Anxiolytics Flashcards
What is the difference between a sedative and a hypnotic drug?
Sedative = calming/anxiolytic effect ideally with little effect on motor or mental functions
Hypnotic = sleep inducing (more pronounced CNS depression than sedation; can be achieved by most sedative drugs simply by increasing dose)
How do most sedative-hypnotic drugs act on GABA-A receptors?
they open the chloride channel, hyperpolarize the cell and thus inhibit the cell; they POTENTIATE GABA-mediated inhibition
What are the parts of the GABA-A transmembrane receptor complex?
1) Cl- channel core
2) pentameric structure
3) endogenous agonist GABA binds alpha or beta subunits
**note that where GABA binds is NOT where Benzos and Barbs etc bind (they bind elsewhere to potentiate GABA’s action)
What part of the GABA subunit do Benzodiazepenes, Barbiturates, and Ethanol bind to?
Benzos: between alpha1-gamma2
Barbs: alpha or beta
Ethanol: alpha
What are the two main GABA-A receptor sub-types and which do benzos bind to?
BDZ1 = omega1; BDZ2 = omega2; diazepam (and most benzos) bind to both!
What are some of the properties of diazepam and most benzodiazepines?
sedation, hypnosis, muscle relaxation, anticonvulsant activity, anterograde amnesia
Benzos vs Barbs: which produce a “ceiling effect” and which produce a linear dose-response?
Benzos have a ceiling effect (no respiratory depression, coma, or death; merely augmenting action of GABA)
Barbs (&alcohol) have full a linear dose-response with CNS depression leading to death because not only do they augment GABA action, but they DIRECTLY open Cl- channels
**Benzos much safer
What are the names of all the Benzodiazepines we need to know for testing purposes?
Diazepam, Chlordiazepoxide, Lorazepam, Flurazepam, Alprazolam, Midazolam, Triazolam
How are the benzos metabolized? What causes unwanted daytime sedation related to this metabolism pathway?
Most undergo microsomal oxidation (Phase I via P450 with only modest P450 induction) and subsequent conjugation.
Daytime sedation is related to production of Phase I metabolites which are active w/long half lives
Name the benzos that don’t produce active metabolites as well as their respective half lives
Midazolam (1.9hr), Triazolam (2.9hr), Alprazolam (12hr), Lorazepam (14hr)
Name the benzos with active metabolites and their respective half lives
Chlordiazepoxide (10hr); Diazepam (43hr); Flurazepam (74 hr); all have active metabolites up to 100hr
What types of drugs are selective for the BDZ1 (ormega1) receptor?
sleeping pills (Zolpidem)
What are the therapeutics of Zolpidem and potential side effects?
Therapeutics: sedation and hypnosis w/out muscle relaxation or anticonvulsant activity with a short 2hr half life
Side Effects: sleep-walking, next morning impairment
What is the name of the benzodiazepine antagonist used to treat overdose of benzos?
Flumazenil
What are some of the drawbacks to Flumazenil?
possible life-threatening withdrawal; seizures in mixed overdoses and non uniform reversals of respiratory depression
How are the Barbiturates metabolized?
Phase I: oxidation (P450) with significant enzyme induction
Phase II: glucuronide formation
What type of drug is Phenobarbital, what is it used to treat, and is it fast or slow onset/elimination?
1) Barbiturate (binds a or b subunit of GABA-a)
2) Antiepileptic/Anticonvulsant
3) Less lipid soluble thus slower onset, slower elimination
What type of drug is Thiopental, what is it used to treat, and is it fast or slow onset/elimination?
1) Barbiturate (binds a or b subunit of GABA-a)
2) Induces anesthesia
3) Highly lipid soluble thus fast on/fast off due to tissue redistribution
What is the order or redistribution of Thiopental in the body?
brain–>muscle–>fat (metabolized by liver; dosed based on lean body mass)
What are the side effects of the barbiturates?
daytime sedation/drowsiness, dose-dependent depression of CNS, psychologic and physiologic dependence w/chronic use, and abrupt withdrawal life-threatening
What would you use to treat acute anxiety versus generalized anxiety?
Acute: benzodiazepines
GAD: antidepressants and/or benzodiazepenes
What is the name of the anti-anxiety medication that does not cause sedation? How does it act?
Buspirone; doesn’t have interaction with GABA-A; instead it may be a partial agonist at 5HT1A receptors
What do you use to treat Panic Disorder? OCD? PTSD?
Panic: SSRIs or benzos
OCD: SSRIs
PTSD: various antidepressants
Which of the benzodiazepines treat short term depression, and bipolar disease?
All of them except for Midazolam!
What does Midazolam used for?
Anesthesia (calming effects, produces anterograde amnesia)
Which benzodiazepine also induces sleep?
Triazolam
Which benzodiazepine also causes sedation?
Alprazolam and Lorazepam
Which benzodiazepine acts as anticonvulsant?
Lorazepam and Diazepam
Which benzodiazepine acts as a muscle relaxant?
Diazepam (by inhibitory effects on polysynaptic reflexes and interneuron transmissions)
What are the adverse effects of sedative hypnotics?
drowsiness and “hangover”, falls (in the elderly), dose-related CNS depression w/other drugs, tolerance, psychological and physiologic dependence with chronic use, anterograde amnesia
