Anxiolytics Flashcards
Used to treat chronic anxiety, i.e. apprehension, restlessness, tension
anxiolytic drug
Decreases activity, moderates excitement and calms the patient
sedative drug
Produces drowsiness and facilitates the onset and maintenance of sleep
hypnotic drug
What are the clinical uses of CNS depressants? (7)
1) Reduce anxiety
2) Induce sleep
3) Sedation before surgery (amnesia-good)
4) Epilepsy
5) Balanced anesthesia for surgery
6) Control of withdrawal syndromes
7) Muscle relaxation
What’s the difference between Type A drugs and Type B drugs?
Type A lead to coma/death with increased dosage. Type B level off around hypnosis
Type A drugs (5)
Barbiturates, alcohol, chloral hydrate, GHB, some other general anesthetics
Type B drugs - what does this mean?
Benzodiazepines - great as anxiolytics!
Phenobarbital (Barbiturate) vs. Diazepam (benzo) : therapeutic index?
Diazepam’s is 10x that of phenobarbital’s
What is GABA?
primary inhibitory NT in brain
What are GABAa receptors like? What do they do?
ligand-gated, fast response. They allow Cl ions to go through membrane which keeps cell’s potential negative which makes AP’s less likely
How do benzodiazepines work on GABAa receptors? What don’t they do?
they increase the GABAa receptors’ affinity for GABA.They do NOT alone open the Cl channel
How do barbiturates work on GABAa receptors?
they increase the amount of opening by GABA AND at high concentrations can open the channel in the absence of GABA
What is the main mechanism of action of benzos? How do they do this? Are benzos agonists?
potentiation of GABA-stimutlation of GABA receptors. They bind to the GABA receptor and cause GABA to bind to the receptor with a higher affinity. They do NOT stimulate the receptor alone!! Therefore, NOT an agonist!! They increase GABA transmission, but only through GABA that has already been released into the synapse.
What do anxiolytics do in animal studies?
“release punishment suppressed behavior”
What are the two main classifications and which is the principle type*?
Type A: Barbituates, Type B: Benzodiazepines*
What is the model agent of barbiturates?
Pentobarbital
What are the model agents of benzodiazepines?
Alprazolam, Diazepam, Lorazepam, Triazolam, Midazolam
What determines the choice of benzodiazepines? What’s an exception?
Pharmacokinetics. Exception: alprazolam for panic disorders and agoraphobia
Where are benzos metabolized?
liver
What’s significant about benzos (metabolites)? Exceptions?
There are many active metabolites with long half-lives >24 hours. Exceptions: Lorazepam and Oxazepam are fast acting and rapidly metabolized. Triazolam is also special- it has an active metabolite but both Triazolam and its metabolite have short half lives.
Are benzos bound to plasma proteins?
Yes. Up to 90% and not easily displaced
What should be a concern about giving benzos to elderly pts?
metabolism is slow…give in low dosages
What are the short acting benzos (5)? Which one is special?
Alprazolam, Lorazepam, Midazolam, Oxazepam, Triazolam. Oxazepam is special because it is IV only (very rapid!)
What are the long acting benzos (1)?
Diazepam
What are the therapeutic effects of benzos (4)?
antianxiety, sedation, hypnosis, anticonvulsants
at low doses, are the anxiolytic actions of benzos associated with little or great CNS depression?
little
at low doses of benzos, what’s up with sedation?
suppression of responsiveness to a constant level of stimulation. tolerance develops within days
Which type of benzos are best for hypnosis? When are another kind used?
Fast acting. Short-acting used if antianxiety action isn’t wanted.
what are some characteristics of hypnotic effects of benzos? tolerance?
latency of onset reduced, stage 2 non-REM sleep increased, REM duration decreased, duration of slow wave reduced. Tolerance over days-weeks…rebound increase in REM with withdrawal
Which benzo is used as an anticonvulsant?
Diazepam - status epilepticus and alcohol withdrawal
What are some side effects of benzos (4)?
1) Respiration: depression if higher than sedating dose (except in pulmonary obstruction: greater sensitivity)
2) Euphoria: fast-acting, short-lived benzos are abused; psychological dependence common with long term use.
3) Paradoxical excitement: associated with “CNS disinhibition”
4) Anterograde amnesia: can’t remember things happening while under effects of drug
What are drug interactions of benzos (4)?
1) additive or even synergistic CNS depression with other sedative hypnotics and alchohol
2) functional cross-tolerance with ethanol and other sedative hypnotics
3) oral contras reduce Diazepam eliminiation
4) asymmetric metabolic cross tolerance with ethanol and barbs
Do benzodiazepines induce liver P450 enzymes?
NO
Do EtOH and barbiturates induce liver P450 enzymes?
YES
What does asymmetric metabolic cross tolerance with barbs and benzos mean?
barbs can induce the liver enzymes that metabolize BOTH barbs AND benzos! over time, half life of barbs becomes shorter. BARBS and BENZOS are metabolized by the same enzymes!
reverse side of liver enzymes stuff?
benzos do NOT induce them. half-lives stay the same with benzo use over time.
What is the antagonist vs. benzos?
Flumazenil
What’s up with Flumazenil?
short half-life, IV only
What are the actions of Barbiturates (3)?
1) Sedative-hypnotic
2) Anticonvulsant properties (but Diazepam preferred!!)
3) Induction of liver microsomal enzymes
What are the (largely historical) therapeutic uses (3)?
1) IV Anesthetic
2) Sedatives
3) Epilepsy
Which barbiturate is used as IV anesthetic? Is it short or long acting?
Thiopental. Ultra-short acting
Which barbiturate is used as sedative?
Pentobarbital
Whcih barbiturate is used for epilepsy?
Phenobarbital
What is the mechanism of barbiturates?
Potentiation of inhibitory neurotransmission GABAa receptor
What are 3 examples of barbiturates and what are their defining characteristics?
Thiopental - ultra short-acting
Phenobarbital - anti-epileptic
Pentobarbital - hypnotic, high abuse potential, replaced by benzos
What are some non-sedative drugs used to treat anxiety (4)? What are their defining characteristics?
1) buspirone: very slow acting, novel structure
2) Beta-adrenergic blockers: decrease sympathetic tone, symptomatic relief of anxiety, e.g. speeches
3) Alpha 2 agonist: Clonidine
4) Tricyclic antidepressants: panic attacks
What are some other sedative/hypnotics (5)? Some notes about them?
1,2) Zolipidem, Zaleplon: act at benzo binding site btu different structure. sedative>anxiolytic…lower abuse potential?
3) Chloral hydrate: restricted to instiutional use, inexpensive, significant toxicity, oral prep for pediatrics
4) Hydroxzine, Diphenhydramine: antihistamines, OTC sedatives/hypnotics, may synergize with morphine for analgesia, anticholinergic side effects (e.g. drymouth), contraindicated for pregnant women
