2. Sedatives anxiolytics Flashcards
Why were barbiturates discontinued?
Dependence / addiction / misuse narrow therapeutic index
Suicide easily done e.g. marylyn munroe and jimmy henricks
Also used as IV induction agents and anti convulsant
So…
Become obsolete as anxiolytics
Classess of sedatives and anxiolytics?
• Antidepressants • Benzodiazepines (1960s) • Z-drugs (1990) • B-blockers • Other – Melatonin – Sedating antihistamine
Properties/formulation of benzodiazepine?
Serendipity? (librium)
Highly lipophilic: so easily absorbed
Well absorbed orally
Highly protein bound (95%) Hepatic metabolism
Active metabolites, so can last for hours
Excreted as glucoronide conjugate.
5 major effects of benzodiazepines?
- Anxiolytic: reduce anxiety (α2 & α3 )
- Hypnotic: induce sleep (α1)
- Reduce muscle t§one
- Anterograde amnesia (pros&cons)
- Anticonvulsant effect
Administration of benzodiazepines?
• Normally given orally or intravenously – (can be given by intranasal or rectal route)
Not advised to be given intramuscular route
Categorisation of benzodiazepines?
SHORT ACTING
Lorazepam, temazepam t1/2 8-12 hours intermediate
LONG ACTING
Diazepam t1/2 20-100
Structure of GABAa receptor?
- Pentameric arrangement
- Central ion channel pore
- 18 possible subunits
- Approx 30 forms of receptor
- Some subunits location specific
Role of GABAa receptor?
- Anaesthetics and benzos allosterically activate the receptor
- Increase the frequency of opening
Act allosterically on GABAa receptors
Sedation mediated via GABAa with α1 subunit
– Anxiolysis mediated via GABAA with α2 & α3 subunits
Flumazenil: Class? Half life? Precipitates? Administration? SE?
Class: Competitive benzo antagonist Half life: Short Precipitates: Agitation and seizures Administration: IV in 100mcg increments SE: N/V
Z drugs:
Act where?
Eg?
Act via benzodiazepine receptors
– Zopiclone
– Zaleplon
– Zolpidem
No benefit over z drugs and short acting benzo
What is tolerance
Is a physiological state characterized by a decrease in the effects of a drug with chronic administration.
Tolerance of benzo?
Tolerance develops quickly for sedative effects
more slowly for anxiolytic & anticonvulsant effects.
Mechanism for tolerance?
- Neuro-adaptive process
- Desensitisation of inhibitory GABA receptors • Sensitisation of (excitatory) NMDA receptors • Adaptions take place on different time scale
What is dependance?
- The drug induces a rewarding experience
- Drug taking becomes compulsive
Genetic component*
Two forms of dependence?
Psychological and physical
Withdrawl is a result of…
dependence
Symptoms of withdrawal?
• Increased anxiety, onset / exacerbation of
depression
• Disturbed sleep
• Pain, stiffness , muscular aches
• Convulsions
• Can occur after relatively short courses of treatment (4 weeks)
Clinical role of sedative and anxiolytic agents?
Enable potentially uncomfortable diagnostic and therapeutic procedures to be carried out Management of acute alcohol withdrawn Management of insomnia Management of generalised anxiety states Other: Anticonvulsants
How to manage acute alcohol withdrawl?
• Acute admissions to hospital
• Supply of alcohol interrupted
• Index of suspicion…
– Alcohol history
– Severity of alcohol dependence questionnaire
– Assessment of withdrawal symptoms
Chlordiazepoxide 1-2 week reducing regime
What are the 4 questions of the CAGE questionnaire when approaching potential alcohol withdrawal cases?
C• Have you ever felt you should Cut down your drinking?
A• Have you ever been Annoyed by other people criticizing your drinking?
G• Have you ever felt Guilty about drinking?
E• Have you ever taken a drink in the morning to steady your nerves or ease a hangover (Eye- opener)?
Alcohol withdrawal symptoms?
**May start 8 hours after drop in alcohol levels (peak day 2) **
Insomnia / anxiety/ restlessness/ agitation
Tremor
Nausea & vomiting
Sweating
Palpitations
Hallucinations auditory / visual/tactile
Seizures
Investigation results that suggest chronic alcohol consumption?
• Raised MCV • Pancytopenia (result of alcohol induced bone marrow suppression • Folate deficiency • Prolonged prothrombin time
How to treat alcohol withdrawl?
Chlordiazepoxide dosing regimes in alcohol withdrawal
How to manage insomnia?
Try not to lol
Assess the source FIRST
Hypnotics reserved for the acutely distressed
Avoid benzo administration for insomnia in elderly bc
- Confusion
- Falls
- Slower metabolism
What is sleep hygiene?
Sleep hygiene aims to make people more aware of behavioural, environmental & temporal factors that may be detrimental or beneficial to sleep
How to encourage good sleep hygiene?
Get into routine
Exercise in morning, not within 4 hrs of sleep
Bedroom = cool, dark, quiet
No caffiene, alcohol or smoke within 6 hrs
Screen time not 30 mins before bed
No day naps
Drug treatment for insomnia?
TO BE AVOIDED
Short acting benzo or z-drug
Lowest dose for shortest period
no repeat prescriptions. Explain? Tolerance makes it ineffective
Considerations when managing prolonged seizures?
DO IT, need to protect patient from injury
Provide 02 is available
Consider/exclude hypoglycaemia
Lorazapam: For seizures 5 mins ++
Route: IV access. If not possibile, then rector diazepam or intranasal/buccal midazolam
Minimal sedation (anxiolysis) definition? Responsiveness Airway Spontaneous ventilation CV function
Responsiveness: Normal response to verbal stimulation
Airway: Unaffected
Spontaneous ventilation: Unaffected
CV function: Unaffected
Moderate sedation/analgesia (conscious sedation) definition? Responsiveness Airway Spontaneous ventilation CV function
Responsiveness: Purposeful* response to verbal or tactile stimulation
Airway: No intervention required
Spontaneous ventilation: Adequate
CV function: Usually maintained
Deep sedation/analgesia? Responsiveness Airway Spontaneous ventilation CV function
Responsiveness: Purposeful response after repeated or painful stimulation
Airway: Intervention may be required
Spontaneous ventilation: May be inadequate
CV function: Usually maintained
General analgesia? Responsiveness Airway Spontaneous ventilation CV function
Responsiveness: Unarousable, even w/painful stimulus
Airway: Intervention often required
Spontaneous ventilation: Frequently inadequate
CV function: May be impaired
Acute anxiety management?
Anxiety is a normal. It becomes a problem if it starts to interfere with your everyday life.
No “quick fix”
Guided self help:
• reduce caffeine, reduce alcohol
• Mantras, mindfulness, worrytime
Cognitive behaviour therapy
Use of benzo in acute anxiety management?
Just don’t!
“Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling, or causing the patient unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic, or psychotic illness.”
Use of b-blockers in acute anxiety treatment?
Helps with tachycardia, palpitations, tremor and sweating
Blocks sympathetic system
Usually: Propranolol
Advantages: non-sedative, no dependence or abuse
SSRI withdrawal profile?
– Nausea / diarrhoea
– Insomnia
– Sexual dysfunction
– Suicidal behaviour (is it toxic in OD)
Use of gabapentin and pregabalin?
Management of chronic pain
Melatonin:
What is it?
Fluctuation of level?
Use?
What is it?
Naturally occurring hormone
Synthesized in pineal gland
Secreted in response to input from retina.
Level change:
High levels at night, low during day
Use:
Clinically often used in children with sleep disturbance.
Law on driving (March 2015)
- This law states that it is an offence to drive with certain drugs above specified levels in the body, whether your driving is impaired or not
- If you are taking these medicines as directed and your driving is not impaired, then you are not breaking the law
- Benzos, opioids, amphetamines
