Anxiolytics and Sedatives Flashcards
What are barbituates used for?
Still used as IV induction agents and anticonvulsive
What are the classes of drugs used for anxiety?
- ANtidepression,
- Benzodiazapines,
- Z-drugs,
- B-blockers,
- Others (melatonin or sedating antihistamines)
In what condition are beta blockers contrainticated?
Asthma
Describe chemical features of benzodiazepine?
Highly lipophilic (get into the brain quickly) which is absorbed orally. Highly protein bound (long half life), Hepatic metabolism into active metabolites. Excreted as glucoronide conjugate.
What are the pharmcokinetics of benzodiazepine?
Allosteric agonists of GABA receptors (selectively permeable to chloride ions).
Because they are highly protein bound, they have a big reservoir so tend to be long acting.
Peak effects from 30mins-2hours.
Has renal excretion
Describe features of GABA receptors
- Pentameric arrangement (two alpha, two beta and one gamma subunits) with central chloride ion channel.
Anaesthetics and benzos allosterically activate the receptor, increasing the frequency of opening
What are the 5 major effects of benzodiazepines?
1) Anxiolytics (reduced anxiety),
2) Hypnotic (induced sleep),
3) Reduce muscle tone,
4) Anterograde amnesia,
5) Anticonvulsant effect
What are the routes of administration of Benzodiazepines?
- Normally given orally or intravenously (can be intranasal or rectal route),
- Not advised to be given IM because it is painful
The sedative/anxiolysis effects of drugs is via what part of the GABA receptor?
Sedation mediated via alpha 1 subunit.
Anxiolysis mediated via GABA(A) with alpha2 and alpha3 subunits.
Name the competitive antagonist of benzodiazepines
Flumazenil however may precipitate to agitation and seizures. It is given IV in 100mcg increments. Side effects of nausea and vomiting.
Describe features of Z drugs
They act via benxodiazepine receptors and while they have similar pharmacodynamic profile, they are structurally different. Shorter half life so less of hangover.
Name examples of Z drugs
- Zopiclone,
- Zaleplon,
- Zolpidem
What is tolerance?
Physiological reaction characterized by a decrease in the effects of drug with chronic administeration
Describe tolerance of Benzodiazepines
- Tolerance develops quickly for sedative effects but slower for anxiolytics and anticonvulsive.
- Occurs due to desensitisation of inhibitory GABA receptors but causes sensitisation of NMDA receptors
What are the concerns of benzodiazepines?
The drug induces a rewarding experience and so taking the drug becomes compulsive.
They enhance highs of other drugs and blunts the lows of other drugs so used as part of polydrug misuse.
Describe features of benzodiazepine withdrawal
- Occurs as a result of physical dependence (can occur after short course of treatment) and causes;
- Increased anxiety,
- Disturbed sleep,
- Pain, stiffness and muscular aches,
- Convulsions
When is it common to prescribe benzodiazepines
- Management of acute alcohol withdrawal,
- Terminal care pathway,
- Enable potentially uncomfortable diagnostic and theraputic procedures to be carried out,
- Anticonvulsive.
Explain the management of alcohol withdrawal
- Take alcohol history, use severity of alcohol dependence questionnaire and assess withdrawal symptoms then use chlordiazepoxide 1-2 week reducing regime
What are the symptoms of alcohol withdrawal?
- Insomnia, anxiety, restlessness or agitation,
Tremor, - Nausea and vomiting,
- Sweating,
- Palpitations,
- Hallucinations (auditory/visual/tactile)
- Seziures
What are investigations suggestive of chronic alcohol consumption?
- Raised MCV,
- Pancytopenia (as a result of alcohol induced bone marrow suppression),
- Folate Deficiency,
- Prolonged prothrombin time
Describe some sleep hygiene measures
- Establish regular pattern of going to bed,
- Exercise,
- Keep bedroom cool, dark and quiet,
- Don’t have caffine, alcohol or smoke within 6 hours of bedtime,
- Avoid screen time for at least 30mins before bed,
- Avoid naps during day,
- Bed is for sleep and sex.
If you MUST prescribe for insomnia then?
Use short acting benzo or z-drugs at the lowest effective dose for shortest time. No repeat prescriptions
Describe the use of benzodiazepines in anticipatory care plans
- Used for management of follow;
- anxiety,
- Massive terminal haemorrhage,
- Agitated delirium,
- Breathlessness or respiratory diseases (alongside opioids)
Often midazolam
Describe the management of prolonged seziures?
Protect patient from injury,
- Provide oxygen if available,
- Consider or exclude of hypoglycaemia,
- If seizures last longer than 5 mins then IV lorazepam but if you can give IV then consider rectal diazepam or intranasal/buccal midazolam.
Describe the management of acute anxiety
Guided self help (reduced caffeine, reduced alcohol, mantras, mindfulness, worry time or CBT),
- Don’t use benzodiazepines!
When are gabapentin and pregabalin used?
Used to management chronic pain and has an inhibitory modulation of excitatory neurotransmitters (glutamate)
Describe features of melatonin?
It is a naturally occurring hormone synthesised in the pineal gland which increases at night. It is secreted in response to input from retina (often used in children with sleep disturbances)
