Pharmacology Quiz: Sulfonamides And Tmp Smx
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Sulfonamides And Tmp SmxQuestion 1 of 20

A 34-year-old patient is prescribed TMP-SMX for a skin and soft tissue infection. Ten days later, she develops fever, sore throat, and a rapidly spreading dusky rash with blister formation and extensive mucosal involvement. A skin biopsy would most likely show which of the following findings?

Subepidermal bullae with linear IgG deposits at the dermoepidermal junction.
Full-thickness necrosis of the epidermis with dermoepidermal separation.
Acantholysis with intraepidermal vesicles.
Spongiosis with perivascular infiltration of lymphocytes and eosinophils.
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Pharmacology Quiz: Sulfonamides And Tmp Smx

Practice Sulfonamides And Tmp Smx in Pharmacology with focused quiz questions that help you check what you know, review explanations, and build confidence with test-style prompts.

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This quiz focuses on Sulfonamides And Tmp Smx, giving you a quick way to practice the rules, question types, and explanations that matter most for Pharmacology.

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Question 1

A 34-year-old patient is prescribed TMP-SMX for a skin and soft tissue infection. Ten days later, she develops fever, sore throat, and a rapidly spreading dusky rash with blister formation and extensive mucosal involvement. A skin biopsy would most likely show which of the following findings?

  1. Subepidermal bullae with linear IgG deposits at the dermoepidermal junction.
  2. Full-thickness necrosis of the epidermis with dermoepidermal separation. (correct answer)
  3. Acantholysis with intraepidermal vesicles.
  4. Spongiosis with perivascular infiltration of lymphocytes and eosinophils.
Explanation: The clinical presentation is highly suggestive of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), a severe mucocutaneous adverse reaction commonly associated with sulfonamides. The characteristic histopathological finding in SJS/TEN is full-thickness necrosis (apoptosis) of the epidermis, leading to separation from the underlying dermis. The other options describe different dermatological conditions: (A) bullous pemphigoid, (C) pemphigus vulgaris, and (D) eczematous dermatitis.

Question 2

A patient is counseled to use sunscreen and protective clothing while taking TMP-SMX. This precaution is necessary to mitigate the risk of a phototoxic reaction, which is mechanistically characterized by:

  1. Drug accumulation in the skin leading to a type IV hypersensitivity reaction upon UV exposure.
  2. Inhibition of melanin synthesis, which reduces the skin's natural photoprotection.
  3. Deposition of drug-antibody immune complexes in dermal blood vessels following UV exposure.
  4. UV light-induced conversion of the drug into a reactive metabolite that causes direct cellular damage. (correct answer)
Explanation: When you encounter questions about drug-induced photosensitivity reactions, focus on understanding the two main mechanisms: phototoxic versus photoallergic reactions. TMP-SMX causes phototoxic reactions, which involve direct chemical damage rather than immune system activation. Phototoxic reactions occur when UV light provides the energy needed to convert an otherwise harmless drug molecule into a reactive species that directly damages cellular components like DNA, proteins, and lipids. This is exactly what happens with TMP-SMX - the drug absorbs UV radiation and becomes chemically activated, leading to immediate cellular injury. Answer D correctly describes this direct photochemical mechanism. Let's examine why the other options are incorrect. Choice A describes a delayed-type hypersensitivity reaction, which characterizes photoallergic reactions (not phototoxic ones) and requires prior sensitization and immune memory. Choice B suggests impaired melanin synthesis, but TMP-SMX doesn't interfere with melanocyte function - the photosensitivity occurs regardless of baseline pigmentation. Choice C describes immune complex deposition, which is a Type III hypersensitivity mechanism unrelated to drug photosensitivity reactions. The key distinction to remember is that phototoxic reactions are immediate, dose-dependent chemical events that can occur on first exposure, while photoallergic reactions are delayed immune responses requiring prior sensitization. For pharmacology exams, when you see photosensitizing drugs like TMP-SMX, fluoroquinolones, or tetracyclines, think "UV + drug = reactive metabolite = direct cellular damage" rather than immune-mediated mechanisms.

Question 3

Administration of a sulfonamide to a neonate with hyperbilirubinemia is contraindicated due to the high risk of kernicterus. What is the direct mechanism by which the sulfonamide precipitates this condition?

  1. Inhibition of UDP-glucuronosyltransferase, decreasing bilirubin conjugation.
  2. Displacement of bilirubin from its binding sites on serum albumin. (correct answer)
  3. Induction of hemolysis, leading to an increased bilirubin load.
  4. Direct neurotoxic effects on the basal ganglia independent of bilirubin levels.
Explanation: Sulfonamides are highly protein-bound and can compete with and displace unconjugated bilirubin from its binding sites on serum albumin. This increases the concentration of free, unbound bilirubin in the plasma. In neonates, whose blood-brain barrier is immature, this free bilirubin can cross into the central nervous system and deposit in the basal ganglia, causing bilirubin-induced neurologic dysfunction (kernicterus).

Question 4

An elderly patient with type 2 diabetes, managed with glipizide, is given TMP-SMX. The patient is brought to the clinic with confusion and diaphoresis. A fingerstick glucose is 45 mg/dL. This adverse event is most likely caused by sulfamethoxazole's ability to:

  1. decrease insulin resistance in peripheral tissues.
  2. inhibit hepatic gluconeogenesis via folate depletion.
  3. displace glipizide from plasma albumin and inhibit its metabolism. (correct answer)
  4. directly stimulate insulin release from pancreatic beta cells.
Explanation: Sulfamethoxazole can cause severe hypoglycemia in patients taking sulfonylureas like glipizide. There are two main mechanisms: 1) Sulfonamides are highly protein-bound and can displace sulfonylureas from albumin, increasing the concentration of free, active drug. 2) Sulfonamides can inhibit the CYP2C9 enzyme, which is responsible for the metabolism of many sulfonylureas, thereby prolonging their half-life and duration of action. The combined effect significantly potentiates the glucose-lowering action of the sulfonylurea.

Question 5

A patient being treated with high-dose TMP-SMX develops acute kidney injury. Urinalysis reveals needle-shaped crystals. This complication is primarily due to the precipitation of which component, and what intervention is most likely to mitigate this risk?

  1. Trimethoprim; alkalinization of the urine.
  2. Sulfamethoxazole and its metabolites; ensuring adequate hydration. (correct answer)
  3. Uric acid; administration of allopurinol.
  4. Calcium oxalate; dietary calcium restriction.
Explanation: Sulfonamides, particularly their acetylated metabolites, have low solubility in acidic urine and can precipitate to form crystals (crystalluria). This can lead to tubular obstruction and acute kidney injury. The primary component responsible is sulfamethoxazole. The most important preventive measure is to maintain adequate hydration and high urine output to keep the drug and its metabolites diluted.

Question 6

A 62-year-old woman with rheumatoid arthritis, well-controlled on weekly low-dose methotrexate, develops a UTI and is prescribed TMP-SMX. Shortly after, she develops severe stomatitis, pancytopenia, and elevated liver enzymes. This presentation of methotrexate toxicity is most likely a result of:

  1. Sulfamethoxazole displacing methotrexate from albumin and trimethoprim inhibiting its renal clearance. (correct answer)
  2. A direct synergistic toxic effect of both drugs on the bone marrow.
  3. TMP-SMX unmasking a latent folate deficiency, which is then exacerbated by methotrexate.
  4. Methotrexate potentiating the risk of a hypersensitivity reaction to sulfamethoxazole.
Explanation: When you encounter drug interaction questions involving methotrexate, focus on the dual mechanisms that can dramatically increase its toxicity: protein displacement and renal clearance inhibition. Methotrexate normally circulates bound to albumin and is cleared renally through active secretion. TMP-SMX creates a dangerous combination by attacking both these protective mechanisms simultaneously. Sulfamethoxazole displaces methotrexate from its albumin binding sites, suddenly increasing free (active) drug levels in the blood. Meanwhile, trimethoprim competes with methotrexate for the same renal transporters, blocking its elimination. This dual hit causes methotrexate levels to skyrocket, leading to the classic toxicity triad: stomatitis (mucosal damage), pancytopenia (bone marrow suppression), and hepatotoxicity. Option B is incorrect because this isn't about direct synergistic toxicity—it's a pharmacokinetic interaction that increases methotrexate exposure. Option C misses the mark; while methotrexate does affect folate metabolism, the acute toxicity here results from increased drug levels, not unmasked folate deficiency. Option D incorrectly suggests a hypersensitivity mechanism when this is clearly dose-related toxicity. The key study point: memorize that TMP-SMX is contraindicated with methotrexate due to this dual pharmacokinetic interaction. On pharmacology exams, when you see methotrexate toxicity scenarios, immediately consider what drugs might displace it from protein binding (sulfonamides, NSAIDs) or block its renal elimination (trimethoprim, probenecid). This interaction is potentially fatal and represents a high-yield exam topic.

Question 7

A patient with HIV and a CD4 count of 80 cells/μL is receiving TMP-SMX as prophylaxis for Pneumocystis jirovecii pneumonia (PJP). The efficacy of TMP-SMX against this organism is based on the fact that Pneumocystis jirovecii:

  1. is a fungus that, unlike most other fungi, must synthesize its own folate de novo. (correct answer)
  2. is a bacterium that has an unusually high requirement for tetrahydrofolate.
  3. possesses a unique cell wall structure that is weakened by folate depletion.
  4. is a protozoan that is unable to salvage folate from the host environment.
Explanation: Pneumocystis jirovecii is an atypical fungus. While most fungi are not susceptible to sulfonamides, P. jirovecii is an exception because it cannot absorb folate from its environment (the human host) and possesses the enzymes for de novo folate synthesis, including dihydropteroate synthase and dihydrofolate reductase. Therefore, its folate synthesis pathway is susceptible to inhibition by TMP-SMX, just like susceptible bacteria.

Question 8

A patient develops a morbilliform rash on day 8 of TMP-SMX therapy. The rash is non-pruritic, non-painful, and there is no mucosal involvement or other systemic symptoms. Which of the following is the most important feature distinguishing this reaction from the more severe Stevens-Johnson syndrome (SJS)?

  1. The timing of onset, as SJS typically occurs within 24 hours of initiation.
  2. The presence of eosinophilia on a complete blood count.
  3. The absence of mucosal erosions and epidermal detachment. (correct answer)
  4. The resolution of the rash upon administration of antihistamines.
Explanation: The key features that distinguish a simple drug exanthem (morbilliform rash) from life-threatening conditions like Stevens-Johnson syndrome (SJS) are the presence of severe signs. SJS is characterized by painful, dusky, or purpuric macules that lead to epidermal detachment (positive Nikolsky sign) and, critically, involvement of at least two mucosal surfaces (e.g., oral, ocular, genital). The absence of these features is the most important differentiating factor.

Question 9

A 72-year-old male with a history of hypertension controlled with lisinopril is treated with trimethoprim-sulfamethoxazole (TMP-SMX) for a urinary tract infection. On day 5 of treatment, he presents to the emergency department with muscle weakness and palpitations. An ECG shows peaked T waves. This clinical presentation is most likely due to trimethoprim-mediated inhibition of which of the following?

  1. Dihydropteroate synthase in renal tubular cells.
  2. Epithelial sodium channels in the collecting duct. (correct answer)
  3. The Na+/K+-ATPase pump in skeletal muscle cells.
  4. Aldosterone synthesis in the adrenal cortex.
Explanation: The patient's symptoms (muscle weakness, palpitations) and ECG finding (peaked T waves) are characteristic of hyperkalemia. Trimethoprim, a component of TMP-SMX, has a structure similar to the potassium-sparing diuretic amiloride. It directly inhibits the epithelial sodium channel (ENaC) in the collecting duct of the nephron. This inhibition reduces sodium reabsorption and consequently decreases potassium secretion, leading to hyperkalemia, especially in patients with renal impairment or those taking other drugs that increase potassium, such as ACE inhibitors (lisinopril).

Question 10

An 80-year-old male stabilized on warfarin for atrial fibrillation is prescribed a 10-day course of TMP-SMX for prostatitis. Three days into therapy, his INR is found to be 8.5 (therapeutic range 2.0-3.0). This significant interaction is primarily caused by which two mechanisms?

  1. Inhibition of bacterial vitamin K synthesis and induction of CYP2C9.
  2. Displacement of warfarin from albumin and inhibition of CYP2C9. (correct answer)
  3. Increased absorption of warfarin from the GI tract and inhibition of P-glycoprotein.
  4. Inhibition of CYP2C9 and induction of renal warfarin clearance.
Explanation: TMP-SMX potentiates the effect of warfarin through two major mechanisms. First, sulfamethoxazole is highly protein-bound and displaces warfarin from its binding sites on albumin, increasing the free, active fraction of warfarin. Second, both trimethoprim and sulfamethoxazole are inhibitors of the cytochrome P450 enzyme CYP2C9, which is the primary enzyme responsible for metabolizing the more potent S-enantiomer of warfarin. The combination of these effects leads to a rapid and significant increase in INR.

Question 11

While TMP-SMX is often considered bactericidal, its clinical efficacy can depend on the host's immune status. In which of the following patient populations would the bacteriostatic nature of the individual components be of greatest concern, potentially leading to treatment failure?

  1. A pregnant patient with an uncomplicated urinary tract infection.
  2. A young adult with community-acquired pneumonia.
  3. A patient with type 1 diabetes and good glycemic control.
  4. A neutropenic patient undergoing chemotherapy for acute myeloid leukemia. (correct answer)
Explanation: Bacteriostatic agents inhibit bacterial growth but rely on a competent host immune system (e.g., neutrophils, macrophages) to clear the non-replicating bacteria. In a patient who is profoundly neutropenic due to chemotherapy, the immune system is unable to perform this function. Therefore, infections in severely immunocompromised hosts ideally require bactericidal agents that can kill the bacteria without assistance from host defenses. The reliance on host immunity is a key limitation of bacteriostatic drugs in this population.

Question 12

A 72-year-old male with a history of hypertension controlled with lisinopril is treated with trimethoprim-sulfamethoxazole (TMP-SMX) for a urinary tract infection. On day 5 of treatment, he presents to the emergency department with muscle weakness and palpitations. An ECG shows peaked T waves. This clinical presentation is most likely due to trimethoprim-mediated inhibition of which of the following?

  1. Dihydropteroate synthase in renal tubular cells.
  2. Epithelial sodium channels in the collecting duct. (correct answer)
  3. The Na+/K+-ATPase pump in skeletal muscle cells.
  4. Aldosterone synthesis in the adrenal cortex.
Explanation: The patient's symptoms (muscle weakness, palpitations) and ECG finding (peaked T waves) are characteristic of hyperkalemia. Trimethoprim, a component of TMP-SMX, has a structure similar to the potassium-sparing diuretic amiloride. It directly inhibits the epithelial sodium channel (ENaC) in the collecting duct of the nephron. This inhibition reduces sodium reabsorption and consequently decreases potassium secretion, leading to hyperkalemia, especially in patients with renal impairment or those taking other drugs that increase potassium, such as ACE inhibitors (lisinopril).

Question 13

A 34-year-old patient is prescribed TMP-SMX for a skin and soft tissue infection. Ten days later, she develops fever, sore throat, and a rapidly spreading dusky rash with blister formation and extensive mucosal involvement. A skin biopsy would most likely show which of the following findings?

  1. Subepidermal bullae with linear IgG deposits at the dermoepidermal junction.
  2. Full-thickness necrosis of the epidermis with dermoepidermal separation. (correct answer)
  3. Acantholysis with intraepidermal vesicles.
  4. Spongiosis with perivascular infiltration of lymphocytes and eosinophils.
Explanation: The clinical presentation is highly suggestive of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), a severe mucocutaneous adverse reaction commonly associated with sulfonamides. The characteristic histopathological finding in SJS/TEN is full-thickness necrosis (apoptosis) of the epidermis, leading to separation from the underlying dermis. The other options describe different dermatological conditions: (A) bullous pemphigoid, (C) pemphigus vulgaris, and (D) eczematous dermatitis.

Question 14

The combination of trimethoprim and sulfamethoxazole demonstrates significant synergy and is often bactericidal, whereas either agent alone is typically bacteriostatic. This synergy is best explained by which of the following principles?

  1. Allosteric activation of each drug by the other at their respective target sites.
  2. Inhibition of two sequential steps in a critical bacterial metabolic pathway. (correct answer)
  3. Sulfamethoxazole increasing the intracellular concentration of trimethoprim.
  4. Trimethoprim preventing the metabolic inactivation of sulfamethoxazole by the bacterium.
Explanation: The synergistic effect of TMP-SMX is a classic example of sequential blockade. Sulfamethoxazole inhibits dihydropteroate synthase, an early step in the bacterial folate synthesis pathway. Trimethoprim inhibits dihydrofolate reductase, a subsequent step in the same pathway. By blocking the pathway at two different points, the combination produces a much greater inhibition of tetrahydrofolate synthesis than either drug alone, often resulting in a bactericidal effect.

Question 15

A 55-year-old man with a history of chronic alcohol use disorder and poor nutrition is hospitalized and started on TMP-SMX. Which of the following adverse effects is this patient at a particularly high risk of developing due to his underlying condition?

  1. Hemolytic anemia
  2. Megaloblastic anemia (correct answer)
  3. Crystalluria and nephrotoxicity
  4. Stevens-Johnson syndrome
Explanation: Patients with chronic alcohol use disorder and poor nutrition are often folate deficient. Trimethoprim inhibits dihydrofolate reductase, the enzyme that converts dihydrofolate to the active tetrahydrofolate. In a patient with pre-existing folate deficiency, this inhibition can precipitate or worsen megaloblastic anemia, which is characterized by impaired DNA synthesis and the presence of large, immature red blood cells.

Question 16

The combination of trimethoprim and sulfamethoxazole demonstrates significant synergy and is often bactericidal, whereas either agent alone is typically bacteriostatic. This synergy is best explained by which of the following principles?

  1. Allosteric activation of each drug by the other at their respective target sites.
  2. Inhibition of two sequential steps in a critical bacterial metabolic pathway. (correct answer)
  3. Sulfamethoxazole increasing the intracellular concentration of trimethoprim.
  4. Trimethoprim preventing the metabolic inactivation of sulfamethoxazole by the bacterium.
Explanation: The synergistic effect of TMP-SMX is a classic example of sequential blockade. Sulfamethoxazole inhibits dihydropteroate synthase, an early step in the bacterial folate synthesis pathway. Trimethoprim inhibits dihydrofolate reductase, a subsequent step in the same pathway. By blocking the pathway at two different points, the combination produces a much greater inhibition of tetrahydrofolate synthesis than either drug alone, often resulting in a bactericidal effect.

Question 17

Administration of a sulfonamide to a neonate with hyperbilirubinemia is contraindicated due to the high risk of kernicterus. What is the direct mechanism by which the sulfonamide precipitates this condition?

  1. Inhibition of UDP-glucuronosyltransferase, decreasing bilirubin conjugation.
  2. Displacement of bilirubin from its binding sites on serum albumin. (correct answer)
  3. Induction of hemolysis, leading to an increased bilirubin load.
  4. Direct neurotoxic effects on the basal ganglia independent of bilirubin levels.
Explanation: Sulfonamides are highly protein-bound and can compete with and displace unconjugated bilirubin from its binding sites on serum albumin. This increases the concentration of free, unbound bilirubin in the plasma. In neonates, whose blood-brain barrier is immature, this free bilirubin can cross into the central nervous system and deposit in the basal ganglia, causing bilirubin-induced neurologic dysfunction (kernicterus).

Question 18

A 25-year-old man of Mediterranean descent is treated with TMP-SMX. He develops fatigue, jaundice, and dark urine. A complete blood count reveals anemia, and a peripheral smear shows bite cells and Heinz bodies. This reaction is most likely due to an inherited deficiency that impairs the regeneration of which of the following?

  1. Tetrahydrofolate
  2. Pyruvate kinase
  3. Methemoglobin reductase
  4. Reduced glutathione (GSH) (correct answer)
Explanation: When you see a patient of Mediterranean descent developing hemolytic anemia after taking TMP-SMX, with bite cells and Heinz bodies on peripheral smear, think glucose-6-phosphate dehydrogenase (G6PD) deficiency. This X-linked disorder is common in Mediterranean populations and creates vulnerability to oxidative stress from certain medications. G6PD is the rate-limiting enzyme in the pentose phosphate pathway, which generates NADPH. Red blood cells rely heavily on NADPH to regenerate reduced glutathione (GSH) from its oxidized form (GSSG). GSH is the cell's primary antioxidant defense system. When G6PD is deficient, cells cannot maintain adequate GSH levels during oxidative stress, leading to hemolysis. TMP-SMX is a classic oxidizing drug that triggers this reaction. Let's examine why the other options don't fit: (A) Tetrahydrofolate deficiency would cause megaloblastic anemia, not acute hemolytic anemia with bite cells and Heinz bodies. (B) Pyruvate kinase deficiency causes chronic hemolytic anemia but isn't triggered by specific medications and doesn't produce this characteristic smear pattern. (C) Methemoglobin reductase deficiency causes methemoglobinemia with cyanosis, not hemolytic anemia. The correct answer is (D) because G6PD deficiency specifically impairs the cell's ability to regenerate reduced glutathione during oxidative stress. Study tip: Remember the classic triad for G6PD deficiency: Mediterranean/African/Middle Eastern ancestry + oxidizing drug exposure + acute hemolytic anemia with bite cells. Common trigger drugs include sulfonamides, antimalarials, and nitrofurantoin.

Question 19

Trimethoprim exhibits selective toxicity against bacterial dihydrofolate reductase (DHFR) over the human equivalent. This selectivity is the basis for its therapeutic use. The affinity of trimethoprim for bacterial DHFR is approximately how many times greater than its affinity for human DHFR?

  1. 10 to 50 times
  2. 100 to 500 times
  3. 1,000 to 5,000 times
  4. 50,000 to 100,000 times (correct answer)
Explanation: The basis for trimethoprim's selective toxicity is its remarkably higher affinity for the bacterial dihydrofolate reductase enzyme compared to the human enzyme. Trimethoprim binds to bacterial DHFR approximately 50,000 to 100,000 times more tightly than it binds to mammalian DHFR. This vast difference in affinity allows for effective inhibition of the bacterial enzyme at concentrations that have minimal effect on the host's folate metabolism, although toxicity can still occur at high doses or in susceptible individuals (e.g., folate deficient).

Question 20

A 62-year-old woman with rheumatoid arthritis, well-controlled on weekly low-dose methotrexate, develops a UTI and is prescribed TMP-SMX. Shortly after, she develops severe stomatitis, pancytopenia, and elevated liver enzymes. This presentation of methotrexate toxicity is most likely a result of:

  1. Sulfamethoxazole displacing methotrexate from albumin and trimethoprim inhibiting its renal clearance. (correct answer)
  2. A direct synergistic toxic effect of both drugs on the bone marrow.
  3. TMP-SMX unmasking a latent folate deficiency, which is then exacerbated by methotrexate.
  4. Methotrexate potentiating the risk of a hypersensitivity reaction to sulfamethoxazole.
Explanation: When you encounter drug interaction questions involving methotrexate, focus on the dual mechanisms that can dramatically increase its toxicity: protein displacement and renal clearance inhibition. Methotrexate normally circulates bound to albumin and is cleared renally through active secretion. TMP-SMX creates a dangerous combination by attacking both these protective mechanisms simultaneously. Sulfamethoxazole displaces methotrexate from its albumin binding sites, suddenly increasing free (active) drug levels in the blood. Meanwhile, trimethoprim competes with methotrexate for the same renal transporters, blocking its elimination. This dual hit causes methotrexate levels to skyrocket, leading to the classic toxicity triad: stomatitis (mucosal damage), pancytopenia (bone marrow suppression), and hepatotoxicity. Option B is incorrect because this isn't about direct synergistic toxicity—it's a pharmacokinetic interaction that increases methotrexate exposure. Option C misses the mark; while methotrexate does affect folate metabolism, the acute toxicity here results from increased drug levels, not unmasked folate deficiency. Option D incorrectly suggests a hypersensitivity mechanism when this is clearly dose-related toxicity. The key study point: memorize that TMP-SMX is contraindicated with methotrexate due to this dual pharmacokinetic interaction. On pharmacology exams, when you see methotrexate toxicity scenarios, immediately consider what drugs might displace it from protein binding (sulfonamides, NSAIDs) or block its renal elimination (trimethoprim, probenecid). This interaction is potentially fatal and represents a high-yield exam topic.