Exam 7: anxiolytic-sedative-hypnotic pharmacology Flashcards
What class is phenobarbital?
barbiturates
What class is lorazepam and diazepam?
Benzodiazepines
What drugs are classified as benzodiazepines?
lorazepam, diazepam
What are examples of barbiturates?
Phenobarbital, pentobarbital, thiopental
What do barbiturates bind to? To do what?
multiple isoforms of the GABAa receptor (in the intramembranous space) to keep it open longer after activation to allow chloride ions to enter the neuron
Do barbiturates increase the duration of GABA-gated chloride channels, or activate the GABA channels?
Cause allosteric change to open up the chloride channel AND KEEP IT OPEN LONGER
What other effects to barbiturates have on the body?
depress excitatory actions of glutamate by binding to AMPA receptors, nonsynaptic membrane effects
Can barbiturates be given orally or IV? what are the effects of either?
oral for anxiolytic effects, IV for anesthetic induction
How quickly do barbiturates effect for sleeping
Thiopentil: 30 seconds, phenobarbital: 20 mins
Where are barbiturates metabolized? How long is their half-life?
Oxidized by hepatic enzymes. 4-5 days
How can you increase excretion or stop an overdose of phenobarbital?
increase urinary pH by administering sodium bicarbonate IV
What are the mechanisms of tolerance to barbiturates?
increase in rate of drug metabolism, changes in responsiveness of the CNS
What are the effects of barbiturates?
Sedation at low doses, hypnosis at higher doses, anesthesia at highest doses
What are the hypnotic effects of barbiturates?
decrease sleep onset, increased stage 2 sleep, decreased REM sleep, stage 4 sleep decreased
What drugs can be used to prevent tonic-clonic seizures?
Phenobarbital and metharbital
At hypnotic doses, what are the effects of barbiturates on respiration and CV system?
No significant changes
Can patients become dependent on barbiturates?
Yes, continuous drug administration required to prevent an abstinence or withdrawal syndrome
What are clinical uses of barbiturates?
Hypnosis, seizure control, anesthesia induction, can be combined to manage GI disorders and others for analgesia
What are examples of benzodiazepines?
Diazepam, lorazepam
What drug class are diazepam and lorazepam in?
Benzodiazepines
Where do benzodiazepines bind?
Extracellular portion of GABAa Chloride channels
What do benzodiazepines do to chloride channel opening events?
Increase the FREQUENCY of the events
What to barbiturates do to chloride channel opening events?
Increase the DURATION of the events
Where are all benzodiazepines metabolized?
In the liver
Are benzodiazepines absorbed rapidly upon oral administration?
Fairly lipophilic, so yes
What is the difference between barbiturates and benzodiazepines in terms of biodisposition?
Benzos have little impact on hepatic drug-metabolizing enzyme activity with continuous use, leading to less drug-drug interaction
What is tolerance of benzodiazepines caused by?
down-regulation of brain GABAa receptors
What are clinical uses of benzodiazepines?
Anxiety, insomnia, seizures, muscle relaxation, preanesthetic medication
What is a worry about the sedating effects of benzodiazepines?
can exert dose-dependent anterograde amnesic effects
What is the effect of benzodiazepines on hypnosis/sleep?
decreased time to fall asleep, increased stage 2 of sleep, decreased, decreased REM, decreased stage 4
What can be used to reverse to depressant actions of benzodiazepines?
Flumazenil
What can be caused by large doses of lorazepam and diazepam when used in combination with other drugs to induce anesthesia?
can cause postanesthetic respiratory depression
What are examples of non-benzo benzo-receptor agonists?
The Z’s: zolpidem, zaleplon, eszoplicone
What is the MOA of zolpidem, zaleplon, eszoplicone?
Bind to benzo’s spot on GABAa receptors more selectively
What is the advantage of using zolpidem, zaleplon, eszoplicone over benzos?
rapid onset, short duration of action (with no residual effects upon waking), slow tolerance effect?
What is buspirone used for?
selective anxiolytic effects, relieves anxiety without significant sedative or hypnotic effects
How long does it take for Buspirone to work (decrease anxiety)?
more than a week
Is buspirone good for acute anxiety attacks?
No, it takes more than 1 week to work
Where is buspirone metabolized? What should it not be taken with?
CYP3A4; erythromycin, ketoconazole, grapefruit juice
What is Ramelteon used for?
useful for patients who have difficulty in falling asleep
Where does remelteon act?
Agonist at melatonin receptors (MT1 MT2) located in suprachiasmatic nuclei (“master clock” of brain)
