Module 9 14 Sulfonamide Antibiotics and Trimethoprim Flashcards
Question
Answer
What role did sulfonamides play in the treatment of bacterial infections when first introduced in the 1930s?
Sulfonamides significantly reduced morbidity and mortality from susceptible infections when first introduced in the 1930s.
What led to the decline in the use of sulfonamides over time?
The development of penicillin and newer antibiotics resulted in a significant decline in the use of sulfonamides.
What are the primary uses of sulfonamides today?
Sulfonamides, especially in combination with trimethoprim, are commonly used for treating urinary tract infections (UTIs).
Are sulfonamides typically bacteriostatic or bactericidal?
Sulfonamides are typically bacteriostatic, meaning they inhibit bacterial growth.
Why are sulfonamides considered as a group rather than focusing on individual prototypes in discussions?
The similarities among sulfonamides are more significant than the differences, making it more practical to discuss them as a group.
What are sulfonamides structurally related to, and how does this relate to their antimicrobial action?
Sulfonamides are structurally related to para-aminobenzoic acid (PABA), a component of folate. Their antimicrobial action is based on this structural similarity to PABA.
How do sulfonamides inhibit bacterial growth?
Sulfonamides inhibit bacterial growth by blocking the synthesis of tetrahydrofolate, which is a derivative of folate. This disruption prevents bacteria from synthesizing essential components like DNA, RNA, and proteins.
Why do sulfonamides not harm mammalian cells?
Sulfonamides do not harm mammalian cells because of the difference in how bacteria and humans acquire folate.
What is the consequence of blocking tetrahydrofolate synthesis in bacteria?
Blocking tetrahydrofolate synthesis in bacteria leads to their inability to produce essential components like DNA, RNA, and proteins, ultimately inhibiting their growth.
How does the mode of folate acquisition by bacteria and mammalian cells explain the selective action of sulfonamides?
Bacteria must synthesize folate, while mammalian cells acquire it directly from the diet. Sulfonamides target the folate synthesis pathway, making them effective against bacteria without harming human cells.
What types of bacteria are susceptible to sulfonamides?
Sulfonamides are effective against gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA), and gram-negative bacilli.
Which other microorganisms are sensitive to sulfonamides?
Sulfonamides also target Listeria monocytogenes, actinomycetes (e.g., Nocardia), chlamydiae (e.g., Chlamydia trachomatis), some protozoa (e.g., Toxoplasma species, plasmodia, Isospora belli), and two fungi: Pneumocystis jirovecii and Paracoccidioides brasiliensis.
What is the status of bacterial resistance to sulfonamides?
Many bacterial species have developed resistance to sulfonamides.
Among which bacterial species is resistance to sulfonamides particularly high?
High resistance is observed among gonococci, meningococci, streptococci, and shigellae.
What are the principal mechanisms of bacterial resistance to sulfonamides?
The main resistance mechanisms are reduced sulfonamide uptake, sufficient synthesis of PABA to overcome inhibition, and alteration in the structure of dihydropteroate synthetase to reduce binding and inhibition by sulfonamides.
How can resistance to sulfonamides be acquired?
Resistance may be acquired through spontaneous mutation or via the transfer of plasmids that carry antibiotic resistance genes, known as R factors.
What was the historical use of sulfonamides in medicine?
Sulfonamides were once widely used for treating bacterial infections.
Why are the applications of sulfonamides now limited?
The limited use of sulfonamides today is primarily due to the introduction of less toxic bactericidal antibiotics and the emergence of sulfonamide resistance.
What is the main medical indication for sulfonamides in the present day?
The principal indication for sulfonamides is the treatment of urinary tract infections (UTIs).
What is the primary medical application of sulfonamides like sulfamethoxazole?
Sulfonamides, especially sulfamethoxazole, are often the preferred drugs for the treatment of acute urinary tract infections (UTIs).
Which bacterium is the leading cause of UTIs, and how does it usually respond to sulfonamides?
Escherichia coli is the most common cause of UTIs, and it typically shows sensitivity to sulfonamides.
Why is sulfamethoxazole, often in combination with trimethoprim, favored for UTI treatment?
Sulfamethoxazole is favored for UTI treatment due to its good solubility in urine and its ability to achieve effective concentrations within the urinary tract.
For which infections is sulfonamides like sulfamethoxazole used as a valuable treatment?
Sulfonamides are useful for nocardiosis, Listeria species infections, and Pneumocystis jirovecii infections.
What are the alternative treatments provided by sulfonamides for Chlamydia trachomatis infections, and which specific infections do they target?
Sulfonamides serve as alternatives to doxycycline and erythromycin for infections caused by Chlamydia trachomatis, including trachoma, inclusion conjunctivitis, urethritis, and lymphogranuloma venereum.
In what protozoal infections are sulfonamides, in combination with pyrimethamine, effective treatments?
Sulfonamides, when combined with pyrimethamine, are used to treat toxoplasmosis and malaria caused by chloroquine-resistant Plasmodium falciparum.
What is the role of topical sulfonamides in medical practice, and where are they applied?
Topical sulfonamides are used to treat superficial eye infections and to prevent bacterial colonization in burn patients.
How does sulfasalazine, a specific sulfonamide, contribute to the treatment of ulcerative colitis, and is its effect based on inhibiting microbial growth?
Sulfasalazine is used to treat ulcerative colitis, but its therapeutic benefits in this condition are not related to inhibiting microbial growth.
How well are sulfonamides absorbed when administered orally?
Sulfonamides are well absorbed after oral administration.
Where are sulfonamides effectively distributed within the body, and what can be the concentration in various body fluids compared to the blood?
Sulfonamides are distributed to various body tissues and fluids, with concentrations in fluids like pleural, peritoneal, ocular, and similar fluids reaching as high as 80% of the concentration in the blood.
Do sulfonamides cross the placental barrier, and what are the implications of this capability?
Yes, sulfonamides can cross the placental barrier, resulting in sufficient drug levels in the fetus. This can lead to both antimicrobial effects and potential toxicity in the developing fetus.
What is the peak concentration time for sulfadiazine, a sulfonamide antibiotic?
The peak concentration for sulfadiazine is reached 3 to 6 hours after administration.
What is the protein binding percentage of sulfadiazine?
Sulfadiazine has a protein binding of 38% to 48%.
How is sulfadiazine metabolized?
Sulfadiazine is metabolized through acetylation.
What is the half-life of sulfadiazine, and how is it primarily eliminated?
The half-life of sulfadiazine is approximately 10 hours, and it is primarily eliminated through urine.
What is the peak concentration time for trimethoprim?
The peak concentration for trimethoprim is reached within 1 to 4 hours after administration.
What is the protein binding percentage of trimethoprim?
Trimethoprim has a protein binding of 44%.
How is trimethoprim metabolized?
Trimethoprim is metabolized through demethylation, oxidation, and hydroxylation.
What are the half-lives of sulfamethoxazole and trimethoprim in combination products like Bactrim?
Sulfamethoxazole has a half-life of 9 to 12 hours, while trimethoprim has a half-life of 8 to 10 hours.
How are sulfamethoxazole and trimethoprim primarily eliminated in the body?
Both sulfamethoxazole and trimethoprim are primarily eliminated through urine.
What is the typical initial dose and subsequent dose for adults taking Sulfadiazine, an oral sulfonamide?
Adults typically receive an initial dose of 2-4 grams, followed by 2-4 grams every 24 hours in divided doses.
How is the dosing regimen different for children over 2 months receiving Sulfadiazine?
Children over 2 months receive an initial dose of 75 mg/kg per day divided into 4-6 doses, followed by a maintenance dose of 150 mg/kg per day (up to 6 grams) in divided doses.
Why is it recommended to avoid taking oral sulfonamides like Sulfadiazine with vitamin C or acidifying drinks?
Avoiding vitamin C and acidifying drinks helps reduce the risk of crystalluria.
What is the dosing regimen for adults taking Sulfamethoxazole (+ trimethoprim) like Bactrim?
Adults take 800 mg SMZ/160 mg TMP tablets every 12-24 hours.
How is the dosing regimen different for children over 2 months receiving Sulfamethoxazole (+ trimethoprim)?
Children initially take 4 mg TMP/kg every 12 hours, which may be increased to 20 mg TMP/kg per day.
What precautions should be taken when using Silver sulfadiazine (Silvadene) topically?
It should not be used on the face to prevent blue-green or gray discoloration.
How should Mafenide (Sulfamylon) be applied topically?
A thin layer should be applied to the affected skin 1-2 times per day, and the cream should cover the burned area.
What is the dosing regimen for Sulfacetamide ophthalmic (Bleph-10, Diosulf, Sodium Sulamyd)?
For the solution, 1-2 drops are administered every 2-3 hours. For the ointment, it is applied every 3-4 hours, with increased time intervals when tapering off.
What is the dosing regimen for adults taking Trimethoprim (Primsol)?
Adults take 100 mg every 12 hours or 200 mg every 24 hours.
How should Trimethoprim be administered to children over 2 months?
Children receive 4-12 mg/kg per day divided into two 12-hour doses and should be administered with food or milk.
What are some of the adverse effects associated with sulfonamides?
Adverse effects of sulfonamides include hypersensitivity reactions, blood dyscrasias, and kernicterus in newborns.
What is hypersensitivity in the context of sulfonamides?
Hypersensitivity refers to an overreaction of the immune system to sulfonamide drugs, resulting in allergic reactions.
What are blood dyscrasias in the context of sulfonamides?
Blood dyscrasias are abnormal changes in blood components, such as red blood cells, white blood cells, and platelets, which can occur as an adverse effect of sulfonamide use.
Who is at risk of developing kernicterus due to sulfonamide exposure?
Kernicterus is a condition that primarily affects newborns, and it can be associated with sulfonamide exposure. It involves the accumulation of bilirubin in the brain, leading to neurological damage.
What percentage of patients may experience hypersensitivity reactions to sulfonamides?
Approximately 3% of patients may experience hypersensitivity reactions to sulfonamides.
What are some mild hypersensitivity reactions associated with sulfonamide use?
Mild hypersensitivity reactions can include rash, drug fever, and photosensitivity.
How can patients minimize the risk of photosensitivity reactions when taking sulfonamides?
To reduce the risk of photosensitivity reactions, patients should:Avoid prolonged exposure to sunlight.Wear protective clothing.Apply sunscreen to exposed skin.
What advice should be given to patients taking sulfonamides regarding the prescribed course of treatment?
Patients should complete the full prescribed course of treatment, even if their symptoms improve before the course is finished.
Why is it recommended that patients taking oral sulfonamides drink at least 8 to 10 glasses of water or noncaffeinated fluids per day?
This is advised to reduce the risk of crystalluria. Caffeine can be consumed in addition to these fluids.
What precautions should patients take to prevent photosensitivity reactions while using sulfonamides?
Patients should:Avoid prolonged exposure to sunlight. Wear protective clothing. Apply sunscreen to exposed skin. Avoid tanning beds.
Why is it important for patients to report signs of hypersensitivity, such as a rash?
Reporting hypersensitivity signs promptly is essential to address any adverse reactions.
In which cases are topical sulfonamides still used, and why have they become less common?
Topical sulfonamides are now less commonly used due to the high frequency of hypersensitivity reactions. They are generally reserved for ophthalmic infections, burns, and bacterial vaginosis caused by Gardnerella vaginalis and a mixed population of anaerobic bacteria.
What is the most severe hypersensitivity response to sulfonamides, and what is its mortality rate?
The most severe hypersensitivity reaction to sulfonamides is Stevens-Johnson syndrome, with a mortality rate of about 25%.
What are the symptoms of Stevens-Johnson syndrome?
Symptoms include widespread skin and mucous membrane lesions, fever, malaise, and toxemia.
Why were long-acting sulfonamides banned in the United States?
Long-acting sulfonamides were banned due to their higher likelihood of inducing Stevens-Johnson syndrome.
Can short-acting sulfonamides also cause Stevens-Johnson syndrome, and how common is this?
Short-acting sulfonamides may rarely cause the syndrome, but the incidence is low.
What action should be taken if any type of skin rash is observed in a patient taking sulfonamides?
Sulfonamides should be immediately discontinued if any type of skin rash is observed.
Who should not be given sulfonamides, and why?
Patients with a history of severe hypersensitivity to chemically related drugs should not be given sulfonamides, although the risk of cross-reactivity with these agents is probably low.
What is the common feature among various drugs listed under “Other Sulfonamide Drugs”?
The common feature is that they contain sulfonamide groups in their chemical structure.
Name some therapeutic classes or medical conditions for which sulfonamide drugs are used.
Sulfonamide drugs are used in various therapeutic classes and medical conditions, including alpha1 blockers, anticonvulsants, antidiabetic agents (sulfonylureas), antidysrhythmic drugs, antimigraine drugs, diuretics (carbonic anhydrase inhibitors, loop diuretics, thiazide and thiazide-related diuretics), protease inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and urocosuric drugs.
Can you provide examples of specific drugs in the “Other Sulfonamide Drugs” category?
Some examples include Tamsulosin, Topiramate, Glimepiride, Furosemide, Celecoxib, and Probenecid.
What medical conditions or diseases are these sulfonamide drugs used to treat?
These drugs are used to treat a wide range of medical conditions, including benign prostatic hyperplasia, epilepsy, diabetes, cardiac arrhythmias, migraines, glaucoma, and HIV infection, among others.
What genetic condition makes individuals more susceptible to hemolytic anemia caused by sulfonamides?
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an inherited trait, can make individuals more susceptible to hemolytic anemia when exposed to sulfonamides.
Who is most commonly affected by G6PD deficiency?
G6PD deficiency is more common among people of African and Mediterranean origin.
What are the symptoms of hemolytic anemia caused by sulfonamides?
Hemolysis can lead to symptoms such as fever, pallor, and jaundice.
Besides hemolytic anemia, what other blood-related complications can sulfonamides cause?
Sulfonamides can also lead to agranulocytosis, leukopenia, thrombocytopenia, and, rarely, aplastic anemia.
What precaution is recommended when sulfonamides are used over an extended period?
Regular blood tests should be conducted to monitor for potential adverse effects, especially when sulfonamides are used for an extended duration.
What is kernicterus, and what causes it in newborns?
Kernicterus is a disorder in newborns caused by the deposition of bilirubin in the brain. It results in severe neurologic deficits and potential death.
How is bilirubin normally prevented from entering the central nervous system (CNS) in infants?
Bilirubin is typically tightly bound to plasma proteins in infants’ blood, preventing it from entering the CNS.
How do sulfonamides contribute to the risk of kernicterus in infants?
Sulfonamides can displace bilirubin from plasma proteins, making it free and able to access the brain.
Why are infants particularly vulnerable to kernicterus when exposed to sulfonamides?
Infants are vulnerable to kernicterus because their blood-brain barrier is poorly developed, allowing bilirubin to enter the brain more easily.
What is the recommended precaution to avoid the risk of kernicterus in infants?
Sulfonamides should not be administered to infants younger than 2 months to prevent the risk of kernicterus.
Who else should avoid sulfonamide use due to the potential risk of kernicterus in infants?
Pregnant patients beyond 32 weeks of gestation and breastfeeding individuals should also avoid sulfonamide use to protect newborns from kernicterus.
Why should infants younger than 2 months not be given sulfonamides?
Infants younger than 2 months should avoid sulfonamides to prevent the risk of kernicterus, a potentially fatal condition.
What should pregnant women be cautious about when it comes to systemic sulfonamides?
Pregnant women should exercise caution with systemic sulfonamides, as they may cause birth defects, especially if taken during the first trimester. Near the end of pregnancy, sulfonamides can lead to kernicterus in the infant.
Why should breastfeeding women on sulfonamides be warned about breastfeeding infants younger than 2 months?
Sulfonamides are secreted in breast milk. Breastfeeding women on sulfonamides should be warned that breastfeeding an infant younger than 2 months can cause kernicterus.
What are the patient care concerns for older adults taking sulfonamides?
Older adults are more susceptible to adverse effects from sulfonamides, and these effects are more likely to be severe. Life-threatening effects, including neutropenia, Stevens-Johnson syndrome, and toxic epidermal necrolysis, occur more frequently in older adults.
Why did older sulfonamides pose a risk to the urinary system?
Older sulfonamides had low solubility, which could lead to the formation of crystalline aggregates in the urinary system, causing irritation, obstruction, and potentially life-threatening complications.
