Antipsychotic Drugs & Mood Stabilizers Flashcards
(53 cards)
What are the TYPICAL antipsychotics?
1st gen
Haloperidol, Chlorpromazine
What are the ATYPICAL antipsychotics?
2nd gen
Clozapine, Risperidone, Olanzapine, Aripiprazole, Quetiapine
What are the 3 Sx’s of Schizophrenia and dopaminergic pathways?
- (+) Sx’s
- (-) Sx’s
- Cognitive dysfunction
What are the (+) Sx’s of Schizophrenia?
- Hallucinations
- Delusions
- Disorganized thought
What are the (-) Sx’s of Schizophrenia?
- Affective blunting; Apathy; Anhedonia (like depression)
- Social withdrawal
What are the Cognitive dysfunction Sx’s of Schizophrenia?
- Declines in attention, language, memory, executive function
What are the 2 parts of the Dopamine hypothesis?
Amphetamine
- Hyperactivity, extreme anxiety, paranoid delusions, hallucinations…..
- Membrane dopamine transporter (can inhibit reuptake & therefore buildup & dopamine can cause psychosis)
Antipsychotic drugs
- Antipsychotic drugs tend to block dopamine
receptors in the dopamine pathways of the brain.
What 4 parts of the Dopaminergic pathways?
- Mesolimbic pathway
- Mesocortical pathway
- Nigrostriatal pathway
- Tuberoinfundibular pathway
What is the Mesolimbic pathway?
- VTA (Ventral Tegmental Area) →(projects to) → Nucleus accumbens in the ventral striatum
- Motivation, reward, addiction, reinforcing behaviour
- HYPERACTIVITY → POSITIVE SYMPTOMS
(A Dopaminergic pathway)
What is the Mesocortical pathway?
- VTA →(projects to) → Prefrontal cortex
- Cognitive function, motivation and emotional response.
- DEFICIT → NEGATIVE SYMPTOMS,
- DEFICIT → COGNITIVE DYSFUNCTION
(A Dopaminergic pathway)
What is the Nigrostriatal pathway?
- SNc (substantia nigra) →(projects to) → caudate nucleus and putamen in the dorsal striatum
- MODULATE MOTOR ACTIVITY, part of the basal ganglia motor loop.
(A Dopaminergic pathway)
What is the Tuberoinfundibular pathway?
- infundibular nucleus in hypothalamus →(projects to) → pituitary gland
- regulates the secretion of prolactin (which)→ INHIBITS PROLACTIN RELEASE.
(A Dopaminergic pathway)
What are antipsychotic drugs?
Antipsychotic drugs are able to REDUCE PSYCHOTIC SYMPTOMS in a wide variety of conditions, including schizophrenia, bipolar disorder and others.
What is the classification of Antipsychotic drugs?
- TYPICAL antipsychotics (1st generation):
– chlorpromazine, haloperidol - ATYPICAL antipsychotics (2nd generation):
– clozapine, risperidone, olanzapine,
quetiapine, aripiprazole
What is the action sites of the TYPICAL antipsychotics (first generation): chlorpromazine, haloperidol?
- BLOCK DOPAMINE D2 RECEPTOR: binding affinity is strong
- NON-SELECTIVELY BLOCK: histamine H1 receptor; muscarinic M receptor; adrenergic α receptor
NO EFFECT ON 5-HT receptor
What is the therapeutic uses of TYPICAL antipsychotics (first generation): chlorpromazine, haloperidol?
- Onset of action is about 1 WEEK
- Effective for POSITIVE symptoms (block Mesolimbic pathway) but not effective for negative symptoms (NO EFFECT ON (-) & Cognitive Sx’s)
- Inhibit D2 receptor in mesolimbic DA pathway → positive symptoms ↓
Why are TYPICAL antipsychotics effective for (+) Sx’s but not (-) Sx’s?
b/c only for psychosis; b/c blocks dopamine D2 r.; inhibiting it
- for (-) Sx’s, you’d want to UPregulate dopamine
What are the adverse effects of TYPICAL antipsychotics (first generation): chlorpromazine, haloperidol?
EXTRAPYRAMIDAL SYMPTOMS (EPS):
- block DA nigrostriatal pathway (which controls motor movement)
- Short-term Tx (hours-months):
– Parkinson’s syndrome
– Akathisia, acute dystonia
– REVERSIBLE
- Long-term treatment (months-years):
- Tardive dyskinesia (repetitive, invol, purposeless movements)
- IRREVERSIBLE
NEUROLEPTIC MALIGNANT SYNDROME:
- A rare but life-threatening reaction (high fever, rigid muscles, etc.)
GALACTORRHEA:
- block tuberoinfundibular pathway: spontaneous flow of milk from breast
OTHER:
- ANTIMUSCARINIC, ANTIHISTAMINERGIC, ANTIADRENERGIC
What are the action sites of ATYPICAL antipsychotics (second generation)
(clozapine, risperidone, olanzapine, quetiapine, aripiprazole)?
- Block dopamine D2 receptor
- Block 5-HT2 receptor
What are the therapeutic uses of ATYPICAL antipsychotics (second generation)
(clozapine, risperidone, olanzapine, quetiapine, aripiprazole)?
- Onset of action is about one week
- Useful for BOTH POSITIVE and
NEGATIVE symptoms
For positive symptoms:
- SIMILAR EFFICACY with typical antipsychotics
- Inhibit D2 receptor in mesolimbic DA pathway → positive symptoms↓
For negative symptoms:
- Block 5-HT2 receptor → ↓Negative symptoms, cognitive dysfunction
Clozapine: reduce suicidal risk in patients with schizophrenia
What is unique about Clozapine (Atypical)?
only one that can REDUCE suicidal risk in patients with schizophrenia
What are the adverse effects of ATYPICAL antipsychotics (second generation)
(clozapine, risperidone, olanzapine, quetiapine, aripiprazole)?
Extrapyramidal symptoms (EPS)
- With lower risk of EPS
- Blocking of 5-HT2 receptor may be a requirement for the reduction in EPS
Others:
- Olanzapine and others: Weight gain, hyperlipidemia
- Clozapine: agranulocytosis; seizures (NOT 1st line (2nd gen) drug)
Describe ATYPICAL vs. TYPICAL in terms of SE’s
TYPICAL:
- as antipsychotic effect increases, EPS SE’s increases
ATYPICAL:
- have to increase antipsychotic effect way more to see increase in EPS SE’s (higher therapeutic window)
What is the drug interaction with Antipsychotic drugs?
Pharmacokinetic interaction:
- Some pharmacokinetic interactions have been reported, but none are of major clinical significance.
Pharmacodynamic interaction:
- Be cautious: use with anti-Parkinson’s drugs (may inhibit antipsychotic effect)
- Enhance EPS: use with metoclopramide
- Produce excess sedation: use with anxiolytics, alcohol, antidepressants, antihistamines
- Produce additive antimuscarinic effects
