Belovich- Antipsychotics/ Atypicals Flashcards
FGAs/SGAs have improved efficacy against positive symptoms
SGAs
Atypicals/ typicals have a reduced risk for EPS, due to less potency for D2 receptors
typicals
Atypical antipsychotics are associated with a syndrome that may increase the risk of coronary artery disease, stroke, and hypertension
metabolic
Clinical effects of atypicals is due to which 2 MOAs?
D2R antagonism and inverse agonism of 5-HT2A
Agonism of 5-HT2A and 5-HT2C receptors is basis for activity of these lsd and mescaline
hallucinatory
Hallucinatory properties of LSD and mescaline led to investigation ofas a basis for schizophrenic symptoms
serotonin
Agonism of 5-HT2A receptors leads to depolarization of neurons, which stabilizes NMDA receptors
• Increased activity may increase psychotic symptoms
glutamatergic
Agonism of 5-HT2C receptors (increased seratonin signaling) inhibits cortical and limbic release
dopaminergic
What type of agonist:
- elicits maximum biological response
full agonist
What type of agonist:
prevents agonist from binding, but does not effect basal activity
antagonist
What type of agonist?
elicits partial maximum response
always antagonist to full agonist
partial agonist
What type of agonist?
prevents agonist from binding, and stabilizes inactive form
desreased in baseline activity
freezes receptor
can be synonymous with antagonist
inverse agonist
Atypical antipsychotic agents have less effect on , but more effect on receptors than typical antipsychotic agents
D2Rs
5-HT2A
Agonism of 5-HT2A receptors leads to depolarization of neurons, stabilizes NMDA receptors
• Inverse agonism increases/reduces activity of these neurons
glutamatergic
reduces
Agonism of 5-HT2C receptors cortical and limbic dopaminergic release
• Inverse agonism of and 5-HT2C receptors may therefore lead to increased/decreased DA in mesocortical structures, but D2 antagonistic properties balance this
increased
ADRs of Antipsychotic agents share close relationship with D2R
affinity
Atypical antipsychotics have lower D2R potency which results in fewer/more on-target ADRs, fewer/more off-target ADRs
fewer on-target
more off-target
Most of the drugs in which group of antipsychotics often produce substantial weight gain?
atypicals
Atypicals have an Increased risk of development of diabetes mellitus, which 2 in particular?
olanzapine
clozapine
Though it is recommended to monitor patients taking atypicals due to ADRs, whcih one in particular is it required to monitor?
Personal and family history of obesity, diabetes, dyslipidemia, hypertension, and cardiovascular disease • Weight and height (so that body mass index can be calculated) • Waist circumference (at the level of the umbilicus) • Blood pressure • Fasting plasma glucose level • Fasting lipid profile
clozapine
While taking atypicals, Regular monitoring of patients with preexisting diabetes should include and sometimes insulin
hemoglobin A1C (HgA1C)
What group of antipsychotics is the first line for treatment of schizophrenia?
atypicals (except clozapine due to risk of agranulocytosis or bowel obstruction)
Why is clozapine the only atypical not suggested for first line treatment?
risk of agranulocytosis (decreased neutrophils) and bowel impaction
What is the concern with elderly patients with dementia-related psychoses and taking atypcials?
increased risk of stroke
Which type of drugs can treat all of the following conditions?
- Schizophrenia (first line, except clozapine)
- Acute mania
- Adjunctive therapy in treatment-resistant depression
- Adjunctive therapy in major depressive disorder
- Post-traumatic stress disorder
- Anxiety disorders
- Behavioral disturbances associated with dementia
Also effective for treating psychotic depression and for psychosis secondary to head trauma, dementia, or treatment drugs
atypicals
Other than primary psychosis, atypicals can be used to treat psychotic depression and for psychosis secondary to head trauma, , or treatment drugs
dementia
Which atypical is reserved for individuals who are refractory to all other antipsychotic agents
• Not a first-line agent because of hematological side effects (hematological)?
clozapine
What atypical can be used as a treatment with persons with severe tardive dyskinesia?
clozapine
Which atypical is a good treatment of persons with a low threshold for EPS?
clozapine
Which atypical is Highly effective in treating mania and depression though carries a strong risk of hematological side effects?
clozapine
What is the MOA of clozapine?
Atypical, inverse agonist of 5-HT2a and low affinity D2 receptor antagonist
What is the most stereotypical ADR for atypicals?
sedation
What are some common minor ADRs of clozapine and what are some more severe ADRs that affect cardiovascular and hematological systems?
minor- sedation, weight gain, constipation
major cardiovascular- myocarditis, cardiomyopathy
major hematological- leukopenia, granulocytopenia, agranulocytosis
Clozapine should be discontinued if the WBC count is below cells/mm3 or the granulocyte count is below 1,500 cells/mm3
3,000
Why must the patient’s baseline of WBCs be monitored while taking clozapine?
Due to possiblility of decrease neutrophile numbers
- white blood cell (WBC) count below 3,500 cells/mm3
- previous bone marrow disorder
- history of agranulocytosis during clozapine treatment
are contraindications for which atypical?
clozapine
- Schizophrenia
- Bipolar Disorder
- Autism Spectrum Disorder
- Adjunctive treatment in major depressive disorder
are all indications for the atypical drug?
aripiprazole
What is the MOA of aripiprazole?
Aripiprazole is a partial agonist of D2 and 5-HT1A
and an antagonist or inverse agonist of 5-HT2a
Which atypical is more friendly for on and off target ADRs?
aripiprazole
Which atypical treats the following indications?
- Schizophrenia
- Acute treatment of manic or mixed episodes with bipolar I
- Maintenance treatment of bipolar I
- Treatment-resistant depression with fluoxetine
olanzapine
What is the MOA of olanzapine?
antagonist of 5-HT2a, D2, muscarinic, and H1 receptors
Other than typical side effets of atypicals, which atypical as ADRs for :
Somnolence, dry mouth, dizziness, constipation, dyspepsia, increased appetite
- Dose-related risk of EPS (akathesia, tremor)
- Transaminase elevation
olanzapine
What is a major black box warning for olanzapine?
Cardiorespiratory arrest and sudden death
Which atypical is used for the following indications?
- Schizophrenia
- Acute treatment of manic episodes with bipolar I
- Bipolar depression
- Off-label uses for sleep, anxiety, delirium at low doses
quetiapine
What is the MOA of quetiapine?
weak antagonist of D2 and 5HT2
Which atypical is the Least likely to cause EPS (with the exception of primavanserin), regardless of dose?
Quetiapine
What is the medication most Preferred in Patients with Parkinson disease who develop dopamine agonist–induced psychosis?
Quetiapine due to being the least likely to cause EPS
Though quetiapine is the least likely to cause EPS (with exception of primavanserin) , there are DDI’s with drugs that increase what cardiovascular effect?
DDI’s with drugs that increase QTc interval
Which antipsychotic is best for the follwing indications:
- Acute and maintenance treatment of schizophrenia in adults and adolescents age 13 - 17 years
- Acute manic episodes in bipolar I disorder (ages 10+)
- Irritability associated with ASD in ages 5 - 16 years
risperiodone
What is the MOA of risperidone?
Antagonist of 5-HT2A, D2, 𝛼-adrenergic (low affinity), and H1 receptors
What are the 2 drugs of choice for first-break psychosis in a young person?
risperidone and aripiprazole
Which atypical elevates prolactin secretion?
risperidone
Rate of relapse (psychosis) may be lower with atypical/typical antipsychotic agents
atypical
Two or more psychotic episodes secondary to schizophrenia usually require years treatment
5
How are most antipsychotics metabolized?
First-pass metabolism
Few/Most antipsychotic drugs are highly lipid soluble and protein bound (92–99%)
Most
At clinical doses, antipsychotic drugs do/do not usually interfere with the metabolism of other drugs
do not
More Pharmacodynamic/Pharmakokinetic DDI’s are more commonly observed
Pharmacodynamic DDI’s
• The low end of the dosage range in should be tried for at least weeks
several
What are the 4 concerning types of drugs that should be avoided due to pharmacodynamics additive effects?
Sedatives
- α-adrenoceptor blockers (hypotension)
- anticholinergic drugs
- quinidine-like action (thioridazine and ziprasidone, an atypical) due to hypotension
Overdose antipsychotic agents are rarely fatal, with the exception of
thioridazine
What do the following symptoms indicate in someone taking antipsychotics?
coma, convulsion, miotic pupils, deep tendon reflexes decreased
hypotension, hypothermia, ventricular tachyarrrhthmias (thioridazine)
Management of overdoses of thioridazine is complicated by cardiac arrhythmias, is similar to that for antidepressants
tricyclic
