**Question:** In cotrimoxazole, sulphamethoxazole and trimethoprim are in the ratio of-

A. 4:1
B. 1:1
C. 2:1
D. 3:1

**Correct Answer:** C. 2:1

**Core Concept:** Cotrimoxazole is a combination of two antimicrobial agents: sulfamethoxazole (SMX) and trimethoprim (TMP). These two components act synergistically to inhibit microbial growth and have been used commonly in the treatment of various infections.

**Why the Correct Answer is Right:** Cotrimoxazole is a prodrug, meaning it requires enzymatic activation to become biologically active. Sulfonamides, like sulfamethoxazole, are converted to their active form by the enzyme sulfonamide demethylase, which is inhibited by trimethoprim. Trimethoprim inhibits dihydrofolate reductase, an essential enzyme for bacteria to produce tetrahydrofolate, a precursor of purines and pyrimidines.

By inhibiting dihydrofolate reductase, trimethoprim prevents the conversion of dihydrofolate to tetrahydrofolate, which results in impaired synthesis of nucleotides and ultimately leads to bacterial cell death.

**Why Each Wrong Option is Incorrect:**

A. Cotrimoxazole has a 2:1 ratio of sulfamethoxazole to trimethoprim, meaning the correct answer is not 4:1.

B. Cotrimoxazole has a 2:1 ratio of sulfamethoxazole to trimethoprim, but the incorrect answer is not 1:1.

C. Cotrimoxazole has a 2:1 ratio of sulfamethoxazole to trimethoprim, which is the correct ratio.

D. Cotrimoxazole has a 2:1 ratio of sulfamethoxazole to trimethoprim, but the incorrect answer is not 3:1.

**Clinical Pearl:** The 2:1 ratio of sulfamethoxazole to trimethoprim in cotrimoxazole ensures that the two components work synergistically to inhibit microbial growth, enhancing their effectiveness against a wide range of bacteria, including Pneumocystis jirovecii, Haemophilus influenzae, and Mycobacterium tuberculosis.

**Why the Correct Answer is Right:** Cotrimoxazole has a 2:1 ratio of sulfamethoxazole to trimethoprim, which ensures that the two components work synergistically to inhibit microbial growth. In this case, the ratio of sulfamethoxazole to trimethoprim is 2:1, which is crucial for the drug's effectiveness against a wide range of pathogens.

**Why Each Wrong Option is Incorrect:**

A. A 4:1 ratio would mean that the concentration of trimethoprim is lower than sulfamethoxazole, which would impair the synergistic effect required for effective antimicrobial activity.

B. A 1:1 ratio would result in an ineffective combination therapy, as trimethoprim would