Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Human Function II > HUF 2-69 Schizophrenia and neuroleptic drugs > Flashcards

HUF 2-69 Schizophrenia and neuroleptic drugs Flashcards

1
Q

Symptoms of schizophrenia

A

Positive Symptoms:

  • Delusion (paranoid)
  • Hallucination
  • Thought disorder (outside agency)
  • Abnormal movements (aggressive behaviour)

Negative Symptoms:

  • Social withdrawal
  • Flattening of emotions

Cognitive Symptoms:

  • Unable to make sense of everyday world
  • Unable to link thoughts with outside events
  • Cannot understand other people’s normal behaviour
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Dopamine pathways related to schizophrenia

A
  1. Mesocortical pathway dysfunction
    => Negative and cognitive symptoms
  2. Mesolimbic pathway overactivity
    => Positive symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Neuroleptic drugs or antipsychotics

A
  • Block mesolimbic DA transmission (+ve. symptoms)
  • For:
    Schizophrenia
    Manic phase of bipolar disorders
    Acute idiopathic psychotic disorders
    Severe agitation / aggressive behaviours

Typical (1st gen.): bind tightly to D2 receptors
e.g. Chloropromazine, Thiothixene, Haloperidol

Atypical (2nd gen.): bind loosely to D2 receptors but also 5HT-2A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Clinical evidence related to therapeutic actions of antipsychotics

A
  1. Affinity towards D2R => clinical efficacy of anti-psychotic effects
    (↑ D2 affinity => ↓ dose needed)
  2. ↑ DA receptor density and [DA] in corpus striatum in brains of schizophrenic patients (postmortem examinations)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Typical antipsychotics can antagonise multiple receptors with diff. potencies

A

Preferentially bind to D2, D4 than 5-HT2A
Can also bind to muscarinic, α and H1

  • Antagonism to D2R => Treat positive symptoms
  • Effective among 70% of patients
  • Sedative (CNS depressing)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Basic research evidence related to therapeuric actions of antipsychotics

A
  1. Drugs that ↑ central dopaminergic activity => +ve. symptoms
    - Normal people with repeated amphetamine intake
    => Psychosis
    ∵ Amphetamine ↑ release of DA from neurons
  2. D2R Antagonists and drugs that block neuronal DA storage => Control +ve. symptoms
    - Prevent amphetamine induced psychotic symptoms
    - e.g. Reserpine: ↓ DA at presynaptic side
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Major mechanism of antipsychotics actions

A

Mesolimbic D2R antagonism

  • DA theory of schizophrenia: hyperactivity of central DA => psychosis
  • +ve. symptoms of schizophrenia related to hyperactivity of mesolimbic DA system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

High potency typical antipsychotics tend to cause more serious adverse effects

A
  • Exaggeration of -ve. symptoms
  • Blockade of nigrostriatal pathway
    => Extrapyramidal symptoms (EPS)
  • Blockade of tuberoinfundibular pathway in hypothalamus
    => dysregulate PRL secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Extrapyramidal symptoms (EPS)

A

Originated in brainstem; modulated by nigrostriatal pathway

Reversible (Benzatropine: anticholinergic drugs):

  • Acute dystonia (days): muscle spasm affecting tongue, face, neck, back
  • Akathisia (days to weeks): motor restlessness, continual pacing
  • (Pseudo-)Parkinsonism (a few weeks): difficulty in initiating movement

Irreversible:
- Tardive dyskinesia (years): abnormal movements of facial ms, trunk, limbs (upreg. of D2R)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Major undesirable endocrine effects of typical antipsychotics

A
  • PRL release from pituitary gland under control of central DA transmission
  • D2R blockade of tuberoinfundibular pathway
    => ↓ DA suppression of PRL release
    => Men: gynaecomastia
    Women: galactorrhea
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Unpredictable life-threatening neurological disorder

A

Neuroleptic malignant syndrome

  • ↑ body temp. > 38°, sweating
  • Confused or altered consciousness (agitation , delirium, coma)
  • Rigid muscles, muscle cramps, tremors
  • Autonomic imbalance e.g. unstable BP
  • Typical antipsychotics (haloperidol, chlorpromazine): greatest risk of neuroleptic malignant syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Antagonism of other receptors => Undesirable effects of antipsychotics

A

Block α => postural hypotension
Block H1 => Sedation / Drowsiness
Block M => dry mouth, urinary retention

  • Potency of receptor blockade
  • High potency drugs tend to have fewer sedative effects and less postural hypotension
    ∵ less dosage needed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Atypical (2nd. gen) antipsychotics

A
  • Lower risk of EPS
  • Relative lower affinity for D2R (transient D2R occupancy; rapid dissociation from D2R)
  • High affinity towards 5-HT2A R
  • Better improvement in -ve. symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

“Atypicality” of atypical antipsychotics

A
  1. 5-HT2A antagonism: high preference toantagonize 5-HT2AR than to D2R (high 5-HT2A/D2 blocking ratio)
    - increase DA transmission in nigrostriatal pathway
    => ↓ risks of EPS
  2. Rapid dissociation from D2R (transient binding)
    => ↓ risks of EPS (nigrostriatal pathway)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Commonly used atypical antipsychotics

A

Clozapine
Olanzapine
Risperidone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Clozapine

A
  • Weak D2R antagonist; greater antagonist activity at D1, D4 and 5-HT2AR
  • Risk of agranulocytosis (fatal in long run)
    ∴ Blood monitoring needed
  • Not recommended for 1st-line treatment
  • Reserved for patients who DO NOT respond to conventional antipsychotic therapy or who have tardive dyskinesia
  • Metabolic changes (glucose metabolism) ; weight gain
    Olanzapine
17
Q

Olanzapine

A
  • Receptor binding profile similar to clozapine
  • Higher affinity for 5-HT2AR than D2R
  • Less likely yo produce serious undesirable effects e.g. agranulocytosis
18
Q

Risperidone

A
  • Higher affinity for 5-HT2AR than D2R

- Higher daily dose => higher EPS risk

19
Q

Weight gain due to atypical antipsychotics

A
  • Olanzapine, Clozapine

Possible mechanisms:

  1. Antagonise H1R => Excessive eating, food craving
  2. Antagonise M => ↓ pancreatic insulin release (hyperglycemia)
  3. Affect adrenergic system => Hyperglycemia, ↓ lipolysis
20
Q

Other common undesirable side effects of atypical antipsychotics

A
  • Type I hypersensitivity (allergic rxn)
  • QT-interval prolongation: block cardiac K+ channels (inward rectifiers) e.g. Clozapine, Risperidone

Block α => postural hypotension
Block H1 => Sedation / Drowsiness
Block M => dry mouth, urinary retention

21
Q

PK profile of antipsychotics

A
  • Highly lipophilic; metabolised in liver
  • High binding to plasma proteins
  • High first-pass metabolism via oral routes
  • Elimination: multiphasic pattern; not strictly first order
    ∴ t1/2 hard to be predicted (8-40 hrs)
  • Patients respond differently to individual antipsychotics
    => Be careful when switching between antipsychotics
22
Q

Potential DDI of antipsychotics

A
  1. Interact with Parkinson treatment drugs
    - ↑ synaptic [DA] e.g. Levodopa
    - Direct stimulation of DAR (DA agonist)
  2. Potentiate sedative effects of other CNS depressants
    e. g. hypnotics/anxiolytics, 1st gen antihistamines
23
Q

Typical and atypical antipsychotics are equally effective towards +ve. symptoms

A
  • Choice of antipsychotics depends on:
    Tolerance to EPS risk
    Effectiveness of managing -ve. symptoms
    Cost

Notes:
1. Use anticholinergic drugs to block motor side effects of antipsychotics (e.g. benzatropine)
2. Several weeks to see clinical effects of antipsychotics (time lag); undesirable effects, weight gain
∴ Patient education => patient is following treatment regimen

Human Function II (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions