Anxiolytic: Barbiturates Flashcards
fill in the blank: anxiety is the_______ of potential danger
physiological responses including _________ _______
- anticipation
- sympathetic activation
what is an anxiolytic, sedative, hypnotic
- anxiolytic-> reducing anxiety or tranquillizing
- sedative-> calming, relaxing, or sleep inducing
- hypnotic-> sleep inducing or sopoforic
what are sympathetic effects
- increased muscle tension, digestive problems and sleep disturbance
fill in the blank:________ _______ cycle is due to performance decrease and fear of failure
escalating anxiety
what disorders does anxiety have high comorbidity with
- depressive disorders and substance abuse
what are rates of alcohol abuse highest with
social anxiety disorders
how is generalized anxiety disorder different from panic attacks
generalized anxiety-> symptoms on anxiety without identifiable cause
panic attacks-> experiencing physiological effects of fear reaction without threatening stimulus
what can panic attack in response to a cue lead to
phobia
what are panic attacks accompanied by
- strong sympathetic NS activation
- increased heart rate, sweating, shortness of breath, choking, fear of losing control or dying
what was the first drug that was widespread to reduce anxiety
alcohol
what are the two contemporary anxiolytics and sedative-hypnotics
barbiturates; benzodiazepine
what are bromides
are sedatives possible through effects on cl- balance in the CNS and were the first effective anticonvulsants
what does bromism result from
- bromide toxicity
-impaired thought and memory, drowsiness, irritability, skin eruption (rash)
what was the first psychoactive barbiturate synthesized and what was it marketed as
- barbital ( relaxing and sopoforic effects)
-> long half-life meant drowsiness extended for days - veronal
true or false: phenobarbital was noted to be faster acting,, shorter duration and have excellent anticonvulsant properties
true
how can barbiturates be classed
according to the relative lipophilicity of the compound
true or false: decreasing the lipophilicity of barbiturates results in slower uptake into the brain and slower sedation
true
how are phenobarbital, amobarbital and thiopental different
- pheno-> low lipho and slow uptake
- amo-> medium lipho and intermediate uptake
- thio-> high lipho and fast uptake
what do low, moderate and high doses result in
- low-> anxiolytic and tranquillizing
- moderate -> sedation and sopoforic
- high-> anesthetic
Ultrashort acting bariturates are ____
anaesthetic ; example: thiopental
true or false: long-acting barbiturates have high lipophilicity and are effective for treating seizure disorders and anxiety
false; low
such as phenobarbital
what kind of side effects are accompanied by anxiolytic effects and what are they
- cognitive side effects
- mental clouding, loss of judgement, slowed reflexes
what is coma and death result of
respiratory depression
true or false: barbiturates induce restful sleep
false; they do not
- short term use does result in rapid sleep but decreased stages 3 and 4
- chronic decreases REM sleep and stages 3 and 4, it also increases spontaneous awakening
high abuse potential is due to rapid______ and _______
tolerance and dependence
when are amphetamines and barbiturates used
- amph-> during the day
- barb-> during the night
what do barbiturates have a high potential to interact with
ethanol
what does decreasing safety margin with tolerance lead to
high potential for overdose
what receptor do barbiturates act at and what does result in
GABA(A) receptor
- positive allosteric modulation increases GABA affinity and prolongs open time
where does an important effect of barbiturates happen
in the reticular formation
- pontine-> normally activates cortical centres
- medullary-> normally suppresses cortical centres
what are the balances of barbiturate effect in the reticular formation
-medullary fist- euphoria resulting from cortical activation
- pontine first- relaxation, drowsiness, sleep from cortical depression
true or false: barbiturates decrease mesolimbic DA release
Paradoically decrease mesolimbic DA release
Activates GABA inhibitory interneuron on VTA –> x Nucleus accumbens
can pentobarbital administration inhibit NAc dopamine release and inhibit ketamine-induced dopamine release
yes it can
in metabolic tolerance what do barbiturates induce in
induces microsomal enzyme leading to greater liver metabolism and leads to cross-tolerance
in pharmacodynamic tolerance what changes are made
cellular changes in GABA(A) receptor function and expression
fill in the blank: tolerance leads to decreased _______ ______
safety margin
look at slides 21,22 and 23 about dependence and withdrawal
what does pharmacological tolerance result in
rebound hyperactivity
for more information please look at slide 24 (thanks)
when did psychosis develop
- 3-5 days after withdrawal lasting as long as 9 days
- delirium, agitation, insomnia, confusion, etc.
- high BP, temperature and pulse
Why does effects of ultra-short acting barbiturates end?
They are highly lipophillic, thus redistribute into fatty tissue
Short/intermediate acting bariturates are _____
sedative
What is an example of a short/intermediate acting barbirturate that acts as a sedative?
Amobarbital
What does the termination of amobarbital depend on? Does this drug have a high abse potential
Liver metabolsim ; yes!
Two ways tolerance develops w/ barbiturates?
Pharmacodynamic: changes in GABA A receptor function and expression
Metabolic: Greater liver enzymes (p450)
Tolerance to sedative/hypnotic (desired efffects) are greater than toelrance to resp. depression —> decrease in safety margin.
