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Drugs and the Brain > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

What are the 4 collective symptoms that form psychosis?

A
  • Delusions
  • Disordered thoughts
  • Hallucinations
  • Catatonia
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2
Q

What two disabilties is active psychosis more disabling than?

A
  • Blindness
  • Paraplegia
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3
Q

What are 8 causes of psychosis?

A
  • Alzheimer’s
  • Schizophrenia
  • Bipolar Disorder
  • Illegal Drugs
  • Prescription Drugs
  • PTSD
  • Sleep deprivation
  • Caffeine intoxication
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4
Q

What is said to be experienced when someone first displays psychotic symptoms?

A

“A brief psychotic episode”

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5
Q

What is a prodromal phase?

A

The period when there are changes in behaviour such as irritability, difficulty concentrating, memory problems or anxiety and depression

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6
Q

How long can the prodromal phase last?

A

Months or even sometimes years

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7
Q

What phase occurs after the prodromal phase?

A

Acute psychotic phase

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8
Q

What has delayed treatment of acute psychosis been shows to produce?

A

Worse outcomes

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9
Q

What are the diagnostic criteria for schizophrenia according to the DSM5?

A
  • 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
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10
Q

What are the 4 positive symptoms of schizophrenia?

A
  • Hallucinations
  • Delusions
  • Disorganised Speech
  • Disorganised behavour or catatonia
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11
Q

What are the 3 negative symptoms of schizophrenia?

A
  • Loss of emotional response
  • Anhedonia
  • Apathy
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12
Q

Which diagnositc criterium is used in the UK for schizophrenia?

A

ICD10

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13
Q

What is schizoaffective disorder?

A

Meets the criteria for Schizophrenia and either major depressive disorder or bipolar

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14
Q

What are the three types of schizoaffective disorder?

A
  • Manic and depressive episodes: bipolar type
  • Depressive only: depressive type
  • Mixed
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15
Q

What percentage of the population suffers from schizophrenia?

A

1%

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16
Q

Which gender is more likely to suffer from schizophrenia and by how many times?

A

Males are 1.4X more likely than females

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17
Q

At what ages does schizophrenia strike?

A

Males: late teens

Females: late 20s (also a peak at around menopause)

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18
Q

What additinal symptoms may be looked for in those with a diagnosis of schizophrenia or schizoaffective disorder?

A
  • Sleep problems
  • Anxiety
  • Cognitive Problems
  • Neurological ‘soft-signs’ such as motor problems and diffculty distinguishing left from right
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19
Q

What is the percentage of people with schizophrenia that commit suicide?

A

5%

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20
Q

What is the most recent mental health act?

A

1983

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21
Q

Where does the term sectioning derive from?

A

Comes from sections of the mental health act

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22
Q

What does sectioning allow for?

A
  • 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
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23
Q

What are the two most common parts of the mental health act and what do these mean?

A

Section 2: 28 day assessment and treatment of disorder

Section 3: 6 month treatment order

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24
Q

How does sectioning come about?

A
  • 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
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25
Q

Can people who are sectioned refuse treatment?

A

Nope (except for ECT)

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26
Q

What are two main risk factors for schizophrenia?

A

Environmental/social

Genetic

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27
Q

What is the likelihood of developing schizophrenia if a near relative is affected?

A

8-10%

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28
Q

What is the concordance rate for twins with schizophrenia?

A

50%

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29
Q

What are tendency genes and how can these cause schizophrenia?

A

Influence of many tendency genes which have a relatively small impact on their own

Often require an environmental imapct too

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30
Q

What is the main environemental factor for the development of schizophrenia?

A
  • Winter birth
  • Contraversial
  • Perhaps due to the maternal exposure to viruses
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31
Q

What are the main two environmental risk ractors for schizophrenia?

A
  • Winter birth
  • Substance abuse
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32
Q

Why is it hard to link schizophrenia to substance abuse?

A

Cause or effect?

Schizophrenics have a high risk for substance abuse

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33
Q

Which substance is known to cause psychosis?

A

amphetamines

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34
Q

What is AKT?

A

Codes for a kinase which inactivates glucagon synthase kinase which is involved in dopamine D2 signalling

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35
Q

What is the homozygous wild-type AKT1 risk for developing schizophrenia under different cannabis usages?

A

Equal risk whether have never used cannabis, used cannabis at weekends or less and used cannabis daily

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36
Q

What is the heterozygous wild-type AKT1 risk for developing schizophrenia under different cannabis usages?

A

Same as the homozygous wild type risk factor

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37
Q

What is the homozygous mutant AKT1 risk for developing schizophrenia under different cannabis usages?

A

Same for never using cannabis and used cannabis at weekends or less

however

the risk increases 7-fold when used everyday

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38
Q

What is an example of environemntal and genetic interactions causing schizophrenia?

A

Interaction of cannabis and the AKT1 mutant gene

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39
Q

What are the social factors which increase the likelihood of developing schizophrenia?

A
  • Difficult childhood conditions such as discrimination, dysfunctional family and abuse/traume
  • May cause epigenetic changes
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40
Q

What two bits of evidence are in favour of schizophrenia being a neurodevelopmental disorder?

A
  • Age of onset (teenage/early adult)- brain changes a lot at this age
  • Structural differences in the brain
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41
Q

What are 3 bits of evidence to suggest that schizophrenia is a neurodegenerative disorder?

A
  • Progression of disease in many cases
  • Reductions in brain volume
  • Possible glutamatergic excitotoxicity
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42
Q

What is the primary toxoplasma gondii host?

A

Cats and other felids

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43
Q

What is the toxoplasma gondii’s secondary host?

A

Any warm blooded animal

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44
Q

What percentage of the world’s population is infected with toxoplasma gondii?

A

30%

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45
Q

What does toxoplasma gondii cause?

A

Cysts in the brain and other tissue

Influence human behaviour perhaps

46
Q

What does toxoplasma gondii do to rodents?

A

Manipulates their behaviour and increases their chances of being eaten by cats

47
Q

What are three bits of evidence for the dopamine hypothesis in the development of schizophrenia?

A
  • Reserpine (antihypertensive agent) depletes dopamine and improves positive symptoms
  • Amphetamine releases dopamine and causes psychosis
  • L-DOPA and dopamine agonists cause psychosis
48
Q

Which dopamine receptor is most associated with schizophrenia?

A

Dopamine D2 receptors

49
Q

How is the mesolimbic dopaminergic pathway possibly associated with schizoprenia?

A
  • Causes emotion, fear and motivation
  • Important in positive symptoms (increased DA)
50
Q

How is the mesocortical dopaminergic pathway possibly associated with schizoprenia?

A
  • Causes emotion, motivation, cognitive control
  • Important in negative symptoms (decreased DA)
51
Q

How is the tuberhypophyseal (HT/pituitary) dopaminergic pathway associated with side effects of schizophrenia?

A

hormone release from pituitary

52
Q

How are is the nigrostriatal dopaminergic pathway associated with side effects of schizophrenia?

A
  • Motor control
  • Important in Parkinson’s disease
53
Q

What area modulates the activity of the mesolimbic pathway?

A

Ventral tegmental area

54
Q

What else does the nigrostriatal pathway regulate and how?

A
  • Input from the substantial nigra to the associative striatum causes excessive DA release
  • Involved in high level cognitive processes- positive symptoms
55
Q

What does the associative striatum do?

A

Involved in assigning salience to stimuli such as threat level

56
Q

What does excess noise in the associative striatum cause?

A
  • Increased salience assigned to unimportnant stimuli
  • Positive symptoms
  • Cognitive impairments (hypodopaminergic corical function)
  • Negative symptoms (impaired reward based learning driven by striatal hyperdopaminergic signalling)
57
Q

What other receptors are involved in causing schizophrenia symptoms?

A
  • NMDA
  • Serotonin
  • Muscarinic receptors
58
Q

How might NMDA receptor dysfunction cause schizophrenia?

A
  • 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
59
Q

How might serotonin receptors cause schizophrenia?

A
  • 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
60
Q

How might muscarinic receptors cause schizophrenia?

A
  • 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
61
Q

What is the most common antipsychotic route?

A

Dopamine D2 antagonists/partial agonists

62
Q

What is an issue with a majority of antipsychotic drugs?

A
  • Very dirty
  • Actions at many different receptor types
  • Lack of selectivity gives rise to side effects
63
Q

What are common side effects of antipsychotics?

A
  • Movement disorder (extrapyramidal)
  • Galactorrhea
  • Cognitive impairment
  • Sedation
  • Weight gain
  • Anti-muscarinic effects
64
Q

What causes the extrapyramidal side effects of schizophrenia?

A
  • Dystonias and tardive dyskinesia
  • Motor striatum D2 receptors
65
Q

What causes the galactorrhea side effects of schizophrenia?

A
  • Inappropriate milk production
  • Tuberohypophyseal D2 receptors inhibit prolactin release (if block these, get too much of this hormone)
66
Q

What causes the cognitive impairment side effects of schizophrenia?

A
  • Possibly D2 inhibition (hypofunction) in the cortex
  • Effects on other receptors such as anti-muscarinic effects
67
Q

What causes the sedation side effects of schizophrenia?

A

H1 antagonism

68
Q

What causes the weight gain side effects of schizophrenia?

A

H1 and 5HTR antagonism- can lead to diabetes and heart disease

69
Q

What causes the anti-muscarinic side effects of schizophrenia?

A

Dry mouth, blurred vision, memory problems, cardiac problems

70
Q

How many people on antipsychotics have type 2 diabetes or are prediabetic?

A
  • 10% T2DM
  • Prediabetic 37%
71
Q

What are three reasons as to why diabetes increase occurs on antipsychotics?

A
  • Obesity
  • Antipsychotic induced insulin resistance
  • Direct effects on beta cells
72
Q

What is antipsychotic induced insulin resistance?

A
  • 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)
73
Q

What direct effects do antipsychotics have on beta cells?

A
  • 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
74
Q

What is the aim of the Early Intervention Psychosis (EIP) scheme?

A
  • Get people treated quickly
  • Target to treat 56% of adults experiencing their fist episode of psychosis within two weeks
75
Q

What is someone who is experiencing fist episode psychosis be offered?

A
  • An antipsychotic drug
  • CBT
  • Family therapy
76
Q

After a single psychotic episode how long will people need to take antipsychotics for?

A

1-2 years- if continue to have episodes, may need to take for life

77
Q

What is the ‘best psychotic drug’?

A
  • 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
78
Q

Why is clozapine expensive?

A

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

79
Q

What are the most common first choices for antipsychotic drugs?

A
  • Olanzapine
  • Risperidone
  • Quetiapine
  • Aripiprazole is becoming more common
80
Q

Give an overview of Chlorpromazine

A
  • The first effective antipsychotic
  • Group 1 Phenothiazine
  • Introduced in 1952-1954
  • Not used very frequently now
81
Q

What are Chlorpromazine’s trade names?

A
  • Largactil
  • Thorazine
82
Q

What are Chlorpromazine’s side effects?

A
  • Sedating
  • Moderate extrapyramidal
  • Moderate muscarinic
  • Moderate galactorrhea
  • Neuroleptic malignant syndrome
83
Q

What are the two classifications of antipsychotic drugs?

A
  • Typical (1st gen)
  • Atypical (2nd gen)
84
Q

What is the 3rd generation of antipsychotics?

A

Different mechanism to the other two, are D2 partial agonists

85
Q

What are the four atypical antipsychotics?

A
  • Clozapine
  • Olanzapine
  • Quetiapine
  • Risperidone
86
Q

What is the 3rd generation drug?

A

Aripiprazole

87
Q

What makes an atypical drug ‘atypical’?

A
  • Lower rate of extrapyramidal side effects
  • Good efficacy against the negatve symptoms of schizophrenia
  • High potency at other (besides D2) receptors
88
Q

What are the 3 key factors that have been hihglighted to be imporntant in the clinical efficacy of atypical drugs?

A
  • 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
89
Q

Which is the least atypical drug and which is the most?

A
  • Least- risperidone
  • Most- Clozapine
90
Q

Give an overview of haloperidol

A
  • 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
91
Q

Give an overview of risperidone

A
  • 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
92
Q

Give and overview of Olanzepine

A
  • 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
93
Q

Give an overview of quetiapine

A
  • 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
94
Q

Give an overview of Aripiprazole

A
  • 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
95
Q

What is neuroleptic malignant syndrome?

A
  • 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)
96
Q

What is the most effective antipsychotic for treatment resistant schizophrenia (TRS)?

A

Clozapine

97
Q

When can clozapine be prescribed?

A

Failure of at least two other drugs, one of which must have been atypical

98
Q

What are the side effects of Clozapine?

A
  • 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
99
Q

What is Clozapine-induced agranulocytosis?

A
  • Loss of white blood cells (supressed immune system)
  • Get an infection- treat with antibiotics
  • Causes death in 4-16% of cases
100
Q

How is clozapine monitoring initiated in patients?

A
  • Often as in-patient
  • Ramped slowly
  • White blood cell count
101
Q

What are the monitoring steps of clozapine monitoring?

A
  • 3rd day (1st week)
  • Weekly (18 weeks)
  • Biweekly (34 weeks)
  • 4 Weeklu thereafter
  • > 2 days missed: start over
102
Q

What are the 3 reasons for non-compliance?

A
  • Lack of belief in illness
  • Side effects
  • Cognitive problems, disorganised life-style
103
Q

What percentage of antipsychotic prescriptions are not filled and what are the noncompliance rates?

A

14% not filled

May be as high as 76%

104
Q

What are different formulations of taking antipsychotics?

A
  • Oral (can have sustained release)
  • Intramuscular injection (involuntary)
  • Intramuscular depot injection
105
Q

What are intramuscular depot injections?

A
  • Involuntary injections for disorganised patients
  • 2/4 weekly injections (easy to remember than daily medicine)
  • Eliminates covert non-compliance
  • Sometimes effect delated
106
Q

Which drugs are available as a depot?

A
  • Risperadone (risperdal consta)
  • Haloperidol
  • Aripiprazole
  • Paliperidone (up to 3 month)
107
Q

What is the term used when antipsychotics are used to subdue patients?

A

Chemical coshes

108
Q

What is a large population of people in which chemical coshes were used on?

A

Alzheimer’s disease

109
Q

In the elderly what do antipsychotics increase the likelihood?

A
  • Stroke
  • Sudden death
110
Q

What drugs are licenced for the elderly and for how long?

A
  • Risperidone
  • Haloperidol
  • Short term use (6wks)

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