Chapter 4 CNS Flashcards
Anxiolytics (‘sedatives’) and most hypnotics action?
Anxiolytics will induce sleep at night and most hypnotics sedate during the day
Dependence
Both physical and psychological
Acute conditions
Risk of dependence
Most commonly used anxiolytics and hypnotics
Benzodiazepines
Which are not recommended?
Meprobamate and Barbiturates - they have more side effects and interactions than benzodiazepines and are much more dangerous in overdosage
Benzodiazepines indications:
Short term relief (two to four weeks only) of anxiety that is severe, disabling, or causing the patient unacceptable distress
Short term mild anxiety inappropriate
Insomnia only when it is severe, disabling or causing the patient extreme distress
Dependence and withdrawal
Withdrawal should be gradual because abrupt withdrawal may produce confusion, toxic psychosis, convulsions
Benzodiazepines withdrawal syndrome
Anytime up to 3 weeks after stopping a long acting benzodiazepines, but may occur within a day in the case of short acting one
Before benzodiazepines use:
Cause of insomnia should be established and alcohol consumption
Sleep onset insomnia
Short acting hypnotic preferred, sedation following day undesirable or elderly
Long acting hypnotics
Poor sleep maintenance - early morning weakening that has daytime effects
When anxiolytics needed during the day
When next day sedation acceptable
Transient insomnia
Sleep well but other factors affect sleep - noise, work, jet lag
Short term insomnia
Related to emotional problems or medical illness
Chronic insomnia
Caused by psychiatric disorders e.g anxiety, drug abuse, depression
When can dependence develop?
After 3-14 days
Withdrawal of hypnotic
Rebound insomnia
Stopping hypnotic
Broken sleep with vivid dreams may persist for several weeks
Short acting hypnotics
Loprazolam, lormetazepam and temazepam act for short time and have little hangover effect
Withdrawal phenomena common with?
Short acting benzodiazepine
Insomnia + anxiety
Long acting benzodiazepines e.g diazepam single dose
Coma
Benzodiazepines can cause coma in hepatic impairment, so shorter half life benzodiazepines are safer (temazepam and oxazepam)
Pregnancy and breast feeding
Avoid - neonatal hypothermia, hypotonia, respiratory depression
Zaleplon, Zolpidem and Zopiclone
Non benzodiazepines hypnotics but act at the benzodiazepines receptor
Shortest duration of action
Zaleplon
Short duration of action
Zolpidem and Zopiclone
Antihistamines
Promethazine - on sale for occasional insomnia
Prolonged action - can cause drowsiness the following day
How long does sedative effect of antihistamine last
Reduce after a few days of continuous use
Side effect of antihistamines
Headache, psychomotor impairment and anti-muscarinic
Alcohol
Poor hypnotic as diuretic action interferes with sleep
Also disturbs sleep pattern and can worsen sleep disorders
Melatonin
Pineal hormone - licensed for short term treatment of insomnia
For adults over 55
Anxiety
Benzodiazepines anxiolytics affective in relieving anxiety states
Inhibit psychological adjustment in bereavement
Benzodiazepines
Dependence likely
history of alcohol or drug abuse
Beta-blockers and anxiety - DONT
Don’t affect psychological symptoms of anxiety - fear, worry, tension
What beta-blockers do in anxiety
Reduce autonomic symptoms - palpitations and tremor
But not muscular tension
Diazepam
Short term use in anxiety or insomnia, also use in epilepsy febrile convulsions, muscle spasm
Diazepam contraindications
CI – resp depression, myasthenia gravis, muscle weakness, alcohol or drug
abuse, personality dis.
Side effects of diazepam
drowsiness, lightheadedness the next day, confusion and ataxia,
amnesia, dependence, Overdosage
Diazepam schedule and others
amnesia, dependence, Overdosage – see pg 39
Schedule CD4-1
Others – chlordiazepoxide, lorazepam, oxazepam, nitrazepam (all CD4-1)
Buspirone
Acts at 5HT1A serotonin receptors
Response to treatment can take up to 2 weeks
Does not alleviate symptoms of benzo withdrawal, so benzo should be slowly stopped before starting buspirone
Barbiturates
Long acting barbiturate phenobarbital – has some use in epilepsy but use as sedative unjustified
Only used for severe insomnia in patients already taking barbiturates – avoided in elderly
Very short acting barbiturate thiopental used in anaesthesia Antipsychotics
Antipsychotics
Neuroleptics/’tranquilisers’
Short term – calm disturbed patients in schizophrenia, brain damage,
mania, delirium, severe anxiety or depression
Schizophrenia
Aim – alleviate suffering and improve cognitive functioning
Antipsychotic drugs relieve Positive symptoms – thought disorder,hallucinations and delusions
Less effective on negative symptoms – apathy and social withdrawal
First generation antipsychotic drugs
Block dopamine D2 receptors in brain
Not selective – many side effects, EPS and elevated Prolactin
Phenothiazines
Group 1 – chlorpromazine, levopromazine and promazine (very sedative and moderate EPS)
Group 2 – pericyazine and pipotiazine (moderate sedative and fewer EPS than 1 and 3)
Group 3 – prochlorperazine, trifluroperazine, fluphenazine, perphenazine (few sedative and antimuscarinic effects but more EPS than 1 and 2)
Butyrophenones
Butyrophenones – benperidol and haloperidol resemble group 3
Thioxanthenes – flupentixol and zuclopentixol
Second generation antipsychotic drugs
Atypical antipsychotics
Have higher affinity for specific D receptors – less side effects Act on a range of receptors unlike first generation
Cautions second generation antipsychotic
High risk of withdrawal, should be stopped gradually
Patients with CV disease, Parkinson’s (exacerbation), epilepsy, seizures, MG prostatic hypertrophy, angle closure glaucoma
CI in comatose states, CNS depression and phaeochromocytoma
Caution in elderly – only used in severe psychotic cases and initial dose should be half of adult dose
Side effects
EPS occur most frequently with phenothiazines, butyrophenones and first gen depot preparations
Parkinsonian symptoms
Dystonia – abnormal face and body movements
Akathesia – restlessness
Tardive dyskinesia – involuntary movements of jaw, tongue
Increased prolactin concentration and hyperprolactinaemia – sexual
dysfunction, reduced bone density, breast enlargement, menstrual changes, galactorrhoea
Parkinsonian symptoms can be supressed if antimuscarinic drugs given Tardive dyskinesia is most serious EPS and often irreversible
o Stopping drug at earliest signs can stop full progression of it
Antipsychotics
Other s/e
Decreased libido
Tachycardia, arrhythmias and hypotension, QT interval prolongation Hyperglycaemia, Diabetes
Weight gain
Temperature changes
Neuroleptic malignant syndrome – hyperthermia, fluctuating consciousness, muscle rigidity, autonomic dysfunction, tachycardia, sweating, urinary incontinence (rare)
Overdose
Antipsychotics choice
Little difference between them
Second gen may be better at treating negative symptoms of schizophrenia and should be used if EPS are a concern
Aripiprazole, clozapine, olanzapine and quetiapine are least likely to cause EPS
Patients should use antipsychotic for 4-6 weeks before it is deemed ineffective
Antipsychotics monitoring
FBC, U&E, LFT at start and then annually
Blood lipids, fasting blood glucose, ECG
BP, prolactin conc, physical health monitoring
Antipsychotic Depot preps
Long acting – maintenance therapy (every 4 weeks)
Can cause higher incidence of EPS than oral preps, but less freq with 2nd gen depot
Zupenthixol and Flupentixol most common
Small test doses, Z track technique and injection site rotation essential
Antimanic Drugs
Use in mania and hypomania and long term bipolar treatment
Antidepressant can be used for co-existing depression but avoid in rapid cycling bipolar disorder
Antipsychotic drugs can also be used as well as lithium, valproate, carbamazepine, olanzapine
Valproate – NOT in women of child bearing age
Lithium
Often as concomitant therapy with antidepressants
Full prophylactic effect of lithium may not be seen until 6-12 months of treatment
Used in prophylaxis and treatment of mania and bipolar disorder
Long term use – associated with thyroid disorders, cognitive and memory
impairment
Risk factors – ACEi, NSAIDS, Diuretics
Patients should be given Lithium treatment packs
Serum Conc lithium
Narrow therapeutic range – regular monitoring and same brand prescribing
0.8-1mmol/L target range (0.4-1mmol/L in elderly)
Routine monitoring every 3 months and if patient has any other disease or significant change in fluid intake
Lithium intoxication: blurred vision, increased GI disturbances (anorexia, vomiting, diarrhoea), muscle weakness, drowsiness, lack of co-ordination Overdose can have fatal toxic effects, signs:
o Tremor, ataxia, dysarthria
o Nystagmus, renal impairment and convulsions
Interactions
Lithium toxicity made worse by sodium depletion – diuretics (esp. thiazides) can be hazardous so avoid
Narrow therapeutic range
Withdrawal
Abrupt discontinuation increases risk of relapse – but no real evidence of withdrawal
Should discontinue dose slowly over 4 weeks – 3 months
S/E
GI, fine tremor, renal impairment
Polydipsia, leucocytosis, weight gain, oedema
Antidepressant
TCA, MAOI, SSRI, and others
Should not be used for mild cases
How long does it take for antidepressant affect to occur?
2 weeks
