Anxiolytics and Sedatives Flashcards
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
How is acute alcohol withdrawal managed?
- Acute admission to hospital, supply of alcohol interrupted
- Index of suspicion (alcohol history, severity of alcohol dependance questionnaire)
- Assessment of withdrawal symptoms
- Chloridiazepoxeide 1-2 week reducing regime
What is involved in the CAGE questionnaire?
- Though about Cutting down?
- Annoyed by other people critisising your drinking
- Guilty about drinking
- Eye-opener - taken a drink in the morning to ease a hangover
What are the symptoms of alcohol withdrawal?
May start 8 hours after drop in alcohol levels (Peak day 2)
- Insomnia / anxiety / restlessness / agitation
- Tremor
- Nausea and vomiting
- Sweating
- Palpitations
- Hallucinations
- Seizures
What investigations are suggestive of chronic alcohol consumption?
- Raised MCV (FBC)
- Pancytopenia (result of alcohol induced bone marrow suppression)
- Folate deficiency
- Prolonged prothrombin time
How is insomnia managed?
- Difficulty geting off or waking up early?
- Assessment? pain/breathlessness
- Good sleep hygiene
- Hypnotics reserved for the acutely distressed
- Caution in elderly (confusion, falls, slower metabolism)
Why are hypnotics advised to not be taken every night in the community?
- Tolerance and dependance (do have hangover effect)
What is sleep hygiene?
Aims to make people more aware of behavioural, environmental and temporal factors that may be detrimental or beneficial to sleep
What is associated with sleep hygiene?
- Regular pattern
- Regular exercise (not just before sleep)
- Bedroom cool, dark, quiet
- Caffeine, alcohol and smoking not advised within 6 hours
- Screen time to be avoided 30 mins before bed
- Naps to be avoided
What is prescribed for insomnis?
- Short acting benzodiazepine or z-drug
- Lowest effective dose for shortest time
- Inform patient no repeat prescriptions and explain why also that may want to take intermittently
How are prolonged seizures managed?
- Protect patient from injury
- Oxygen
- Consider / exclude hypoglycaemia
- Longer than 5 mins - IV lorazepam
- IV access not available consider rectal diazepam or intranasal / buccal midazolam
If you are giving sedation for therapeutic procedure what are you aiming for?
Conscious sedation (sleepy but can respond to commands, can maintain own airway)
When can spontaneous ventialtion be inadequate?
- Deep sedation / analgesia (may be inadequate)
- General anaesthesia (frequently inadequate) (CV function may also be impaired)
How is acute anxiety managed?
- CBT
- Mantras, minduflness, worrytime
- Reduce caffeine, reduce alcohol
When are benzodiazepines recommended?
Indicated for short-term (2 to 4 weeks) relief of anxiety that is severe and disabling
What other drug besides benzodiazepines can be used to treat anxiety?
- Beta blockers (usually propanolol)
- SSRIs
- Gabapentin and pregabalin (also chronic pain)
What are the effects of Beta blockers on anxiety?
- Somatic symptoms of anxiety
- Sympathetic system decreased
- Helps with tachycardia, palpitations, tremor, sweating
- Propranolol
What is melatonin?
- Naturally occuring hormone synthesised in pineal gland
- liscensed for insomnia of those >55
- Used for children with neurological disability (e.g cerebral palsy)
What is the law on driving (march 2015) in relation to prescribed drugs?
- Not clear
- If driving is impaired you arebbreaking the law
- In relation to benzodiazepines, opioids and amphetamines
What percentage of doctors become substance dependant in theor lifetime?
- 10 - 14 % of all doctors
- ~ 2.7 times higher in anaesthetists than other physician groups
