brain areas include basal ganglia, cerebellum, thalamus, and pons with significant myelin loss. 1. False. There are generally more male users of benzodiazepines (BZDs) than female users. 2. A. a short-acting barbiturate. Short-acting barbiturates are more likely to lead to addiction or abuse. 3. C. Seconal. Seconal is a barbiturate and not a benzodiazepine. 4. When benzodiazepines bind to the GABAA receptor, they increase the frequency of chloride channel openings, but when barbiturates bind, they increase the duration that the chloride channel is open. 5. D. Benzodiazepines have a higher therapeutic index than barbiturates. 6. False. Barbiturates and BZDs are not recommended for use in the elderly because they can have prolonged effects and increased sensitivity rather than being metabolized too fast. 7. True. GHB has an excitatory effect at low doses and a depressant effect at higher doses. 8. False. Inhalants are not among the safest drugs used by adolescents; they can be extremely toxic and dangerous. 9. Inhalants are often categorized into three forms: - Volatile substances (e.g., adhesives like glue) - Anesthetics (e.g., nitrous oxide) - Nitrites (e.g., amyl nitrite) 10. Rohypnol and Quaalude are Schedule I drugs. Phenobarbital, diazepam, and chloral hydrate are not Schedule I; they are categorized differently. Amyl nitrite may vary in classification depending on jurisdiction.