Exam I - Anxiolytics Flashcards
Drug List
GABA receptors
Barbiturates
-phenobarbital
Drug List
GABA receptors
Benzodiazepines
- diazepam
- triazolam
- aplrazolam
- clonazepam
- midazolam
Drug List
GABA receptors
Benzodiazepine Receptor Agonists
- zolpidem
- eszopiclone
Drug List
GABA receptors
Benzodiazipine Receptor Antagonists
-flumazenil
Drug List
Melatonin Congener
-ramelteon
Drug List
5-HT1a receptor agonist
-buspirone
Sedative
Definition
- CNS depressant
- calming/tranquilizing effect
- ideally minimal effect on motor/mental
Sedative
Drug classes
- benzos
- barbiturates
- alcohol
- antipsychotics
- antidepressants
- antihistamines
Hypnoptic
Definition
- sleep-inducing or promoting
- not all hypnotics are sedatives
Anxiolytic
Definition
- reduce anxiety
- not all are sedative
- broad umbrella of drugs; “anxiety” heterogeneous
Sedative-Hypnotics
Graded Dose response
-low dose anxiolytic/sedative
-high dose hypnotic
-very high dose coma, anesthesia, death
-linear relationship for traditional drugs (e.g. barbs)
-benzos are safer, non-linear; proportionately VERY high dose needed
for coma/anesthesia/death
Indications
Panic Disorder
Agoraphobia
1) antidpressants (SSRI)
2) alprazolam (risk of dependence)
Indications
Social Phobia
1) psychotx
2) SSRI
3) clonazepam
4) Beta blockers (tremors)
Indications
Specific Phobia
psychotx
Indications
GAD
1) benzos (alprazolam, diazepam)
2) buspirone
3) antidepressants
Barbiturates
Phenobarbitol
Mechanism
- binds GABA A receptor
- increased Cl- flux
- hyperpolarizes neuron, inhibits
- suppresses glutamate transmission to AMPA receptors
- directly open Cl- channel at HIGH concentrations (toxicity)
Barbiturates
Phenobarbitol
ADME
- low tx index
- linear dose-response
- induce CYP enzymes
Barbiturates
Phenobarbitol
Adverse
- dependence/addiction
- low TI: overdose
Barbiturates
Phenobarbitol
Indications
- anesthesia
- seizure disorders
- rarely used as sedative
Benzodiazepines
Mechanism
- bind GABA A recepotors
- facilitate GABA-mediated Cl- influx
- do NOT have direct effect on Cl- channels
- specificity for GABA receptors
- full agonists (except zolpidem, which is specific for a1 subunit)
Benzodiazepines
Receptor Antagonists
(Flumezanil)
Mechanism
-competitively inhibits BZ receport agonists
Benzodiazepines
Indications/Effects
- anterograde amnesia (high dose)
- anesthesia (IV adjunct)
- anticonvulsant (clonazepam)
- skeletal muscle relaxations
Benzodiazepines
Adverse
- amnesia
- disinhibition
- dependence
- resp depression
- contra’d sleep apnea
- rebound anxiety/insomnia
Sleep Disorders
Indications
Triazolam
Epilepsy
Indications
Clonazepam, Diazepam
Anesthesia
Indications
- Midazolam IV
- for amnestic component
Benzodiazepines
ADME
-slow absorption
-midazolam, diazepam, aplrazolam, triazolam
more quickly absorbed
-metab’d to active metabolites by CYP3A4
-many metabolites have half life > 50 hrs
-conjugated to inactive glucuronides for renal exretion
Benzodiazepines
Half Lives
long >12: diazepam, clonazepam
medium 6-12: alprazolam
short <6: triazolam, midazolam
Benzodiazepines
Safety Profile
- relatively safe (high tx index, flatter dose-response)
- flumazenil for OD antagonism
- no/low drug-drug interactions
- long duration (one dose daily)
Benzodiazepines
Adverse
- addiction
- tolerance
- dependence (rebound insomnia/anxiety)
- anterograde amnesia
- weight gain, nausea, headache, light-headedness
- potentiate EtOH CNS depression
Benzodiazepine
Receptor Antagonist
Indiciations
- post-surgery anesthesia
- OD
- short acting
Benzodiazepine
Receptor Antagonist
Adverse
-can precipitate withdrawal
Buspirone
Mechanism
- non-sedative anxiolytic
- partial agonist at CNS 5-HT1a receptors
- minor effects at a1, a2, D2 receptors
- efficacy takes 1+ weeks (not useful in acute anxiety)
Buspirone
Indications
GAD
Buspirone
ADME
- rapidly absorbed
- several active metabs from first pass
Buspirone
Safety Profile
- no tolerance/dependence/abuse
- no psychomotor agitation
Buspirone
Adverse
-chest pain, tachycardia, palps, dizziness,
nervousness, tinnitus, GI problems
-contra’d MAOIs
Hypnotics and REM
- REM decreases with hypnotics
- REM rebound when withdrawn
Sleep and age
- latency to fall asleep
- increased number of awakenings
- total sleep may or may not change
Melatonin Receptor Agonists
Ramelteon
Mechanism
-agonist at MT1 and MT2 receptors
Melatonin Receptor Agonists
Ramelteon
Indications
-insomia, delayed sleep onset, circadian rhythm d/o
Melatonin Receptor Agonists
Ramelteon
Adverse
- dizziness
- hyperprolactinemia
Z drugs (zolpidem, eszopiclone) indications
-short-term (<3 wks) sleep d/o tx
Z drugs
adverse
- tolerance/dependence
- suppress REM/”deep sleep”
- anterograde amnesia, sleepwalking
- dose reduce for hepatic dysfxn
- dose reduce for cimetidine
- resp depression at high dose
Z drugs
Mechanism
-bind GABA A receptors with a1 subunit
Z drugs
ADME
- short acting
- clearance decreased in elderly, reduce dosage
