Antipsychotics Flashcards
what is DUP
duration of untreated psychosis
what is DUP a predictor of
poor outcomes in psychotic illness
what does the NHS offer for psychosis treatment?
multidisciplinary teams that offer service: early intervention in psychosis
aim to get people treated quickly
national target: treat 56% of people experiencing their first episode of psychosis in the first 2 weeks
what age are most EliP service users
younger adults
what will someone experiencing their first episode of psychosis typically be offered?
an antipsychotic drug, CBT and family therapy (‘family intervention’)
how long to people need to take antipsychotics after a single episode?
most people need to take antipsychotics for 1-2 years to minimise the chance of relapse
people who have multiple episodes may need to continue for life
who prescribes antipsychotic medication
specialists
i.e., psychiatrists attached to hospitals or community mental health services
when someone has been established on an effective treatment, their GP may take over responsibility for writing prescriptions and will be responsible for the routine health care of the patient
which drugs have lowest potencies
haloperidol
risperidone
pimozide
trifluoperazine
higher potency drugs
chlorpromazine
clozapine
sulpiride
most expensive drug
Clozapine is expensive because of its specialized prescribing procedures
However, the cost for this drug does not factor in monitoring, which can add as much as £12 per day (US costs so probably lower in UK).
common first choice antipsychotic
olanzapine, risperidone and quetiapine are common choices as they are low cost and usually the side effects are usually manageable
Aripiprazole is also becoming more common.
first effective antipsychotic (1952/1954)
chlorpromazine
CPZE
chlorpromazine equivalent - way of referring to potencies - standardisation
side effects of chlorpromazine
Very sedating
Moderate extrapyramidal (movement disorders)
Moderate muscarinic
Moderate galactorrhea
Neuroleptic malignant syndrome
first generation drug
earliest drugs to be developed
competitive antagonist at dopamine D2 receptors
high prevalence of extrapyramidal side effects
e.g. haloperidol
2nd generation drugs
newer drugs that are also termed “atypical” antipsychotics
antagonist at dopamine D2 receptors
have a lower prevalence of extrapyramidal side effects
Actions at a wide range of receptors such as 5HT2
clozapine
better efficacy against the negative symptoms of schizophrenia?
3rd generation
D2 partial agonist
newest drugs
aripiprozol
factors that may be important in the clinical efficacy of atypical drugs
High affinity at 5HT2A receptors compared to D2 receptors
High affinity at 5HT2C receptors compared to D2 receptors
A rapid dissociation rate from D2 receptors
least atypical drug
risperidone
only has high affinity for dopamine D2 and D3 receptors and 5HT2A receptors
most atypical drug
clozapine
targets widest range of receptors
what is the best drug for difficult cases of schizophrenia?
clozapine
secondary use of haloperidol
antiemetic and to treat Tourette’s syndrome
haloperidol side effects
lower sedative effects
fewer cholinergic side effect
high risk of EPS (extrapyramidal side effects)
(than chlorpromazine)
restlessness
neuroleptic malignant syndrome
risperidone side effects
has a moderate risk of EPS
can cause sedation and weight gain in the early stages of treatment.
One of the most frequent side effects is galactorrhea (milky discharge from the nipples) in both men and women (though more common in women).
olanzapine side effects
low risk of EPS
very sedating
high risk of hyperglycaemia
high level of muscarinic side effects
notorious for causing weight gain
quetiapine side effects
characterized by having a very low risk of EPS
can cause moderate weight gain
a high risk of hyperglycaemia
It is also very sedating
has moderate anticholinergic actions.
antipsychotics drugs associated with diabetes risk
quetiapine and olanzapine
aripiprazol
has a relatively benign side effect profile
lower tendency to produce weight gain and EPS than some other atypicals.
neuroleptic malignant syndrome
Like malignant hyperthermia, NMS is characterized by muscle contractions and tremors and a high body temperature
may also cause autonomic dysfunction and confusion/loss of consciousness.
the mechanism of NMS
thought to arise because of antagonism of dopamine receptors
with polymorphisms in the D2 receptor also contributing a genetic risk factor
what is malignant hypothermia a potential side effect of? what is the mechanism?
general anaesthetics
neuromuscular junction blocking drugs
due to mutations in the ryanodine receptors
why was clozapine withdrawn?
agranulocytosis lead to suppressed immune system (1-2% patients)
infection
death
when is clozapine prescribed
failure of at least two other drugs, on of which must have been an atypical drug
side effects clozapine
agranulocytosis
cardiac effects
muscarinic effects
H1 histamine receptor effects
cardiac effects clozapine
heart failure, myocarditis (rare)
hypotension, tachycardia (25% of patients)
-drop in blood pressure can induce tachycardia
how to minimise cardiac effects with clozapine
start the patient on a very low dose of clozapine and gradually increase his to a therapeutic dose
clozapine muscarinic side effects
complex effects at acetylcholine receptors
constipation: can be fatal (rupture the bowel)
-action as antagonist at M3 receptors
-can be managed using stool softeners and laxatives
hypersalivation
clozapine agonist at M4? metabolite of clozapine agonist at M1?
action of clozapine as an H1 histamine receptor
highly sedating
weight gain/ induce type 2 diabetes
what scheme do go on if on clozapine
national monitoring scheme
clozapine monitoring
Often initiated as in-patient
Ramped in slowly
White blood cell count
Monitoring
-3rd day (1st week)
-weekly (18 weeks),
-Rest of the year biweekly (34 weeks)
-4 weekly for the rest of time on clozapine
> 2 days treatment missed: start initiation process over!
blood testing for clozapine light meaning
Green light: given enough to last until next test
Amber result: enhanced monitoring
Red result: taken of clozapine immediately
medication that overlaps between BP and schizophrenia
antipsychotic drugs play an important role in managing mania in bipolar disorder
-can be given in combination with classic mood stabilizers like lithium, valproate and lamotrigine.
Conversely, mood stabilizers are sometimes given to augment the effects of antipsychotics when treating schizophrenia.
-This can sometimes be useful in tackling treatment resistant schizophrenia.
reason for non compliance with antipsychotics
lack of belief in illness
Consider side effects of medication to be worse than the illness itself
cognitive problems, disorganized life-style, therefore, may forget to fill their prescription
how many antipsychotic prescriptions not filled
14%
non compliance rated may be as high as 76%
types of antipsychotic formulation
oral (voluntary): most common
sustained release
-some available in the form
intramuscular injection
benefit of sustained release drugs
only needs to be taken once a day, easier to remember and remain compliant with medication
when are intramuscular injections used
involuntarily in psychiatric emergency situations
getting someone started on an antipsychotic when they enter a psychiatric hospital
benefits of intramuscular depot injection
Useful for disorganized patients/ patient that forgets to take their medication on a regular basis
benefits of intramuscular depot injection
Useful for disorganized patients/ patient that forgets to take their medication on a regular basis
only have to come to the clinic every 2/4 weeks for injection
eliminates covert non-compliance
what drugs are available as depot
Risperidone (Risperdal consta)
Pipotiazine (depot only)
Haloperidol
Aripiprazole
Paliperidone (lasts up to 3 month depot)
which drugs depot lasts up to 3 months
Paliperidone
useful for someone that struggles to manage their medication in tablet formation
negatives of intramuscular depot injections
Sometimes effect delayed
-take a while for steady state to build up in patients plasma
Not all drugs available as depot
how does an intramuscular depot injection work?
Inject a large amount of antipsychotic but it is either contained in biodegradable beads or is complexed with fatty acids
-inject into large muscle, often patients backside
beads/ compounds break down over time and release a steady stream of the antipsychotic into the patients blood stream (Over weeks, maybe months)
antipsychotics use in dementia/ Alzheimer’s
Needs to be for as short a period and as low a dose as possible
-risperidone and haloperidol are currently the only antipsychotics licensed for this purpose (but many others used off-license)
extensive use in patients with dementia, taking use of sedative properties of drug
-use of antipsychotics as ‘chemical coshes’ has declined dramatically in recent years
Increased risk of stroke and sudden death
Risperidone licensed for short-term use (6 wks)
non pharmacological treatments of schizophrenia
talking therapies
talking therapies
CBT for psychosis can improve symptoms in people already receiving antipsychotic medication
cognitive therapy may also be useful if a patient is refusing to take antipsychotics
significant reduction in positive and negative symptoms in patients only receiving cognitive therapy
talking therapies
CBT for psychosis can improve symptoms in people already receiving antipsychotic medication
cognitive therapy may also be useful if a patient is refusing to take antipsychotics
significant reduction in positive and negative symptoms in patients only receiving cognitive therapy
