chapter 12 - sedative hypnotic drug classes

What is the mechanism of action of the barbiturates drug class?

low doses: bind to GABA receptor-mediated chloride channel prolonging channel opening, chloride influx and membrane hyperpolarization. generation of action potentials are reduced and neuronal activity is inhibited. inhibition in the reticular formation promote sedation or sleep

high doses: general CNS depression. mechanism not well understood

What are the drug indications of the barbiturates drug class?

• sedation

• hypnosis (no longer recommended)

• anticonvulsant (only two are antiepileptic)

• general anesthetics

What are the contraindications for the barbiturates drug class?

• acute intermittent porphyria

• pregnancy (avoided)

• *** administer with caution, these are frequently used to attempt suicide

What are the adverse affects of the barbiturate drug class?

• disruption of REM sleep

• depressed reflexes and impaired judgement

• lethargy

• incoordination

• drowsiness

• dry mouth

• automatism: elderly patients are sensitive to CNS side effects particularly with memory difficulties and mental confusion

What are the pharmacokinetics of the barbiturates drug class?

• 30-60 minute onset

• DMMS metabolism and inactivation

• excreted mostly through urinary system

What are the drug interactions of the barbiturates drug class?

• enzyme inducers: can lead to tolerance and increased metabolism of other drugs (ex: oral anticoagulants, oral contraceptives)

• potentiate action of CNS depressants

• alcohol

What are the addiction or liability issues with the barbiturates drug class?

• after prolonged and excessive use, both physical dependence and tolerance can result

• can also lead to cross-tolerance with other CNS depressants (ex: alcohol and benzodiazepines)

• overdose results in depression of all brain activity including vital functions in medulla oblongata contributing to hypotension

• ***no antidote for overdose

What are the drugs in the barbiturates drug class?

• phenobarbital

• pentobarbital

• amobarbital

• secobarbital

What are the details for phenobarbital?

• long-acting (6-12 hours)

• anticonvulsant and antiepileptic

• schedule IV

• ROA: PO,IV,IM

What are the details for pentobarbital?

• intermediate-acting (4-6 hours)

• anticonvulsant (parenteral)

• schedule II

• ROA: PO, IV, IM, recta

What are the details for amobarbital?

• anticonvulsant (parenteral administration)

• schedule II

• ROA: PO, IV

What are the details for secobarbital?

• short-acting (2-4 hours)

• indicated for patients who struggle falling asleep NOT staying asleep

• schedule II

• ROA: PO, IV, IM

What is the mechanism of action for the benzodiazepines drug class?

bind to receptor on chloride channel and combines with GABA activity to increase frequency of channel opening. this results in hyperpolarization and reduced neuronal activity. reduced activity in reticular activating system leads to sedation and hypnosis (depending on dose)

What are the drug indications for the benzodiazepines drug class?

• sedation

• hypnosis (particularly when complicated with anxiety)

• anxiety

• muscle relaxant

• anticonvulsant

• antiepileptic

• alcohol withdrawal (only 2)

• preoperative sedation

• induction of general anesthesia

• monitored anesthesia care (MAC)

• sedation and amnesia (with NMDB) for endotracheal intubation

• conscious sedation

What are the contraindications for the benzodiazepines drug class?

• pregnancy

What are the pharmacokinetics for the benzodiazepines drug class?

• well absorbed from GI, lipid-soluble, rapidly enter CNS

• metabolized by DMMS (some active metabolites for longer DOA)

  • excreted mainly by urinary tract

What are the drug interactions for the benzodiazepines drug class?

• potentiate actions of CNS depressants (ex: barbiturates)

• alcohol, grapefruit juice

• cimetidine: enzyme inhibitor, can increase DOA of benzodiazepines

What are the addiction or liability issues with the benzodiazepines drug class?

• dependence is possible as is abuse

• overdose results in excessive CNS and respiratory depression

• ***antidote is flumazenil

What are the drugs in the benzodiazepines drug class?

• flurazepam

• temazepam

• triazolam

• ***flumazenil

What are the details for flurazepam?

• long-acting, several active metabolites

• active metabolites prolong action into the following day “hangover effect”

• schedule IV

• ROA: PO

What are the details for temazepam?

• intermediate-acting, no active metabolites (***gelatin capsule delays onset, takes 1-2 hours before sleep onset)

• schedule IV

• ROA: PO (hard gelatin capsule)

What are the details for triazolam?

• short-acting

• adverse effects: rebound insomnia and increased daytime anxiety

• schedule IV

  • ROA: PO

What are the details for flumazenil?

• benzodiazepine receptor antagonist

• used to reverse effects of overdose

• antagonizes eszopiclone, zaleplon, and zolpidem

• ***may cause seizures, special warning to medical personnel to be prepared to manage seizures

What is the mechanism of action for the miscellaneous category of sedative-hypnotic drugs?

selectively bind to subunit of benzodiazepine receptor on chloride channel and increase inhibitory effects on GABA

***ramelteon: melatonin agonist

What are the addiction and liability issues for the miscellaneous category of sedative-hypnotic drugs?

low risk for tolerance, dependence, and withdrawal reactions, withdrawal reactions tend to occur with abrupt cessation after prolonged use

What are the drugs in the miscellaneous category of the sedative-hypnotic drugs?

• eszopiclone (Lunesta)

• zaleplon (Sonata)

• zolpidem (Ambien)

• ramelteon (Rozerem)

What are the details for eszopiclone (Lunesta)?

• drug indication: induce and maintain sleep

• adverse effects: dizziness, mild memory impairment, headache, dry mouth

• schedule IV

• ROA: PO

What are the details for zaleplon (Sonata)?

• drug indication: sleep induction

• adverse effects: dizziness, headache, minor GI disturbances

• ***elderly may experience mental confusion and memory disturbances

• schedule IV (rapidly absorbed and short duration of action)

• ROA: PO

What are the details for zolpidem (Ambien)?

• drug indication: decrease nighttime awakenings and increase total sleep time

• adverse effects: dizziness, headache, nausea

• ***elderly may experience mental confusion and memory disturbance

• schedule IV (rapidly absorbed and rapid onset of action)

• ROA: PO

What are the details for ramelteon (Rozerem)?

• drug indications: promote sleep onset

• adverse effects: dizziness, headache, minor GI disturbances

• not associated with drug dependence, not a controlled substance

• ROA: PO