Question

Cilastatin is used to inhibit the metabolism of which antibiotic by dehydropeptidase? (A) ceftazidime (B) imipenem (C) piperacillin (D) vancomycin (E) bacitracin

Short answer

Cilastatin inhibits the metabolism of imipenem.

Step-by-step solution

Identify the Function of Cilastatin

Cilastatin is a compound used in combination with certain antibiotics to inhibit their metabolism by dehydropeptidase enzymes, which are found in the kidneys.

Recognize the Role of Dehydropeptidase

Dehydropeptidase is an enzyme that can degrade certain antibiotics, specifically carbapenems, in the renal tubules. This degradation reduces the efficacy of these antibiotics.

Match Cilastatin with Antibiotic

Cilastatin is specifically used with imipenem, a carbapenem antibiotic. Imipenem is susceptible to hydrolysis by dehydropeptidase, and cilastatin is co-administered to prevent this metabolism and prolong its effectiveness.

Eliminate Incorrect Options

Ceftazidime, piperacillin, vancomycin, and bacitracin are antibiotics that do not require cilastatin for protection against dehydropeptidase. Ceftazidime is a cephalosporin, piperacillin is a penicillin, and vancomycin and bacitracin are not affected by dehydropeptidase.

Conclusion

Based on the above understanding, cilastatin is used to inhibit the metabolism of imipenem by dehydropeptidase.

Key concepts

Dehydropeptidase Inhibition

Dehydropeptidase is a specific type of enzyme found in the renal tubules of the kidneys. Its main role is to break down certain compounds, including some antibiotics, which can lead to the loss of their therapeutic effects.

When a patient is prescribed a carbapenem antibiotic like imipenem, it becomes crucial to ensure the drug remains effective in the body. This is where the role of dehydropeptidase inhibition comes into play. Cilastatin is the compound that is used for this purpose. It works by blocking this enzyme, thereby preventing the breakdown of imipenem.

This mechanism of inhibiting the dehydropeptidase enzyme ensures that imipenem remains active for a longer period in the bloodstream, maintaining its antibiotic potency. This is critical in effectively treating infections by maximizing the efficacy of the drug.

Antibiotic Degradation

Antibiotic degradation refers to the process by which antibiotics are broken down and rendered ineffective, usually by enzymatic action. In the case of certain antibiotics like imipenem, degradation happens because of the dehydropeptidase enzyme activity in the kidneys.

The degradation of antibiotics can lead to suboptimal therapeutic concentrations in the body, which may result in the inability to effectively eliminate infections. This is significant because if the antibiotic doesn't last long enough in the system, it can allow the infection to persist and potentially become resistant.

Cilastatin is co-administered with imipenem to prevent such degradation by inhibiting the enzyme responsible. This protection ensures that the antibiotic remains intact and efficacious until it performs its action against bacterial pathogens.

Carbapenems

Carbapenems are a class of highly effective antibiotics used to treat a wide range of infections. They are beta-lactam antibiotics, similar to penicillins and cephalosporins, but with a broader spectrum of action.

Imipenem is one of the most well-known carbapenems and is used against various gram-positive, gram-negative, and anaerobic bacteria. However, carbapenems can be particularly susceptible to enzymatic degradation within the body.

To counter this, imipenem is administered with cilastatin. By preventing the hydrolysis of imipenem, cilastatin allows the drug to remain effective for longer periods, ensuring that it can properly combat bacterial infections. This combination is essentially important in clinical settings where robust treatment is required.

Renal Tubule Enzymes

Renal tubule enzymes are proteins within the kidneys that play roles in various metabolic processes, including drug metabolism. Among these enzymes is dehydropeptidase, which specifically acts on imipenem.

The presence of this enzyme in the renal tubules means that as imipenem circulates through the kidneys, it risks being broken down before it can exert therapeutic effect. This is why inhibiting this enzyme is crucial when administering imipenem.

By pairing imipenem with cilastatin, the natural action of renal tubule enzymes is hindered, allowing imipenem to retain its active form. This, in turn, helps maintain the potency of the antibiotic, granting it the time required to effectively attack and eliminate the infection-causing bacteria.