Anxiolytics Flashcards
use of anxiolytics?
tx sxs of anxiety and panic d/os
difference btw a sedative and a hypnotic?
sedative: calm the pt and reduces anxiety w/o inducing normal sleep; site of action is the limbic system which regulates thought and mental fxn
hypnotic: initiate and maintain normal sleep; site of action is ascending RAS which maintains wakefulness
5 things that can cause fatal withdrawal?
alcohol benzos barbituates chlorohydrate miltown (SOMA) all can cause CV arrest and death
common physical ssxs of anxiety?
tachycardia, trembling, sweating, palpitations
other methods of treatment?
psychotherapy including cognitive behavioral therapy
btw benzos and barbiturates which causes more neural depression? which can cause LOC? which has a higher therapeutic index? which can cause respiratory or cardiac depression? which effects REM sleep and can cause withdrawal?
barbiturates cause more neuronal depression, can cause LOC, have a low therapeutic index, can cause respiratory and cardiac depression, suppress REM sleep and can cause withdrawal sxs as well as hangover
benzos have less neuronal depression, a higher therapeutic index, they do not affect respiratory or cardiac fxn and have no effect on sleep
1st anxiolytic drug class to be developed?
barbiturates
action site for barbiturates vs benzos?
both seem to affect GABA sites on cell membranes of neurons in the CNS but not in the exact same location
general MOA of barbiturates and benzos?
when bind to GABA receptors, receptor site changes configuration and affinity of that site for holding on to GABA increases
what is the chief inhibitory neurotransmitter in the CNS of vertebrates?
gamma-aminobutyric acid (GABA)
what are GABAa receptors? GABAb?
GABAa: ligand-gated ion channels (ionotropic receptors)
GABAb: G protein coupled receptors (metabotropic receptors)
what type of receptors does Ach bind to?
muscarinic and nicotinic
what receptors does serotonin bind to?
5-HT3 and metabotropic receptors
glutamate binds to what receptors?
inonotropic and metabotropic receptors
blocking GABA receptors can cause what? as well as being deficient in GABA…
seizure activity
so postulated augmenting GABA fxn can afford protection against seizures
classifications of barbiturates?
long acting - duration longer than 8 hrs
intermediate acting - duration of 4 hrs
short acting - duration less than 4 hrs
ultra short acting - duration less than 1 hr
increasing dosing of barbiturates can cause what?
can produce calming effect as well as sedation
at a higher level (IV) can cause sleep followed by anesthesia
at still higher dosing can cause coma and death
they do not raise pain threshold and have no analgesic properties
ultra short acting barbiturate?
thiopental/pentothal
use of thiopental/pentothal?
usu used in induction phase of general anesthesia
has also been used as a “truth serum” to weaken resolve of pt
also first of three drugs administered during most lethal injections in the US
SEs of thiopental/pentothal?
CNS depressant so can cause CV and respiratory depression resulting in hypotension, apnea and airway obstruction
how are short acting barbiturates usu given? example?
IV or PO
pentobarbital/nembutal
how are short acting barbiturates commonly used? schedule of all of them?
used for insomnia and pre-operative sedation, physician-assisted suicide in OR, anesthesia and euthanasia in animals
all are schedule II drugs
ex of intermediate acting barbiturate? commonly used for what?
ex: butalbital/fiorinal
primarily used for insomnia and pre-operative sedation; added to aspirin or acetaminophen for migraine and cluster h/as
primary use of long acting barbiturates now? example?
primarily used to tx seizure d/os
phenobarbital/luminal
potential problems with barbiturates and why benzos are more commonly used now?
drug tolerance
psychological and physical dependence
severe withdrawal sxs
potential for coma, respiratory failure and death (particularly when EtOH consumed)
most widely used class of anxiolytic drugs?
benzodiazepines
MOA of benzos?
bind to specific high affinity sites on cell membrane of neurons in CNS which are adjacent but separate from GABA receptor sites
this binding enhances the affinity of GABA receptors for circulating endogenous GABA
their binding causes Cl- ion to influx into the nerve cells = hyperpolarization = more difficult for excitatory neurotransmitters to depolarize the nerve cell
uses of benzos?
anxiety, sedative and hypnotic, anticonvulsant tx, muscle relaxation
when are short acting benzos used? examples?
used for pts w/sleep onset insomnia
exs: alprazolam, estazolam, temazepam, triazolam
short acting benzo that is utilized for sedation and anxiety prior to upper and lower GI endoscopy, general anesthesia? how is it given?
midazolam/versed
given IV, but also available in syrup form
effects of midazolam/versed? indicated for what? long term use to tx what is not recommended?
effects: sedative, hypnotic, anxiolytic, anticonvulsant, skeletal muscle relaxant, amnesia
indicated for acute management of aggressive, violent or delirious patients
long term use in tx of seizure d/os is not recommended dt development of tolerance
when is midazolam/versed used?
premedication for anesthesia
induction and maintenance of anesthesia
rectally for emergency tx of seizures in children
prior to endoscopy and sedation in intensive care units
premedication before surgery to inhibit unpleasant memories
what can occur with discontinuation of midazolam/versed?
rebound insomnia
longer duration benzos are used to tx what? example?
used to tx insomnia as well as anxiety
ex: diazepam/valium
what class of drugs account for the majority of ER visits?
benzos - oxycodone was the most frequently implicated
class of diazepam/valium? indications? MOA? how to give?
class: benzo
indications: anxiolytic, sedative, muscle relaxant, seizure control
MOA: binds to benzo receptors in CNS to enhance GABA activity
give PO, IV; rapidly absorbed PO
SEs of diazepam/valium? withdrawal? its use for insomnia has been replaced by what other class of benzos?
SEs: drowsiness, impaired mentation, tolerance, addiction, rebound insomnia may occur after drug discontinuation
withdrawal can be severe esp when used chronically
has been replaced by shorter acting benzos
two benzo-like or non-benzo drugs used for tx? how do they work?
zolpidem (ambien)
zaleplon (sonata)
work by increasing GABA receptor affinity for endogenous GABA by interaction w/receptors that are neither benzo receptor sites nor barbiturate receptor sites
class of zolpidem/ambien? duration? use?
short-acting non-benzo hypnotic that potentiates GABA by binding to GABAa receptors at same location as benzos
works quickly and has a short 1/2 life
effective in initiating sleep; higher doses can act as an anticonvulsant and muscle relaxant but these uses have not been approved
class of eszopiclone/lunesta? indications? MOA? how to give?
class: benzo-like hypnotic
indications: insomnia
MOA: potentiation of GABA effect on chloride ion channels by binding to a specific receptor site not involved w/the binding of benzos
give PO, rapid onset
SEs of eszopiclone/lunesta?
impaired mentation prior to sedation, minimal drowsiness upon waking, minimal change in mentation relative to all other benzos
class of ramelteon/rozerem? MOA?
class: sedative hypnotic, melatonin agonist
MOA: melatonin receptor agonist, high binding affinity at the melatonin MT1, MT2 receptors - by binding at these receptors the drug mimics and enhances the action of endogenous melatonin which has been associated w/maintenance of circadian sleep rhythm through inhibitor activity of MT1, MT2 systems
ramelteon’s affect on GABAa receptors?
does not show any appreciable binding to GABAa (assoc w/anxiolytic effects, muscle relaxation, amnesic effects)
benzo withdrawal sxs?
occur either when person taking them has developed tolerance and stops taking them or pt stops taking the drug abruptly (w/o having developed tolerance)
ssxs: seizures, h/a, phonophobia, sweating, insomnia, pain, wt loss, shaking, blurred vision, photophobia, depression, nervousness - most serious is suicide!
general rule of dosing-withdrawal sxs?
generally, the higher the dose and the longer a benzo has been used/more rapidly it is discont. = the more likely that severe withdrawal sxs will occur
how long will benzo withdrawal sxs last for?
will last until the body reverses the physical dependence it has created - it will do so by making adaptations to the now drug-free environment and return the brain to normal function
benzo overdose SEs? MC sx of benzo overdose?
death as a result of overdose and CNS suppression
overdose is relatively uncommon but in combo with EtOH, barbiturate or opioids it greatly increases the risk for death as a SE
MC overdose sx: signs of intoxication w/impaired balance, ataxia, slurred speech
drugs that can increase benzo levels? drugs that can decrease benzo levels?
increase benzo levels = drugs that inhibit the P4503A4 pathway: ketonazole, fluconazole, nefazodone
decrease benzo levels = drugs that induce the P4503A4 pathway: carbamazepine
ways to tx benzo overdose?
adsorbed by activated charcoal
gastric lavage w/activated charcoal is not beneficial in pure benzo overdose but if taken in combo w/other drugs there may be a benefit of gastric “decontamination”
can enhance elimination of drug w/hemodialysis, hemoperfusion or forced diuresis (thought to have little effect)
use of flumazenil/romazicon? how to administer? dosing?
benzo receptor antagonist that can rapidly reverse the effects of benzos
IV admin only
multiple doses must be given to maintain reversal of benzo particularly if pt has overdosed w/longer acting benzo b/c flumazenil itself has a short half life
combining benzos w/what 4 other things increases the risk of benzo overdose and death?
benzos + EtOH, barbiturates, opioids or tricyclic antidepressants
flumazenil/romazicon is effective at reversing what SE of benzo overdose but not what other SE?
effective at reversing CNS depression assoc w/benzo overdose but less effective at reversing respiratory depression
SE administering flumazenil/romazicon can cause when trying to tx a benzo overdose?
in pts who are benzo dependent can cause abrupt withdrawal syndrome or seizures (particularly if they’re on the benzos to control seizures)
can also cause dizziness, nausea, agitation
C/Is for flumazenil/romazicon use?
hx of seizures, pts who have ingested additional substances that lower seizure threshold, tachycardia, widened QRS complex, anti-cholinergic sxs or hx of long-term benzo use
