Pharm: Sedative Hypnotics Flashcards
How do benzodiazepines distribute through the body and how are they metabolized?
- Widely distributed throughout body: CNS, placenta, breast-milk
- Hepatic metabolism (CYP3A4) and excretion via kidney
What are the benefits of using benzodiazepines for anxiety states?
Risks?
Benefits
- High therapeutic index; antagonist available for OD (flumazenil)
- Low-risk of drug-drug interactions
- Minimal effect of cardiovascular or autonomic function
Risks
- Dependence
- Depression of CNS
Which benzodiazepine has the fastest rate of onset?
2nd fastest?
Diazepam = fastest
Alprazolam = 2nd fastest
How does Diazepam differ from Alprazolam in terms of half-life, active metabolites and rate of onset?
- Diazepam: long half-life (>100 hr); has active metabolite; very fast onset
- Alprazolam: short half-life (12-15); no active metabolite; fast onset
Which benzodiazepine has a short half-life (5-14 hr), no active metabolite, and the slowest rate of onset?
Oxazepam
Which 2 benzodiazepines have the shortest half-lifes?
Triazolam and Midazolam
Which 4 benzodiazepines have the longest half-lives all >100 hr and all have active metabolites?
- Chlordiazepoxide
- Clorazepate
- Diazepam
- Flurazepam
_______________________________
Benzos with long half-lives are more likely to cause cumulative effects with multiple effects
What is the effect of barbituates on CYP450 enzymes?
Can induce CYP450 enzymes
What is the prototype ultra-short acting barbituate used in anesthesia?
Thiopental
What is the prototype short-acting barbituate that is used for insomnia?
Secobarbital
What is the prototype long-acting barbituate that is used for seizures?
Phenobarbital
What are 3 of the newer sedative hypnotics that are used as sleep aids?
- Eszopiclone (Lunesta)
- Zolpidem (Ambien)
- Zaleplon (Sonata)
Which newer sedative hypnotic has the advantage of coming in a biphasic release formulation for sustained sleep maintenance?
Zolpidem (Ambien)
Which newer sedative hypnotic has the longest half-life?
Eszopiclone (Lunesta)
What are 4 AE’s associated with the sedative drug, Ramelteon?
- Dizziness
- Somnolence
- Fatigue
- Endocrine changes –> ↓ testosterone and ↑ prolactin
What is Buspirone used for and what must you keep in mind when prescribing this drug?
- Approved for tx of generalized anxiety disorder
- Anxiolytic effects may take more than a week to become established (less effective in acute panic disorders)
BBW for Midazolam
IV Midazolam: assc w resp depression and arrest when used for sedation in non-critical scenarios
Why does Diazepam stick in the body for so long?
It has a prolonged terminal elimination half-life bc of its active metabolite (N-desmethyldiazepam), up to 100 hours
Diazepam/Valium contraindications:
- Myasthenia gravis
- Severe resp insufficiency
- Hepatic insufficiency
- Sleep apnea
- Acute narrow angle glaucoma
____________________________________
Don’t use with alcohol or in psychotic patients
Triazolam
- Indication
- BBW
Indication = short term insomnia treatment
BBW = use w opioid causes profound sedation, coma, and death
Lorazepam
- Indication
Indication = seizures and pre-surgery anxiety
Flurazepam
- Indication
Short term insomnia Rx to help with falling asleep, nocturnal awakening, and early awakening
Ramelteon
- Indication
- MOA
Indication = difficult sleep onset
MOA = agonist of MT1 and MT2 melatonin receptors
Zaleplon
- Indication
- MOA
Indication = short-term insomnia
MOA = GABA-BZ receptor complex
What benzo may be given IM/IV for preop sedation?
Midazolam
Busiprone
what should you know about use?
benefit?
metab?
- for anxiety: takes over 1wk to work
- does not cause sedation, hypnosis, euphoria, ms relaxant effects
- metab by CYP3A4
Which newer sedative hypnotic has CNS depressant effects and cannot be taken with EtOH?
Eszopiclone (Lunesta)
