Antipsychotics- Gulsevin Flashcards
What is psychosis?
collection of symptoms that lead to loss of contact with reality: hallucinations, delusions, disordered thinking. typically we see this with pt with schizophrenia, BPD, and possibly Parkinson’s, Alzheimer’s, or age related dementia
What are the positive symptoms of schizophrenia?
-hallucinations
-delusions
-disorganized speech
-disorganized behavior
What are the negative symptoms of schizophrenia?
-social withdrawal
-blunted affect
-poverty of speech
-lack of energy and motivation
-anhedonia (lack of enjoyment/pleasure in life)
-cognitive problems
What are the symptoms of mania in BPD?
-racing thought
-inflated self-esteem
-feeling of euphoria
engagement of risk behavior
-reduced need to eat/sleep
-delusions/hallucinations
What are the symptoms of depression in BPD?
-difficulty concentrating or making decisions
-low self esteem
-low mood
-loss of interest of activities
-inability to eat or sleep or excessive sleeping
-anxiety/hopelessness/suicidal thoughts
How are antipsychotic used for schizophrenia treatment?
used for relief of positive symptoms
What are the classes of first generation antipsychotics?
-phenothiazine
-thioxanthene
- butyrophenone
What is the Dopamine Hypothesis of Schizophrenia?
positive symptoms result from hyperactivity of mesolimbic dopamine
What is the overall MOA of first generation of antipsychotics?
inhibit dopamine neurotransmission (typically at D2 receptors)
What are the side effects of phenothiazine derivatives?
neuroleptic symptoms (labile blood pressure, tachypnea, tachycardia, sialorrhea, diaphoresis, flushing, skin pallor, and incontinence)
What is the cause of Extrapyramidal Symptoms?
deficiency of dopamine in nigrostriatal DA pathway
What is the cause of Tardive Dyskinesia?
chronic D2 blockade in nigrostriatal DA pathway
What are the adverse effects of typical antipsychotics?
-muscarinic antagonist activity= anticholinergic SE (dry mouth, constipation, blurred vision, increased HR)
-histamine (H1) activity= sedation, weight gain
-alpha1 antagonist activity= hypotension, sedation
What is the most potent first gen antipsychotic?
haloperidol
State the potency of first gen antipsychotics from least to most potent
lowest= thioridazine
-prochlorperazine
-loxapine
-perphenazine
-thiothixene
-trifluoperazine
-pimozide
-fluphenazine
highest= haloperidol
What first gen antipsychotics can be used to treat schizophrenia?
-all phenothiazines derivatives (chlorpromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine)
-all thioxanthene derivatives (thiothixene, thioproperazine)
-haloperidol
-pimozide
-loxapine -> amoxapine (tricyclic antidepressant metabolite)
What first gen antipsychotics can be used for BPD?
-all phenothiazines derivatives (chlorpromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine)
-all thioxanthene derivatives (thiothixene, thioproperazine)
-haloperidol
-pimozide
-loxapine -> amoxapine (tricyclic antidepressant metabolite)
What first gen antipsychotics can be used for Tourette’s Syndrome?
butyrophenones
-haloperidol
-pimozide
What first gen antipsychotic can be used for N/V associated with surgical procedures?
droperidol (butyrophenone)
What makes an antipsychotic atypical?
doesn’t bind D2 receptors as well as “typical” antipsychotics and binds well to 5-HT2A receptors (although typical antipsychotics may also do this)
What is the general theory of second gen antipsychotics (atypical)?
5HT2A antagonist activity along with D2 antagonist activity, serotonin modulates dopamine differently depending on the area of the brain
What is the result of blocking 5-HT2A receptors in the mesolimbic dopamine pathway?
blocking 5HT2A does not interfere with dopamine antagonism= D2 blockade improves positive symptoms
What is the result of blocking 5-HT2A receptors in the mesocortical tract?
blocking 5HT increases dopamine release= improves negative symptoms
What is the result of blocking 5-HT2A receptors in the nigrostriatal dopamine pathway?
blocking 5HT2A receptors increases dopamine release which competes with D2 antagonist and less blockade= improved EPS and tardive dyskinesia symptoms
What drugs are 6-7-6 tricyclic atypical antipsychotics?
-clozapine
-olanzapine
-quetiapine
-asenapine
What are unique characteristics of Asenapine (6-7-6 atypical antipsychotic)?
-fewer muscarinic side effects
-oral delivery not possible due to extensive glucuronidation in the liver, so formulated as sublingual tab or transdermal patch
-should NOT be used with strong CYP1A2 and CYP2D6 inhibitors
What drug is a selective 5HT2 antagonist that can be given in combo with Haloperidol to decrease EPS symptoms?
ritanserin
What are the indications of Risperidone?
schizophrenia, BPD, and irritability associated with autistic disorder
What is the MOA of Risperdone?
D2 and 5HT2A antagonist
What are the preparations of Risperidone?
oral tab, solution, disintegrating tab, powder for IM injection (IM DOA= 2-4 weeks -> paliperidone (active metabolite))
What are the rare but serious side effects of Iloperidone?
stoke and QT prolongation
What are the side effects of Quetiapine?
QT prolongation, muscarinic side effects, sedation (but is seen as a positive for schizophrenic and BPD pt with insomnia and anxiety)
What is the MOA of Ziprasidone and what makes that unique?
D2, 5HT2A, and D3 antagonist but 5HT1A agonist which possesses anxiolytic effects that can improve cognition and working memory
What are the characteristics of third gen antipsychotics?
-D2 partial agonist + serotonin effects
-longer t1/2 lives
What is the use of third gen antipsychotic, Aripiprazole?
adjunctive treatment for schizophrenia, BPD, and MMD
What drugs are adjunctive treatment for schizophrenia, BPD, and MDD?
aripiprazole, bexipiprazole, and cariprazine
