Anti-Psychotics Flashcards
Define Psychosis
- Derangement of personality
- Loss of contact with reality
- Delusions
- Hallucinations
All disorders in this class (schizophrenia spectrum and psychotic disorder) share some form of the syndrome psychosis with abnormalities in one or more domains
- delusions,
- hallucinations,
- disorganized thinking,
- abnormal motor behavior and negative symptoms.
How prevelant is schizophrenia
seen in 1.1% US adults
*60% adults with schizophrenia use healthcare system in 12 month period
You need to have two or more symptoms in 1 month period to be dx with schizophrenia, at least one is a core positive which is:
Delusions, hallucinatins, disorganized speech
What are the negative or a other symptoms seen in schzophrenia
Grossly disorganized or catatonic behavior Negative Symptoms – Blunted affect – Lack of spontaneity – Poor abstract thinking – Poverty of thought – Social withdrawal
Explain dopamine synthesis and it’s role in schizophrenia
Schizophrenia results from hyperactivity of dopaminergic neurons or their receptors, particularly those with terminals in limbic areas of the brain.
*All effective antipsychotics interact with dopamine system
Dopamine pathway
ORiginates in A10
key for arousal, memory, stimulus processing, locomotor activity, MOTIVATIONAL behavior
Domapine hyperactivity here–> Positive symptoms
Mesolimbic tract
Dopamine pathway
Originates in A10
Key for Cognition, communication, social activity
Diminished dopaminergic activity–> negative symptoms
Mesocortical Tract
Originates in A9, see Doamine blockade that increaes EPS
( Blockade 5-HT2a and see decreased EPS, and parkinsonism
Nigrostriatal pathways
dopamine blockade here leads to increased prolactin release
Tuberoinfundibular tract
How does body regulate dopamie release
Have reuptake by DAT
D2/D3 receptor on pre-syaptic neuron senses level of DA and can inhibit release
MAO breaks it down
What Dopamine receptors have a role in guanyl or adenylyl cyclase ACTIVATION and increase IP3 and Ca channels
Ca activation is seen in the D1 and D5 receptors
What dopamine receptors have role in guanyly or adenyly cylcase INHIBITION of IP3 channels and k channels
D2, D3, D4
We see strong correlation of clinical potency of drug and affinity for ______
Dopamine D2 receptors
What is the goal of D2 drugs
they block the D2 receptor on presynaptic cell to increae DA production and release, cell isn’t getting it’s feedback of having enough dopamine: also have blockages of DA activation on post synaptic side
How do Atypical Antipsychotics such as Clozapine and Risperidone work?
Block DA receptor AND block 5-HT2 receptors in forebrain with greater potency
Clhopromazine, fluphenazine, trifluoperazine and thioridazine are all examples of
Typical antipyschotics
Risperidone, Clozapine and Olanzepin are all examples of
Atypical anthpyschotics
PharmK of antipyschotics
Oral absorption, Lipid soluble, Protein binding = large volume distribution, complex metabolism
What therapy has the best outcome for pts with pyschosis
Medications and Social therapy
Antipyschotics:
o Typical drugs differ only in_____.
o The negative symptoms of schizophrenia are not well treated by the ____ agents.
o_____ drugs, in addition to treating positive symptoms, may be more effective in treating negative symptoms.
potency
older typical
Atypical
What three actions do we see in antipyschotic drugs
decreased psychotic behavior, sedation, extrapyramidal effects
What side effects do we owrry about with antipyschotics?
o Dystonias
o Parkinsonism Early Reactions - more with typicals
o Akathisia
o Tardive dyskinesia – Late reaction may be less frequent with atypicals
Pt comes in with spasm of tongue, neck and back. You find out she was put on antipsychotics receltnly. What is the appx timefrine she’s been on the drugs and what is she experiencing?
Acute Dystonia
happens 1-5 days after starting antipyschotics
Pt comes to clinic complaining of rigidity and feels like he’s drooling more. You note he has a masked face and cogwheeling during your physical exam. He states he started taking clozapine recently. What rxn is he experiencing and apx how long would you guess he’s been on drugs?
Parkinsonism
5-30 days post starting meds
You are checking on a pysch pt you started on risperidone. She seemed very aggitated during your visit and kept moving around. How long ago did you start risperidone, what’s going on
pt has Akathisia: is an EPS seen about 5-60 days post starting antipychotics
What is a long term complication that can result from taking antipyschotics
Tardivve dyskenisia; months to years and see oral-facial dyskinesias and choreoathetoid movements
What are some other side effects of antipyschotics
- Anticholinergic ‐ dry mouth, blurred vision, urinary retention
- Orthostatic hypotension
- Neuroendocrine effects - result of dopamine receptor blockade
- Allergic and idiosyncratic effects - liver, blood and cutaneous
What antipyschotic causes cardiac effects
Thioridazine
What pts do we need to be aware of before starting them on antipyschotics?
people with seizure disorders: you see decreased seizure threshold
What antipyschotics is weight gain prevelant in?
Weight gain -Diabetes related events are more common with atypicals, particularly olanzapine, risperidone, clozapine and quetiapine
A potentially lethal hypodopaminergic side effect of antipsychotic drugs.
• Hyperthermia, Parkinson‐like symptoms (muscular rigidity and tremor), mutism and possible death.
Neuroleptic Malignant Syndrome
How do you cure Neuroleptic malignant syndrome
Treatment includes cooling and hydration, bromocriptine and dantrolene
Original antipsychotics: low to medium potency, sedative, pronounced anticholinergic effects
Phenothiazines
Chlorpromazine, Triflupromazine and Vesprin are examples of
Phenothiazines
What are my typical antipyschotics that are low potency, sedatving with less extrapyramidal effects. Its a piperidine side chain
Thioridazine
What type of drug are Trifluoperazine and Fluphenazine and what is their profile
Typical antipyschotics; have piperazine side chain
High potency, less sedative but more EPS
Typical Antipyschotic drugs from Thioxanthine
- non-nitrogen contaning
- similar to penothiazines
Clorprothixene, Thiothixene
Haloperidol is a
Typical antipyschotic
high potency, less sedating, pronounced anthicholinergic effects
Pimozide is a
Typical antipyschotic
Potent neuoleptic, lots of sides, can tx Tourettes and used secondary to Haloperidol
Pimozide
Why did we create Atypical antipyschotics
- Need for better antipsychotic drugs
- More acceptable side-effect profile
- More efficacious in treating negative symptoms of schizophrenia
- Clozapine (Clozaril®
- Olanzapine (Zyprexa)
- Risperidone (Risperdal)
- Quetiapine (Seroquel
- Aripiprazole (Abilify)
- Ziprasidone (Geodon)
- Asenapine (Saphris)
- Iloperidone (Fanapt)
- Lurasidone (Latuda)
- Paliperidone (Invega®)
List of Atypical Antipyschotics
What are the benefits of Atypical antipyschotics over typicals
Lower incidence of extrapyramidal symptoms, lower Tardive, impoveds negative sypmptoms, improvement of + symptoms in pts that typicals didn’t work
