Anxiolytics and Sedatives Flashcards
(43 cards)
What is a barbiturate?
- CNS depressant
- Obsolete as anxiolytics
- Associated with addiction
- Used as IV induction (bipentone) agents and anti-convulsants
Name different classes of drugs which can be used to treat anxiety [symptoms] ?
- Antidepressants
- Benzodiazepines
- Z-drugs
- B-blockers
- Melatonin
- Sedating antihistamine
What are properties associated with benzodiazepines?
- Highly lipophilic
- Well absorbed orally
- Highly protein bound (95%)
- Hepatic metabolism
- Active metabolites
- Excreted as glucoronide conjugate
What are the 5 main effect of benzodiazepines?
- Anxiolytic: reduce anxiety (a2 and a3)
- Hypnotic: induce sleep (a1)
- Reduce muscle tone
- Anterograde amnesia (pros and cons)
- Anticonvulsant effect
What is the main difference between different benzodiazepines?
Duration of action
How can benzodiazepines be given?
- Orally
- IV
- Intranasal or rectal
- NOT IM
What are the short acting benzodiazepines?
- Lorazepam
- Temazepam
- t1/2: 8 - 12 hours
What are the intermediate benzodiazepines?
Flunitrazepam
What are the long-acting benzodiazepines?
Diazepam
- t1/2: 20 - 100 hours
Describe the structure of GABA(A) receptors?
- Pentameric arrangement
- 2 alpha sub units, 2 Beta sub units and 1 gamma sub unit
- Central ion channel pore
- 18 possible sub units
What do benzodiazepines bind to?
Act allosterically GABA receptors - increase frequency of opening
- Different part of GABA receptor to GABA
What can act on GABA(A) receptors?
- Benzodiazepines
- Alcohol
- General anaesthetics
- Z-drugs
What travels throught the central ion channel?
Cl-
What is flumazenil used for clinically?
- Reverse the effect of benzodiazepines
- Competitive benzodiazepine antagonist
- Short half-life compared with benzodiazepines
- May precipitate agitation and seizures
- Given IV in 100mcg increments
- Side effects of nausea and vomiting
What are Z drugs?
- Alternatives to benzodiazepines - bind to benzodiazepines on GABA receptors
- Structurally different but have a very similar pharmacodynamic profile,slightly shorter acting
Name the “Z” drugs
- Zopiclone
- Zaleplon
- Zolpidem
What is the definition of tolerance?
A physiological state characterized by a decrease in the effects of a drug with chronic administration
How does tolerance affect benzodiazepines?
Develops quickly for sedative effects, more slowly for anxiolytic and anticonvulsant effects
What is involved in the mecahnism of tolerance in benzodiazepines?
- Neuro-adaptive process
- Desensitisation of inhibitory GABA receptors
- Sensitisation of (excitatory) NMDA receptors
- Adaptations take plae on different time scale
What is associated with dependance of benzodiazepines?
- Drug induces rewarding experience
- Drug taking becomes compulsive
- Psychological dependance
- Physical dependance
- Genetic factors
What are the effects of benzodiazepine withdrawal?
- Result of physcial dependance
- Increased anxiety, onset / exacerbation of depression
- Disturbed sleep
- Pain, stiffness, musular aches
- Convulsions
- Can occur after relatively short course of treatment
What was added to Rohypnol to make it less easy to “spike” people?
Blue dye
What is a recent concern associated with benzodiazepine use?
Alzheimer’s
What is the clinical role of sedative and anxiolytic agents?
- To enable potentially uncomfortable diagnostic and therapeutic procedures to be carried out
- Management of acute alcohol withdrawal
- Management of insomnia (not first line)
- Management of generalised anxiety states (not first line)
- Other: anticonvulsant
