Flashcards in Lecture 79: Antipsychotics Deck (38):
Typical antipsychotics are pure..
Atypical antipsychotics are both...
Dopamine antagonists and 5HT2A antagonists
Antipsychotics are also called
All DA receptors are...
Neuroleptics act on...which is coupled to? This causes
D2; Gi; less DA neurotransmission
Low potency antipyschotic
Mid potency antipyschotic
High potency antipyschotics (2)
Anitpsychotic "potency" is based on...Why is this important?
D2 Blockade; higher potent = less dirty
Describe "dirty" SEs of antipsychotics via receptors
ACh, H1, alpha1 blockade
Therapeutic use of antipsychotics (5)
Primary and secondary psychotic disorder, mood disorders (bipolar and MDD w/ psychotic features), severe agitation, delirium, Tourette's
What drugs are available once-a-month dosing?
DA-related effects of antipsychotics and pathway
1. Parkinsonian-like (nigrostriatal); 2. Relief of psychosis (mesolimbic); 3. Increased negative symptoms (mesocortical); 4. Elevated prolactin --> breast enlargement/lactation (tuberoinfundibular pathway)
Neurological adverse effects (3). Which drugs convey highest risk?
1. Extrapyramindal symptoms (EPS; Parkinsonism, acute dystonia, akathisia); 2. Tardive dyskineasia; 3. Neuroleptic malignant syndrome; high potency drugs
How many patients get neuroleptic-induced Parkisonism (%)? When do they occur? What is treatment? Why?
15%; within several months; anticholinergics --> typically balance b/t DA and ACh, if you block DA, you should block ACh to re-achieve balance
Describe acute dystonic reaction: symptoms, when it occurs, treatment
Spastic contractions in face and body; occurs quickly (within days); anticholinergic
Describe akathisia: symptoms
Subjective feeling of inner restlessness w/ objective increased motor activity
Describe tardive dyskinesia: symptoms, onset (%), treatment
Writhing movements of mostly face; 5%/year (long-term use); not reversible --> stopping/switching antipsychotic
Describe neuroleptic malignant syndrome: symptoms, onset time, mortality (%)
Autonomic symptoms (fever, sweating), motor & behavior symptoms (rigidity, dystonia, agitation, confusion); can occur ANY TIME; 20-30% if untreated
Other antipsychotic SEs by 3 receptors and 1 other important SE
M1, H1, alpha1 receptor blockade; cardiac (QT prolongation)
Clozapine, risperidone, olazapine, ziprasidone, quetiapine, aripiprazole
What makes an antipsychotic atypical (2)
1. D2 AND 5HT2A antagonists; 2. Rapid dissociation from D2 receptor
Why does 5HT2A antagonism work? How does it work in real patients?
Turns off GABA interneuron --> more DA release (tempering DA blockade); complicated net actions on DA activity, varies per patient
Theoretical benefits of atypicals and which are true/not true (4)
Reduced EPS (true), reduced hyperprolactinemia (true), cognitive enhancement (not true), improved adherence (not true)
How to choose an antipsychotic? Example.
Look at receptor binding profile (i.e. olazapine blocks H1 more than risperidone, so it is more sedating, good for agitated people)
Therapeutic use of antipsychotics (3)
1. Psychotic disorders; 2. Mood disorders w/ psychotic features; 3. Treatment resistant MDD; 4. Aggression/irritability in children with autism (Risperidone)
T/F: Atypicals are associated with off-label uses
How is Aripiprazole different?
"Third generation" --> partial agonist at DA D2 receptor and 5-HT1A; antagonist at 5-HT2A
What is the most effective AND drug of choice for treatment resistant schizophrenia? What's interesting about this drug and why is it not always first line?
Clozapine; low potency as D2-receptor antagonist; potentially irreversible risk of agranulocytosis
Risperidone has similar SEs to...why?
Typicals because it is a strong blocker of D2
Adverse effect of atypical antipsychotics
Metabolic syndrome: visceral obesity, low insulin resistance, high triglycerides, hypertension low HDL-cholesterol
Mortality with atypical antipsychotics
2-3x increased mortality from all causes
What are the "worst" atypicals for metabolic syndrome. Best?
Clozapine and olanzapine; aripiprazole
Other adverse effects of antipsychotics
Cardiac, sedation, EPS (risperidone), seizures...
Rare serious SEs of clozapine
Agranulocytosis and myocarditis
What is a common off label use of antipsychotics? Good data? Why is this concerning?
Treat behavioral disturbances in ELDERLY; NO; can cause over sedation/falls (orthostatic hypotension), increases ALL CAUSES of mortality
The only two antispychotics shown to increase cognition/social life. But these are...Why?
Clozapine and olanzapine; 2nd line; more likely to induce metabolic syndrome (and scary SEs)