Antipsychotics Flashcards
What are the 4 collective symptoms that form psychosis?
- Delusions
- Disordered thoughts
- Hallucinations
- Catatonia
What two disabilties is active psychosis more disabling than?
- Blindness
- Paraplegia
What are 8 causes of psychosis?
- Alzheimer’s
- Schizophrenia
- Bipolar Disorder
- Illegal Drugs
- Prescription Drugs
- PTSD
- Sleep deprivation
- Caffeine intoxication
What is said to be experienced when someone first displays psychotic symptoms?
“A brief psychotic episode”
What is a prodromal phase?
The period when there are changes in behaviour such as irritability, difficulty concentrating, memory problems or anxiety and depression
How long can the prodromal phase last?
Months or even sometimes years
What phase occurs after the prodromal phase?
Acute psychotic phase
What has delayed treatment of acute psychosis been shows to produce?
Worse outcomes
What are the diagnostic criteria for schizophrenia according to the DSM5?
- Two symptoms of negatve or positive derivative (at least one of hallucinations, delusions or disorganised speech however) that must be present for a month
- Continuous signs of disturbance for at least 6 months
- Not explained by something else
What are the 4 positive symptoms of schizophrenia?
- Hallucinations
- Delusions
- Disorganised Speech
- Disorganised behavour or catatonia
What are the 3 negative symptoms of schizophrenia?
- Loss of emotional response
- Anhedonia
- Apathy
Which diagnositc criterium is used in the UK for schizophrenia?
ICD10
What is schizoaffective disorder?
Meets the criteria for Schizophrenia and either major depressive disorder or bipolar
What are the three types of schizoaffective disorder?
- Manic and depressive episodes: bipolar type
- Depressive only: depressive type
- Mixed
What percentage of the population suffers from schizophrenia?
1%
Which gender is more likely to suffer from schizophrenia and by how many times?
Males are 1.4X more likely than females
At what ages does schizophrenia strike?
Males: late teens
Females: late 20s (also a peak at around menopause)
What additinal symptoms may be looked for in those with a diagnosis of schizophrenia or schizoaffective disorder?
- Sleep problems
- Anxiety
- Cognitive Problems
- Neurological ‘soft-signs’ such as motor problems and diffculty distinguishing left from right
What is the percentage of people with schizophrenia that commit suicide?
5%
What is the most recent mental health act?
1983
Where does the term sectioning derive from?
Comes from sections of the mental health act
What does sectioning allow for?
- Allows for compulsory hospitilization and treatment
- Person must be a danger to themselves or others
- Gives powers ot medical professionals, social workers and the police
What are the two most common parts of the mental health act and what do these mean?
Section 2: 28 day assessment and treatment of disorder
Section 3: 6 month treatment order
How does sectioning come about?
- Application made by the nearest relative or “approved mental health professional” (AMHP)
- Must be seen by two doctors (one must be a psychiatrist and AMHP
Can people who are sectioned refuse treatment?
Nope (except for ECT)
What are two main risk factors for schizophrenia?
Environmental/social
Genetic
What is the likelihood of developing schizophrenia if a near relative is affected?
8-10%
What is the concordance rate for twins with schizophrenia?
50%
What are tendency genes and how can these cause schizophrenia?
Influence of many tendency genes which have a relatively small impact on their own
Often require an environmental imapct too
What is the main environemental factor for the development of schizophrenia?
- Winter birth
- Contraversial
- Perhaps due to the maternal exposure to viruses
What are the main two environmental risk ractors for schizophrenia?
- Winter birth
- Substance abuse
Why is it hard to link schizophrenia to substance abuse?
Cause or effect?
Schizophrenics have a high risk for substance abuse
Which substance is known to cause psychosis?
amphetamines
What is AKT?
Codes for a kinase which inactivates glucagon synthase kinase which is involved in dopamine D2 signalling
What is the homozygous wild-type AKT1 risk for developing schizophrenia under different cannabis usages?
Equal risk whether have never used cannabis, used cannabis at weekends or less and used cannabis daily
What is the heterozygous wild-type AKT1 risk for developing schizophrenia under different cannabis usages?
Same as the homozygous wild type risk factor
What is the homozygous mutant AKT1 risk for developing schizophrenia under different cannabis usages?
Same for never using cannabis and used cannabis at weekends or less
however
the risk increases 7-fold when used everyday
What is an example of environemntal and genetic interactions causing schizophrenia?
Interaction of cannabis and the AKT1 mutant gene
What are the social factors which increase the likelihood of developing schizophrenia?
- Difficult childhood conditions such as discrimination, dysfunctional family and abuse/traume
- May cause epigenetic changes
What two bits of evidence are in favour of schizophrenia being a neurodevelopmental disorder?
- Age of onset (teenage/early adult)- brain changes a lot at this age
- Structural differences in the brain
What are 3 bits of evidence to suggest that schizophrenia is a neurodegenerative disorder?
- Progression of disease in many cases
- Reductions in brain volume
- Possible glutamatergic excitotoxicity
What is the primary toxoplasma gondii host?
Cats and other felids
What is the toxoplasma gondii’s secondary host?
Any warm blooded animal
What percentage of the world’s population is infected with toxoplasma gondii?
30%
What does toxoplasma gondii cause?
Cysts in the brain and other tissue
Influence human behaviour perhaps
What does toxoplasma gondii do to rodents?
Manipulates their behaviour and increases their chances of being eaten by cats
What are three bits of evidence for the dopamine hypothesis in the development of schizophrenia?
- Reserpine (antihypertensive agent) depletes dopamine and improves positive symptoms
- Amphetamine releases dopamine and causes psychosis
- L-DOPA and dopamine agonists cause psychosis
Which dopamine receptor is most associated with schizophrenia?
Dopamine D2 receptors
How is the mesolimbic dopaminergic pathway possibly associated with schizoprenia?
- Causes emotion, fear and motivation
- Important in positive symptoms (increased DA)
How is the mesocortical dopaminergic pathway possibly associated with schizoprenia?
- Causes emotion, motivation, cognitive control
- Important in negative symptoms (decreased DA)
How is the tuberhypophyseal (HT/pituitary) dopaminergic pathway associated with side effects of schizophrenia?
hormone release from pituitary
How are is the nigrostriatal dopaminergic pathway associated with side effects of schizophrenia?
- Motor control
- Important in Parkinson’s disease
What area modulates the activity of the mesolimbic pathway?
Ventral tegmental area
What else does the nigrostriatal pathway regulate and how?
- Input from the substantial nigra to the associative striatum causes excessive DA release
- Involved in high level cognitive processes- positive symptoms
What does the associative striatum do?
Involved in assigning salience to stimuli such as threat level
What does excess noise in the associative striatum cause?
- Increased salience assigned to unimportnant stimuli
- Positive symptoms
- Cognitive impairments (hypodopaminergic corical function)
- Negative symptoms (impaired reward based learning driven by striatal hyperdopaminergic signalling)
What other receptors are involved in causing schizophrenia symptoms?
- NMDA
- Serotonin
- Muscarinic receptors
How might NMDA receptor dysfunction cause schizophrenia?
- May be that glutamate dysfunction is the root cause
- NMDA antagonists cause psychosis e.g ketamine
- AMPAkines (positive allosteric modulators) may be new therapeutic approach
How might serotonin receptors cause schizophrenia?
- LSD causes psychosis
- Apathy, avolition in SCZ similar to depression
- Probably not root cause of SCZ but 5HT receptor activity may give better therapeutic profile
How might muscarinic receptors cause schizophrenia?
- mAChR antagonists worsen negative and cognitive symptoms
- Muscarinic agonists may be useful
- But mAChR antagonists activity gives better side effect profile
- Subtype selective allosteric modulators may be useful
What is the most common antipsychotic route?
Dopamine D2 antagonists/partial agonists
What is an issue with a majority of antipsychotic drugs?
- Very dirty
- Actions at many different receptor types
- Lack of selectivity gives rise to side effects
What are common side effects of antipsychotics?
- Movement disorder (extrapyramidal)
- Galactorrhea
- Cognitive impairment
- Sedation
- Weight gain
- Anti-muscarinic effects
What causes the extrapyramidal side effects of schizophrenia?
- Dystonias and tardive dyskinesia
- Motor striatum D2 receptors
What causes the galactorrhea side effects of schizophrenia?
- Inappropriate milk production
- Tuberohypophyseal D2 receptors inhibit prolactin release (if block these, get too much of this hormone)
What causes the cognitive impairment side effects of schizophrenia?
- Possibly D2 inhibition (hypofunction) in the cortex
- Effects on other receptors such as anti-muscarinic effects
What causes the sedation side effects of schizophrenia?
H1 antagonism
What causes the weight gain side effects of schizophrenia?
H1 and 5HTR antagonism- can lead to diabetes and heart disease
What causes the anti-muscarinic side effects of schizophrenia?
Dry mouth, blurred vision, memory problems, cardiac problems
How many people on antipsychotics have type 2 diabetes or are prediabetic?
- 10% T2DM
- Prediabetic 37%
What are three reasons as to why diabetes increase occurs on antipsychotics?
- Obesity
- Antipsychotic induced insulin resistance
- Direct effects on beta cells
What is antipsychotic induced insulin resistance?
- Antipsychotic inhibits a component of the insulin signalling cascade Akt
- By decreasing the phosphorylation of one of the targets of the insulin receptor kinase activity, insulin receptor substrate 1 (IRS-1)
What direct effects do antipsychotics have on beta cells?
- Can cause pancreatic beta cell dysfunction in severall ways
- Act on the muscarinic, dopamine, adrenergic and serotonergic receptors they can decrease insulin secretion
- May also decrease cellular concentrations of ATP, which would also decrease insulin secretion
- Antipsychotics may damage beta cells and induce apoptosis
What is the aim of the Early Intervention Psychosis (EIP) scheme?
- Get people treated quickly
- Target to treat 56% of adults experiencing their fist episode of psychosis within two weeks
What is someone who is experiencing fist episode psychosis be offered?
- An antipsychotic drug
- CBT
- Family therapy
After a single psychotic episode how long will people need to take antipsychotics for?
1-2 years- if continue to have episodes, may need to take for life
What is the ‘best psychotic drug’?
- TRICK
- There is no such thing as patients can respond differently from one another to the same drug
- Some patients find certian side effects particularly difficult to deal with
Why is clozapine expensive?
Because of its specialised prescribing procedures. However, the cost for this drug does not factor in monitoring which can add as much as 12 pound per day
What are the most common first choices for antipsychotic drugs?
- Olanzapine
- Risperidone
- Quetiapine
- Aripiprazole is becoming more common
Give an overview of Chlorpromazine
- The first effective antipsychotic
- Group 1 Phenothiazine
- Introduced in 1952-1954
- Not used very frequently now
What are Chlorpromazine’s trade names?
- Largactil
- Thorazine
What are Chlorpromazine’s side effects?
- Sedating
- Moderate extrapyramidal
- Moderate muscarinic
- Moderate galactorrhea
- Neuroleptic malignant syndrome
What are the two classifications of antipsychotic drugs?
- Typical (1st gen)
- Atypical (2nd gen)
What is the 3rd generation of antipsychotics?
Different mechanism to the other two, are D2 partial agonists
What are the four atypical antipsychotics?
- Clozapine
- Olanzapine
- Quetiapine
- Risperidone
What is the 3rd generation drug?
Aripiprazole
What makes an atypical drug ‘atypical’?
- Lower rate of extrapyramidal side effects
- Good efficacy against the negatve symptoms of schizophrenia
- High potency at other (besides D2) receptors
What are the 3 key factors that have been hihglighted to be imporntant 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
Which is the least atypical drug and which is the most?
- Least- risperidone
- Most- Clozapine
Give an overview of haloperidol
- One of the most common used typical antipsychotics
- As well as being used for psychosis, it is also used as an antiemetic and to treat Tourette’s syndrome
- It is available in a variety of formulations
- Has a lower sedative effect than chlorpromazine and fewer cholinergic side effects, it has a high risk for extrapyramidal side effects (EPS). Can also cause restlessness and neuroleptic malignant syndrome
Give an overview of risperidone
- Was the first new antipsychotic since clozapine
- Belongs to the second generation (atypical)
- Has moderate risk of EPS and it can cause sedation and weight gain in the early stages of treatment. One of the most frequent side-effects is galactorrhea
- Is available in a variety of formulations
Give and overview of Olanzepine
- Is an atypical with the name Zyprexa
- It has a low risk of EPS but is very sedating, has a high risk of hyperglycaemia and high levels of muscarinic side effects. It is also notorious for weight gain
- Have been woes for the manufacturer Eli Lily due to the diabetes risk
Give an overview of quetiapine
- Is characterised by having a very low risk of ESPs
- Is a second generation atypical drug
- Can casue weight gain and has a high risk of hyperglycaemia, it is also very sedating and has moderate anticholergic actions
- Its brand name is Seroquel
- It is available as an immediate release and a sustained release tablet
- Has controversy as there are lawsuits against Astra Zeneca about its diabetes risk
Give an overview of Aripiprazole
- Trade name is Abify
- Is atypical however, is sometimes classified as a third generation drug because of its mechanism
- Has benign side effects with lower tendency to produce weight gain and EPS than other atypicals
What is neuroleptic malignant syndrome?
- Characterised by muscle contractions, tremors and high body temperatures
- May also cause autonomic dysfunction, confusion and loss of consciousness
- Thought to arise becauce of antagonism of dopamine receptors (with polymorphisms in the D2 receptor also contributing a genetic risk factor)
What is the most effective antipsychotic for treatment resistant schizophrenia (TRS)?
Clozapine
When can clozapine be prescribed?
Failure of at least two other drugs, one of which must have been atypical
What are the side effects of Clozapine?
- Agranulocytosis (1-2% of patients)
- Cardiac effects (heart failure, hypotension-trachycardia 25%)
- Muscarinic effects (constipation, hypersalivation, M4 agonist, metabolite M1 agonst)
- Highly sedating
- Weight gain/diabetes
What is Clozapine-induced agranulocytosis?
- Loss of white blood cells (supressed immune system)
- Get an infection- treat with antibiotics
- Causes death in 4-16% of cases
How is clozapine monitoring initiated in patients?
- Often as in-patient
- Ramped slowly
- White blood cell count
What are the monitoring steps of clozapine monitoring?
- 3rd day (1st week)
- Weekly (18 weeks)
- Biweekly (34 weeks)
- 4 Weeklu thereafter
- > 2 days missed: start over
What are the 3 reasons for non-compliance?
- Lack of belief in illness
- Side effects
- Cognitive problems, disorganised life-style
What percentage of antipsychotic prescriptions are not filled and what are the noncompliance rates?
14% not filled
May be as high as 76%
What are different formulations of taking antipsychotics?
- Oral (can have sustained release)
- Intramuscular injection (involuntary)
- Intramuscular depot injection
What are intramuscular depot injections?
- Involuntary injections for disorganised patients
- 2/4 weekly injections (easy to remember than daily medicine)
- Eliminates covert non-compliance
- Sometimes effect delated
Which drugs are available as a depot?
- Risperadone (risperdal consta)
- Haloperidol
- Aripiprazole
- Paliperidone (up to 3 month)
What is the term used when antipsychotics are used to subdue patients?
Chemical coshes
What is a large population of people in which chemical coshes were used on?
Alzheimer’s disease
In the elderly what do antipsychotics increase the likelihood?
- Stroke
- Sudden death
What drugs are licenced for the elderly and for how long?
- Risperidone
- Haloperidol
- Short term use (6wks)
