antianxiety, relaxants, sedative hypnotics, etOH Flashcards
Alprazolam (Xanax)
Benzo
intermediate acting
anxiolytic
Chlordiazepoxide (Librium)
Benzo
long acting
Anxiolytic, Anticonvulsant, Withdrawal suppressant
Diazepam (Valium)
Benzo, Centrally acting musc. relaxant
long acting
Anxiolytic, Anticonvulsant, Anesthesia supplement,
Withdrawal suppressant, Muscle relaxant (for spasms)
Lorazepam (Ativan)
Benzo, Centrally acting musc. relaxant
intermediate acting
Hypnotic, Anxiolytic, Anesthesia supplement, Withdrawal suppressant
Midazolam (Versed)
Benzo
short-acting
Induction or supplement to anesthesia
Temazepam (Restoril)
Benzo
intermediate-acting
hypnotic
Triazolam (Halcion)
Benzo
short acting (good to help fall asleep)
hypnotic
Flumazenil (Romazicon)
BENZODIAZEPINE ANTAGONIST
antag. at benzo receptor
not v. useful in emergencies: benzos don’t depr. resp that much, won’t reverse barb/opiate/etOH induced resp depr.
- used in anesthesiology: post-op when given benzo, block effects, come out quicker
- can trigger seizures in pts dependent on benzos/barbs/etOH
Butalbital (Fiorinal)
BARBITURATE
for tension ha, centrally acting relaxant
Pentobarbital (Nembutal)
BARBITURATES
intermediate/short acting
sedative-hypnotics
Phenobarbital
BARBITURATES
long acting
tx for epilepsy, anticonvulsant
Thiopental (Pentothal)
BARBITURATES
ultra-short acting
not currently used
IV induction of sx anesthesia
used for execution, then pancuronium (NM blocker)–>then K to stop heart
Balcofen (Lioresal)
CENTRALLY ACTING MUSCLE RELAXANT
analog of GABA, acts as agonist at GABAb
dec. skel. musc tone
tx spasticity (UMN probs)
rehab medicine
adverse: CNS depression, musc. wkness, dependence/abuse potential
Cyclobenzaprine (Flexeril)
CENTRALLY ACTING MUSCLE RELAXANT
related to tricyclic antideps.
most widely prescribed muscle relaxant
doesn’t work as well as benzos
don’t operate machinery, drive
highly sedating
Diazepam (Valium)
CENTRALLY ACTING MUSCLE RELAXANT
muscle spasms
Metaxalone (Skelaxin)
CENTRALLY ACTING MUSCLE RELAXANT
Tizanidine (Zanaflex)
CENTRALLY ACTING MUSCLE RELAXANT
alpha2 agonist (like Clonidine) CNS effects: dec. skel musc. tone
very sedating (take at night)
Alcohol
MISC. ANXIOLYTIC AND SEDATIVE-HYPNOTIC
anxiolytics, sedative, relaxant
Buspirone (Buspar)
MISC. ANXIOLYTIC AND SEDATIVE-HYPNOTIC
anti-anxiety, NO musc. relaxation, NOT sedating
Gammahydroxybutyrate (GHB)
MISC. ANXIOLYTIC AND SEDATIVE-HYPNOTIC
abused: party/club, date rape
GABA analog, crosses BBB
ergogenic effect: body building
Melatonin
MISC. ANXIOLYTIC AND SEDATIVE-HYPNOTIC
nutritional suppl, not prescription, OTC
can normalize sleep patterns- “shift-work disorder”, travel
no effect on REM sleep (good quality sleep!)
don’t work well for most
Ramelteon (Rozerem)
MISC. ANXIOLYTIC AND SEDATIVE-HYPNOTIC
melatonin-rec agonist
jet-leg, etc.
Zolpidem (Ambien)
MISC. ANXIOLYTIC AND SEDATIVE-HYPNOTIC
longer acting (6-8 hrs)
widely presc. sleep med
newer, even less effect on REM sleep (good!)
non-benzos, but benzo agonist, bind receptors
enhance GABA-stim Cl- influx
less anxiolytic, less musc relaxant
should be prescribed short term
Zaleplon (Sonata)
MISC. ANXIOLYTIC AND SEDATIVE-HYPNOTIC
short acting (2-4 hrs)
help getting to sleep initially
or take in middle of night
Oxazepam (Serax)
Benzo
intermediate-acting
sleep aid
Hypnotic, Anxiolytic
Disulfiram (Antibuse)
etOH tx
inhibits of aldehyde dehydrogenase : blocks conversion of acetaldehyde to acetate
“acetaldehyde sickness”
*induces unpleasant rxn: flushing, ha, nausea, confusion
encourages abstinence
hepatotoxicity
also inhibits p450, drug interactions
Acamprosate (Campral)
etOH tx
decrease cravings for alcohol
may involve glutamate and GABA receptors, block NMDA receptors, stimulate GABA-A rec.
less potential for hepatoxicity than others
can use combo with naltrexone
Naltrexone (ReVIA)
etOH tx
long-acting opioid antagonist
reduce craving for alcohol in alcoholic
hepatotoxicity can make pain worse
other form: vivitrol: repo injection
Eszopiclone (Lunesta)
MISC. ANXIOLYTIC AND SEDATIVE-HYPNOTIC
longer acting (6-8 hrs)
act at benzo receptors (benzo agonist) but NOT benzos
action of these drugs
graded dose dep depression of CNS function
see graph
barbituate curve
steep curve, more potent than etOH
used to prescribe enough barb sleeping pills to kill someone
etOH curve
not v. potent, but steep response curve!
benzo curve
produce graded effects earlier, but plateau, so less likely to cause death
safer
benzo generalities
safer than Barbs, less likely to depr. resp. in OD
anticonvulsant for seizures
anxiolytic, acute panic/phobia disorders
GAD more tx by antideps
centrally acting musc. relaxant
benzos mech of action
(benzo binding enhances GABA) GABA A receptors
influx of Cl—>hyper polarized–>less likely to reach AP
barb mech of action
barbs also enhance GABA-med opening of Cl- channels
CAN ALSO open Cl- themselves (benzos can’t)
*dangerous
what else enhances GABA stim. Cl- influx
etOH
(why etOH/benzos/barbs share similar effects and exhibit cross-tolerance) and benzos (ativan) can be used to suppress etOH withdrawal (cross-dependence)
higher dose SEs
sedation drowsiness, lightheadedness (lower doses)
mental clouding, psychomotor impairment, ataxia
(drunk-like)
memory impairment: anterograde amnesia (new mem.)- good in benzos for unpleasant procedures
disinhibitions
used for date-rape
euphoria, hangover, rebound anxiety, mild resp. depression, tolerance, dependence
*teratogen
rohypnol vs valium for date rape
rohypnol more soluble in drinks
CNS side effects may be especially pronounced in ??
elderly patients
or OD
if take valium (longer acting benzos) to sleep…
have “hangover effect” in morning
may experience rebound anxiety
especially with short acting drugs such as triazolam (HALCION) or etOH
-perpetrates cycle of dependence
one benzo that is more likely to cause respiratory depression?
also ??
midazolam (VERSED)
powerful, state of anesthesia
enhanced resp. depression when taken with other resp. depressors (opioids: narco, etc)
tolerance develops rapidly to
sedative - hypnotic effects
i.e. to help sleep
decreasing effects, use short term for insomnia
tolerance does not dev. as rapidly to
anxiolytic effect (good!)
get anxiety relief w.out as much sedation
benzo dependence?
physical and psychological
w.drawal symptoms
agitation, anxiety, irritability, insomnia, abdominal cramps, sweating, and seizures
to avoid benzo withdrawal
gradually wean pt off drug by dec. dose by 10% every 2-3 days for 2-3 wks
very serious benzo w/drawal symptoms
delerium, tremors
grand mal seizures (may be status epilepticus)
life-threatening–>tx!
if dependent on short acting drug
if dep. on longer acting drug
withdrawal syndrome will tend to be fairly intense, but of a short duration (e.g. 1-5 days)
less intense, but 5-30 days
benzos and preggos
don’t use! possible teratogenicity
benzo effect on sleep
decrease sleep latency (time needed to fall asleep)
increase time spent in stage 2 non-REM sleep
dec. time spent in REM sleep (but we need some!)–>so decreases quality of sleep
“REM rebound” when go off benzos: crazy dreams
drug suppresses REM sleep the most
etOH (poor quality sleep)
then barbs
then benzos
diazepam has to undergo
Phase 1 oxidative metabolism–>long lived active metabolites
longer acting drugs
then Phase 2: conjugated to glucuronide and excreted
*not easy for alcoholic (liver failure) pts to get rid of–>toxicity
some benzo metabolites
are active!
may be even harder to get rid of
lorazepam and oxazepam are directly
conjugated to glucuronide and excreted (no Phase 1: oxidation)
*better for liver failure pts
drugs that can inhibit the oxidative metabolism of benzos–>prolong action
Cimetidine (Tagamet)
disulfiram (antabuse)
INH
benzos can inc. serum levels of
digoxin, and possibly phenytoin
barbs vs benzos
better anesthetic effect
anticonvulsants effects
more euphoric effect
respiration depression
barbs are metabolized by
why drug interactions??
hepatic microsomal system
induction of microsomal enzymes–>potential for drug interactions
barbs adverse effects
worse then benzos
GI upset, nausea
allergic reactions, skin
aggravation of acute intermittent porphyria–>induce hepatic enzymes involved in porphyrin synthesis
(vs. benzos: do not induce hepatic drug metabolizing enzymes)
?? effects greatly reduced by phenobarbital
Warfarin
barb abuse
?
barb poisoning
suicide
CNS depression
tx symptomatically, no antidotes
Buspirone (Buspar) 2
does not act thru ??
cannot be used for ??
newer drug, slower acting, 2-4 weeks!
does not act thru GABA mech, may be partial agonist at serotonin (5-HT)
WILL NOT suppress symps of etOH w.drawal, need to use benzos
better than benzos for long term alcoholic psych care
*don’t use benzos, too similar to etOH, trigger
sedative/hypnotic SEs
CNS depression
REM rebound
antihistamines sometimes used for
sedation
*Hydroxyzine (ATARAX, VISTARIL)
*promethazine (PHENERGAN)
diphenhydramine(benadryl)
propranolol
B-blocker
used for anxiolytic affects
-dec. HR, HTN, etc
-helps “stage fright”
etOH metabolism in liver
90%
zero order kinetics: constant rate, independent of concentration
metabolized @ 7-10 g/hour
alcohol dehydrogenase pathway
microsomal etOH oxidizing system (MEOS)
alcohol dehydrogenase pathway
etOH + NAD–>acetaldehyde*
*excess accumulation may be toxic
MEOS
etOH + NADPH–>acetaldehyde
low doses: most by etOH dehydrogenase pathway
- this pathway used more @ higher doses and induced w. chronic consumption
- tolerance and drug interactions
aldehyde metabolism
acetaldehyde–>acetate–>H2O + CO2
via aldehyde dehydrogenase
*inhibited by disulfiram
some Asians have lower levels aldehyde dehydrogenase
etOH probs
N/V, e-lyte abnormalities
sleep probe
resp. depression
CV: flushing, warmth, HTN, cardiomyopathies, arrhythmias
hangovers from ??
acetaldehyde buildup alcohol analogs present in beverages metabolic changes and dehydration resulting from acute alcohol intoxication pharmacodynamic changes in the brain
benefits of drinking
mod use (1-2 drinks/day) shown to inc. conc. of HDL, dec. LDL
etOH withdrawal: onset, duration
mild?
severe?
6-24 hrs after last drink, typ. resolve in 5 days
mild: anxiety, irritability, insomnia, nausea, sweating, tachycardia, palpitations, hypertension.
severe: anxiety, fear, hallucinations (alcohol hallucinosis), delirium, tremors (delirium tremens), grand mal seizures, hypertension, tachycardia, arrhythmias *emergency
etOH withdrawal tx
antipsychotics?
benzos: diazepam, lorazepam, and oxazepam
phenytoin (dilantin) to control seizures
no anti psychs, make seizures worse
*clonidine for ANS/CV effects
vitamins
goal etOH withdrawal tx
prevent seizures, delirium, arrythmias
general use of benzos
anxiety sedative-hypnotics acute etOH w.drawal convulsive seizure, status epilepticus skel musc spasms preanesthetic med and supplement induction of anesthesia
