E1: Sedative-hypnotics And Anxiolytics Flashcards
What kind of drugs are used for short term treatment of insomnia?
Sedative hypnotics
What is the DOC for enuresis?
TCAs
What kind of channels are GABA receptors?
Cl channels
What does activation of GABAa receptors do?
Causes depression of electrical activity, which decreases anxiety and promotes sleep
What is the MOA of barbiturates?
-Binds to GABA receptor and stimulates Cl influx, which produces inhibition independent of GABA
What are the effects of barbiturates?
- Marked CNS depressant, hypnosis
- cause euphoria
What kind of drug is phenobarbital?
What is it commonly used for?
- Long acting barbiturates
- often used as anticonvulsants
How are barbiturates metabolized?
- metabolized by the liver
- induces CYP450s with chronic use
What are the side effects of barbiturates?
- CNS depression: drowsiness, mood distortion, impaired judgment
- Paradoxical excitement
- vertigo, n/v/d
- severe physiological and psychological dependence
What are the contraindications of barbiturates?
- porphyria: enhance porphyrins synthesis
- pulmonary insufficiency: may cause respiratory depression
- Supra-additive effects
Why are barbiturates dangerous drugs?
They do not have a ceiling effect and have a low margin of safety
-Supra-additive effects with alcohol
What are the most commonly used group of anxiolytics and sedative-hypnotics?
Benzodiazepines
How are benzodiazepines metabolized?
-metabolized by CYP34A in the liver where it is converted to active metabolites
Which benzos have a long duration of action?
Diazepam and flurazepam
Which benzos have and intermediate duration of action?
Alprazolam and oxazepam/lorazepam
Which benzo has a short duration of action?
Midazolam
What is the MOA of Benzos?
- Bind to specific sites of the GABAa receptor, increases affinity of the receptor to GABA prolonging its action
- effect is dependent on GABA
Are benzos or barbiturates safer? Why?
Benzos are safer because they have a ceiling effect
What is the DOC for anxiety?
Benzos
What are the anxiety disorders that benzos are not used for?
- OCD
- Agoraphobia and panic disorders
- post traumatic stress
- anxiety and children and adolescents
What benzos are commonly used for insomnia?
Flurazepam and temazepam
What benzos are commonly used for status epilepticus?
Diazepam and lorazepam
Which benzo is used in preparation for anesthesia for short surgical procedures?
Midazolam
Which benzo causes anterograde amnesia?
Midazolam
Which benzo is often used for muscle relaxation?
Diazepam
Which Benzos can be given to provide a tapered withdrawal?
Chlordiazepoxide, diazepam, and lorazepam
What are the side effects of Benzodiazepines?
- CNS depression: dizziness, sedation, confusion
- Paradoxical excitement
- Supra-additive effects
- sleep related behaviors
What is paradoxical excitement?
-stimulation, hyperactivity, and aggressive behavior that may occur due to dis-inhibition of suppressed behavior, common in the elderly
What are the contraindications to Benzodiazepines?
- Should not be given during pregnancy unless absolutely necessary
- sleep apnea
- elderly
What is important to remember about Benzodiazepines and withdrawal?
- Abrupt discontinuation can cause rebound increases in insomnia and anxiety
- BZs should be tapered very slowly following chronic use
What kind of drug is Flumazenil?
Benzodiazepine antagonist
What is the MOA of Flumazenil?
-Competes with BZs for GABA receptor and reverses the effects of BZs
What is the major adverse effect of Flumazenil?
- Triggers withdrawal and seizures in patients who are physically dependent upon BZs
- do not used in patients with history of seizures
What are the “Z” drugs?
Zolpidem (ambien), Zaleplon (Sonata), and Eszopiclone (lunesta)
What is the MOA of the “Z” drugs?
Bind to the BZ1 subtype of the GABA receptor to increase GABA mediated inhibition
Which of the “z” drugs has a long half life?
Eszopiclone
What are the side effects of the “z” drugs?
- High margin of safety
- Diarrhea and nausea
- sleep related behavior
- rebound insomnia
- Withdrawal symptoms
What is the MOA of Suvorexant?
- Antagonist at orexin receptors
- Orexins are involved in regulating the sleep wake cycle and promote wakefulness
How is suvorexant metabolized?
Metabolized by CYP3A4
What are the contraindications for suvorexant?
Narcolepsy
What is the MOA of Ramelteon?
- melatonin analogue, resets the sleep wake cycle
- promotes sleepiness with no GABA effect
How is Ramelteon metabolized?
CYP450 in the liver
What are the side effects of Ramelteon?
- Additive sedation with alcohol and other sedative hypnotics
- drowsiness, dizziness, and nausea
When is Benadryl indicated for insomnia?
Useful for occasional insomnia and are especially useful in someone who has been addicted to Benzos or alcohol
What is the MOA of Chloral Hydrate?
-Acts similarly to barbiturates on GABAa receptor, converted to trichloroethanol which causes sedation
Is chloral hydrate a safe drug?
No it has a low margin of safety, high doses induce respiratory and vasomotor depression
What are the side effects of Chloral hydrate?
- gastric irritation, nausea, vomiting, and cardiac arrhythmias
- long term use may cause liver damage and fatal intoxication
What is the use of Buspirone?
Relieves anxiety without producing sedation
What is the MOA of Buspirone?
Partial agonist at the postsynaptic serotonin receptor
-Full agonist for presynaptic serotoninc receptors
How is Buspirone metabolized?
CYP3A4 in the liver
