A 27-year-old man with schizophrenia comes to the emergency department due to an acute muscle spasm in his neck that developed several days after starting treatment with haloperidol. He is extremely distressed and unable to turn his head. The patient is treated with intravenous diphenhydramine, which relieves his symptoms within minutes. A psychiatrist is consulted, and recommendations are made to discontinue haloperidol and start the second-generation antipsychotic quetiapine because of its lower risk for similar dystonic side effects. In addition to dopamine D2 receptor antagonism, this new medication has which of the following pharmacological properties?

Question

A 27-year-old man with schizophrenia comes to the emergency department due to an acute muscle spasm in his neck that developed several days after starting treatment with haloperidol.  He is extremely distressed and unable to turn his head.  The patient is treated with intravenous diphenhydramine, which relieves his symptoms within minutes.  A psychiatrist is consulted, and recommendations are made to discontinue haloperidol and start the second-generation antipsychotic quetiapine because of its lower risk for similar dystonic side effects.  In addition to dopamine D2 receptor antagonism, this new medication has which of the following pharmacological properties?

Quizplus · Accepted Answer

11ec160b_3c4e_a195_9249_f3bf5f3fef0e_MD0001_00 This patient developed an acute dystonic reaction (a type of extrapyramidal symptom [EPS]) several days after exposure to the first-generation antipsychotic (FGA) haloperidol. FGAs have a high risk of causing EPS due to their potent dopamine D2 receptor antagonism. Management of an acute dystonic reaction includes treatment with diphenhydramine or benztropine and switching to an agent with a lower propensity for producing EPS, such as a second-generation antipsychotic (SGA). In addition to dopamine D2 receptor antagonism, SGAs (eg, olanzapine, quetiapine) also block serotonin receptors, specifically the 5-HT2A receptor. Compared with FGAs, SGAs block 5-HT2A receptors more potently than D2 receptors and have lower binding affinity at the dopamine receptor site, which is thought to explain the reduced risk of causing EPS. Although SGAs have a low risk of EPS, they are associated with a greater risk of metabolic adverse effects. (Choice A) Dopamine reuptake inhibition, usually in combination with norepinephrine reuptake inhibition, is the mechanism of action of many drugs used to treat ADHD (eg, methylphenidate, bupropion). (Choice B) Dopamine D2 partial agonism is one of the mechanisms of action of the SGAs aripiprazole and brexpiprazole. (Choice C) The monoamine oxidase enzyme normally breaks down monoamines (eg, dopamine, norepinephrine, serotonin). The class of antidepressants known as monoamine oxidase inhibitors (eg, phenelzine, tranylcypromine) block these enzymes, thereby increasing availability of the respective monoamines. (Choice E) Serotonin and norepinephrine reuptake inhibition is the mechanism of action of serotonin and norepinephrine reuptake inhibitors (eg, venlafaxine) and tricyclic antidepressants (eg, amitriptyline). Educational objective: Second-generation antipsychotics block 5-HT2A receptors and have lower binding affinity at dopamine D2 receptor sites, which is associated with a lower risk of extrapyramidal side effects. __________ References: Comparison of the anti-dopamine D2 and anti-serotonin 5-HT(2A) activities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof. (http://www.ncbi.nlm.nih.gov/pubmed/23427194) Second-generation antipsychotics and extrapyramidal adverse effects. (http://www.ncbi.nlm.nih.gov/pubmed/24995318) Safety, tolerability, and risks associated with first-and second-generation antipsychotics: a state-of-the-art clinical review. (http://www.ncbi.nlm.nih.gov/pubmed/28721057)

A 27-Year-Old Man with Schizophrenia Comes to the Emergency Department