13: Anxiolytics Flashcards
Define a depressant. What are they referred to as a group? What is the most widely used and what is the most widely prescribed?
Drugs that slow activity in the nervous system.
Group: sedative-hypnotics.
Alcohol most widely used, benzodiazepines most widely prescribed.
What do inhalants act as? Who are the primary users? Explain how long acute intoxication occurs, overdose risk, and damage due to long-term use.
Act as CNS depressants. Users primarily adolescent or preadolescent (e.g., solvents, glue, paint thinners, fuels).
Acute intoxication few minutes, stupor for hours. Overdose may be fatal - respiratory depression or cardiac arrhythmias.
Long-term use may cause permanent damage to CNS, PNS, liver, kidney, heart, and muscle.
How to treat for inhalants? Any withdrawal?
Treatment: monitoring of airways, breathing, circulation. Inhalant identification helps to apply appropriate detoxification procedure.
Withdrawal does not usually occur, but sx of such are typical.
What is the difference between a tranquilizer/anxiolytic vs. a sedative/hypnotic? What are the four classes of anxiolytics?
Tnquilizer/anxiolytic used to treat anxiety or agitation, whereas sedative/hypnotic is to sedate and aid sleep.
Barbiturates: not commonly used today. Benzodiazepines: most common.
Others: meprobamate, methaqualone.
Z-drugs: (like zolpidem, erzopiclone) fairly new.
What are the three drugs that precede barbiturates? When were they synthesized, used clinically, and what do they do? Any adverse effects?
Chloral hydrate: synthesized in 1832; used clinically in 1870. Induces sleep in less than an hour. Abuse leads to gastric irritation.
Paraldehyde: synthesized in 1829; used clinically in 1882. Effective with a wide safety margin. Noxious taste and odor.
Bromides: widely used as a sleep agent in patent medicines; appeared in OTC drugs through the 1960s. Can accumulate in the body and cause toxic effects.
What was the first barbiturate used clinically? What are barbiturates grouped on and how are doses used?
Barbital (Veronal) became the first barbiturate to be used clinically in 1903.
Grouped on the basis of the time of onset and duration of activity.
Low-dose, long-acting forms used for daytime relief of anxiety. Higher-dose, shorter-acting forms used to induce sleep.
What is the time of onset and duration of action for short-acting, intermediate-acting, and long-acting barbiturates?
Short-acting: time of onset is 15 minutes, duration of action is 2 to 3 hours.
Intermediate-acting: time of onset is 30 minutes, duration of action is 5 to 6 hours.
Long-acting: time of onset is 1 hour, duration of action is 8+ hours.
This ultra-short acting barbiturate is used as an anesthetic for brief surgical procedures. It is also known as a “truth serum” due to its relaxing properties. What is the name of this drug and why does it have a bad history?
Sodium pentothal (thiopental).
One of the drugs administered for the death penalty.
What was the first modern anxiolytic? Is it still used as one?
Meprobamate.
Still available as a prescription drug, although largely replaced by benzodiazepines; it is a muscle relaxant.
Which anxiolytic was not initially monitored when prescribed then quickly became widely misused and abused?
Methaqualone (soapers).
What was the first benzodiazepine and why were they better than barbiturates? What is the current state of benzodiazepines?
Chlordiazepoxide (Librium) in 1960.
Reduces anxiety without inducing sleep, much larger safety margin than barbiturates, physical dependence rare, overdose rare and usually only when combined with other depressants like alcohol.
Diazepam introduced in 1970, became best-selling prescription drug for a time. BDZs most frequently prescribed psychotropic medications.
Regarding benzodiazepines, what factors influence overdose deaths, psychological dependence, and physical dependence?
Overdose: more likely for drugs sold in higher doses.
Psychological dependence: more likely with drugs with a rapid onset of effects.
Physical dependence: more likely with drugs that have short duration of action.
Describe the basic pharmacology of benzodiazepines.
Weak acid, pKa, range 3.5-5.
Range in lipid solubility, EtOH increases absorption. Absorbed from digestive system in 1h.
What is the mechanism of action for benzodiazepines? Is it similar to barbiturates?
Benzodiazepine receptors are near GABA receptors. Activation of GABA-benzodiazepine receptor complex causes influx of chloride ions, causing neurons to hyperpolarize or to become inhibited.
Barbiturates act at a separate binding site nearby and increase actions of GABA on its receptors as well. Both enhance normally inhibitory effects of GABA.
Which GABA receptors are anxiolytic and which ones are sedative?
α1 = sedation α2 = anxiolytic
What do nonbenzodiazepine hypnotics? Give three examples of nonbenzodiazepine hypnotics.
Selectively target the GABA-A receptor.
Ambien, Sonata, Lunesta.
Describe nonbenzodiazepine hypnotics. What are they otherwise known as and why have recommended doses dropped significantly?
Depressant drugs that do not have the chemical structure of benzodiazepines but have similar effects.
Otherwise known as Z-drugs. Reduced due to research showing impairment of driving skills next day after taking a pill.
Do BDZs have inhibitory effects? How do they effect sleep?
Inhibition: barbiturates reduce respiration, BDZs do not. Muscle relaxants, anti-convulsants.
Sleep: reduce sleep latency, increase sleep time. Reduced N-REM, stages 3 and 4 of slow-wave sleep (tolerance builds).
What is the duration of action for secobarbital, phenobarbital, and diazepam? How does diazepam compare to chlordiazepoxide?
Secobarbital: short-acting barbiturate (t½ = 15-40h).
Phenobarbital: long-acting barbiturate, less likely to produce psychological dependence (t½ = 50-120h).
Diazepam (t½ = 20-100h) has more rapid onset than chlordiazepoxide (t½ = 5-30h) but has a longer duration of action due to slow metabolism.
Describe rohypnol. Why is it controversial and illegal?
10x more potent than diazepam, produces profound intoxication when mixed with alcohol. Reports surfaced of the drug being slipped into drinks and used as a “date-rape” drug.
Which provinces have the highest rate of BDZ prescription?
Alberta, Atlantic Canada, Yukon.
Are there any sex differences with regards to BDZ usage?
Females use more than males.
What were the results of a study which measured alprazolam with a Trier Social Stress Test?
Alprazolam significantly reduced ACTH and cortisol. TSST also induced a pronounced increase of epinephrine and norepinephrine.
Subjects felt significantly more tired than placebo-treated control subjects. Mood and calmness were slightly reduced in the placebo group.
Which four BDZs are among the top 100 prescribed drugs in the U.S.?
Xanax, Ativan, Klonopin, Valium.
