Sedative-hypnotics Flashcards
What are the general effects of sedative-hypnotics?
muscle relaxation calming effect anticonvulsant effects sleepiness sedation (decreased irritability) anterograde amnesia anesthesia **cardiac and respiratory depression (can cause death!)
As you increase the dose of sedative-hypnotics, was CNS effects occur?
lowest dose = anti-anxiety -> sedation -> hypnosis -> anesthesia -> coma/death
Why are benzodiazepines safer than barbiturates?
1) benzodiazepines have an antagonist (flumazenil) that will reverse an overdose 2) benzodiazepines require much higher doses than barbiturates to get the same CNS effect and generally will not have any effect greater than anesthesia
Why can you absolutely NOT drink any alcohol while on a sedative-hypnotic?
Because alcohol is also a sedative hypnotic and all these drugs have additive effects on CNS depression. Adding alcohol is like overdosing on your prescription
Where on the GABA-A receptor does GABA bind? Where do the benzodiazepines bind? What is the mechanism of action of benzodiazepines? Where do the newer, nonbenzodiazepine hypnotics bind?
GABA binds between the alpha and beta subunits
Benzodiazepines bind at a different site than GABA, between the alpha and gamma subunits. The mechanism of action of benzodiazepines is to enhance GABA’s ability to bind to the GABA-A receptor and increase the frequency of channel opening
The new, nonbenzodizepine hypnotics bind to the same site as benzodiazepines but are more selective than the benzos (only specific alpha subunits, alpha1, of the GABA receptors)
Where on the GABA-A receptor do barbituates bind? What is their mechanism of action?
Barbiturates bind at a different site than the benzodiazepines or GABA
Barbiturates increase the duration of Cl- channel opening
What CNS effects does the alpha1 subunit in GABA-A receptors influence? Alpha2 and alpha3? Alpha5?
alpha1 - sedation, ataxia, amnesia
alpha2/3 - anxiolytic, muscle relaxing
alpha5 - memory impairment(?)
What are the common barbiturates? What is their clincial use?
butalbital - one part of a cocktail for headache medicine
phenobarbital - seizures
thiopental - was used for inducing anesthesia and the death penalty but no longer in use in the US
Secobarbital - short term treatment of insomnia; sedative prior to anesthesia for surgery
What are the absorption properties of barbiturates? How are barbiturates metabolized? What can happen after long term use of barbiturates? How are barbiturates eliminated?
Absorption and distribution is extremely fast because the drug is very lipophilic
Barbiturates are metabolized to alcohols, ketones and acids slowly. Chronic use of barbiturates will induce the cytochrome P450 enzymes, leading to many drug interactions
Elimination is mostly renal
Alkalinizing urine will increase renal elimination
What drug is absolutely contraindicated when a patient has porphyria?
barbiturates
What are the benzodiazepine drugs? Are they short, intermediate or long acting?
short acting = midazolam
Intermediate = alparzolam (xanax) and lorazepam (ativan)
long acting = clonazepam (klonopin) and diazepam (valium)
What are the clinical uses of benzodiazepines?
status epilepticus
panic disorder, generalized anxiety disorder
specific phobias
insomnia
alcohol withdrawal
muscle spasms
parasomnias/sleep disorders
induction of anesthesia (midazolam)
acutely agitated patients
mania and catatonia
Which benzodiazepines do NOT have phase I metabolism by cytochrome P450 enzymes? Which benzodiazepines have phase I metabolism but very short half-lives of the active metabolites?
lorazepam, oxazepam, temazepam
These can be used in patients with liver disease (chronic alcoholics with liver failure that are going through withdrawal need these three drugs)
midazolam have a very short half life
Many benzos have very long half lives
What are the newer nonbenzodiazepines hypnotics?What are the clinically used for?
All used as hypnotics for insomnia and sleep disorders - NO anti-anxiety effects
zolpidem (ambien)
zaleplon (sonata)
eszopiclone (lunesta)
What are the absorption properties of the nonbenzodiazepine hypnotics? Metabolism properties? Elimination properties?
Rapid absorption, rapid metabolism, rapid elimination
Since these drugs help you fall asleep, you don’t want them to be long acting
What are the pathways of alcohol metabolism?
Ethanol -> acetylaldehyde -> acetate
First step can be accomplished by two mechanisms: alcohol dehydrogenase or the MEOS (microsomal ethanol oxidizing system) which consists of a couple of cytochrome P450 enzymes.
Second step is accomplished by aldehyde dehydrogenase
What drugs affect the alcohol metabolic pathway? What are they used for?
fomepizole inhibits alcohol dehydrogenase; used for methanol and ethylene glycol poisoning to inhibit these chemicals from being metabolized into toxic metabolites.
Disulfiram (antabuse) inhibits aldehyde dehydrogenase; used to treat alcohol dependence/abuse by causing build up of acetylaldehyde which causes nausea, vomiting, flushing, dizziness and headache.
