Anxiolytic and Hypnotic Drugs Flashcards
What does it mean for a drug to be an anxiolytic?
Gives calming effects and relief of anxiety
What does it mean for a drug to be a hypnotic?
Promotes drowsiness, promotes onset and maintenance of sleep
What are some examples of benzodiazepines?
Lorazepam, diazepam, chlordiazepoxide, triazolam
What are some examples of barbituates?
Thiopental, pentobarbital
What are some examples of other anxiolytic and hypnotic drugs?
Buspirone, zopiclone
How do benzodiazepines work?
Bind to the GABA-A receptor and enhance its GABA actions to reduce the excitability of the neurons and increases the frequency of channel-opening events
CNS depressants
Low affinity for GABA-B
What is GABA?
The primary inhibitory neurotransmitter in the brain
What is the GABA-A receptor?
A chloride channel that allows chloride influx, hyperpolarizes neurons and decreases neuronal activity
How do barbituates work?
Bind to GABA-A and increase the duration of channel-opening events
Inhibit glutamate AMPA receptor
GABA-mimetic at high doses
What determines the speed of onset of these drugs?
The lipophilicity of the drug or its ability to cross the BBB
Triazolam has the fastest onset of benzodiazepines.
What determines the duration of effects of these drugs?
Redistribution due to lipophilicity
Biotransformation (phase I, CYP P450, conjugation-phase II) made more water-soluble
Many phase I metabolites of benzodiazepines are active
Which benzodiazepines have short half-lives?
Lorazepam, oxazepam, alprazolam, triazolam
Which benzodiazepines have long half-lives?
Chlordiazepoxide, diazepam, prazepam, flurazepam
Which benzodiazepines are used for hypnotics or anxiolytics?
Short half lives for hypnotic
Long half lives for anxiolytic (cumulative effects with multiple doses)
Which populations should be special consideration for benzodiazepine use?
Pregnant and breastfeeding patients, older patients, those with liver disease, obese patients
How do the duration of action of barbiturates vary?
Ultra short acting (30 minutes): Thiopental for induction of anesthesia Short acting (18-48 hours): Secobarbital, phenobarbital for hypnotic and sedative Long acting (4-5 days): Phenobarbital for seizures
What are the therapeutic uses of benzodiazepines?
Relief of anxiety
Treatment of insomnia
Sedation and amnesia before and during surgical procedures
Treatment of epilepsy and seizure states
Muscle relaxation in specific neuromuscular disorders
Control of ethanol or other sedative-hypnotic withdrawal
What are some examples of anxiety disorders?
Generalized anxiety disorder (GAD), panic disorder, social phobia, PTSD, OCD
What are some symptoms of anxiety disorders?
Feelings of panic, fear and uneasiness, uncontrollable, obsessive thoughts, nightmares, sleeping problems, cold or sweaty hands, shortness of breath, numbness or tingling in hands or feet, muscle tension, nausea, dry mouth
How are benzodiazepines used in anxiety treatment?
Used for the management of acute anxiety states and for rapid control of panic attacks
Alprazolam
What is the first choice treatment for long term management of GAD and panic disorders?
Selective serotonin reuptake inhibitors (SSRIs)
What are some symptoms of insomnia?
Sleep deprivation from trouble falling asleep or staying asleep.
Lying awake for a long time before falling asleep, sleeping for short periods, waking up too early
What occurs in stage 1 of non-REM sleep?
Light sleep during which the muscles begin to relax
What occurs in stage 2 of non-REM sleep?
Brain activity slows down and eye movement stops
What occurs in stages 3/4 of non-REM sleep?
Deep sleep during which all eye and muscle movement ceases
Slow waves
What occurs during rapid eye movement (REM) sleep?
Paradoxical sleep, rapid eye movement where most muscles are paralyzed
How do benzodiazepines work to aid in insomnia treatment?
Decrease the latency to sleep onset and increase stage II NREM
Decrease both REM and slow wave sleep
What should you look for in a drug to treat those with difficulty falling asleep?
Use a fast acting, but shorter duration drug like triazepam
Start with low doses
What should you look for in a drug to treat those with frequent awakenings?
Use a drug with medium duration like lorazepam
Start with low doses
Which benzodiazepines are the 1st choices to be used in conjunction with anesthetics during surgery?
Midazolam, lorazepam
Use before and during medical procedures to produce sedative effects and cause anterograde amnesia
Which kinds of seizures are benzodiazepines used to treat?
Generalized tonic-clonic status epilepticus, absence seizures, partial seizures
Which benzodiazepines are used as an anticonvulsant?
Lorazepam, diazepam and clonazepam
Which benzodiazepines are used as a muscle relaxant?
Diazepam
How do benzodiazepines work during alcohol withdrawal?
Substitute in for alcohol and reduce the risk of withdrawal related seizures
What is the therapeutic index of barbiturates?
Low, less than benzodiazepine
What are barbiturates used for?
Anticonvulsant in epilepsy and seizure (not first choice)
Phenobarbital for generalized tonic-clonic seizures.
Component of balanced anesthesia (enchance inhibitory neurotransmission, inhibit excitatory neurotransmission)
What are the stages of CNS depression?
Sedation to hypnosis to anesthesia to coma
What should you know about thiopental?
Rapid induction of anesthesia (30-40 sec) with rapid clearance and redistribution from brain (short duration)
Likely to cause hyperalgesia
What is thiopental used for?
To induce anesthesia often followed by an inhalation agent
What are some adverse effects of benzodiazepines?
Drowsiness, confusion, anterograde amnesia, dizziness, lethargy, ataxia (can persist and cause hangover daytime effects)
Tolerance and dependence
What should not be used at the same time as benzodiazepines?
Other CNS depressants (alcohol)
What is tolerance?
Decreased responsiveness to a drug following repeated treatment (metabolic and pharmacodynamic)
Down regulation of brain BZD receptors
What is dependence?
An altered physiologic state that requires continuous drug administration to prevent withdrawal symptoms
What are some symptoms of benzodiazepine withdrawal?
Relapse or rebound anxiety, insomnia, restlessness
Occurs more with short half life BZDs
What are some risk factors for benzodiazepine abuse?
Women, elderly, low socioeconomic status, unemployment, stress
Who are benzodiazepines cautioned in?
Older patients, liver disease, obesity
What are contraindications for benzodiazepine use?
Myasthenia gravis, narrow-angle glaucoma, alcoholism, pregnant, breastfeeding, severe sleep apnea
What is flumazenil?
A benzodiazepine competitive antagonist that is used to reverse the CNS depressant effects of a benzodiazepine overdose
Give IV, caution is BZDs are given for seizures
What are some adverse effects of barbiturates?
CNS depression which can cause cardiac and vascular depression
Social abuse
Physical dependence (more severe withdrawal)
Metabolic and pharmacodynamic tolerance
How does buspirone work?
Acts as a partial agonist at the serotonin 5-HT1A receptor
Acts as an antagonist at the dopamine D2 receptor
What is buspirone used for?
As an anxiolytic to relieve anxiety but effects take a week to be felt so unsuitable for acute anxiety states
Used in generalized anxiety states, less effective in panic disorders
What are the adverse effects of buspirone?
Tachycardia, palpitations, dizziness
No tolerance, withdrawal, abuse, alcohol interactions
What should not be taken with buspirone?
Do not use with monoamine oxidase inhibiitors (MAOi)
How does zopiclone work?
Targets the GABA-A receptor, specific for alpha 1.
Enhances GABA-mediated neuronal inhibition
What is zopiclone used for?
Short-term insomnia
Increases in stage 2 NREM sleep
Minimal muscle relaxing and anticonvulsant effects
What are the adverse effects of zopiclone?
Drowsiness, memory impairment, dizziness, fatigue
Low risk of tolerance and dependence
Antagonized by flumazenil
