[PHARM] Sedative-Hypnotic drugs [Izard] Flashcards
What are the 4 classes of Sedative/Hypnotic Drugs?
Benzodiazepines
Benzodiazepine Antagonists
Barbiturates
Misc/Newer Drugs
Give examples of each of the following:
Benzodiazepine
Short Acting –>
Intermediate Acting –>
Long Acting –>
Short Acting –> Triazolam
Intermediate Acting –> Alprazolam
Long Acting –> Flurazepam
Give examples of each of the following:
Barbiutrates
Ultra Short Acting –>
Short Acting –>
Long Acting –>
Ultra Short Acting –> Thiopental
Short Acting –> Secobarbital
Long Acting –> Phenobarbital
What is the difference between a Sedative and a Hypnotic?
A Sedative is a drug that DECREASES CNS ACTIVITY (Calms reciepient)
–(Usually an adverse effect of many other drugs, but these are faster acting)
A Hypnotic is a drug that PRODUCES DROWSINESS and facilitates onset of sleep
With increased continued doses of Benzodiazepines vs Barbiturates what are the effects of each on the CNS?
Benzodiazepines –> LEVEL OFF
Barbiturates –> CONTINUE LINEARLY affecting CNS.
List the receptors that each work on:
Benzodiazepines
Barbiturates
Misc (Newer)
Benzos –> GABA (A) Receptors
Barbiturates –> GABA (A) Receptors
Misc –> GABA (A) and Melatonin Receptors
How are Benzos metabolized and excreted?
CYP3A4 (phase 1) and then Glucoronidation (phase II)
Excreted via Kidneys (Elimination Half life [2-100 hours])
What is the MOA of Benzos?
Binds to GABA (A) Receptor, and enhances GABA’s effects (Shifts dose response curve to the left)
Increases Cl influx
Increases Hyperpolarization
Decreases AP
What are the 10 Benzodiazepines?
Alprazolam
Chlordiazepoxide
Clonazepam
Clorazepate
Diazepam
Flurazepam
Lorazepam
Midazolam
Oxazepam
Triazolam
Which Benzos are used to treat Anxiety?
Which drugs are NOW better used to treat anxiety?
Alprazolam
Diazepam
Clonazepam
Lorazepam
(etc)
SSRI’s
Which of the following would be more likely to cause cumulative effects (drowsiness) with multiple doses, and why?
Diazepam or Alprazolam?
Diazepam, because its half life is >100 hours, and with longer half lives you are more likely to have an increase in the active metabolite in the system, and this will cause cumulative effects.
Alprazolam is metabolised by what enzyme?
it is indicated for what uses?
What specific cases can it be used and not used in?
What are some general warnings?
CYP3A4
Anxiety, Panic Disorder (w or w/o Agoraphobia)
Okay for use in –> Open Angle Glaucoma
NO for use in –> Acute Narrow Angle Glaucoma
Dependence and Withdrawl reactions, and Seizures
How is the drug Midazolam given?
What is it given for?
What is the black box warning for Midazolam?
Given IM or IV
For Preop sedation/anxiolysis/amnesia (in combo with other CNS depressants)
IV midazolam can cause Respiratory Depression/Arrest
When taking the Drug Diazepam, how long is the terminal elimination half-life of the active metabolite N-Desmethyldiazepam?
in what situations can this half-life be increased?
What is Diazepam used for?
up to 100 hours
With mild to moderate cirrhosis (+500 hours)
Tx of Anxiety, and Acute Alcohol Withdrawl
What situations are Diazepam contraindicated?
Known Hypersensitivity to Diazepam
Pediatric Pts (under 6 months)
Myasthenia Gravis
Severe Respiratory Insuff
Severe Hepatic 3 Insuff
Sleep Apnea
Open Angle Glaucoma –> can be used
Acute Narrow Angle Glaucoma –> can’t be used
When can you not used Diazepam?
tx of Psychotic Pts
with ingestion of Alcohol and other CNS Depressant drugs
Uses:
Oxazepam –>
Triazolam –>
Chlordiazepoxide –>
Oxazepam –> Anxiety, Anxiety w/ Depression, Acute Alcohol Withdrawl
Triazolam –> Short Term Tx of Insomnia (Cant be used with OPIODS)
Chlordiazepoxide –> Anxiety, Acute Alcholism Withdrawl, Preop Apprehension/Anxiety (Cant be used with OPIODS)
Uses:
Flurazepam –>
Lorazepam –>
Flurazepam –> Insomnia
Lorazepam –> Seizures (Epilepsy), Pre Op Anxiety
What is the drug Flumazenil used for?
What is the black box warning for this drug?
Management of Benzo overdose, by complete or partial reversal of the sedative effects of benzos
May cause Seizures
List the 6 Barbiturates?
Amobarbital
Butabarbital
Pentobarbital
Phenobarbital
Secobarbital
Thiopental
Barbiturates are used for?
Anxiety
Epilepsy/Seizures
Induce Sleep (Extreme Insomnia)
Anesthetics
Tension Headaches
Counteracts stimulant effects of Cocaine/Meth
Which drug classes are widely distributed throughout the body (Into the CNS, Placenta, Breast Milk)?
Barbiturates
Benzodiazepines
How are Barbiturates metabolized and excreted?
Metabolized –> via Liver
Excreted –> via Kidney
Can induce CYP450 enzymes
Which Barbiturate is excreted unchanged (20-30%)?
Phenobarbital
USES:
Ultra Short Acting –> Thoipental –>
Short Acting –> Secobarbital –>
Long Acting –> Phenobarbital –>
Ultra Short Acting –> Thoipental –> Anesthesia
Short Acting –> Secobarbital –> Insomnia
Long Acting –> Phenobarbital –> Seizures
Thiopental is administered via what route?
and is indicated for what uses?
IV
Sole Anesthetic Agent (15 min procedures)
induction of Anesthesia
Hypnosis during balanced anesthesia
controling convulsive state following inhalation anesthesia
Neurosurgical pts with increased intracranial pressure
What are some of the unique adverese rxns of Thiopental?
Respiratory Dep
Myocardial Dep
Cardiac Arrhythmias
Prolonged Somnolence
Sneezing
Coughing Bronchospasm
Laryngospasm/Shivering
Secobarbital is used for what?
Contraindicated in whom?
Short term tx of Insomnia (loses its affect after 2 weeks)
NO in:
Hypersensitivty to barbiturates
History of manifest or latent porphyria
impairment of liver fxn
Respiratory dz
What do you need to think about if a pt is taking Secobarbital/Phenobarbital/Flurazepam/Zaleplon and they have failure of insomnia to remit after 7-10 days of tx?
Primary Psychiatric or Medical Illness
Phenobarbital is contraindicated in what patients?
In which pts should you administer Phenobarbital with caution?
Known Barbiturate Sensitivity
History of Manifest or Latent Porphyria
Mentally Depressed, Suicidial tendencies, Drug Abuse pts
Which drug has been shown to induce liver microsomal enzymes, thus increasing and/or altering the metabolism of barbiturates and other drugs?
Phenobarbital
In treatment of Insomnia list the uses?
Benzos –>
Zolpidem/Zaleplon/Eszopiclone –>
Benzos –> Daytime sedation
Zolpidem/Zaleplon/Eszopiclone –> Sustained Sleep Maintenance
Ramelteon is an agonist at what receptors?
It is metabolized by which enzyme?
Which drugs can you not take with this drug?
What warnings are given for this drug?
Melatonin (MT1, MT2) Receptors
CYP1A2
Fluvoxamine, SSRI, CYP1A2 Inhibitor
Be careful with Psychiatric Disrder pts
What are the only approved tx of
Eszopiclone (Lunesta)
Zolpidem (Ambien)
Zaleplon (Sonata)
Tx of Sleep Disorders
These Newer Sleep aides (Eszopiclone, Zolpidem, Zaleplon) are metabolized in the liver by what enzymes and exctreted by what?
CYP3A4 (p450 metabolism)
Excreted via the Kidney
Short Half-lifes
Do the newer hypnotics (sleep aides) have any Anxiolytic, Anesthetic, Anti-convulsant, muscle relaxing, respiratory or cardiovascular effects?
NO!
Buspirone is used for?
Does it cause Sedation, Hypnotic, Euphoric, anticonvulsant, muscle relaxant effects?
It is extensively metabolized by?
Generalized Anxiety Disorder
NO! (its a newer sedative-hypnotic drug)
CYP3A4
List the 7 Misc/ Sedative Hypnotic Drugs
Buspirone
Chloral Hydrate
Eszopiclone
Meporbamate
Ramelteon
Zaleplon
Zolpidem
Zolpidem can cause what in depressed pts?
Worsening of depression, suicidal thinking (like SSRI’s)
Uses:
Meprobamate –>
Chloral Hydrate –>
Meprobamate –> Anxiety Disorders (slows activity of the brain to relax)
Chloral Hydrate –> Short-term use as a Sedative (Sleep Medicine)
