Anxiolytic And Hypnotic Drugs Flashcards
What Anxiolytic drugs do we need to know? (which is a BDZ antagonist?) (7)
- Alprazolam
- Buspirone
- Clonazepam
- Chlodizepoxide
- Diazepam
- Flumazenil (BDZ antagonist)
- Lorazepam
What Hypnotic drugs do we need to know? (8)
- Chloral hydrate
- Eszopiclone
- Flurazepam
- Secobarbital
- Ramelteon
- Triazolam
- Zaleplon
- Zolpidem
What muscle relaxants do we need to know? (2)
- Baclofen
- Tizanidine
What age group has the highest percentage of persons with anxiety disorders?
Age 30-44 (35%)
GAD is described as generalized persistent anxiety for at least _ months duration
1
What are some psychological correlates of GAD?
- Apprehensive expectation
- Worry, fear, and anticipation of misfortune to self and others
- Hyperattentiveness
- Distractibility, difficulty in concentrating
- Insomnia, feeling on edge, impatience
What are some somatic correlates of anxiety?
- ANS arousal (sweating, tachycardia, cold clammy hands, dry mouth, GI upset, frequent urniation)
- Voluntary Muscle Activation - Jitteriness
What types of waves are present in the following stages of the sleep/awake cycle?
- Awake:
- Drowsy:
- Stage 1:
- Stage 2:
- Stage 4:
- REM sleep:
- Awake: low voltage, random fast
- Drowsy: alpha waves
- Stage 1: theta waves
- Stage 2: sleep spindle and k complexes
- Stage 4: delta waves
- REM sleep: low voltage-random, fast with sawtooth waves
What neurotransmitters are associated witht the following types of sleep?
- Slow-wave sleep:
- REM sleep:
- Slow-wave sleep: Serotonin
- REM sleep: Norepinephrine
What is insomnia? What is hypersomnia?
- Insomnia - disorders of initiating and maintaining sleep
- Hypersomnia - disorders of excessive sleep or sleepiness
What drugs are used to treat anxiety AND insomnia?
- Benzodiazepines (and related drugs)
- SSRIs (commonly used)
- Buspirone
- Classical Antihistamines
- Alcohol, Cannabis, Opiates
- Barbiturates
Where is GABA localized in the brain?
- Substantia Nigra
- Globus Pallidus
- Hippocampus
- Limbic Structures (Amygdala)
- Hypothalamus
- Spinal Cord
What is the precursor for the formation of GABA?
Glutamate (from mitochondria)
What effect does GABA elicit when bound to the BDZ receptor?
Allows flow of chloride ions through the cell membrane leading to hyperpolarization
What is the Benzodiazepine antagonist (blocks action at benzodiazepines at the receptor)?
Flumazenil
What is the MOA of Buspirone?
Partial agonist for 5-HT1A - inhibitions of adenylate cyclase and opens K+ channels
What benzodiazepines are used to treat anxiety?
- Diazepam
- Chlordiazepoxide
- Alprazolam
- Lorazepam
- Clonazepam
Which benzodiazepine has a short duration and causes forebrain depression?
Which benzodiazepine has a long duration and causes broad CNS depression?
- Which benzodiazepine has a short duration and causes forebrain depression?
- Alprazolam
- Which benzodiazepine has a long duration and causes broad CNS depression?
- Diazepam
Which Benzodiazepines are used as hypnotics?
- Flurazepam
- Triazolam
- Lorazepam
- Zolpidem
- Zaleplon
- Eszopiclone
Compare Diazepam and Lorazepam in terms of the following…
- Lipophilicity:
- Onset of action:
- Active metabolites:
- Duration of action after single dose:
- Lipophilicity:
- Loarzepam is less lipophilic than Diazepam
- Onset of action:
- Diazepam has a fast onset of action
- Lorazepam has slower absorption and onset
- Active metabolites:
- Diazepam has active metabolites that change redistribution speed in multiple dose situations
- Duration of action after single dose:
- Lorazepam has a longer duration of action
What are the CNS affects associated with Benzodiazepines?
- Decreased anxiety
- Sedation
- Hypnosis
- Muscle relaxation
- Anterograde amnesia (IV administration)
- Anticonvulsant action
- Minimal CV and respiratory actions at therapeutic doses
What drug interactions are associated with benzodiazepines?
- Produce additive CNS depression with other depressant drugs (ethanol, sedative hypnotics, sedating antihistamines)
- Drugs that affect hepatic metabolism (cimetidine)
Which benzodiazepine can also be used as a muscle relaxant?
Which can be used for alcohol withdrawal?
Which can be used for acute manic episodes?
- Which benzodiazepine can also be used as a muscle relaxant? - Diazepam
- Which can be used for alcohol withdrawal? - Chlordiazepoxide
- Which can be used for acute manic episodes? - Clonazepam
What are the symptoms of benzodiazepine withdrawal?
- Anxiety
- Insomnia
- Irritability
- Headache
- Hyperacusis
- Hallucinations
- Seizures
How do you treat benzodiazepine abuse?
- Graudal dose reduction
- Switch to longer acting drugs
How long does it take for the therapeutic effects of Buspirone to occur?
What makes it different than the benzodiazepines?
Therapeutic effects take 1-2 weeks to occur
Less sedating than benzodiazepines and does not potentiate other sedative-hypnotics and depressants nor suppress symptoms of their withdrawal (no cross tolerance)
What are the effects of hypnotic benzodiazepines on sleep?
- Decreased latency to sleep
- Increases in stage 1 and 2 sleep; decreased time in stage 3 and 4 sleep and REM sleep
- Rebound insomnia upon withdrawal
What are the adverse effects of hypnotics?
- Daytime sedation
- Ataxia
- Rebound insomnia
- Toelrance and dependence
- Occasional idiosyncratic excitement and stimulation
- Increased death rate associated with use (possibly)
Zolpidem and Zaleplon
Binding site:
Use (aside from as a hypnotic):
Effect on stage 3 and 4 sleep:
Zolpidem and Zaleplon
- Binding site: BDZ receptor on GABA receptor complex
- Use (aside from as a hypnotic): weak anxiolytic, muscle relaxant and anticonvulsant
- Effect on stage 3 and 4 sleep: stage 3 and 4 sleep preserved (unlike benzodiazepine hypnotics)
What are the differences between Zolpidem and Zaleplon in terms of duration of action, onset of action, and elimination half life?
- Duration of action
- Zolpidem: 5-6 hours (7-8 in sustained release)
- Zaleplon: Shorter duration of action
- Onset of action
- Zaleplon has a faster onset of action
- Elimination half life
- Zaleplon has a shorter terminal elimination half-life
Other Hypnotic Drugs
What is the MOA of Eszopliclone?
What is the MOA of Ramelteon?
- Eszopliclone - similar mechanism to zolpidem and zaleplon - interaction with GABA-receptor complex at binding domains close to or allosterically coupled to BDZ receptor
- Ramelteon - Melatonin MT1 and MT2 receptor agonist
What classification of drugs are raidly absorbed and distributed, highly lipid soluble, and eliminated primarily by renal excretion?
Barbiturates
What are the pharmacological actions (adverse effects) of barbiturates?
- General CNS depression
- Anticonvulsant
- Respiratory depression
- CV effects (decreased blood pressure)
- Induction of hepatic drug metabolism
- Exacerbation of acute intermittent porphyria
- Tolerance/Dependence/Poisoning
What drug interactions are associated with barbiturates?
- Additive with other CNS depressants such as alcohol, other sedative hypnotics and antihistamines
- Drugs that affect microsomal drug metabolism
Describe the lipid solubility, onset of action, and duration of Thiopental and Secobarbital
- Thiopental
- High lipid solubility; 0.5 minutes onset of action, 0.2 hours duraiton of action
- Secobarbital
- Moderate lipid solubility; 10-15 minutes onset of action; 3-4 hours duration of action
What is chloral hydrate?
What is its active metabolite?
What is its clinical use?
- What is chloral hydrate?
- An aldehyde hydrate with a pungent taste
- What is its active metabolite?
- Trichloroethanol
- What is its clinical use?
- Treats insomnia
What is the MOA of Suvorexant?
Orexin receptor antagonist
Orexins are neuropeptide central promoters of wakefulness through excitement of brain regions involved in arousal and attention
How is Diazepam used as a muscle relaxant?
Its action in reducing spasticity is at least partly mediated in the spinal cord - can be used in patients with muscle spasm of almost any origin including local trauma
What is the MOA of the skeletal muscle relaxant, Baclofen?
How does it differ from Diazepam?
- What is the MOA of the skeletal muscle relaxant, Baclofen?
- GABA-mimetic agent that works at GABA-B receptors causing hyperpolarization and presynaptic inhibition
- How does it differ from Diazepam?
- Produces much less sedation
What is the MOA of Tizanidine?
What are its side effects?
What drugs does it interact with?
- α2- adrenergic agonist that is related to clonidine – may enhance most presynaptic and postsynaptic inhibition
- SE: drowsiness, hypotension, dry mouth and asthenia
- Interacts with ciprofloxacin and fluvoxamine (CYP1A2 inhibitors)
What toxin can be used for long acting effects on local muscle spasms?
Botulinum toxin
What is the MOA and clinical use of Dantrolene?
- Reduces skeletal muscle contraction by interfering with excitation-contraction coupling in the muscle fiber
- Used in treatment of malignant hyperthermia
