Dermatologic Pharmacology Flashcards

A 58-year-old male with extensive plaque psoriasis is being managed with weekly low-dose methotrexate. To mitigate the risk of hepatotoxicity, which of the following is the most crucial long-term monitoring strategy according to consensus guidelines?

Answer: Monthly assessment of serum aminotransferases and periodic procollagen III aminopeptide (PІІІNP) levels

Consensus guidelines for monitoring methotrexate-induced hepatotoxicity in psoriasis focus on regular laboratory surveillance. This includes frequent monitoring of liver transaminases (e.g., ALT) and, in many guidelines, periodic assessment of PIIINP, a marker of fibrogenesis. Liver biopsy is reserved for patients with persistently elevated liver enzymes or PIIINP levels, or those with multiple risk factors for liver disease. Abdominal ultrasound is not a primary screening tool for fibrosis. While a weekly CBC is essential for monitoring for myelosuppression, it does not assess for hepatotoxicity.

A 45-year-old patient with onychomycosis is prescribed a course of oral itraconazole. The patient also takes atorvastatin for hyperlipidemia. This drug combination significantly increases the risk for which of the following adverse events?

Answer: Rhabdomyolysis

Itraconazole is a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system. Atorvastatin, lovastatin, and simvastatin are metabolized by CYP3A4. Co-administration of itraconazole leads to significantly elevated plasma concentrations of the statin, which dramatically increases the risk of myopathy and rhabdomyolysis. The other options are not characteristic interactions for this specific drug pair.

A 66-year-old male with dermatitis herpetiformis is started on dapsone. Before initiating therapy, which laboratory test is mandatory to prevent a severe, dose-related adverse reaction?

Answer: Glucose-6-phosphate dehydrogenase (G6PD) level

Dapsone can induce oxidative stress on red blood cells, leading to hemolysis. Patients with a G6PD deficiency have a reduced ability to protect their red blood cells from this oxidative damage, placing them at high risk for severe, dose-dependent hemolytic anemia upon starting dapsone. Therefore, screening for G6PD deficiency is required before initiating therapy.

Tazarotene is a third-generation topical retinoid used for acne and psoriasis. Its therapeutic effect is primarily mediated through selective binding to which of the following receptors?

Answer: Retinoic acid receptors (RAR-β and RAR-γ)

Tazarotene is a prodrug that is converted to its active form, tazarotenic acid. Tazarotenic acid exerts its effects by selectively binding to retinoic acid receptors (RARs), with a particular affinity for RAR-β and RAR-γ. It has little to no affinity for retinoid X receptors (RXRs). This receptor selectivity is thought to contribute to its specific clinical effects and side-effect profile.

A dermatologist prescribes topical 5-fluorouracil (5-FU) cream for a patient with multiple actinic keratoses on the face. What is the primary mechanism of action of this agent?

Answer: It functions as a pyrimidine analog that inhibits thymidylate synthase, disrupting DNA synthesis.

5-fluorouracil is a pyrimidine analog that, once converted to its active metabolite fluorodeoxyuridine monophosphate (FdUMP), forms a stable complex with the enzyme thymidylate synthase. This action blocks the synthesis of thymidine, a necessary component of DNA, leading to cell death in rapidly proliferating cells such as those in actinic keratoses.

The FDA has issued a boxed warning for topical calcineurin inhibitors, such as tacrolimus and pimecrolimus. What is the primary concern cited in this warning?

Answer: A theoretical risk of malignancy, including skin cancer and lymphoma, although a causal link has not been established.

The boxed warning for topical calcineurin inhibitors (TCIs) states that although a causal relationship has not been definitively established, rare cases of malignancy (e.g., skin cancer and lymphoma) have been reported in patients treated with TCIs. This warning was based largely on data from systemic use in transplant patients and animal studies, and its application to topical use remains controversial.