antipsychotics Flashcards
Essentials in diagnosing schizophrenia
social withdrawal lose thought associations (shift topic to topic) Autistic absorption in inner thoughts Auditory hallucinations Delusions Sx at least 6 months
What are the different types of schizo
Schizophrenic d/o Delusional d/o Schizoaffective d/o Schizophreniform d/o Brief psychotic d/o
What are the dopaminergic pathways
Mesolimbic: + Sx
Mesocortical: - Sx
Nigrostriatal: EPS, tardive dyskinesia
Tuberophypophyseal: hyperPRL
What are + Sx
suspicious
delusions
hallucinations
conceptual disorganization
What are - Sx
flat affect
alogia (aphasia)
anhedonia
avolition
What are cognitive Sx
impaired attention
impaired memory
impaired executive function
What is the hypothesis behind schizophrenia Tx
5-HT2a receptor block; modulate release of dopamine, NE, glutamate, GABA, and ACh
Block post-synaptic D2 receptors in CNS, mesolimbic (+), and striatal (EPS)
What can hypofunction of NMDA receptors on GABA neurons lead to
Diminished inhibitory influences on neuronal function
Glutamate can lead to hypertsimulation of cortical neurons
(idk what any of this means- slide 9)
What other receptors are involved in PD of antipsychotics
A-adrenergic blocking action
5-HT2/2a antagonists
5-HT1d agonists
D2 and 5-HT1a partial agonists
What are first gen antipsychotics
Chlorpromazine Fluphenazine Haloperidol Loxapine Perphenazine Thioridazine Thiothixene Trifluperazine
What are second gen antipsychotics
Aripiprazole Clozapine Lurasidone Olanzipine Risperidone (not all inclusive)
What are the overall PK of antipsychotics
Well absorbed Lipid soluble Bound to plasma proteins Metabolized by liver enzymes Renally eliminated Long half lives
What ADE should you monitor on someone taking antipsychotics
Akathisia (inner restlessness) Anticholinergic ADE Glucose intolerance HLD Orthostatic hypotension HyperPRL Sedation Sexual dysfunction Tardive dyskinesia Weight gain
Monitor for these ADE in specific antipsychotics
Clozipine (2): Agranulocytosis (WBC), Sialorrhea (excess drooling Inhaled Loxapine (1): Bronchospasm, respiratory distress/depression/arrest Long acting Olanzapine (2): post-injection sedation, delirium syndrome
Antipsychotic toxicity can lead to
Dose dependent EPS: bradykinesia, rigidity, tremoe, akathisia, dystonias
Tardive dyskinesia: choreathetoid movements of lips and buccal muscle (appear at 6 months-yrs later)
How do you treat toxicities associated with antipsychotics
Dose dependent EPS (parkinson like Sx): muscarinic blockers and Diphenhydramine
Tardive dyskinesia: No Tx
What specific drugs treat EPS 2/2 antipsychotics
Benztropine, Trihexyphenidyl (antimuscarinic)
Diphenhydramine (antihistamine)
Amantadine (D agonist)
Lorazepam, Diazepam, Clonazepan (benzos)
Propranolol (BB)
Haloperidol is usually automatically paired with
Benztropine (anti-muscarinic)
Schizophrenia Tx addresses
Psychosocial component Psychiatric pharm co-occurring mental d/o Tx adherence Medical problems
Goal for schizo Tx is
First 7 days: decrease agitation, hostility, anxiety, aggression. Normalize sleep and eating
Wk 2-3: improve socialization, self-care, mood
Wk 6-8: Improve formal thought disorder
How do you maintain therapy (avoid relapses) in schizo
Continue meds for 12 mo. after remission of first episode, but most recommend 5 years
Lifetime lowest dose of pharm therapy
Taper Clozapine and other 1st gens slowly to avoid cholinergic rebound
How do you switch someone to a different antipsychotic
Taper the first down slowly and d/c over 1-2 weeks
At the same time, initiate the new antipsychotic and taper upward
What agents are used to treat Bipolar disorder
Lithium*: Tx manic phase, and prevent recurrent manic and depressive episodes
Valproic acid, Carbamazepine, Lamotrigine, Quetiapine, Olanzapine
What do you need to do when treating bipolar disorder (with meds)
Include antipsychotics and benzos during initiation to slow the onset of lithium or valproic acid
What can monotherapy with antidepressants do to bipolar patients
Precipitate mania!
Diagnosis needs to be correct w/ bipolar b/c SSRI’s expose mania
How does lithium work
Increase volume of brain structures that regulate emotions (pre-frontal cortex, hippocampus, amygdala)= Neuroprotective
Reduces excitatory NT (dopamine, glutamate) and increases inhibitory NT (GABA)
-Suppresses IP3 and DAG signaling
What are the PK of lithium
Absorption: complete in 6-8 hrs, peak plasma in 30min-2hr
Distribution: no protein binding. some sequestered in bone
Metabolism: none
Excretion: Urine (renally)! half life is 20 hrs
What are the effects of Lithium
No sedation! no specific ANS or CNS receptors
Lithium clearance is decreased by
Thiazides
NSAIDs
Toxic ADE of lithium are
tremor edema Hypothyroid* renal dysfunction *Pregnancy category D
What are newer drugs used for manic component of bipolar disorder and their ADE
Carbamazeoine: ataxia, diplopia
Lamotrigine: nausea, dizziness, HA
Valproic acid: GI distress, weight gain, alopecia
-unclear mechanism
What are toxicities of new manic Tx drugs
Carbamazepine: hematotoxicity
Lamotrigine: Rash
Valproic acid: hepatic dysfunction, weight gain
First line for hypomania
Lithium, valproate, carbamazepine, Second gen antipsychotics
Consider + Benzo to combat initial insomnia
First line for mania
2-3 drugs: lithium, valproate, second gen antipsychotic + a benzo short term for insomnia, or lorazepam for catatonia
First line for mild-moderate depressive episode
Optimize or initiate: Lithium, Quetipine, Lurasidone
First line for severe depressive episode
Optimize or initiate: lithium, Quetipine, Lurasidone
Add fluoxetine ot olanzapine if also w/ psychosis
