Podcast
Questions and Answers
What is a defining feature of synthetic antimicrobial agents?
What is a defining feature of synthetic antimicrobial agents?
What was identified as the active substance resulting from the bioactivation of Prontosil rubrum?
What was identified as the active substance resulting from the bioactivation of Prontosil rubrum?
Which of the following is NOT one of the classifications of sulfonamides?
Which of the following is NOT one of the classifications of sulfonamides?
Why was the dye Prontosil rubrum significant in the development of antibiotics?
Why was the dye Prontosil rubrum significant in the development of antibiotics?
Signup and view all the answers
What characteristic distinguishes sulfasalazine in the context of sulfonamides?
What characteristic distinguishes sulfasalazine in the context of sulfonamides?
Signup and view all the answers
What is the pKa of the carboxyl group of PABA?
What is the pKa of the carboxyl group of PABA?
Signup and view all the answers
Which sulfonamide is mentioned as having a pKa of approximately 5.0?
Which sulfonamide is mentioned as having a pKa of approximately 5.0?
Signup and view all the answers
What is a consequence of sulfonamide drugs binding to plasma proteins?
What is a consequence of sulfonamide drugs binding to plasma proteins?
Signup and view all the answers
Which group is responsible for making the nitrogen in sulfanilamide partially electropositive?
Which group is responsible for making the nitrogen in sulfanilamide partially electropositive?
Signup and view all the answers
Why is sulfisoxazole acetyl preferred in pediatric preparations?
Why is sulfisoxazole acetyl preferred in pediatric preparations?
Signup and view all the answers
What factors may contribute to resistance against sulfonamides?
What factors may contribute to resistance against sulfonamides?
Signup and view all the answers
What is the primary use of sulfadiazine in its silver salt form?
What is the primary use of sulfadiazine in its silver salt form?
Signup and view all the answers
Which organisms are commonly susceptible to sulfisoxazole?
Which organisms are commonly susceptible to sulfisoxazole?
Signup and view all the answers
Which sulfa drug is utilized for the treatment of ulcerative colitis and Crohn's disease?
Which sulfa drug is utilized for the treatment of ulcerative colitis and Crohn's disease?
Signup and view all the answers
What physiological process is commonly associated with the excretion of sulfonamides?
What physiological process is commonly associated with the excretion of sulfonamides?
Signup and view all the answers
What is the most common adverse effect associated with sulfa drugs?
What is the most common adverse effect associated with sulfa drugs?
Signup and view all the answers
Which statement best describes the mechanism of action of Mafenide Acetate?
Which statement best describes the mechanism of action of Mafenide Acetate?
Signup and view all the answers
What role does dihydrofolate reductase play in bacterial metabolism?
What role does dihydrofolate reductase play in bacterial metabolism?
Signup and view all the answers
Which condition is least associated with sulfacetamide?
Which condition is least associated with sulfacetamide?
Signup and view all the answers
What distinguishes Silver Sulfadiazine in its mechanism of action compared to other sulfanilamides?
What distinguishes Silver Sulfadiazine in its mechanism of action compared to other sulfanilamides?
Signup and view all the answers
What potential serious adverse effects can occur with sulfa drug use?
What potential serious adverse effects can occur with sulfa drug use?
Signup and view all the answers
What is the standard ratio of trimethoprim to sulfamethoxazole in co-trimoxazole?
What is the standard ratio of trimethoprim to sulfamethoxazole in co-trimoxazole?
Signup and view all the answers
Which of the following infections can co-trimoxazole treat?
Which of the following infections can co-trimoxazole treat?
Signup and view all the answers
What are the most common side effects associated with trimethoprim-sulfamethoxazole?
What are the most common side effects associated with trimethoprim-sulfamethoxazole?
Signup and view all the answers
What type of bacterial resistance to trimethoprim is increasingly common?
What type of bacterial resistance to trimethoprim is increasingly common?
Signup and view all the answers
What is the primary therapeutic application of trimethoprim as a single agent?
What is the primary therapeutic application of trimethoprim as a single agent?
Signup and view all the answers
Which bacterium has been reported to overexpress dihydrofolate reductase in resistant strains?
Which bacterium has been reported to overexpress dihydrofolate reductase in resistant strains?
Signup and view all the answers
Co-trimoxazole is used to treat which of the following diseases?
Co-trimoxazole is used to treat which of the following diseases?
Signup and view all the answers
Which preparation forms of co-trimoxazole are available?
Which preparation forms of co-trimoxazole are available?
Signup and view all the answers
Study Notes
Synthetic Antimicrobial Agents
- Synthetic antimicrobial agents are not derived from natural products, so they aren't considered "antibiotics."
- Some synthetic antimicrobial agents are highly effective and widely used for treating infections.
Sulfonamides
- Prontosil rubrum, a red dye, was found to be active against streptococcal infections in vivo (in living organisms) but not in vitro (in a lab setting).
- The active component, p-aminobenzenesulfonic acid amide (sulfanilamide), is a byproduct of Prontosil rubrum metabolism in the liver.
- Sulfonamides are effective because they are similar to p-aminobenzoic acid (PABA), a crucial component in bacterial growth.
Bioactivation of Prontosil
- Prontosil is converted to sulfanilamide in the body (bioactivation).
Mechanism of Action
- Sulfonamides are structurally similar to PABA, a substrate for dihydropteroate synthase.
- By mimicking PABA, sulfonamides prevent the production of dihydrofolic acid which is a precursor to DNA synthesis.
Nomenclature of Sulfonamides
- Sulfonamide is a broad term, encompassing three types: -Aniline sulphonamides -Prodrugs that require activation -Non-aniline sulphonamides
Structure-Activity Relationships
- The functional groups that differ include the carboxyl of PABA and the sulfonamide moiety of sulfanilamide.
- The sulfonamide's aromatic ring has a strongly electron-withdrawing character causing the nitrogen atom to be partially electropositive..
- PABA's carboxyl group has a pKa of approximately 6.5
- Substituting one of the -NH2 groups in PABA for an electron withdrawing ring slightly decreases acidity and increases antibacterial activity.
Structure-activity relationships (continued)
- Reducing the pKa of the sulfonamide molecule to the range of PABA improves its activity.
- Examples: pKa of sulfisoxazole is approximately 5.0
- Clinically useful sulfonamides vary in the heterocyclic aromatic substituents on the sulfonamide nitrogen..
Pharmacokinetics
- Orally administered sulfonamides are well absorbed in the gastrointestinal tract, distributed widely, and eliminated by the kidney.
- They can bind to plasma proteins.
- Certain sulfonamides (like sulfisoxazole) can displace other protein-bound drugs and bilirubin (affecting newborns).
- Metabolism involves acetylation and glucuronidation.
- Resistance can occur due to decreased sensitivity of dihydropteroate synthase or increased production of PABA.
Therapeutic Applications
- Sulfisoxazole acetyl is used in pediatric preparations due to its tasteless nature.
- It is active against various bacterial organisms.
- Other sulfonamides are used topically (e.g., silver sulfadiazine for burns) or ophthalmically (e.g., sulfacetamide).
- Sulfonamides are used in the treatment of ulcerative colitis and Crohn's disease (sulfasalazine).
Co-trimoxazole
- A combination of trimethoprim and sulfamethoxazole, used against bacterial and certain fungal infections.
- Used for various infections, including urinary tract infections (UTIs)
Mechanism of action (Trimethoprim)
- Trimethoprim inhibits dihydrofolate reductase, which is crucial for bacterial DNA synthesis. This prevents the production of tetrahydrofolic acid
- The selectivity of trimethoprim against bacterial compared to mammalian enzyme arises from subtle (but significant) enzyme architectural differences.
Resistance
- Bacterial resistance to trimethoprim is becoming more common.
- Mechanisms of resistance involve mutations, like an amino acid change in certain enzymes, and overexpression of enzymes.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on synthetic antimicrobial agents, specifically sulfonamides and their mechanisms of action. This quiz covers the bioactivation of Prontosil and its impact on treating infections. Explore the structural similarities that enable sulfonamides to inhibit bacterial growth effectively.
