Mkgrady8 Neuro 5 Hypnotic/antianxiety Agents

Front 1

what do hyponotic agents produce

Back 1

a state of drowsiness; promote onset and maintenance of sleep; pt can be awakened readily; used in the treatment of insomnia

Front 2

what were the mainline antianxiety agents (anxiolytics) and how do they relate to this lecture

Back 2

SSRIs (like fluoxetine) and SNRIs (venlafaxine) are the first line treatment for most anxiety disorders; MANY ARE ALSO HYPNOTICS; THEY REDUCE TENSION, NERVOUSNESS, FEAR, AND APPREHENSION

Front 3

hypnotics: effects on sleep

Back 3

all drugs used as hypnotics alter the characteristics of sleep from normal; barbiturates and alcohol strongly depress REM; benzos strongly depress stages 3 and 4 of non REM; when REM is depressed for prolonged periods, a rebound increase in REM occurs associated with increased intensity and frequency of dreaming where nightmares may occur and the disturbance of sleep patterns may cause insomnia creating a vicious cycle of dependence; most non benzo hypnotics lose effectiveness after 2 weeks and some benzos can work up to 4-6 weeks

Front 4

drug withdrawal insomnia

Back 4

When hypnotic drugs are stopped, manypatients experience a rebound insomnia that promotes a feeling ofcontinued need for the drug. Longer-acting benzodiazepines tend toproduce less of this, but such agents may produce daytime sedation andpsychomotor impairment

Front 5

most common MOA of the hypnotics (and some anxiolytics)

Back 5

act at GABAA receptor; GABA is the major CNS inhibitory neurotransmitter and is chloride conducting so when GABA binds it opens the channels which hyperpolarizes the neuron which inhibits neuronal activity; benzos bind and increase the frequency of channel opening; barbiturates prolong the open time of the channels

Front 6

barbiturates: chemistry, classification

Back 6

they hypnotic barbs are weak acids; phenobarbital is especially useful as an anticonvulsant; long acting (phenobarbital), short to intermediate acting, and ultra short acting

Front 7

barbiturates: pharmacokinetics

Back 7

most routes of admin can be used (use oral for hypnotics); well absorbed; acidity means that it can get into the CNS; renal excretion so alkalinization of the urine can markedly shorten the duration of action of phenobarbital (and renal disease can prolong); also metabolized by the liver; barbs are dangerous because at high enough conc they can act by themselves to open the GABA channels which can cause sedation --> coma --> death IMPORTANT

Front 8

barbiturates: CNS effects

Back 8

enhance GABAAR responses by prolonging open time; high doses= open channel directly; hyperpolarization= NEURONAL INHIBITION; sedation --> hypnosis --> cognitive impairment --> anesthesia (LARYNGOSPASM) --> respiratory depression --> death

Front 9

barbiturates: CV effects

Back 9

slight decrease in BP; depression of vasomotor centers at toxic doses --> circulatory collapse

Front 10

barbs: hepatic effects

Back 10

induction of P450 enzymes; enhanced metabolism of barbiturates and ALL DRUGS METABOLIZED BY P450 ENZYMES; do not use barbs in pts with acute intermittent porphyria

Front 11

how to treat barb poisonsing

Back 11

if its phenobarbital then alkalinize the urine; general supportive measures; MAINTAIN AIRWAY and give O2; consider lavage; severe poisoning= CV, renal collapse; NO CNS stimulants

Front 12

review of therapeutic applications of barbs

Back 12

antianxiety and sedation (essentially replaced by benzos), hypnosis (essentially replaced by benzos), intravenous anesthesia (largely replaced by other drugs), anticonvulsant (epilepsy, tetanus, eclampsia, status epilepticus, convulsant drug poisoning)

Front 13

benzos: pros

Back 13

HAVE REPLACED BARBS for hypnosis (but effect is much less than that of barbs); safer (higher therapeutic index), tolerance is lower, lower chance of addiction, less drug interactions; CANNOT OPEN GABA CHANNELS BY ITSELF

Front 14

what are the 3 benzos to know

Back 14

diazepam, alprazolam, and triazolam

Front 15

other clinical uses of benzos

Back 15

anxiety disorders, depression with anxiety or agitation, panic disorders and agoraphobia, spastic musculoskeletal disease, seizure disorders, alcohol withdrawal syndrome, premedication for surgery, sleep disorders, anxiety reaction to psychedelic drugs, adjunct to GI and CV disorders, adjunct in treatment of schizophrenic pts

Front 16

what would be ideal in a hypnotic

Back 16

short acting to facilitate sleep and keep the pt asleep; short acting benzo problems= early AM awakening, anxiety, rebound insomnia

Front 17

bebzos: side effects and toxicity

Back 17

mostly psychomotor and cognitive; more apparent in the elderly; HIGH THERAPEUTIC INDEX so usually not lethal

Front 18

flumazenil

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BENZO ANTAGONIST; no activity in its own right; reverse the effects of ingested or administered benzo agonist (GABA can still act); ineffective for most other sedatives; can trigger withdrawals (withdrawals from the benzo)

Front 19

zolpidem

Back 19

aka ambien; structurally not a benzo but binds to same site on GABAAR as benzo (binds to a subtype of the GABAAR); good hypnotic with less effects on stages of sleep; low incidence of rebound insomnia and daytime sedation; women metabolize it slower so need to take smaller doses

Front 20

zaleplon

Back 20

structurally not a benzo but binds to the same site on GABAAR as benzos; good hypnotic with less effects on stages of sleep; low incidence of rebound insomnia and daytime sedation; short half life (1 hr)

Front 21

eszopicline

Back 21

structurally not a benzo but binds to the same site on GABAAR as benzos; good hypnotic with less effects on stages of sleep; low incidence of rebound insomnia and daytime sedation; short half life (1 hr)ch

Front 22

cloral hydrate

Back 22

metabolized to trichloroethanol; short duration; no enzyme induction; tolerance/dependence= withdrawal can be severe

Front 23

buspirone

Back 23

atypical anxiolytic; NOT A HYPNOTIC; not a GABAAR drug; acts at 5-HT1A and DA-2 receptor; cannot substitute for a benzo; does not produce tolerance and physical dependence

Front 24

ramelteon

Back 24

hypnotic; not a GABAAR drug; not a controlled substance; agonist for melatonin MT1 receptor which promotes onset of sleep; does not produce tolerance and physical dependence; well tolerated, nausea/vomiting

Front 25

suvorexant

Back 25

hypnotic; not a GABAAR drug; not a controlled substance; antagonist for orexin receptor which promotes onset of sleep; does not produce tolerance and physical dependence; day after somnolence which is sometimes severe

Front 26

baclofen

Back 26

skeletal muscle relaxant; GABAB receptor drug= inhibitory at cord and brain, antispasmodic useful in treatment of multiple sclerosis or spinal injury; NOT an anxiolytic; few side effects

Front 27

dantrolene

Back 27

skeletal muscle relaxant; reduces spasticity; interferes with Ca2+ release in skeletal muscle; useful in malignant hyperthermia due to general anesthetics