Anxiolytics

Question 1

use of anxiolytics?

Answer 1

tx sxs of anxiety and panic d/os

Question 2

difference btw a sedative and a hypnotic?

Answer 2

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

Question 3

5 things that can cause fatal withdrawal?

Answer 3

alcohol
benzos
barbituates
chlorohydrate
miltown (SOMA)
all can cause CV arrest and death

Question 4

common physical ssxs of anxiety?

Answer 4

tachycardia, trembling, sweating, palpitations

Question 5

other methods of treatment?

Answer 5

psychotherapy including cognitive behavioral therapy

Question 6

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?

Answer 6

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

Question 7

1st anxiolytic drug class to be developed?

Answer 7

barbiturates

Question 8

action site for barbiturates vs benzos?

Answer 8

both seem to affect GABA sites on cell membranes of neurons in the CNS but not in the exact same location

Question 9

general MOA of barbiturates and benzos?

Answer 9

when bind to GABA receptors, receptor site changes configuration and affinity of that site for holding on to GABA increases

Question 10

what is the chief inhibitory neurotransmitter in the CNS of vertebrates?

Answer 10

gamma-aminobutyric acid (GABA)

Question 11

what are GABAa receptors? GABAb?

Answer 11

GABAa: ligand-gated ion channels (ionotropic receptors)
GABAb: G protein coupled receptors (metabotropic receptors)

Question 12

what type of receptors does Ach bind to?

Answer 12

muscarinic and nicotinic

Question 13

what receptors does serotonin bind to?

Answer 13

5-HT3 and metabotropic receptors

Question 14

glutamate binds to what receptors?

Answer 14

inonotropic and metabotropic receptors

Question 15

blocking GABA receptors can cause what? as well as being deficient in GABA…

Answer 15

seizure activity

so postulated augmenting GABA fxn can afford protection against seizures

Question 16

classifications of barbiturates?

Answer 16

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

Question 17

increasing dosing of barbiturates can cause what?

Answer 17

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

Question 18

ultra short acting barbiturate?

Answer 18

thiopental/pentothal

Question 19

use of thiopental/pentothal?

Answer 19

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

Question 20

SEs of thiopental/pentothal?

Answer 20

CNS depressant so can cause CV and respiratory depression resulting in hypotension, apnea and airway obstruction

Question 21

how are short acting barbiturates usu given? example?

Answer 21

IV or PO

pentobarbital/nembutal

Question 22

how are short acting barbiturates commonly used? schedule of all of them?

Answer 22

used for insomnia and pre-operative sedation, physician-assisted suicide in OR, anesthesia and euthanasia in animals
all are schedule II drugs

Question 23

ex of intermediate acting barbiturate? commonly used for what?

Answer 23

ex: butalbital/fiorinal

primarily used for insomnia and pre-operative sedation; added to aspirin or acetaminophen for migraine and cluster h/as

Question 24

primary use of long acting barbiturates now? example?

Answer 24

primarily used to tx seizure d/os

phenobarbital/luminal

Question 25

potential problems with barbiturates and why benzos are more commonly used now?

Answer 25

drug tolerance
psychological and physical dependence
severe withdrawal sxs
potential for coma, respiratory failure and death (particularly when EtOH consumed)

Question 26

most widely used class of anxiolytic drugs?

Answer 26

benzodiazepines

Question 27

MOA of benzos?

Answer 27

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

Question 28

uses of benzos?

Answer 28

anxiety, sedative and hypnotic, anticonvulsant tx, muscle relaxation

Question 29

when are short acting benzos used? examples?

Answer 29

used for pts w/sleep onset insomnia

exs: alprazolam, estazolam, temazepam, triazolam

Question 30

short acting benzo that is utilized for sedation and anxiety prior to upper and lower GI endoscopy, general anesthesia? how is it given?

Answer 30

midazolam/versed

given IV, but also available in syrup form

Question 31

effects of midazolam/versed? indicated for what? long term use to tx what is not recommended?

Answer 31

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

Question 32

when is midazolam/versed used?

Answer 32

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

Question 33

what can occur with discontinuation of midazolam/versed?

Answer 33

rebound insomnia

Question 34

longer duration benzos are used to tx what? example?

Answer 34

used to tx insomnia as well as anxiety

ex: diazepam/valium

Question 35

what class of drugs account for the majority of ER visits?

Answer 35

benzos - oxycodone was the most frequently implicated

Question 36

class of diazepam/valium? indications? MOA? how to give?

Answer 36

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

Question 37

SEs of diazepam/valium? withdrawal? its use for insomnia has been replaced by what other class of benzos?

Answer 37

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

Question 38

two benzo-like or non-benzo drugs used for tx? how do they work?

Answer 38

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

Question 39

class of zolpidem/ambien? duration? use?

Answer 39

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

Question 40

class of eszopiclone/lunesta? indications? MOA? how to give?

Answer 40

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

Question 41

SEs of eszopiclone/lunesta?

Answer 41

impaired mentation prior to sedation, minimal drowsiness upon waking, minimal change in mentation relative to all other benzos

Question 42

class of ramelteon/rozerem? MOA?

Answer 42

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

Question 43

ramelteon’s affect on GABAa receptors?

Answer 43

does not show any appreciable binding to GABAa (assoc w/anxiolytic effects, muscle relaxation, amnesic effects)

Question 44

benzo withdrawal sxs?

Answer 44

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!

Question 45

general rule of dosing-withdrawal sxs?

Answer 45

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

Question 46

how long will benzo withdrawal sxs last for?

Answer 46

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

Question 47

benzo overdose SEs? MC sx of benzo overdose?

Answer 47

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

Question 48

drugs that can increase benzo levels? drugs that can decrease benzo levels?

Answer 48

increase benzo levels = drugs that inhibit the P4503A4 pathway: ketonazole, fluconazole, nefazodone
decrease benzo levels = drugs that induce the P4503A4 pathway: carbamazepine

Question 49

ways to tx benzo overdose?

Answer 49

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)

Question 50

use of flumazenil/romazicon? how to administer? dosing?

Answer 50

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

Question 51

combining benzos w/what 4 other things increases the risk of benzo overdose and death?

Answer 51

benzos + EtOH, barbiturates, opioids or tricyclic antidepressants

Question 52

flumazenil/romazicon is effective at reversing what SE of benzo overdose but not what other SE?

Answer 52

effective at reversing CNS depression assoc w/benzo overdose but less effective at reversing respiratory depression

Question 53

SE administering flumazenil/romazicon can cause when trying to tx a benzo overdose?

Answer 53

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

Question 54

C/Is for flumazenil/romazicon use?

Answer 54

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