Anxiety Disorders and Treatments Quiz

Sedative-Hypnotic Drugs

• Sedative is a drug that calms a person, reducing excitement.
• Hypnotic produces sleep-like normal sleep.
• Sedative-hypnotic drugs in small doses are sedatives and in large doses are hypnotics.
• Sedation and hypnosis are different degrees of CNS depression.

Anxiety

• Anxiety can be a normal emotion and a psychiatric illness.
• A certain amount of anxiety is helpful, acting as a stimulant and improving efficiency.
• Excessive anxiety, disproportionate to the situation, becomes a pathological, disabling condition requiring treatment.

Anxiety Classification

• Primary Anxiety Disorders:
  • Generalized anxiety disorder (GAD): Apprehensive and tense with no specific reason.
  • Panic disorder: Unexpected anxiety attacks.
  • Phobic disorders: Fears of specific situations (e.g., agoraphobia).
  • Obsessive-compulsive disorder (OCD): Repetitive behaviors or thoughts.
  • Post-traumatic stress disorder (PTSD): After traumatic events (e.g., rape, warfare).
• Secondary Anxiety Disorders: Caused by medical conditions or substances.

Anxiety and Anxiolytic Drugs

• Anxiety is one of the most common mental disorders.
• Anxiety is a state of tension, apprehension, or unease, stemming from known or unknown sources.
• Physical symptoms of severe anxiety mimic fear, involving sympathetic activation (e.g., tachycardia, sweating).
• Mild anxiety is a common life experience and usually doesn't need treatment.
• Severe or chronic anxiety may be treated with anxiolytics (anti-anxiety drugs).

Classification of Sedatives and Hypnotics

• Benzodiazepines (BZDs): Diazepam (Valium)
• Barbiturates: Phenobarbital
• Nonbenzodiazepine hypnotics: Zolpidem, zopiclone, zaleplon, eszopiclone
• Others: Melatonin, ramelteon, suvorexant

Benzodiazepines

• Widely used anxiolytics.
• Replaced barbiturates in anxiety and insomnia treatment due to their perceived safety and effectiveness.
• Although commonly used, they are not always the best choice.
• Certain antidepressants (SSRIs) and non-benzodiazepine hypnotics may be preferable in some cases.

Pharmacokinetics of BZDs

• Typically administered orally or intravenously (occasionally rectally in children).
• Oral absorption is variable; intramuscular route less reliable.
• Triazolam absorption is rapid.
• High volume of distribution.
• Short duration of action despite long elimination half-lives.
• Metabolized in the liver; some undergo enterohepatic recycling.
• Metabolites often have long half-lives, leading to cumulative effects.
• Clorazepate is a prodrug.
• Crosses the placental barrier.

Duration of Action of Benzodiazepines

• Classified by duration of action as long-acting, intermediate-acting, and short-acting.

Mechanism of Action of BZDs

• Bind to GABA A receptors, distinct from GABA-binding sites.
• Potentiate GABAergic inhibition at all levels of the nervous system.
• Enhance GABA's ability to open chloride channels, increasing frequency of channel opening.
• Chloride entry into neurons leads to hyperpolarization, reducing neuronal excitability.

Pharmacological Actions of BZDs

• Reduction of anxiety: At low doses, benzodiazepines are anxiolytics, working to selectively enhance GABAergic transmission.
• Anterograde amnesia: Temporary memory problems are also associated with benzodiazepine use.
• Sedative/hypnotic effects: Used as hypnotics in higher doses, reducing latency to sleep, increasing stage 2 NREM sleep duration while reducing REM and stage 4 NREM sleep duration.
• Anticonvulsant: Reducing seizure activity (partially mediated by GABA A receptors.)
• Muscle relaxant: High doses can relax skeletal muscles by increasing presynaptic inhibition in the spinal cord.

Uses of BZDs

• Anxiety: Used in anxiety disorders including those associated with depression and schizophrenia, but generally not for everyday stress management. Longer-acting agents (clonazepam, lorazepam, diazepam) favored for prolonged treatment as they have less tolerance. Alprazolam for short- and long-term panic treatment.
• Insomnia: Short-acting (triazolam) useful for falling asleep problems. Intermediate-acting (temazepam) helpful for frequent awakenings. Long-acting (flurazepam) rarely used due to extended half-life concerns; especially in the elderly due to the risk of accumulating the drug.
• Muscular disorders: Diazepam to treat muscle spasms and spasticity.
• Diagnostic procedures: Used intravenously for sedative-amnesic and muscle-relaxant effect.
• Pre-anesthetic medication: Used in pre-op procedures to reduce anxiety and induce amnesia, often combined with other CNS depressants.
• Alcohol withdrawal: Long-acting BZDs can help manage withdrawal symptoms.

Adverse Effects of BZDs

• Generally well-tolerated; common side effects include drowsiness, confusion, amnesia, lethargy, weakness, blurred vision, ataxia, and impaired motor coordination.
• Paradoxical irritability and anxiety can occur in some patients.
• Tolerance and dependence potential less than barbiturates.
• Withdrawal symptoms vary depending on the specific BZD and whether use is short-term or long-term. Withdrawal symptoms in short-acting benzodiazepines are more intense than in those of long acting.
• Administration to pregnant women can pose risks to the developing fetus.

Tolerance and Dependence of BZDs

• Chronic use leads to a decreased responsiveness to benzodiazepines.
• Associated with a reduction in GABA receptor density.
• Anti-anxiety effects may be less subject to tolerance than sedative/hypnotic effects.
• Dependence can develop within weeks/months of continued use.
• Physiological dependence: Removal evokes unpleasant symptoms opposite to the medication's effects.
• Psychological dependence: Compulsion to use the drug and anxiety upon separation from it.

Benzodiazepine Antagonist (Flumazenil)

• Competitive antagonist to benzodiazepines.
• Reverses both benzodiazepine agonist (CNS depression) and benzodiazepine inverse agonist effects.
• Not used orally due to high first-pass metabolism.
• Administered intravenously for rapid onset of action useful for overdose.

Barbiturates

• Historically principal sedative hypnotics/anesthetics.
• Replaced by BZDs because of associated tolerance and harmful side effects.
• Highly lethal in overdose.
• Association with dependence and severe withdrawal symptoms.
• Classified as ultra-short-acting (thiopental), short-acting (pentobarbital), and long-acting (phenobarbital).

Pharmacokinetics of Barbiturates

• Usually well-absorbed orally.
• Wide tissue distribution, high lipid solubility
• Rapid onset of action.
• Redistributed to adipose tissue, leading to short duration of action.
• Metabolized and excreted in the urine.
• Cross the placenta and may depress the fetus.
• Potent inducers of microsomal liver enzymes.

Mechanism of Action of Barbiturates

• Enhance GABAergic transmission by prolonging the duration of GABA-mediated chloride channel openings.
• At high concentrations, can exert GABA-mimetic effect.
• Possibly also have actions at glutamate receptors.

Pharmacological Actions of Barbiturates

• CNS depression: Wide range of CNS effects. Sedation, hypnosis, amnesia, and respiratory depression.
• Anesthesia: Used in high doses
• Anticonvulsant: Reduced seizure activity in some cases
• Respiratory system depression.
• CVS: Hypnotic doses may cause slight decrease in BP and HR. Overdose can lead to significant decrease in these
• Skeletal muscles: decreased excitability
• Liver enzyme induction
• Produces euphoria, which can lead to addiction potential.
• Adverse reactions such as hangover, distortion of mood, impaired judgement/motor skills, excitement/irritability in children.

Therapeutic Uses of Barbiturates

• Anesthesia (historically)
• Anticonvulsant (status epilepticus, generalized tonic-clonic seizures)
• Neonatal jaundice (as an enzyme inducer)

Adverse reactions of Barbiturates

• Hangover due to residual CNS depression
• Mood distortion
• Impaired judgement and fine motor skills
• Excitement/irritability in children
• Respiratory depression (severe in patients with pre-existing respiratory issues), even in therapeutic doses.
• Tolerance/dependence (more prominent than in BZDs)
• Physical/psychological dependence, high abuse potential.
• Withdrawal symptoms (anxiety, restlessness, hallucinations, delirium, convulsions).
• Drug interactions (e.g., potentiates effects of alcohol).

Other Anxiolytic Agents

• Newer, non-benzodiazepine agents (e.g., zolpidem, zopiclone, eszopiclone) have effects similar to BZDs, but with less risk of dependence.
• Classified as non-benzodiazepine hypnotics.
• Acts to bind to the GABA A receptor, facilitating inhibitory signal transmission.
• Improved profile of side effects and less tolerance compared to BZDs. Useful in short-term treatment of insomnia.

Melatonin-Receptor Agonist

• Melatonin is a hormone that regulates sleep-wake cycles.
• Ramelteon is a melatonin receptor agonist.
• Used orally for sleep-onset insomnia.
• Increases total sleep duration without withdrawal problems.
• Less likely to lead to tolerance, but fatigue and dizziness are possible side effects; prolactin elevation noted in some.
• Used for non-24 hour sleep-wake cycle disorders in some patients.

Orexin Receptor Antagonist

• Suvorexant blocks orexin receptors to prevent wakefulness.
• Useful in chronic insomnia and narcolepsy.

Buspirone

• Useful long-term treatment of Generalized Anxiety Disorder (GAD).
• Slow onset of action makes it less helpful for acute anxiety.
• Has a different mechanism of action than benzodiazepines; partial 5-HT1A agonist.
• Lacks the anticonvulsant and muscle relaxant effects.
• Mild side effects, low dependence potential.
• Not suitable for acute anxiety treatment.
• Appears safe in pregnancy.

Antidepressants

• SSRIs and SNRIs can treat chronic anxiety disorders.
• Often used in combination with benzodiazepines initially for patients with difficulty managing anxiety during the first week.
• Antidepressant dose can be reduced after effectiveness is observed, and eventually benzodiazepine use can cease.

Antihistamines

• Sedating antihistamines like diphenhydramine, hydroxyzine, and doxylamine are effective for mild insomnia.
• However, they have undesirable effects (e.g., anticholinergic effects).
• Commonly available over-the-counter.

Test your knowledge on anxiety disorders, their characteristics, and treatments. This quiz covers primary anxiety disorders, physical symptoms, and drug classifications. Answer questions about sedative-hypnotics and the levels of anxiety requiring treatment.