Sulfonamides and Antimetabolites Overview

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Questions and Answers

What is the primary mechanism by which sulfonamides exert their antimicrobial effect?

Inhibition of protein synthesis

Interference with folate production (correct)

Disruption of cell wall synthesis

Inhibition of DNA synthesis

Which of the following bacterial species is known to be stimulated by sulfonamides rather than inhibited?

Escherichia coli

Salmonella

Rickettsiae (correct)

Shigella

Based on the information provided, which of the following statements accurately describes the spectrum of activity for sulfonamides?

Sulfonamides are primarily effective against anaerobic bacteria.

Sulfonamides are effective against a broad range of bacteria, including gram-positive and gram-negative species. (correct)

Sulfonamides are exclusively effective against gram-positive bacteria.

Sulfonamides are only effective against specific types of bacteria, such as Escherichia coli and Salmonella.

Which of the following is NOT a common route of administration for sulfonamides?

Inhalation (C) Signup and view all the answers

What is a primary limitation of topical sulfonamide formulations?

High risk of sensitization (D) Signup and view all the answers

Which of the following statements about sulfonamide bioavailability is correct?

The extent of protein binding varies among different sulfonamide drugs. (D) Signup and view all the answers

Which of the following factors is NOT a major difference between various sulfonamides?

Mechanism of action (A) Signup and view all the answers

Based on the provided information, which of the following is a common first-line indication for sulfonamide use?

Uncomplicated urinary tract infections (UTIs) (D) Signup and view all the answers

Which of the following routes of administration is considered less desirable for sulfonamides due to their low activity and high risk of allergic sensitization?

Topical (B) Signup and view all the answers

Which of the following conditions are typically treated with sulfonamides via the oral route?

Intramuscular (B) Signup and view all the answers

What is the primary reason sulfonamides are typically administered intravenously rather than intramuscularly?

Sulfonamides are alkaline in nature and can cause tissue damage with intramuscular injection. (D) Signup and view all the answers

Which of the following is NOT a characteristic of sulfonamide metabolism and excretion?

Sulfonamides are primarily metabolized in the stomach. (B) Signup and view all the answers

Which of the following is true regarding sulfonamides and bacterial resistance?

Sulfonamide resistance has contributed to the decline in their use for certain infections. (B) Signup and view all the answers

Silver sulfadiazine is preferred to mefenide acetate for wound infection prevention due to which of the following reasons?

Silver sulfadiazine is less toxic and causes fewer side effects. (D) Signup and view all the answers

Intravenous sulfonamides are usually reserved for which type of patients?

Patients who cannot take medication orally. (B) Signup and view all the answers

Which of the following is an example of a sulfonamide commonly used for urinary tract infections?

Sulfisoxazole (C) Signup and view all the answers

What are common side effects associated with sulfonamides?

Skin rashes (A) Signup and view all the answers

Which condition may result from the crystallization of sulfonamides in urine?

Nephrotoxicity (C) Signup and view all the answers

How can the side effects of crystalluria be mitigated?

Maintaining an alkaline urine pH (C) Signup and view all the answers

What is kernicterus and how is it related to sulfonamide usage?

It is an accumulation of bilirubin in the brain due to displacement by sulfas. (A) Signup and view all the answers

Which of the following sulfonamides is a newer soluble agent used to treat crystalluria?

Sulfamethoxazole (D) Signup and view all the answers

What type of hematological disturbances can sulfonamides induce?

Hemolytic anemia (B) Signup and view all the answers

What is a direct toxicity effect of sulfonamides?

Nephrotic syndrome (C) Signup and view all the answers

Which of the following is not a common side effect of sulfonamides?

Hyperkalemia (A) Signup and view all the answers

Which enzyme is directly inhibited by sulfonamides, leading to the disruption of the folate pathway?

Dihydropterotate synthetase (C) Signup and view all the answers

What is the primary reason why sulfonamides exhibit selective toxicity?

Humans obtain folate from their diet, unlike bacteria (A) Signup and view all the answers

Which of the following is NOT a reason why the use of sulfonamides has become limited in recent practice?

High incidence of severe side effects (C) Signup and view all the answers

Trimethoprim, another antimetabolite, acts by inhibiting which enzyme?

Dihydrofolate reductase (C) Signup and view all the answers

Why is Trimethoprim considered to have selective toxicity?

It has a much higher affinity for bacterial dihydrofolate reductase than for the human enzyme (C) Signup and view all the answers

Which of the following statements about the structure of sulfonamides is CORRECT?

Sulfonamides share a structural similarity to PABA, which allows them to compete with PABA for the dihydropterotate synthetase enzyme (A) Signup and view all the answers

Which of these statements about the activity of sulfonamides is TRUE?

Sulfonamides inhibit the synthesis of bacterial folic acid, which is essential for purine, pyrimidine, and some amino acid synthesis (A) Signup and view all the answers

Study Notes

Sulfonamides (Antimetabolites)

Sulfonamides block the folate pathway, inhibiting DNA, RNA, and protein synthesis.
Tetrahydrofolate donates single carbon molecules for purines, pyrimidines, and certain amino acids.
Structurally similar to PABA, sulfonamides compete with PABA, preventing its incorporation into the folate pathway.
Trimethoprim inhibits dihydrofolate reductase, preventing DHF reduction to THF. This has low affinity for human dihydrofolate reductase, leading to selective toxicity.

Sulfonamides Introduction

Antimicrobial agents, less frequently used due to more potent alternatives.
Still valuable in chemotherapy.

Chemistry of Sulfonamides

Basic structure is sulphanilamide and analogues.
Substitutions on the amino group may reduce bacteriostatic activity.
PABA (p-Aminobenzoic acid) is crucial for this chemical pathway.

Sites of Antimetabolite Action

Sulfonamides compete with PABA for dihydropteroate synthetase.
This blocks folic acid and one-carbon carrier (THF) synthesis.
Essential cofactors for purines, pyrimidines, and amino acids are not produced.
Sulfonamides are bacteriostatic and toxic to organisms that synthesize their own folic acid.
Selective toxicity: Limited effect on organisms utilizing preformed folic acid, like humans.
Organisms susceptible to sulfonamides cannot utilize preformed folic acid but must synthesize from PABA.

Pharmacokinetics of Sulfonamides

Administered orally, parenterally, topically, and as suppositories.
Three main categories: oral absorbable, oral non-absorbable, and topical.
Most are well absorbed from the GI tract.
Poorly absorbed sulfonamides are limited to GI tract use.

Clinical Uses

Topical use (e.g., sodium sulfacetamide for bacterial conjunctivitis, silver sulfadiazine for wound infection, mafenide acetate for wound treatment)
Oral use for urinary tract infections (sulfa drugs, for example, sulfamethoxazole) and other bacterial infections
Intravenous use for severe infections or patients unable to tolerate oral medications (sodium salts of some sulfonamides)

Toxic Effects

Allergic reactions and direct toxicity are possible side effects.
Common effects include fever, skin rashes, photosensitivity, urticaria.
Possible side effects include crystalluria, nephrotoxicity, and hematuria. Possible other reactions include haematopoietic disturbances, hepatitis, dermatitis, and psychosis

Contraindications

Use in new-borns and pregnant women is contraindicated due to the potential for kernicterus

Resistance to Sulfonamides

Resistance may arise from plasmid transfer or mutations.
Mechanisms include enzyme alteration, decreased uptake, and increased PABA synthesis.

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Description

This quiz covers the structure, function, and action of sulfonamides as antimetabolites in antimicrobial therapy. Learn about their role in blocking the folate pathway and how they compare to other agents. Additionally, understand the chemistry involved and the implications for chemotherapy.