Antipsychotics Flashcards
Schizophrenia
thought disorder characterized by divorcement from reality
Positive symptoms of Schizophrenia
Psychotic detentions- hallucination, delusion, paranoid, grandeur
Disorganized dimension- speech and behavior
Negative Sx of schizophrenia
5 A's Avolition Ahendonia Asocial Alogia Affect blunted
Progression of Schizophrenia
fluctuates between acute episodes and remission.
After initial episode pts will never regain their baseline function
Goal of treating schizophrenia
Prevent exacerbations
Pts will be on meds for life- this and the side effects make compliance very difficult
What pathways are involved in Schizophrenia
Da pathways Nigrostriatal Mesocorticol Mesolimbic Tuberoinfundibular
Nigrostriatal effects of shizophrenia
Da blockade
movement disorders- this is where extrapyramidal effects occur
Mesolimbic effects of schizophrenia
Da hyperactivity results in the positive symptoms
Mesocortical effects of shizophrenia
Da hypoactivity
causes negative symptoms
Tuberoinfundibular effects of schizophrenia
Da blockage decreases blockage of prolactin so more prolactin is released resutling in
ammenorhea and galactorrhea
What pathway is targeted by typical antipsychotics
D2 receptors, antagonists
Work on positive symptoms
How are typical antipscychotics broken down
High potency vs low potency based on affinity for D2 receptors
What is the effect of this difference in affinity for D2 receptors
Extrapyramidal systems or not
high affinity= more EPS
low affinity= less EPS, but more AE at other receptor types
what are the other receptor types targeted by typical antipsychotics
M, H1, alpha adrenergic
High potency APs
potent at D2 receptors but less potent at other receptors, thus inc risk of EPS
ex: Haloperidol
Low potency APs
higher potency at other receptors- antimuscarinic activity, anti histamine activity, anti alpha adrenergic activity.
Dec incidence of EPS
ex: Chlorpromazine
What are the 5 main Da related AE of typical APs
Dystonia Pseudoparkinsonism Akathesia Tardive dyskinesia Neuroleptic Malignant syndrome
Describe D2 blockage and Dystonia
protlonged painful muscle spasm- torticolus, Oculogyric Crisis
Tx with IV anticholinergics to restore Da/ Ach balance (Ach is anti kinetic, Da is prokinetic)
Describe D2 blockage and pseudoparkinsonism
Resembles idiopathic PD, but has bilateral and faster onset
no real tx, but may develop tolerance to this
Akasthesia
restless and inability to sit still or stay calm
tx betablockers or benzos
Tardive dyskinesia
involuntary muscle movements normally oral or with the jaw
this is caused by an up-regulation of D2 receptors in the nigrostriatal pathway
this may be untreatable and irreversible
tx: lowe dosage switch to an atypical
Neuroleptic malignant syndrom
muscle tension causes excess heat and disruption of the normal thermoregulatory proceses
Signs: lead pipe rigidity, fever over 38 C, myoglobinuria, altered consciousness
potentially fatal
tx: discontinue current meds, supportive, antiparkinsonian meds (Da agonist Bromocriptime)
only atypical antipsychotics should be used after this (not even risperidone)
Antimuscarinic AE of Aps
constipation
dry mouth
urinary retention
but also reduces EPC by acting on the Ach/Da imbalance by reducing Ach so there is more Da
Anti alpha 1 AE of AP
orthostatic Hypotension
Anti Histaminic AE of AP
weight gain
drowsiness
endocrine AE of APs
Hyperprolactinemia- by blocking Da- inc Prolactin Women: galactorrhea and amehorhrea Men: Gynecomastia and galactorrhea both have sexual dysfunction tx by switching to atypicap APs
Atypical APs
work on positive Sx by blocking Da
improves negative Sx by blocking 5HT2A in the mesocortical pathway which inc dopamine release.
Move Da blockage to between 60 and 80% rather than 100% with the typicals (causes EPS, TD, and endrocine AE)
What do atypical APs do in the mesocortical pathway
inc DA in frontal areas thus reversing hyporontality, alleviating negative Sx
What do atypical APs due for endocrine AEs
decrease prolactin release thus block the prolactin related AE
Atypical APs- names
Clozapine Risperidone Olanzapine Quetiapine Ziprasidone Apriprazole
Risperidone
only atypical that causes EPS Sx b/c has most DA blockage (exceeds the 80%)
Clozapine
prototype- most effective for pos Sx, neg Sx, and suicide prevention
causes fatal AE: agranulocytosis, seizure, and weight gain
measure WBC and do not use if WBC <3000
when is clozapine used
Clozapine is only used if pts have failed 2 atypical APs
Atypical AEs
weight gain
hyperglycemia
lipid abnormalities
Order of metabolic AE
Clozapine= olanzapine>risperidone> quetiapine>Ziprasidone and aripiprazole
mirrors efficacy
What should be monitored at baseline and as pts take atypical APs
obesity and CV risks
quetiapine
lowest D2 binding
DOC for psychosis with PD
