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Zorluk: OrtaPsychopharmacology and Psychological Therapies

A 62-year-old man is evaluated in the hospital due to rapidly worsening mental status. He was admitted three days ago for complicated cellulitis of the right lower extremity and was started on intravenous linezolid. His past medical history is significant for major depressive disorder, for which he has taken fluoxetine for several years. Today, he developed sudden-onset severe agitation, restlessness, and confusion. His temperature is 39.2°C (102.6°F), blood pressure is 165/100 mmHg, pulse is 124/min, and respirations are 22/min. Physical examination demonstrates excessive diaphoresis and shivering. Neurological examination reveals prominent hyperreflexia and inducible ankle clonus bilaterally in the lower extremities. Initial management with intravenous normal saline, cooling blankets, and intravenous lorazepam does not sufficiently control his severe symptoms. Which of the following is the most appropriate next step in pharmacologic management?

  1. Administer cyproheptadineCevap
  2. B
    Administer dantrolene
  3. C
    Administer bromocriptine
  4. D
    Administer benztropine
  5. E
    Administer physostigmine

Cevap

The most appropriate next step is to administer cyproheptadine.
This patient is experiencing serotonin syndrome, a potentially life-threatening condition caused by excessive serotonergic neurotransmission. It is classically precipitated by the combination of a selective serotonin reuptake inhibitor (SSRI), such as fluoxetine, and a monoamine oxidase inhibitor (MAOI). Linezolid is an antibiotic that also possesses reversible nonselective MAOI activity, making it a dangerous precipitant when combined with other serotonergic agents. The clinical triad includes altered mental status, autonomic hyperactivity (fever, tachycardia, diaphoresis), and neuromuscular abnormalities (hyperreflexia, clonus). Initial management consists of discontinuing the offending agents, providing supportive care (IV fluids, cooling), and administering benzodiazepines (e.g., lorazepam) for agitation and tremor. When supportive measures and benzodiazepines fail to control severe symptoms, cyproheptadine—a 5-HT1A and 5-HT2A receptor antagonist—is the appropriate pharmacological treatment.

Adım Adım Çözüm

1
Analyze the patient's medication list for dangerous interactions.
The patient is taking fluoxetine (a selective serotonin reuptake inhibitor) and linezolid (an antibiotic with reversible, nonselective monoamine oxidase inhibitor activity).
Identifying concurrent medications is necessary to determine the underlying pathophysiology of the acute clinical deterioration.
2
Correlate the physical examination findings with the medication interaction.
The triad of altered mental status, autonomic hyperactivity (fever, tachycardia, diaphoresis), and neuromuscular abnormalities (hyperreflexia, clonus) points strictly to Serotonin Syndrome.
Differentiating serotonin syndrome from other toxidromes (like NMS or anticholinergic toxicity) dictates the correct antidote.
3
Determine the appropriate sequential management based on symptom severity.
Because the patient's symptoms are severe and refractory to initial supportive measures and benzodiazepines (lorazepam), administration of cyproheptadine is indicated.
Cyproheptadine is a specific 5-HT2A receptor antagonist that directly counteracts the excessive serotonergic tone causing the syndrome.

Anahtar Kavram

Serotonin syndrome is a potentially life-threatening condition caused by excess serotonergic activity, often triggered by combining SSRIs with MAOIs (including linezolid). It is managed initially with supportive care and benzodiazepines, followed by cyproheptadine for refractory or severe cases.
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Psychopharmacology and Psychological Therapies

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