Examkin

Soru

Zorluk: ZorPsychopharmacology and Psychological Therapies

A 29-year-old man is brought to the emergency department by his partner due to a rapidly spreading rash and fever. Over the past 48 hours, he developed flu-like symptoms followed by painful, erythematous macules on his chest and back. Physical examination reveals a temperature of 39.2°C (102.6°F). The macules have coalesced into large areas of blistering, and the epidermis sloughs off with gentle lateral pressure. Ulcerations are visible on his buccal mucosa and vermilion border. The patient has a 4-year history of bipolar I disorder and has been maintained on divalproex sodium. Three weeks ago, he sought treatment for a severe depressive episode, and his psychiatrist added a second medication to his regimen. The new medication was prescribed at a starting dose of 25 mg daily. Which of the following pharmacokinetic or pharmacodynamic mechanisms best explains the pathogenesis of this patient's current dermatologic emergency?

  1. Inhibition of hepatic glucuronidation by the maintenance mood stabilizerCevap
  2. B
    Induction of cytochrome P450 enzymes by the maintenance mood stabilizer
  3. C
    Autoinduction of hepatic metabolism by the newly added psychotropic agent
  4. D
    Synergistic blockade of voltage-gated sodium channels in the epidermis
  5. E
    Decreased renal clearance of the newly added agent due to volume depletion

Cevap

Inhibition of hepatic glucuronidation by the maintenance mood stabilizer
The correct answer is inhibition of hepatic glucuronidation by the maintenance mood stabilizer. The patient is presenting with Stevens-Johnson syndrome (SJS) or Toxic Epidermal Necrolysis (TEN), a life-threatening mucocutaneous reaction characterized by a blistering rash, mucosal ulcerations, and a positive Nikolsky sign. In the context of bipolar disorder, the most likely medication added for a depressive episode that causes SJS is lamotrigine. Lamotrigine is metabolized in the liver primarily by UDP-glucuronosyltransferase (UGT). The patient's maintenance medication, divalproex sodium (valproic acid), is a potent inhibitor of UGT. When lamotrigine is added to a valproate regimen without appropriate dose adjustments, its clearance is halved, leading to a rapid and dangerous increase in plasma lamotrigine levels. This significantly elevates the risk of SJS/TEN. Therefore, when initiating lamotrigine in a patient taking valproate, the starting dose must be reduced by 50% (typically 25 mg every other day) and titrated much more slowly.

Adım Adım Çözüm

1
Identify the acute clinical syndrome based on the physical examination findings.
The patient has fever, a blistering rash with a positive Nikolsky sign (epidermal sloughing), and mucosal ulcerations, which is highly characteristic of Stevens-Johnson syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).
Recognizing this dermatologic emergency is critical to identifying the offending pharmacological trigger.
2
Determine the most likely offending psychotropic medication added to the patient's regimen.
The patient was prescribed a medication for bipolar depression starting at 25 mg daily. Lamotrigine is a first-line treatment for bipolar depression and is known to carry a black box warning for SJS/TEN.
Connecting the psychiatric indication (bipolar depression) and the typical starting dose (25 mg) points directly to lamotrigine.
3
Analyze the pharmacokinetic interaction between the maintenance therapy and the newly added agent.
The patient was already on divalproex sodium (valproic acid). Valproic acid is a potent inhibitor of UDP-glucuronosyltransferase (UGT), the primary enzyme responsible for metabolizing lamotrigine.
Understanding drug metabolism is required to explain why standard dosing led to a toxic outcome in this specific patient.
4
Apply the interaction mechanism to the dosing error.
Because valproic acid inhibits UGT, it significantly decreases lamotrigine clearance. The standard starting dose of 25 mg daily is therefore too high in this context and leads to toxic lamotrigine levels, precipitating SJS/TEN. The dose should have been reduced by 50% (to 25 mg every other day).
This confirms that the inhibition of hepatic glucuronidation by the maintenance medication is the correct mechanism for the toxicity.

Anahtar Kavram

Valproic acid inhibits UDP-glucuronosyltransferase (UGT), which doubles the plasma concentration of concurrently administered lamotrigine. To mitigate the severe risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the starting dose of lamotrigine must be reduced by 50% when a patient is taking valproic acid.
Bu soruyu puanla

Konular

Psychopharmacology and Psychological Therapies

Bu konudan daha fazla soru