Sedatives anxiolytics Flashcards
Barbituants
- narrow therapeutic index
- Obsolete as anxiolytics
- Still used as IV induction agents
- Anti convulsants
Properties of benzodiazepines
- Highly lipophilic
- Well absorbed orally
- Highly protein bound
- Hepatic metabolism
- Active metabolites
What are Benzodiazepines excreted as?
Gluconoride conjugate
What are the major effects of benzodiazepines?
- Anxiolytic: reduce anxiety
- Hypnotic: induce sleep
- Reduce muscle tone
- Anterograde amnesia (pros and cons)
- Anticonvulsant effects
Administration of benzodiazepines
- Normally given orally or intravenously
- Can be given by intranasal or rectal route
- Not advised to be given intramuscular route
Describe the structure of GABA a receptors
- Pentameric arrangement
- Central ion channel pore
- 18 possible subunits
- Approx 30 forms of receptor
What allosterically activates the GABA a receptor
- Anaesthetics
* Benzodiazepines
What is flumazenil
Competitive bezodiazipine antagonist
What are the side effects of flumazenil?
- nausea
- Vomiting
- may precipitate agitation and seizures
How is flumazenil given?
IV in 100microgram increments
What are Z drugs?
- Act via benzodiazepine receptors
- Zopiclone
- Zalepam
- Zolpidem
What is tolerance?
Physiological state characterised by a decrease in the effects of a drug with chronic administration
Describe the tolerance of benzodiazepines
- Tolerance develops quickly for sedative effects
* More slowly for anxiolytic and anticonvulsant effects
What is the mechanism for tolerance?
- Neuro adaptive process
- Desensitisation of inhibitory GABA receptors
- Sensitisation of (excitatory) NMDA receptors
- Adaptions take place on different time scale
Describe dependence
- Drug induces a rewarding experience
- Drug taking becomes compulsive
- Psychological dependence
- Physical dependence
- Genetic factors
Describe withdrawal
- A result of physical dependence
- Increased anxiety, onset/exacerbation of depression
- Disturbed sleep
- Pain, stiffness, muscular aches
- Convulsions
- Can occur after relatively short courses of treatment
What are the clinical roles for sedatives and anxiolytic agents?
- enable potentially uncomfortable diagnostic and therapeutic procedures to be carried out
- management of acute alcohol withdrawal
- Management of insomnia
- Management of generalised anxiety states
- other: anticonvulsant
Index of suspicious of alcohol dependence
- Alcohol history
- Severity of alcohol dependence questionnaire
- Assessment of withdrawal symptoms
CAGE questionnaire
- Have you ever felt you should cut down on your drinking?
- Have you ever been annoyed by other people criticising your drinking?
- Have you ever felt guilty about drinking
- Have you ever taken a drink in the morning to steady your nerves or ease a hangover
What are the symptoms of alcohol withdrawal?
- Insomnia/anxiety/ restlessness/ agitation
- Tremor
- Nausea and vomiting
- Sweating
- Palpitations
- Hallucinations auditory/visual/tactile
- Seizures
When do symptoms of alcohol withdrawal start and when do they peak?
- May start 8 hours after drop in alcohol levels
* Peak day 2
What investigations are suggestive of chronic alcohol consumption?
- Raised MCV
- Pancytopenia
- Folate deficiency
- Prolonged prothrombin time
why may someone with chronic alcohol consumption have pancytopenia?
Alcohol induced bone marrow suppression
What drug can be given in alcohol withdrawal?
Chlordiazepoxide
What is sleep hygiene?
Aims to make people more aware of behavioural, environmental and temporal factors that may be detrimental or beneficial to sleep
Good sleep hygiene
- establish a regular pattern of going to bed and getting up
- Get regular exercise preferably in the morning but not within 4 hours of going to bed
- Keep your bedroom cool, dark and quiet
- Don’t have caffeine, alcohol or smoke within 6 hours of bedtime
- Avoid screen time for at least 30 minutes before bed
- Avoid naps during the day
- Bed is for sleep and for sex
If you must prescribe for insomnia, what should you do?
- Short acting benzodiazepine or z-drug
- Lowest effective dose for shortest time
- Inform patient no repeat prescriptions and explain why
Management of prolonged seizures
- Protect the patient from injury
- Provide oxygen if available
- Consider/exclude hypoglycaemia
- Seizures lasting longer than 5 minutes: IV lorazepam
- If intravenous access not available, consider rectal diazepam or intranasal or buccal midazolam
What is melatonin?
- Naturally occurring hormone synthesised in the pineal gland
- high levels at night, low during the day
- Secreted in response to input from the retina
