Class 3-psychotic disorders Flashcards
INDUCED PSYCHOTIC DISORDERS- MEDICATION
o Dopamine agonists o Chloroquine o Corticosteroids o Fluoroquinolones o Stimulants * Several other drugs suspected in case reports
DOES CANNABIS CAUSE SCHIZOPHRENIA?
o Patients who have genetic predisposition may be at greater risk o Other risk factors : - Earlier age of cannabis use - Frequency of use - THC potency
NEUROTRANSMITTERS INVOLVED with psychotic disorders
- Dopamine
- Serotonin
- Glutamate
- GABA
- Acetylcholine
DOPAMINE (DA)- RECEPTORS
D1 to D5
PHARMACODYNAMICS, which one:
TRANSPORTERS G-PROTEIN-COUPLED RECEPTORS
ENZYMES ION CHANNELS
G-PROTEIN-COUPLED RECEPTORS
Dopamine binds to what receptor
D2 receptors
DOPAMINE PATHWAYS
A. MESOLIMBIC PATHWAY
B. MESOCORTICAL PATHWAY
C. NIGROSTRIATAL PATHWAY
D. TUBEROINFUNDIBULAR PATHWAY
MESOLIMBIC PATHWAY
Pleasure, euphoria, interest, energy, dependance
MESOCORTICAL PATHWAY
Dorsolateral area : intellectual functions
Ventral tegmentum area : integration of emotions
NIGROSTRIATAL PATHWAY
Relay for motor behavior
VOIE TUBÉRO-INFUNDIBULAIRE
Regulates prolactin secretion
MESOLIMBIC PATHWAY- SCHIZOPHRENIA
- «Hyperactivity » or excess dopamine
- Contributes to positive symptoms of schizoprenia
- e.g. hallucinations, delusions
MESOCORTICAL PATHWAY- SCHIZOPHRENIA
- «Hypoactivity » or lack of dopamine
- Contributes to negative symptoms of schizophrenia
1ST GENERATION ANTIPSYCHOTICS
CLASSIFICATION BY POTENCY
HIGH POTENCY
• + incisive, better effect on psychotic symptoms
• E.g. haloperidol: very specific only binds to D2
MEDIUM POTENCY
• E.g. loxapine
LOW POTENCY
• + sedative, better effect on agitation
• E.g. chlorpomazine
1ST GENERATION ANTIPSYCHOTICS- ????? RECEPTOR ????
D2 antagonist
NIGROSTRIATAL PATHWAY- D2 RECEPTOR ANTAGONIST
Variety of movement disorders named extrapyramidal symptoms (EPS)
DYSTONIA
Description: Bizarre, involuntary tonic contractions of skeletal muscle; most common dystonias are buccal spasms, oculogyric crisis, facial grimacing er tics
Onset: - Usually within 24 – 96 h of medication initiation or dose change
- Can sometimes come later during treatment or on
discontinuation of treatment (withdrawal dystonia)
Incidence - 0,6 – 8,3 %
Risk factors /antipsychotics involved
- Younger men
- High potency antipsychotic (e.g. haloperidol) and increased dose
DYSTONIA
PREVENTION
- Start the antipsychotic at a low dose
- Gradually increase the dose
- Plan for the administration of an anticholinergic drug if the patient as an antecedent of dystonic reaction
- e.g. during agitation
DYSTONIA
TREATMENT
- Reduce dose or change antipsychotic
- Mild to moderate symptomss :
- Benztropine 1 – 2 mg PO
- Diphenhydramine 25 – 50 mg PO
- Moderate to severe symptoms :
- Benztropine 1 – 2 mg IM
- Diphenhydramine 25 – 50 mg IM
AKATHISIA
Description: Feeling of distress or discomfort, often referred to legs; inner or motor restlessness, inability to sit or stand still.
Onset - Often within the first 2 to 3 weeks after starting treatment
- 90 % dans les 2 premiers mois
Prevalence - 35 %
Risk factors / antipsychotics involved - Aripiprazole and lurasidone often involved in practice
AKATHISIA
PREVENTION
- Start the antipsychotic at a low dose
- Gradually increase the dose
AKATHISIA
TREATMENT
- Reduce dose or change antipsychotic
- Beta-blocker (e.g. propranolol 10 mg BID)
- Side effects : ↓HR, hypotension
- Benzodiazepines (e.g. lorazepam, clonazepam)
- Use the smallest effective dose
- Anticholinergics less effective than in other EPS
PSEUDOPARKINSONISM
Description Generalized slowing of involuntary movements (bradykinesia/akinesia) with masked facies and reduction in arm movement; most noticeable
signs are rigidity (cogwheel) and tremor at rest
* Bradykinesia : motor retardation
** Akinesia : decrease in spontaneous movements
Onset
- Usually develops several days after treatment initiation
Prevalence - Variable : 20- 35 %
Risk factor / antipsychoticsinvolved
- Female gender
- Increased age
- High potency antipsychotics (mostly FGA) and increased dose
PSEUDOPARKINSONISM
PREVENTION
- Start the antipsychotic at a low dose
- Gradually increase the dose
PSEUDOPARKINSONISM
TREATMENT
- Reduce dose or change antipsychotic
- Anticholinergics
- E.g. benztropine 1 – 6 mg/day
- E.g. diphenhydramine 25 – 300 mg/day
- Beta-blockers (e.g. propranolol)
- If severe tremors or resistance to other treatments
TARDIVE DYSKINESIA
Description: Stereotypical involuntary movements including sucking/smacking of lips, lateral jaw movements, and fly-catching darting of tongue ;
may be choreiform or purposeless quick movements
Probably caused by hypersensitivity of D2 receptors due to prolonged blockage
Onset - Appears months to years after initiation of antipsychotic treatment
Prevalence - 13,1 – 32,4 %
Risk factors / antipsychotics involved
- Female, older age
- African American
- Use of an FGA
- Higher dose / longer duration of antipsychotic treatment
TARDIVE DYSKINESIA
PREVENTION
- Use an antipsychotic or anticholinergic only
if indicated - Try to reduce the dose if patient stable
TARDIVE DYSKINESIA
TREATMENT
- Changing the antipsychotic to quetiapine or
clozapine
if u take them off to quickly, can exacerbate tardive dyskinesia - Damage is sometimes permanent
- Other possible treatments
- vitamin B6, tetrabenazine, gingko biloba,
clonazepam
EPS TREATMENT
ANTICHOLINERGICS
TREATMENT
- Start a low dose when the patient has EPS
- Parkinsonism: continue for 2 to 3 months and then gradually remove
EPS TREATMENT
ANTICHOLINERGICS
PROPHYLAXIS?
- Generally not recommended
- Sometimes with an antipsychotic in an
emergency situation (agitation)
ANTICHOLINERGICS
SIDE EFFECTS
o Dry mouth o Blurred vision o Mydriasis o Tachycardia o Constipation o Urinary retention o Delirium o Confusion ** older patients are more sensitive
TUBEROINFUNDIBULAR PATHWAY- D2 RECEPTOR ANTAGONIST
• Hyperprolactinemia
HYPERPROLACTINEMIA
SYMPTOMS
- Galactorrhea
- Amenorrhea
- Sexual side effects
- Long-term :
- Osteoporosis
- May interfere with fertility
HYPERPROLACTINEMIA
TREATMENT
- Changing the antipsychotic
- Add a D2 partial agonist
- E.g. aripiprazole or brexpiprazole
- Add a dopamine agonist
- E.g. cabergoline or bromocriptine
ATYPICAL ANTIPSYCHOTICS : 2ND GENERATION
MECHANISM OF ACTION
MESOLIMBIC PATHWAH
D2 RECEPTOR ANTAGONIST
ATYPICAL ANTIPSYCHOTICS : 3RD GENERATION
MECHANISM OF ACTION
MESOLIMBIC PATHWAH
D2 RECEPTOR PARTIAL AGONIST
• Intrinsic activity lower than DA :
↓hyperactivity of dopamine in the mesolimbic
pathway
ATYPICAL EFFECT
Common mechanism of action of 2nd and 3rd generation antipsychotics
5-HT2A receptor antagonists
• Increased dopamine release
• It’s like ‘cutting the brake’
5-HT2A receptor antagonists
MESOCORTICAL PATHWAY
Possible improvement of negative symptoms?
5-HT2A receptor antagonists
NIGROSTRIATAL PATHWAY
Less EPS
ATYPICAL ANTIPSYCHOTICS : 3RD GENERATION
NIGROSTRIATAL PATHWAY
D2 RECEPTOR PARTIAL AGONIST
Less EPS
RISPERIDONE / PALIPERIDONE
EPS
Side effects similar to FGA :
- EPS
- Especially at high doses
- E.g. risperidone 4 mg/day
ARIPIPRAZOLE / LURASIDONE
EPS
- Akathisia more common in practice
ATYPICAL ANTIPSYCHOTICS
MECHANISM OF ACTION
TUBEROINFUNDIBULAR PATHWAY
5-HT2A RECEPTOR ANTAGONIST
Less hyperprolactinemia
ATYPICAL ANTIPSYCHOTICS
HYPERPROLACTINEMIA
RISPERIDONE / PALIPERIDONE
Side effects similar to FGA :
- Hyperprolactinemia
- Especially at high doses
- E.g. risperidone 4 mg/day
ATYPICAL ANTIPSYCHOTICS
HYPERPROLACTINEMIA
ARIPIPRAZOLE / BREXPIPRAZOLE
- Sometimes used as an adjuvant to an antipsychotic in cases of hyperprolactinemia
If atypical antipsychotics ↑ dopamine via the antagonism of the 5-HT2A receptor, is there a ↓ of their antipsychotic effect?
No, because there are no (or few) 5HT2A receptors in the meso-limbic pathway
ATYPICAL ANTIPSYCHOTICS
SUMMARY OF BENEFITS
-Neutral or beneficial effect on negative symptoms
-Lower incidence of extrapyramidal symptoms
-Lower incidence of hyperprolactinemia
BUT, disadvantage on metabolic effects
METABOLIC EFFECTS
- Weight gain
- Hypercholesterolemia
- Hyperglycemia / glucose intolerance
- Hypertension
Less/ more metabolic effects with 3rd generation
antipsychotics
less
Which Rx have more metabolic effects
Clozapine, olanzapine > quetiapine > risperidone
Weight gain
Mechanism of action :
- H1 receptor antagonist • ↑ sedation, ↓ physical activity • ↑ appetite - 5-HT2C receptor antagonist • Changing the action of serotonin on appetite