Lecture 1 & 2: Pathophysiology and Pharmacology of Schizophrenia And Case Study Flashcards

1
Q

What is Psychosis?

A
  • Mental health condition characterised by a disconnection from reality. (Ability to distinguish what is real or not)
  • Can occur in a variety of psychiatric disorders: Schizo
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the symptoms of Psychosis?

A
  • Hallucinations
  • Delusions
  • Disorganised Thinking
  • Affecting behaviour, emotional regulation and social functioning
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is Schizophrenia?

A
  • A chronic severe mental disorder.
  • Affects how a person thinks, feels, losing touch of reality
  • No cure
  • Suggest genetic association
  • Starts early on (20s and 30s)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are positive symptoms associated with Schizophrenia?

A
  • Delusions - False held belief (not true)
  • Hallucinations - perception of something in absence of stimuli (smell, sight, visual)
  • Disorganised Speech
  • Unusual behaviour and agitation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What can Schizophrenia cause?

A
  • Bio: Genetic load, Dopamine and Glutamate dysregulation
  • Psycho: Concrete thinking, difficulties with abstract thought, Issues with sensory filtering
  • Social: Increased incident in urban environment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the differences between Psychosis and Schizophrenia?

A
  • Psychosis is broad and schizo is a specific diagnosis. Psychosis is a primary symptom
  • Psychosis is temp and triggered by factors. Schizo is long term and chronic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are amphetamines and what do they do to Schizo?

A
  • Type of stimulant drug that affects CNS by increasing levels of dopamine and norepinephrine.
  • Dopamine agonists - can give psychotic symptoms. This can cause dysregulation of neurotransmitter leading to it worsening
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the mechanism of action of amphetamines?

A
  • Stimulate release of dopamine and norepinephrine
  • Block reuptake of dopamine and norepinephrine - remains in presynpatic cleft
  • Inhibition of monoamine oxidase - enzyme responsible for breaking down neurotransmitters
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Chlorpromazine and its mechanism of action and some side effects?

A
  • First gen antipsychotic drug
  • Blocks D2 receptors in the brain
  • Tardive Dyskinesia: Involuntary movement in face and mouth, Anticholinergic effects: Urinary retention and dry mouth
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do dopamine, its receptors and the negative feedback?

A
  • Dopamine is stored into synaptic vesicles via VMAT2 (Vesicular monoamine transporter)
  • Dopamine released acts on 5 types of post synaptic receptors (D1-5)
  • Presynaptic D2 autoreceptor acts as a negative feedback mechanism- regulates the release of dopamine from Presynaptic neuron
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the types of dopamine receptors?

A
  • Type 1 & 5 - similar in structure and drug sensitivity (D1 like) don’t have clinically relevant antipsychotic effects
  • Types 2, 3, 4 are similar in structure (D2 like). Only D2 receptor is blocked by antipsychotic drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the different dopamine pathways?

A
  • Mesocortical:
  • Nigrostriatal:
  • Mesolimbic:
  • Tuberoinfundibular:
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What symptoms are associated with the mesolimbic pathway dysfunction and what does it control?

A
  • Depression, reduced motivation, and pleasure.
  • Links the ventral tegmental area (VTA) to the Limbic system
  • It regulates emotion, reward and motivation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the function of the mesocortical dopamine pathway?

A
  • Connects the VTA to the prefrontal cortex
  • regulating cognition, attention, and executive function.
  • Difficulty with planning and decision-making
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the role of the nigrostriatal pathway?

A
  • Transmits dopamine from the substantia nigra to the striatum, crucial for voluntary movements.
  • Typical symptoms
  • Chronic blocking can produce tardive dyskinesia (movement disorder) facial & tongue movements such as constant chewing, grimace
  • Limb movements are quick and jerky
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens to the tuberoinfundibular pathway when dopamine levels are reduced?

A
  • This pathway connects dopamine neurons to the arcuate nucleus of the hypothalamus to the pituitary gland
  • Prolactin secretion increases, leading to hyperprolactinemia and galactorrhea (milk production not associated with/ breastfeeding) and sexual dysfunction
17
Q

What are the side effects of cholinergic M1 antagonism?

A
  • Dry mouth
  • Blurred Vision
  • Constipation
  • Cognitive blunting
18
Q

What is the ideal antipsychotic drug? What will it target/not?

A
  • Ideal drug will decrease dopamine in the mesolimbic to treat positive symptoms (hallucinations)
  • Increase dopamine in mesocortical to treat negative and cognitive symptoms (depressive)
  • Leaving nigrostatial and tuberoinfundibular pathways to avoid side effects
19
Q

What are the types of atypical (newer) antipsychotics?

A
  • Pines - Olanzapine, Quetiapine
  • Dones -Risperidone
  • 2 Pips: Aripiprazole (partial agonist)
  • Rip: Cariprazine (partial agonist)
20
Q

What are some first gen low potency and higher potency antipsychotics?

A
  • First gen low potency: Chlorpromazine
  • First gen high potency: Haloperidol
21
Q

What are some 2nd generation antipsychotics? and what are the differences between the generations?

A
  • Aripiprazole
  • Quetiapine
  • Risperidone
  • Olanzapine
  • First gen have high incidence of extra pyrimidal side effects. They have varying affinity for D2 receptor and target serotonin receptor
  • 2nd gen can have metabolic side effects
  • Theory proposes that 1st gen bind more tightly than dopamine to D2 receptor. 2nd gen bind more loosely
22
Q

What type of receptors do resperidone and paliperidone work on?

A
  • Resp: strong binding for serotonin and dopamine d2, a1/2 adrenergic receptors. Low affinity for H1.
  • Pali: a major active metabolite of resp. centrally active D2 and serotonin antagonist. Antagonist for a1/2. Better w/ cognition
23
Q

What receptors do Olanzapine and Quetiapine work on?

A
  • Olan: high affinity to serotonin and medium dopamine receptors. Highest for H1 - causes weight gain
  • Quet: Dirty drug but has low EPS side effects but causes sedation
24
Q

What are the some receptors that second generation antipsychotics work on?

A
  • Risperidone: D2, serotonin, a1
  • Olanzapine: works on all (mostly serotonin, D2, M1)
  • Aripiprazole: D2 mostly and some others
  • Quetiapine: serotonin, a1
25
Q

What are the types of delusion?

A
  • Delusion of reference: Read into somethinmg/overthink/ normal things have special meaning
  • Delusion of grandeur: Think you are God/more important
  • Paranoid delusion: People trying to get you
26
Q

What are the types of disorganised speech?

A
  • Derailment : talk about something then about something else not relevant
  • Tangentiality: Talk about subject but not answer question
  • Incoherence: Say words and words dont make sense
27
Q

What are some negative symptoms of Schizophrenia?

A
  • Alogia (Poverty of speech, talk slowly)
  • Lack of socialization
  • Avolition (Not able to engage in goal sustaining activities)
  • Loss of emotional connectedness
  • Loss of executive functions
28
Q

What are som e first generation (typical) antipsychotics and what receptor do they all work on?

A
  • Haolperidol
  • Chlorpromazine - also works on M1 (more sedative)
  • All work on dopamine receptor. D2 receptor antagonist
29
Q

What are the 3 main stages of treating someone with schizophrenia?

A
  • Acute stage: Aim to calm patient and prevent harm
  • Stabilisation stage: patient becoming stable. Symptoms under control
  • Stable phase: Treatment plan long term, no exacerbation of symptoms. No positive but can negative symptoms
30
Q

What is the main problem with first generation antipsychotics?

A
  • Extrapyrimidal symptoms: dystonia (bad, painful muscle spasms, stiff neck early sign), reversible
  • Tardive dyskinesia: Has involuntary movement of jaw (irreversible)
  • Akathisia: Restlessness of hands and legs. Reversible
31
Q

What is a main side effect of Risperidone (2nd gen)?

A
  • Hyperprolactanemia (high level of prolactin in blood)
  • High levels of prolactin but not pregnant (false belief)
32
Q
A
33
Q

What is a main side effect of olanzapine (2nd gen) and why should ciprofloxacin not be used with it?

A
  • Pain in her lower back and foul smelling urine (signs of UTI), it also causes weight gain
  • Cipro - quinolone antibiotic (narrow spectrum)
  • Cipro inhibits CYP1A2 which is meant to metabolise Olanzapine - leads to elevated levels (more side effects: drowsiness and tremor)
34
Q

What are some things that should be monitored when taking 2nd gen antipsychotics?

A
  • Weight (BMI)
  • Waist circumference
  • Blood pressure
  • Blood glucose and lipids
  • Long term can lead to diabetes, heart attack and stroke
35
Q

Why is Clozapine good and not good?

A
  • 2nd gen antipsychotic and most effective. Used in treatment resistant schizo
  • Associated w/ neutopaenia and agranulocytosis. Less neutrophils (cant fight infections)
36
Q

What are some considerations when taking clozapine?

A
  • Reduces peristalsis (constipation)
  • Might get seizures
  • Myocarditis (inflammation of the heart)
  • Drooling
  • Smoking: induces metabolic enzymes. If stopped wont be induced. High dose will be toxic