Pharmacology-Sleep & Anxiety Drugs Flashcards
Targets of anxiety medications?
NE, 5-HT, GABA, Melatonin.
When are beta-blockers a good treatment for anxiety?
Just treating the physical symptoms of increased HR and sweating. It will not decrease mental clouding.
What are the diagnostic criteria for insomnia?
Difficulty initiating or maintaining sleep. Clinically significant distress. 3+ nights per week for 3+ months. Not related to narcolepsy, apnea, circadian rhythm, parasomnia, drug abuse or another mental disorder.
What waves are present in the different stages of sleep?
Awake = low voltage. Drowsy = alpha waves. Stage 1 = theta waves. Stage 2 = sleep spindles & K complexes. Deep sleep = delta waves. REM sleep = low voltage sawtooth waves.
A 44 year old lawyer comes to see you. He recently was divorced and is having difficulty sleeping 4-5 nights a week for the past three months. What is your diagnosis? How do you treat him?
Transient insomnia. This is due to stress and life changes. You might treat him with hypnotics for 1-3 days, but no more than 2-3 weeks. If you need to treat him longer you would use benzodiazepines.
What sleep drugs should you not be prescribing to chronic insomniacs?
Hypnotics & Benzodiazepines. Patients will develop tolerance and addiction.
What are the two flavors of sleep apnea?
Obstructive (collapse of the throat) and Central (failure of initiation to breath)
Why do people with sleep apnea not sleep well?
When they stop breathing they are aroused from sleep, which causes them to stay in stage 1 sleep most of the night.
Why type of sleep “disorder” involves circadian disturbances?
Graveyard shifts, travel to different time zones etc.
How do GABAa receptor agonists work?
They bind to the receptor, which causes it to open more than when just GABA binds, lots of Cl- enters and the cell hyperpolarizes. Note that each class of agonists bind to a different GABA subunit.
Which drugs are safer barbiturates or benzodiazepines? Why is the other one less safe?
Benzodiazepines. Adding a high dose of barbiturates opens the GABA channel without GABA present. They also inhibit AMPA (glutamatergic excitatory) receptors and nAChRs (prevent contraction of diaphragm).
What is the major problem with barbiturates?
They have low therapeutic index and overdose can be fatal. Note that these drugs are used in capital punishment, euthanasia and physician-assisted suicide.
Why have deaths like those of Jimi Hendrix decreased in recent decades? Why have they increased in recent years?
Introduction of benzodiazepines has decreased the amount of high risk barbiturate prescribing. In recent years, abuse from buy barbiturates on the street has increased as well as overdose deaths.
A patient comes to the ED stumbling around, yelling at the nurses and vomiting everywhere after a night out on the town. However, his BAC is 0. What symptoms might you expect to see in this guy if he gets worse and how do you treat him?
He has barbiturate poisoning, which early on resembles alcohol intoxication. Late symptoms include CNS depression, hypoxia and shock. You treat him supportively for shock, induce vomiting to get the drug out, hydrate and NEVER give CNS stimulants.
Why don’t you feel as rested as you’d like to after taking barbiturates for sleep?
Despite increased sleep time, deep and REM sleep are decreased.
Why do barbiturates have so many drug-drug interactions?
They induce CYP450 and patients can develop tolerance, requiring higher doses.
Why is self medicating of barbiturates really dangerous?
Tolerance to the intoxicating effects of the drug is fast, but tolerance to respiratory depression is slow.
What happens when you withdraw barbiturates from someone who has developed tolerance to the drug?
On the drugs, they develop tolerance which pushes their medicated AND basal state more towards excitation. When the drug is removed, their true basal state is revealed and they can have 1-2 days of insomnia and possible life-threatening conditions.
What are the long, intermediate & short acting barbiturates? What are they used for?
Long: Phenobarbital (antiseizure and rare daytime sedative). Intermediate: Pentobarbital (hypnotic, preoperative, ER, status epilepticus). Short: Thiopental (induction & maintenance of anesthesia)
How are barbiturates metabolized?
Liver, then excreted renally. 30% may be excreted in urine unchanged.
How are the actions of short acting barbiturates typically terminated?
They are highly lipophylic and redistribute from the CNS to the muscle and fat. Chronic medicating of barbiturates will take a long time to clear from the body because of this redistribution into fat and muscle.
What is the difference in mechanism of action of barbiturates vs. benzodiazepines?
Barbiturates increase the time the GABA receptor is open. Benzodiazepines increase the frequency at which the GABA receptor opens. The real clinically observant different is that benzodiazepines cannot independently open GABA receptors, do not affect nAChRs or AMPA and thus do not depress CNS functions.
What situations would you use benzodiazepines in ?
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What side effects come with benzodiazepines?
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What benzodiazepines are metabolized into active metabolites?
Lorazepam (no intermediate activity). Flurazepam w/t1/2 of 2 hrs. -> metabolite w/t1/2 of 47-100 hrs. Diazepam w/t1/2 20-90 hrs. -> secondary metabolite w/t1/2 40-100 hrs -> tertiary metabolite 3-21 hrs.
Why are the z-drugs (non-benzodiazepines) prescribed over benzodiazepines?
Benzodiazepines bind to the alpha-1 (causing sedation & anterograde amnesia) and alpha-2 (causing anxiety & muscle relaxation) subunits of the GABAa receptor. The z drugs only bind to alpha-1, and thus have no muscle relaxation or anxiety effects.
What side effects do you need to warn patients of when they are on z drugs?
Note that patients on ambien have been associated with sleep walking, sleep eating, sleep driving and allergic reactions. Anxiety, tremor, agitation, rebound insomnia and withdraw have also been noted.
What drug is used to treat narcolepsy and cataplexy?
Sodium oxybate (GHB)
How do benzos work as muscle relaxants?
Activation of the GABAa receptor on the post-synaptic alpha-motor neuron opens Cl- channels, hyperpolarizes it and muscle spasms decrease.
How does baclofen work as muscle relaxant?
Activation of the GABAb receptor (GPCR found presynaptically and post-synaptically). This allows K+ to come out of pre and post synaptic terminals, hyperpolarizing both. It prohibits Ca2+ entry into presynaptic terminal.
How does Tizanidine work as a muscle relaxant?
Alpha-2 adrenergic agonist. Decreased glutamate release at the stretch reflex arc.
What muscle relaxant is contraindicated in patients with ALS? Why?
Dantrolene. It acts directly on smooth muscle to decrease Ca2+ release from sarcolplasmic reticulum and inhibits muscle contraction. You don’t want generalized muscle weakness in people already weak from ALS.
