Question

Persons with a high acetyltransferase activity will have comparatively lower plasma levels of which drug? (A) pyrazinamide (B) rifabutin (C) amikacin (D) ethambutol (E) dapsone

Short answer

Dapsone (E) will have lower plasma levels.

Step-by-step solution

Identify the Role of Acetyltransferase

Acetyltransferase is an enzyme responsible for the acetylation process, a part of drug metabolism. This enzyme, particularly in forms such as N-acetyltransferase, is involved in the metabolism of several drugs. High acetyltransferase activity can lead to rapid metabolism of certain drugs, decreasing their plasma levels.

Recognize Drugs Affected by Acetylation

Drugs affected by acetylation, and thus the activity of acetyltransferase, include isoniazid, hydralazine, procainamide, and certain sulfonamides like dapsone. These drugs are known to be metabolized by acetylation.

Analyze Each Option

Among the given options, dapsone is a sulfonamide. It is commonly known that dapsone is metabolized by acetylation. High acetyltransferase activity would therefore lead to increased metabolism and lower plasma levels of dapsone.

Conclusion Based on Analysis

From the analysis, the drug that would have lower plasma levels due to high acetyltransferase activity is dapsone. The other drugs listed, such as pyrazinamide, rifabutin, amikacin, and ethambutol, are not prominently affected by acetylation.

Key concepts

Acetyltransferase Activity

Acetyltransferase is an enzyme that plays a critical role in the body's drug metabolism processes. It specifically helps in the transfer of acetyl groups, a process known as acetylation. This enzyme is notable for its involvement in the metabolism of several drugs, particularly those that need to undergo acetylation to be metabolized effectively.

In the context of pharmacology, there are different types of acetyltransferase enzymes, each responsible for the acetylation of different drugs. One of the well-studied types is the N-acetyltransferase, which varies in activity among individuals. This enzyme's activity can be influenced by genetic factors, resulting in individuals being categorized as either "slow" or "rapid" acetylators.

Rapid acetylators have high acetyltransferase activity, leading to quicker metabolism of drugs metabolized by acetylation. Consequently, these individuals might experience reduced effectiveness of such medications due to lower plasma drug levels.

Drug Metabolism

Drug metabolism is a vital process in pharmacology that determines the fate of drugs administered into the body. The process involves chemical modifications that make drugs easier to eliminate from the body. Acetylation, performed by acetyltransferase enzymes, is one of several metabolic pathways.

A drug goes through two main phases in drug metabolism. In Phase I, the drug undergoes chemical reactions such as oxidation, reduction, or hydrolysis. In Phase II, conjugation reactions like acetylation take place to further increase the drug's water solubility. This facilitates its excretion.

The rate at which different individuals metabolize drugs can vary based on genetic, environmental, and physiological factors. Understanding these differences is crucial for determining proper drug dosages to attain effective therapeutic levels without causing toxicity.

• An understanding of drug metabolism helps in predicting drug interactions.
• Knowledge of a patient's metabolic rate can guide personalized medication plans.

Sulfonamides

Sulfonamides are a group of antibiotics that are known to be affected significantly by the acetylation process. One of the most notable sulfonamides that undergoes acetylation is dapsone, which is used to treat various infections and inflammatory conditions.

These drugs have a sulfonamide group as part of their molecular structure, influencing their mechanism of action and metabolism. The acetylation process helps to modify the sulfonamide so that it can be excreted more efficiently. However, for individuals with rapid acetyltransferase activity, this means the sulfonamide (e.g., dapsone) is metabolized quicker, leading to potentially lower therapeutic levels.

It's essential for healthcare providers to be aware of the patient's acetylator status to adjust the dosages of sulfonamides appropriately. This ensures that the medication remains effective, while minimizing risks associated with either under-treatment or toxicity.

Acetylation Process

The acetylation process is an essential biochemical reaction that occurs in the liver, facilitated by acetyltransferase enzymes. This process involves attaching an acetyl group to drug molecules, altering their chemical structure to make them more water-soluble for easier excretion by the kidneys.

Not all drugs undergo acetylation, but those that do are significantly impacted by the process. For affected drugs, such as dapsone, their pharmacokinetics can change based on how quickly the acetylation occurs. There are genetically diverse groups of rapid and slow acetylators, which affects how long a drug remains active in the body.

• Understanding the acetylation process can assist healthcare professionals in predicting the duration of a drug's activity.
• The knowledge of a patient's acetylation capacity can inform dose adjustments, particularly for drugs that rely heavily on this process.

As a result, pharmacogenomics, the study of how genes affect drug metabolism, plays a pivotal role in the personalization of medication regimens.