3. Anti-Psychotic Drugs Flashcards
Clozapine is used for recurrent suicidal behavior and what is used for hallucinations/delusions associated with parkinson disease psychosis?*** mentioned this 5 times
Pimavanserin
All of the following are what?
hallucinations, delusions, disorganized speech/thinking, agitiation, abnormal motor behavior
Positive Symptoms usually due to too much Dopamine
All of the following are what?
apathy, avolition, alogia, cognitive deficits (working memory), social withdrawal
Negative Symptoms
Mesolimbic pathway causes the positive symptoms, the mesocortical pathway causes the negative symptoms, the nigrostriatal pathway causes EPS (extrapyramidal symptoms - pseudoparkinsonism), and the tuberoinfundibular pathway causes what symptom?
Hyperprolactinemia
All of the following are what kind of antipsychotics? Chlorpromazine Fluphenazine Perphenazine Thioridazine Trifluoperazine Haloperidol Loxapine Pimozide Thiothixene
First generation agents aka conventional aka typical
All of the following are what kind of antipsychotics? Iloperidone Lurasidone Paliperidone Riseperidone Ziprasidone Aripiprazole Brexpiprazole cariprazine Asenapine Clozapine Olanzapine Quetiapine Pimavanserin
Second Generation Agents aka novel aka atypical
What is the primary difference between the first and second generation antipsychotics?
Reduced movement disorder side effects seen w SGA
The FGAs primarily block dopamine type 2 (D2) post-synaptic receptors, more so than serotonin receptors (5HT), they also block other receptors which cause the side effects, including, muscarininc, histaminic (H1), D2 receptors in nigrostriatal (EPS) and tuberoinfundibular (prolactin) pathways, as well as what other receptor?
Alpha adrenergic pathways (a1)
*Note: M/H1/A1 receptors blocked just like TCAs
When muscarinic receptors are blocked by FGAs, one may see dry mouth, constipation, urinary retention, blurred vision and sedation, when A1 is blocked you may see orthostatic hypotension, dizziness and syncope, and when histamine is blocked what can be seen?
Sedation
also can see QTc prolongation and seizures
Dopamine associated side effects include hyperprolactinemia seen as amenorrhea, galactorrhea, gynecomastia, decreased libido, extrapyramidal symptoms EPS and what are also caused by FGAs?
tardive dyskinesia (TD) (chronic/permanent)
When there is a higher amount of FGAs blocking the D2 dopamine receptor, there is a higher risk of EPS side effects, what is the amount of D2 receptor occupancy by FGAs that causes EPS?
75% or 3/4 of all D2 receptors blocked will cause this
The FGAs are divided into two categories based on potency. The low potency agents cause more sedation, hypotension and seizure threshold reduction, the two FGAs in this category include thioridazine and?
Chlorpromazine
There are high potency FGAs that cause more movement (EPS) and endocrine effects (hyper prolactin), these two agents are known as fluphenazine and?
Haloperidol
There are important antidotes for dopamine associated side effects- treatments for EPS include anticholinergic agents such as benztropine and trihexyphenidyl, and antihistamine agents such as?
Diphenhydramine
Treatments for tardive dyskinesia (TD) include 2 drugs that are selective vesicular monoamine transporter 2 (VMAT2) inhibitors, which include deutetrabenazine and?
Valbenazine
Second Generation antipsychotics (SGAs) not only block dopamine type 2 (D2) post synaptic receptors but they also block?
5HT2A more strongly!
FGAs block D2>5HT, and SGAs are opposite
SGAs are the first line treatment, the reason why SGAs work is because the stronger block to 5HT2A increases DA in the mesocortical pathway which may contribute to the improved negative and cognitive symptoms as well as reduced?
EPS side effects
Some SGAs also block other D(1,3-5) receptors and have greater propensity to be an agonist/antagonist on one or more other 5HT receptors, the SGAs can be divided into?
4 categories based on MOA
What category do the following SGAs fit into? Iloperidone Lurasidone (also partial 5HT1A agonist) Paliperidone (metab of risperidone) Risperidone Ziprasidone
5HT2A/DA Receptor Antagonists
What category do the following SGAs fit into?
Aripiprazole
Brexpiprazole
Partial DA/5HT1A Receptor Agonists (in addition to DA/5HT antagonists)
What category do the following SGAs fit into? Asenapine Clozapine Olanzapine Quetiapine
Multi-Acting Receptor Target Agents
What category do the following SGAs fit into?
Pimavanserin
Inverse Serotonin Agonist/Antagonist (parkinson’s psychosis treatment)
What category do the following SGAs fit into?
Cariprazine
BOTH 5HT2A/DA receptor antagonists AND Partial DA/5HT1A receptor agonists
A shift in side effects can be seen from FGAs to SGAs, in first generation there was more neurologic SE including EPS and TD, now the concern is more metabolic side effects, including: DM, CVD, Hyperglyc, Insulin resistance, Dyslipidemia and?
Weight gain *
Other side effects associated with SGAs include QTc prolongation/ECG changes, negative inotropic actions (risk greater for women, elderly and pt on antiarrhythmics), and STROKE which is great risk in elderly with?
Dementia (class warning)
When administering clozapine, you must monitor WBCs and need to be registered to REMS program to administer due to the rare SE of agranulocytosis. What drug is assoc with drug reaction w eosinophilia and systemic symptoms (DRESS) seen as skin eruption, eosinophilia, atypical lymphocytosis, lymphadenopathy, and internal organ involvement?
Olanzapine
What is a rare but potentially fatal side effect from antipsychotic medications, seen as severe parkinsons like movement disorder with wide spread muscle contraction, alerted mental status, hyperthermia and dehydration?
Neuroleptic Malignant Syndrome NMS
Neuroleptic Malignant Syndrome NMS which is a SE of antipsychotics can be treated with what (ANTIDOTE), used in malignant hyperthermia, causes ryanodine receptor to be occupied and CLOSED allowing peripheral muscle to relax?
Dantrolene
There are many baseline parameters needed to be assessed before starting SGAs, including: lipids, weight (BMI), blood pressure, waist circumference, personal/fam history of metabolic and CV diseases and?
Serum Glucose (since SE of SGAs are majorly metabolic)
after dose escalation or switching agents, combination therapy may be necessary… What SGA is commonly used for drug resistant disease, and psychotic with anti-suicidal thoughts/behaviors?
Clozapine- very effective drug, but many SE
Adherence to mediaction is critical during psychotic disorder treatment, non-adherence can be managed with Long-Acting* Injectable Agents* (LAIA’s)- every 2-12weeks depedning on the agent, dose and patient factors, drugs are remembered by the ROAP…
Risperidone
Olanzapine
A
Paliperidone palmitate (dont need to know)
Aripiprazole Lauroxil
The drugs worst and best for weight gain and DM
Best: fluphenazine, haloperidol/cariprazine, aripiprazole, ziprasidone
Worst: Olanzapine and?
Clozapine
The drugs worst and best for Hypercholesterolemia
Best: aripiprazole*, cariprazine, ziprasidone
Worst: Olanzapine and?
Clozapine
The drugs worst and best for EPS / TD
Worst: Haloperidol, Risperidone, Fluphenazine
Best: Clozapine and?
Quetiapine
The drugs worst and best for prolactin elevation
Worst: Haloperdol, Fluphenazine, Thioridazine, Risperidone (SGA)
Best: ?
Aripiprazole
The drugs worst and best for Sedation (SE)
Best: Fluphenazine, Aripiprazole, Cariprazine, Risperidone, Ziprasidone
Worst: Chlorpromazine, Thioridazine, and?
Clozapine
The drugs worst and best for Orthostatic Hypotension
Worst: Thioridazine (also worst for anticholinergic SE)
Best: Aripiprazole, Fluphenazine and?
Haloperidol
The drugs worst and best for QTc prolongation
Worst: Ziprasidone, Chlorpromazine, IV Haloperidol
Best: Fluphenazine, Aripiprazole, Lurasidone and
Cariprazine
