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A 50-year-old woman presents with acute onset fever and chills for the past hour. She mentions earlier in the day she felt blue, so she took some St. John’s wort because she was told by a friend that it helps with depression. Past medical history is significant for hypertension, diabetes mellitus, and depression managed medically with captopril, metformin, and fluoxetine. She has no history of allergies. Her pulse is 130/min, the respiratory rate is 18/min, the blood pressure is 176/92 mm Hg, and the temperature is 38.5°C (101.3°F). On physical examination, the patient is profusely diaphoretic and extremely irritable when asked questions. Oriented x 3. The abdomen is soft and nontender with no hepatosplenomegaly. Increased bowel sounds are heard in the abdomen. Deep tendon reflexes are 3+ bilaterally and clonus is elicited. The sensation is decreased in the feet bilaterally. Mydriasis is present. Fingerstick glucose is 140 mg/dL. An ECG shows sinus tachycardia but is otherwise normal. Which of the following is the most likely cause of this patient’s condition?
Practice US Medical PG questions for Drug interactions with antifungals. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Drug interactions with antifungals Explanation: ***Serotonin syndrome*** - The patient's presentation with **fever, diaphoresis, hypertension, tachycardia, hyperreflexia, clonus, mydriasis**, and **agitation** after combining an **SSRI (fluoxetine)** with **St. John's wort** (a serotonin-enhancing herbal supplement) is highly characteristic of serotonin syndrome. - This condition results from excessive serotonergic activity in the central and peripheral nervous system. *Sepsis* - While **fever, chills, and tachycardia** can be indicators of sepsis, the presence of specific neurological and neuromuscular signs like **hyperreflexia, clonus, and mydriasis** points away from it. - The patient's **irritable state and normal mental orientation** is less typical for severe sepsis, which often involves altered mental status. *Anaphylactic reaction* - **Anaphylaxis** presents with rapid onset of symptoms such as **urticaria, angioedema, bronchospasm, and hypotension**, which are not observed in this patient. - There is no history of allergen exposure, and the prominent neurological symptoms are not typical of anaphylaxis. *Diabetic ketoacidosis* - **DKA** is characterized by **hyperglycemia, metabolic acidosis, and ketonemia**, often presenting with Kussmaul respirations and fruity breath odor. - The patient's **fingerstick glucose (140 mg/dL)** is not significantly elevated, and there is no mention of deep, rapid breathing or other DKA-specific symptoms. *Neuroleptic malignant syndrome* - **NMS** is typically associated with exposure to **dopamine antagonists (antipsychotics)** and is characterized by **severe muscle rigidity, hyperthermia, altered mental status, and autonomic instability.** - While some symptoms overlap, this patient's history of St. John's wort and fluoxetine points to increased serotonin, and the specific neuromuscular findings like clonus are more indicative of serotonin syndrome.
Drug interactions with antifungals Explanation: ***Fibrates can potentiate the risk of myositis when given with statins*** - **Fibrates** and **statins** can both independently cause muscle toxicity (myopathy, rhabdomyolysis). - When used concomitantly, especially **gemfibrozil** with statins, there is an **increased risk of muscle adverse events** due to pharmacokinetic interactions that raise statin levels. - This combination requires careful monitoring and is often avoided; **fenofibrate** is preferred over gemfibrozil when combination therapy is needed. *Fibrates inhibit the rate-limiting step in cholesterol synthesis* - This statement describes the mechanism of action of **statins**, which inhibit **HMG-CoA reductase**, the rate-limiting enzyme in cholesterol synthesis. - Fibrates, on the other hand, act primarily by activating **PPAR-alpha receptors**, leading to altered lipid metabolism (increased lipoprotein lipase activity, decreased VLDL synthesis). *Fibrates can cause significant skin flushing and pruritus* - **Niacin (nicotinic acid)** is the lipid-modifying agent most commonly associated with significant **skin flushing and pruritus**, mediated by prostaglandin release. - Fibrates do not cause significant flushing; their side effects include GI disturbances, gallstones, and potential muscle toxicity. *Fibrates can increase the risk of cataracts* - This is **not an established adverse effect** of the fibrate class. - While **clofibrate** (an older, largely discontinued fibrate) showed some association with cataracts in older studies, this is not a recognized risk with modern fibrates like **fenofibrate** and **gemfibrozil**. - Current fibrate therapy does not require routine ophthalmologic monitoring for cataracts. *The primary effect of fibrates is to lower LDL* - The primary effect of **fibrates** is to significantly **lower triglycerides** (by 30-50%) and **increase HDL cholesterol** levels (by 10-20%). - While they can cause a modest decrease in LDL cholesterol (10-15%), this is not their primary or most pronounced lipid-modifying effect. - Fibrates are primarily indicated for **hypertriglyceridemia** and mixed dyslipidemia.
Drug interactions with antifungals Explanation: ***Fluconazole*** - The patient's **odynophagia**, low **CD4+ count**, and high **HIV viral load** are highly suggestive of **esophageal candidiasis**. - **Fluconazole** is the initial empiric treatment of choice for suspected esophageal candidiasis in HIV-positive patients, given its high efficacy and good tolerability. *Nystatin* - **Nystatin** is typically used for **oral candidiasis (thrush)**, which presents with white plaques in the mouth. - The patient has a **clear oropharynx** and **odynophagia**, indicating esophageal involvement, for which nystatin is less effective. *Oral swab and microscopy* - While an **oral swab** can confirm oral candidiasis, it is not sufficient for diagnosing **esophageal candidiasis**. - Given the patient's symptoms of odynophagia and high clinical suspicion in an immunocompromised patient, empiric treatment is preferred over initial diagnostic testing for uncomplicated esophageal candidiasis. *Methylprednisolone* - **Methylprednisolone** is a corticosteroid used to reduce inflammation and is not indicated for the treatment of **candidal infections**. - Using corticosteroids in an immunocompromised patient with an active opportunistic infection could worsen his condition. *Esophageal endoscopy and biopsy* - **Esophageal endoscopy and biopsy** are typically reserved for patients who **fail empiric antifungal therapy** or present with **atypical symptoms** not consistent with candidiasis. - Given the clear clinical picture, initial empiric treatment with fluconazole is the standard first step.
Drug interactions with antifungals Explanation: **Topical miconazole** - The rash described, especially in a lifeguard who is frequently exposed to moisture, suggests **tinea corporis** (ringworm), a **dermatophyte fungal infection**. - **Topical imidazole antifungals** like miconazole are the first-line treatment for localized tinea infections. *Phototherapy* - **Phototherapy** (e.g., UVB or PUVA) is used for chronic widespread dermatoses like **psoriasis** or severe **atopic dermatitis**, not typically for localized fungal infections. - This rash is likely **infectious** and requires an antifungal agent for resolution. *Reassurance* - The rash is described as **progressively larger** and **pruritic**, indicating an active and symptomatic process that requires intervention, not just reassurance. - Delaying treatment could lead to further spread or secondary bacterial infection. *Topical erythromycin* - **Topical erythromycin** is an **antibiotic** used to treat bacterial skin infections, such as **acne vulgaris** or impetigo. - It would be ineffective against a fungal infection like tinea corporis. *Topical hydrocortisone* - **Topical hydrocortisone** is a **corticosteroid** that reduces inflammation and itching. - While it might temporarily alleviate symptoms, it can actually worsen fungal infections by suppressing the local immune response, leading to **tinea incognito**.
Drug interactions with antifungals Explanation: ***Amphotericin B*** - **Amphotericin B** is known for its significant side effects, including **nephrotoxicity** (leading to elevated BUN and creatinine, and potentially anemia due to reduced erythropoietin production) and **infusion-related reactions** like headache and hypotension. - It works by binding to **ergosterol** in fungal cell membranes, forming pores that lead to cell death, but it can also bind to cholesterol in mammalian cell membranes contributing to its toxicity. *Griseofulvin* - **Griseofulvin** primarily acts by binding to **keratin** and interfering with fungal **mitosis**; it does not bind to ergosterol. - Its main side effects include **GI upset**, headache, and photosensitivity, but not prominent nephrotoxicity or hypotension in the manner described. *Flucytosine* - **Flucytosine** is an antimetabolite that is converted to **5-fluorouracil** within fungal cells, interfering with RNA and DNA synthesis. It does not bind to ergosterol. - Its major adverse effects include **bone marrow suppression** (leukopenia, thrombocytopenia) and liver enzyme elevation, not the constellation of symptoms (hypotension, renal failure) described. *Fluconazole* - **Fluconazole** is an azole antifungal that inhibits **ergosterol synthesis** by blocking fungal cytochrome P450 enzymes. It does not directly bind to ergosterol. - While it can cause some GI upset and liver enzyme elevation, it is generally well-tolerated and less associated with acute nephrotoxicity or hypotension compared to Amphotericin B. *Terbinafine* - **Terbinafine** inhibits **squalene epoxidase**, an enzyme involved in ergosterol synthesis, rather than binding directly to ergosterol itself. - Its main side effects include **GI disturbances**, headache, and liver enzyme abnormalities, but typically not the severe nephrotoxicity and hypotension associated with Amphotericin B.
Drug interactions with antifungals Explanation: ***Decreased glucan synthesis*** - **Anidulafungin** is an **echinocandin** antifungal drug that inhibits the synthesis of **β-(1,3)-D-glucan**, a crucial component of the fungal cell wall. - By disrupting the fungal cell wall, **anidulafungin** causes **osmotic instability** and ultimately leads to cell lysis and death, making it effective against *Candida* infections. *Binding to tubulin* - This is the mechanism of action of **griseofulvin**, an antifungal agent primarily used for dermatophyte infections. - **Griseofulvin** interferes with **microtubule formation**, thus inhibiting fungal mitosis. *Inhibition of squalene epoxidase* - This is the mechanism of action of **terbinafine**, an antifungal drug commonly used for dermatophyte infections like onychomycosis. - **Terbinafine** blocks the synthesis of **ergosterol**, an essential component of the fungal cell membrane, by inhibiting **squalene epoxidase**. *Decreased DNA synthesis* - This mechanism is associated with **flucytosine**, an antifungal agent that is converted to 5-fluorouracil inside fungal cells. - **Flucytosine** then inhibits fungal **DNA and RNA synthesis** and is often used in combination with amphotericin B for severe systemic candidiasis or cryptococcosis. *Binding to ergosterol* - This is the mechanism of action of **polyene antifungals** like **amphotericin B** and **nystatin**. - These drugs bind to **ergosterol** in the fungal cell membrane, forming pores that lead to leakage of intracellular contents and cell death.
Drug interactions with antifungals Explanation: ***Oropharyngeal candidiasis*** - **Inhaled corticosteroids** like beclomethasone can suppress the local immune response in the oral cavity and pharynx, leading to opportunistic fungal infections. - This condition, commonly known as **thrush**, presents as white patches on the tongue and oral mucosa, which can be mitigated by rinsing the mouth after inhaler use. *Hypoglycemia* - **Inhaled corticosteroids** typically have minimal systemic absorption at low doses and are not associated with hypoglycemia. - **Hypoglycemia** is more commonly associated with diabetes treatment or conditions affecting glucose regulation. *Easy bruisability* - While **systemic corticosteroids** can cause skin thinning and easy bruising with long-term use, **inhaled corticosteroids** at low doses have very limited systemic effects. - The risk of easy bruisability is extremely low with the prescribed treatment in this patient. *Bradycardia* - **Beta-agonists** (like albuterol) can cause tachycardia, but inhaled corticosteroids themselves do not significantly affect heart rate. - **Bradycardia** is not a characteristic adverse effect of beclomethasone; it is typically associated with certain cardiac conditions or medications like beta-blockers. *High-pitched voice* - **Inhaled corticosteroids** can sometimes lead to hoarseness or dysphonia due to local irritation or candidiasis of the vocal cords, but not specifically to a high-pitched voice. - A high-pitched voice is not a recognized adverse effect; rather, a change in voice quality such as hoarseness is more typical.
Drug interactions with antifungals Explanation: ***Oral griseofulvin*** - This patient presents with symptoms highly suggestive of **tinea capitis (ringworm of the scalp)**, which is characterized by an **itchy rash**, **hair loss**, and **occipital lymphadenopathy**. Oral antifungal treatment, such as **griseofulvin**, is the **most appropriate initial management** for tinea capitis because topical agents alone are generally ineffective due to the infection's deep follicular location. - **Griseofulvin** acts by inhibiting fungal cell division and is deposited in keratin precursor cells, making the newly grown hair resistant to fungal invasion. It is highly effective against dermatophytes causing tinea capitis. *Topical mupirocin* - **Mupirocin** is an **antibiotic** used to treat **bacterial skin infections**, such as impetigo. - It would not be effective against **tinea capitis**, which is a fungal infection, and thus is an inappropriate treatment. *Topical permethrin* - **Permethrin** is a **topical insecticide** primarily used to treat **pediculosis (lice infestations)** and scabies. - While the patient's sibling had pediculosis, the patient's symptoms (itchy rash, hair loss, lymphadenopathy) are more consistent with **tinea capitis**, a fungal infection, making permethrin ineffective. *Calcipotriene* - **Calcipotriene** is a **vitamin D analog** used topically to treat **psoriasis** by slowing down the excessive growth of skin cells. - It has no antifungal properties and would not be effective in treating **tinea capitis**. *Shampoo containing zinc pyrithione* - **Zinc pyrithione** is an antifungal and antibacterial agent commonly found in shampoos for treating conditions like **seborrheic dermatitis (dandruff)** and mild forms of tinea versicolor. - While it has some antifungal properties, it is generally **insufficient as a sole treatment** for **tinea capitis**, which requires systemic antifungal therapy due to the involvement of hair follicles.
Drug interactions with antifungals Explanation: ***Fluconazole*** - Fluconazole is a potent **CYP450 inhibitor**, specifically **CYP2C9 and CYP3A4**, which can significantly increase the levels of drugs metabolized by these enzymes, such as **theophylline**. - The patient's symptoms of nausea, palpitations, anxiety, tremor, and tachycardia are consistent with **theophylline toxicity**, which would be exacerbated by co-administration with fluconazole. *Amphotericin B* - Amphotericin B is a powerful antifungal, but its primary side effects include **nephrotoxicity**, **infusion-related reactions** (fever, chills, rigors), and **electrolyte disturbances**, not theophylline toxicity. - It is typically reserved for **severe systemic fungal infections** and is not a first-line treatment for uncomplicated **oral candidiasis**. *Griseofulvin* - Griseofulvin is used to treat **dermatophyte infections** (tinea infections) and is not active against *Candida*. - Its main side effects include **gastrointestinal upset**, **headache**, and **photosensitivity**, and it does not significantly interact with theophylline. *Terbinafine* - Terbinafine is an allylamine antifungal primarily used for **dermatophyte infections**, particularly **onychomycosis**, and is not effective for candidiasis. - While it can cause liver enzyme elevation, it does not typically lead to theophylline toxicity or the constellation of symptoms described. *Nystatin* - Nystatin is a **topical or oral non-absorbable antifungal** used for superficial candidal infections, including oral thrush. - It is not absorbed systemically, so it has **virtually no drug interactions** or systemic side effects, and therefore would not cause theophylline toxicity.
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ketoconazole
ketoconazole
antiandrogen
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Question: ketoconazole
Answer: antiandrogen
Extra Information: hirsutism of PCOSgeneral inhibition of steroid synthesisgynecomastian, amenorrhea
Question: Griseofulvin inhibits the action of fungal cell _____
Answer: microtubules
Extra Information: https://onlinemeded.org/spa/microbiology/fungi/acquire?ref=anki
Question: For more severe Tinea infections or persistent Onychomycosis (manifestations of dermatophytes), oral _____ is used
Answer: Griseofulvin
Extra Information: Watch Epidermophyton spp., Trichophyton spp., Microsporum spp. (dermatophytes) [https://dashboard.sketchy.com/study/medical/courses/medical-microbiology/units/medical-microbiology-fungi/videos/medical-microbiology-fungi-cutaneous-mycoses-epidermophyton-spp-trichophyton-spp-microsporum-spp-dermatophytes?utm_source=anki&utm_medium=partnership&utm_campaign=february_update&utm_content=medical] https://onlinemeded.org/spa/dermatology/superficial-skin-infections/acquire?ref=anki
Question: Which antifungal agent inhibits fungal protein synthesis? _____
Answer: Flucytosine
Extra Information: https://onlinemeded.org/spa/microbiology/fungi/acquire?ref=anki
Question: Which azole is used to treat invasive aspergillosis? _____
Answer: Voriconazole
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Question: Which azole antifungal is especially prone to inhibition of human CYP450? _____
Answer: Voriconazole
Extra Information: Watch Azoles [https://dashboard.sketchy.com/study/medical/courses/medical-pharmacology/units/medical-pharmacology-antimicrobials/videos/medical-pharmacology-antimicrobials-antifungals-azoles?utm_source=anki&utm_medium=partnership&utm_campaign=february_update&utm_content=medical] https://onlinemeded.org/spa/microbiology/fungi/acquire?ref=anki
Question: Flucytosine is primarily used for _____ meningitis
Answer: cryptococcal
Extra Information: https://onlinemeded.org/spa/microbiology/fungi/acquire?ref=anki
Question: Which antifungal is metabolized to 5-fluorouracil in fungal cells? _____
Answer: Flucytosine
Extra Information: https://onlinemeded.org/spa/microbiology/fungi/acquire?ref=anki
Question: How is Amphotericin B associated nephrotoxicity prevented? _____
Answer: Hydration w/ IV saline
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Question: Azoles are a class of antifungals that can cause _____-toxicity
Answer: hepato
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