Antipsychotic Pharmacology Flashcards
Antipsychotics are separated into first generation and second generation. What is the major difference between the generations?
Reduction in movement disorder AEs from first to second gen
MOA of first generation antipsychotics (aka “conventional” or “typical”)
Primarily block dopamine type 2 (D2) postsynaptic receptors
[D2»_space; 5HT2]
Also block one or more other receptors with varying potencies — primarily inducing AEs
First gen antipsychotics may increase risk of _____ prolongation and ______ activity
QTc; seizure
Many AEs of first gen antipsychotics are based on their inhibition of various other receptors, including muscarinic, histamine, alpha-adrenergic (primarily alpha 1), and D2 receptors in nigrostriatal and tuberoinfundibular pathways.
What AEs are associated with first gen antipsychotic-induced inhibition at muscarinic receptors?
Dry mouth Constipation Urinary retention Blurry vision Sedation
Many AEs of first gen antipsychotics are based on their inhibition of various other receptors, including muscarinic, histamine, alpha-adrenergic (primarily alpha 1), and D2 receptors in nigrostriatal and tuberoinfundibular pathways.
What AEs are associated with first gen antipsychotic-induced inhibition at histamine receptors (primarily H1)?
Sedation
Many AEs of first gen antipsychotics are based on their inhibition of various other receptors, including muscarinic, histamine, alpha-adrenergic (primarily alpha 1), and D2 receptors in nigrostriatal and tuberoinfundibular pathways.
What AEs are associated with first gen antipsychotic-induced inhibition at alpha-adrenergic receptors?
Orthostatic hypotension
Dizziness/syncope
Many AEs of first gen antipsychotics are based on their inhibition of various other receptors, including muscarinic, histamine, alpha-adrenergic (primarily alpha 1), and D2 receptors in nigrostriatal and tuberoinfundibular pathways.
What AEs are associated with first gen antipsychotic-induced inhibition at D2 receptors in nigrostriatal pathway?
Extrapyramidal symptoms (EPS) — acute akathisia/dystonia/parkinsonism-like
Tardive dyskinesia
Many AEs of first gen antipsychotics are based on their inhibition of various other receptors, including muscarinic, histamine, alpha-adrenergic (primarily alpha 1), and D2 receptors in nigrostriatal and tuberoinfundibular pathways.
What AEs are associated with first gen antipsychotic-induced inhibition at D2 receptors in tuberoinfundibular pathway?
Hyperprolactinemia —> amenorrhea, galactorrhea, gynecomastia, decreased libido
Treatment options for EPS adverse effects of first gen antipsychotics (akasthesia, dystonia, parkinsonism-like syndrome)
Anticholinergic agents — benzotropine and trihexyphenidyl
Antihistamines — diphenhydramine
[these are both used for acute tx and maintenance]
Treatment for tardive dyskinesia induced by first gen antipsychotic’s activity at nigrostriatal pathway
Valbenazine
Deutetrabenazine
[Selective vesicular monoamine transporter 2 (VMAT2) inhibitors]
The first gen antipsychotics are separated into low potency and high potency agents. What is the difference between the two categorizations?
Low potency cause more sedation, hypotension, and reduction of seizure threshold
High potency cause more movement (EPS) and endocrine (prolactin) effects
List the 5 first gen antipsychotics based on their categorization as either low potency or high potency agents
Low potency agents:
- Chlorpromazine
- Thioridazine
High potency agents:
- Fluphenazine
- Haloperidol
- Thiothixene
Second generation antipsychotics are also referred to as “Novel” or “atypical” antipsychotics. What 6 drugs are in this category?
Aripiprazole Clozapine Olanzapine Quetiapine Risperidone Ziprasidone
What second generation antipsychotic is used in the treatment for recurrent suicidal behavior?
Clozapine
MOA of second generation antipsychotics
Block both D2 postsynaptic receptors and 5HT-2A
[5HT-2A»_space; D2]
Note: some block one or more other DA receptors (1, 3-5) and also have greater propensity to be an agonist/antagonist on one or more other 5HT receptors (other than 5HT2A blockade)
_______________________
[5HT2A antagonism in PFC theorized to increase DA transmission in mesocortical pathway — May contribut to improved negative and cognitive symptoms and reduced EP adverse effects]
Adverse effects of second gen antipsychotics
Weight gain
Metabolic effects — hyperglycemia/insulin resistance, hyperlipidemia
Other rare side effects: QTc prolongation, stroke, agranulocytosis, drug reaction w/eosinophilia and systemic symptoms (DRESS), neuroleptic malignant syndrome (NMS)
Second gen antipsychotics may cause QTc prolongation/ECG changes due to ______ ionotropic actions; there is greater risk of this in women, elderly, and those on _______
Negative; antiarrhythmics
The risk of stroke with second gen antipsychotics is greater in what pt population?
Elderly pts with dementia
T/F: all antipsychotics carry an increase in risk of all-cause mortality
True
Which second gen antipsychotic is most associated with AE of agranulocytosis, and thus requires WBC monitoring via REMs program
Clozapine
Clinical features of Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) that may occur with second generation antipsychotics
Very rare, potentially life-threatening drug-induced hypersensitivity reaction
Includes skin eruption, hematologic abnormalities (eosinophilia, atypical lymphocytosis), LAD, and internal organ involvement (liver, kidney, lung)
Long latency (2-8 wks) between drug exposure and onset; Prolonged course with frequent relapses despite discontinuing culprit drug
Frequent association with reactivation of latent HHV infection
Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) is most commonly associated with which second gen antipsychotic?
Olanzapine
Neuroleptic Malignant Syndrome (NMS) is an AE of second gen antipsychotics. What are the clinical features?
Rare potentially fatal severe parkinson-like movement disorder with widespread muscle contraction
Mesocortical effects (AMS), nigrostriatal effects (rigidity, rhabdomyolysis), hypothalamic effects (hyperthermia), autonomic dysfunction (dehydration)
Treatment for neuroleptic malignant syndrome (NMS) if it occurs as an AE of second gen antipsychotics
Dantrolene — inhibits Ca release at ryanodine receptor in SR —> peripheral mm. relaxation
