Question

Which drug is most likely to cause drug interactions due to inhibition of human cytochrome P450 enzymes? (A) amphotericin B (B) fluconazole (C) caspofungin (D) naftifine (E) itraconazole

Short answer

The drug most likely to cause interactions due to P450 inhibition is itraconazole.

Step-by-step solution

Identify the Role of Cytochrome P450

Cytochrome P450 enzymes are essential for the metabolism of many drugs. They are involved in the oxidation of organic substances and are crucial in drug metabolism and elimination.

Recognize the Common Inhibitors

Identify drugs known to inhibit cytochrome P450 enzymes, such as azole antifungals including fluconazole and itraconazole. These are known inhibitors, which can increase the levels of other drugs metabolized by P450 enzymes and thus cause drug interactions.

Evaluate the Given Options

Analyze the options provided: amphotericin B, fluconazole, caspofungin, naftifine, and itraconazole. Note that amphotericin B and caspofungin are not typically linked to P450 inhibition, while azole antifungals like fluconazole and itraconazole often are.

Determine the Drug with Highest Risk

Among fluconazole and itraconazole, itraconazole is more commonly associated with strong P450 inhibition. It has a broader spectrum of inhibition across various cytochrome P450 enzymes compared to fluconazole.

Key concepts

Drug Interactions

Drug interactions occur when one drug affects the activity of another drug when both are administered together. These interactions can change how a drug works or increase the risk of side effects. Understanding drug interactions is crucial for ensuring patient safety and the effectiveness of therapeutic treatments. Some drugs can block the enzymes that break down other drugs, leading to higher concentrations in the blood and increased effects or side effects. Others can speed up the breakdown of a drug, making it less effective. Monitoring and managing drug interactions help clinicians provide better care to patients by adjusting dosages or choosing different medications.

Azole Antifungals

Azole antifungals are a class of medications used to treat fungal infections. They work by inhibiting an enzyme essential for the synthesis of ergosterol, a key component of fungal cell membranes. This inhibition weakens the cell membrane, leading to the death of the fungus. Azoles are very effective but are known for their potential to cause drug interactions due to their effect on cytochrome P450 enzymes. This enzyme inhibition can lead to significant increases in the levels of other drugs, requiring careful monitoring and dosage adjustments when patients are on azole antifungals. Common azole antifungals include fluconazole and itraconazole, each with specific characteristics and uses.

Drug Metabolism

Drug metabolism is the process by which the body breaks down and converts medication into active chemical substances. This process primarily occurs in the liver and involves enzymes, with cytochrome P450 being the most important family of enzymes involved. Metabolism affects how long a drug stays active in your system and its overall efficacy. The rate of metabolism can be influenced by various factors, including genetics, age, diet, and the presence of other drugs. Interactions with drugs that inhibit or induce metabolic enzymes can lead to changes in the effective concentration of the drug, potentially causing toxicity or reduced therapeutic effect. Understanding drug metabolism helps in predicting drug behavior in the body and planning appropriate dosing regimens.

Fluconazole

Fluconazole is a commonly prescribed azole antifungal used to treat a variety of fungal infections. It is known for its effectiveness and relative safety profile. Fluconazole selectively inhibits certain fungal enzymes, contributing to its ability to effectively combat infections. However, it also inhibits specific cytochrome P450 enzymes in humans, which can lead to drug interactions. Inhibiting these enzymes may increase the levels of other drugs that are metabolized by them, necessitating careful management when fluconazole is prescribed alongside other medications. While fluconazole has a narrower range of cytochrome P450 inhibition compared to other azoles, it still requires attention to potential interactions.

Itraconazole

Itraconazole is a broad-spectrum azole antifungal with a potent effect on a wide range of fungal infections. Similar to fluconazole, itraconazole works by inhibiting the synthesis of ergosterol in fungi, crucial for maintaining fungal cell membrane integrity. One of the defining features of itraconazole is its strong inhibition of cytochrome P450 enzymes. This makes itraconazole a frequent cause of drug interactions. It can lead to significant increases in the plasma concentrations of other drugs metabolized by these enzymes, which can be both an advantage and a limitation. The potent inhibition by itraconazole often demands adjustments in the dosing of accompanying medications to prevent adverse effects, making therapeutic monitoring particularly important for patients on this medication.