Pharm 8 - Hypnotics Flashcards
- Discuss the receptor site of action for barbiturates.
o Amnesia—loss of memory, occurs at low doses of anesthetics (α5-GABAA)
o Analgesia—affected by anesthetics and other factors (e.g. opiates, glycine in spinal cord)
o Sedation—longer response times, slurred speech, decreased motor activity; GABAA is a common factor
o Hypnosis—loss of righting reflex in rats, sleep in humans; also GABAA (β2 and β3 subunit suggested)
o Overall barbiturates are agonists at GABA receptor sites.
- Discuss the receptor site of action for barbiturates.
o Amnesia—loss of memory, occurs at low doses of anesthetics (α5-GABAA)
o Analgesia—affected by anesthetics and other factors (e.g. opiates, glycine in spinal cord)
o Sedation—longer response times, slurred speech, decreased motor activity; GABAA is a common factor
o Hypnosis—loss of righting reflex in rats, sleep in humans; also GABAA (β2 and β3 subunit suggested)
o Overall barbiturates are agonists at GABA receptor sites.
- Apply the indications for phenobarbital and secobarbital to a clinically-relevant case scenario.
Phenobarbital – preop sedation, agonist at GABA receptor sites, slow onset so not used orally as hypnotic, narrow therapeutic window, hyperactivity in kids.
- Secobarbital - short-term treatment for insomnia, not available in parenteral forms in used, short-term use in acute psychosis.
. Discuss how stimulation at these sites alters cell function and how this influences the overdose potential of benzodiazepines.
Benzodiazepines Pharmacodynamics:
o This group of hypnotics/anxiolytics acts at a site on GABAA receptors that is separate from the GABA site itself.
o From this site the action of GABA in opening chlorine ion channels is increased, but no effect without GABA, therefore body can compensate.
- Describe BZ withdrawal and give symptoms. Apply the appropriate withdrawal paradigm to a clinically-relevant case scenario.
- Chance of physical dependence is great when used for prolonged periods, withdrawal may follow, restlessness, anxiety, weakness, and generalized seizures, Must taper 25% per week to 50% of dose, than 1/8 dose afterward.
- Describe the general receptor type upon which zolpidem and zaleplon act.
Zolpidem:
o Non-benzodiazepine agent used as sedative hypnotic.
o Acts at GABAA type 1 only, I.e. less anti-convulsant effect.
o Rapid onset, given before retiring.
Zaleplon:
o Short-acting sedative, non-BZ, pyrazolopyrimidine acts at type1 GABA receptors (omega1).
o Fast onset and short terminal elimination half-life.
o May have anxiolytic actions.
Describe the particular MOA for propofol.
Propofol - stimulates GABA release, used for ambulatory surgery, no nausea and sense of well-being, metabolized rapidly and 99% changed before excretion, not for children due to acidosis, pain at injection site.
Apply the population in which etomidate is useful to a clinically-relevant case scenario.
- good in patients with limited cardiovascular reserve, does not lower bro; not analgesic so opoids also needed, less rapid than with proposal, acts on neurosteroids and affects GCs, pain on injection, myoclonus, and post-op nausea and vomiting.
- Apply one advantage and one disadvantage in the use of buspirone for persistent anxiety to a clinically-relevant case scenario.
Advanatage: Relief of persistent anxiety w/in 2-4 weeks, no potential for abuse, maintain cognitive skills, use with alcohol and other CNS agents, not cross reactive with benzos
- Disadvantages of buspirone: may be less effective in revent benzo users, gradual onset of action, not effective in panic disorder
What are the different uses for anxiolytics with slow and fast onset of action.
- Slow onset anxiolytics are used for panic disorders and slower onset of action (buspirone) are used for chronic anxiety disorders.
- Apply switching a patient from a BZ to Buspirone to a clinically-relevant case scenario.
Buspirone
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- Apply the indications for phenobarbital and secobarbital to a clinically-relevant case scenario.
Phenobarbital – preop sedation, agonist at GABA receptor sites, slow onset so not used orally as hypnotic, narrow therapeutic window, hyperactivity in kids.
- Secobarbital - short-term treatment for insomnia, not available in parenteral forms in used, short-term use in acute psychosis.
. Discuss how stimulation at these sites alters cell function and how this influences the overdose potential of benzodiazepines.
Benzodiazepines Pharmacodynamics:
o This group of hypnotics/anxiolytics acts at a site on GABAA receptors that is separate from the GABA site itself.
o From this site the action of GABA in opening chlorine ion channels is increased, but no effect without GABA, therefore body can compensate.
- Describe BZ withdrawal and give symptoms. Apply the appropriate withdrawal paradigm to a clinically-relevant case scenario.
- Chance of physical dependence is great when used for prolonged periods, withdrawal may follow, restlessness, anxiety, weakness, and generalized seizures, Must taper 25% per week to 50% of dose, than 1/8 dose afterward.
- Describe the general receptor type upon which zolpidem and zaleplon act.
Zolpidem:
o Non-benzodiazepine agent used as sedative hypnotic.
o Acts at GABAA type 1 only, I.e. less anti-convulsant effect.
o Rapid onset, given before retiring.
Zaleplon:
o Short-acting sedative, non-BZ, pyrazolopyrimidine acts at type1 GABA receptors (omega1).
o Fast onset and short terminal elimination half-life.
o May have anxiolytic actions.
