Anxiolytics & Hypnotics Flashcards
What are anxiolytics?
drugs that decrease anxiety + stress
What are hypnotics?
A drug that induces sleep in insomnia
What is insomnia?
difficulty in initiation & maintenance of sleep
What is hypersomnia
excessive sleep or sleepiness
What does tolerance of a drug mean?
↓ drug effect requiring ↑ of dosage → same
effect
What is physical & physiological dependence?
stopping of a drug →
unpleasant symptoms
Classification of anxiolytics & hypnotics
1- barbiturates
2- benzodiazepines
3- 5-HT blockers
4- Miscellaneous
classification of benzodiazepines
1- hypnotics -> Flurazepam
2- anxiolytic -> Diazepam
3- anticonvulsant -> Clonazepam
4- anesthesia -> Midazolam
5- muscle relaxant -> Diazepam
what is an allosteric site example?
BZs don’t bind to GABA receptors themselves but they bind to one next to it to potentiate GABA receptors
mode of action of BZs
BZ binds to specific sites on the cell membrane adjacent to GABA receptors -> GABA receptors contain primary agonist binding site (GABA) & multiple allosteric sites -> conformational change in receptor -> cl- channel opens -> increase cl- conductance -> hyperpolarization -> CNS depression
BZs receptor ligands
Agonists: e.g. BZs & zolpidem → anxiolytic effect.
Antagonists: e.g. flumazenil→ block anxiolytic effect.
Inverse agonists: e.g. picrotoxin & β-carbolines -> anxiety & seizures (opposite of BZs, toxic CNS stimulant)
BZ Long-acting BZs 1-3 days
diazepam
BZ intermediate-acting 10-20 hrs
lorazepam
BZ short-acting 3-8 hrs
oxazepam
which BZ drug is most likely to be abused? what is its duration of action?
oxazepam
Metabolism & Excretion of BZs
liver microsomal enzymes
as glucuronides
Effects of BZ
1- Drowsiness, confusion -> extreme CNS depression
2- anterograde memory confusion -> useful in anesthesia
3- ataxia & respiratory depression -> extreme doses
Overcoming toxicity of BZs
flumazenil IV
Withdrawal symptoms of BZ
confusion, sweating, anxiety, agitation,
palpitation, restlessness, insomnia & tension
induced by short-acting derivatives >
long-acting ones (related to elimination t½)
Interactions of BZ
Toxicity of alcohol & other CNS depressants.
Patients with hepatic dysfunction or hypersensitivity to BZs.
Enzyme inducers & inhibitors. (affects other drugs dosage)
Action of Barbiturates
increase the opening duration of GABA receptors -> increase GABA transmission
decrease activation of glutamate receptors
Pharma actions of barbiturates
sedation -> hypnosis -> anesthesia -> respiratory depression -> death
therapeutic uses of barbiturates
anesthesia -> thiopental
anticonvulsant -> phenobarbital
Barbiturates Long-acting 1-2 days
phenobarbital
barbiturates short-acting 3-8 hours
secobarbital
Barbiturates ultra short-acting 20 min
thiopental
barbiturates metabolism + excretion
liver microsomal enzymes & in urine
barbiturates side effects
- Drowsiness & impaired concentration.
- Drug hangovers.
- Respiratory & circulatory depression.
- Enzyme induction.
- Addiction
barbiturates withdrawal
1- anxiety, tremors, weakness
2- seizures
3- nausea, vomiting
4- cardiac arrest, death
Barbiturate management of toxicity
1- artificial respiratory
2- gastric lavage
3- hemodialysis
4- alkalinization of urine (changing ph of urine so it isn’t reabsorbed)
barbiturates contraindications
1- hepatic or renal disease
2- drug interactions due to enzyme induction
3- allergic reactions
barbiturates side effects
induces cytochrome p450s -> acute porphyria
atypical drugs
1- drugs that act through BZ receptors
2- drugs that act through melatonin receptors
3- drugs that act through serotonin receptors
4- drugs that act through orexin receptors
drugs that act through BZ receptors
ZOLPIDEM ZALEPLON
- increase in chloride channel flow
- bz1 receptor agonist
- less effect on cognition
- used in insomnia
- less likely to be abused
drugs that act through melatonin receptors
RAMELTEON
- used in insomnia
- less likely to be abused
drugs that act through orexin receptors
SUVOREXANT
-orexin receptor antagonist
-hypnotic properties
-HME interaction
5-HT Receptor Antagonists (serotonin antagonist)
Buspirone
-selective anxiolytic
-no effect on GABA
-5-ht partial agonist
-GAD
- non-sedative
-safe in pregnancy + elderly
-slow onset
Miscellaneous drugs classification
Chloral hydrate
hydroxine
b blockers
alcohol
Chloral hydrate (miscellaneous drugs)
GIT Distress -> not used anymore
hydroxine (miscellaneous drugs)
antihistaminic (main job) but crosses brain barrier so it has anxiolytic effects
useful in abuse history
B blockers (miscellaneous drugs)
decrease tremors associated with anxiety e.g stage fright -> not safe tho
Alcohol (miscellaneous drugs)
toxicity outweighs sedation
toxic effects: nausea, vomiting, drug abuse, liver cirrhosis
potentiates CNS depressants
DISULFIRAM to quit
Mechanism -> decrease aldehyde dehydrogenase -> increase acetyladehyde level -> flushing, hyperventilation, tachycardia, nausea
