p.16
Pharmacokinetics of Sulfonamides
How do antacids like calcium carbonate affect fluoroquinolone absorption?
They reduce their absorption.
p.3
Mechanism of Action of Antifolates and Quinolones
What is the effect of inhibiting dihydropteroate synthase?
It inhibits bacterial folic acid synthesis.
p.20
Mechanism of Action of Quinolones
How does Nitrofurantoin work?
By damaging bacterial DNA.
p.27
Clinical Case Studies Related to Antifolate and Quinolone Use
What is the clinical presentation of the 40-year-old male with HIV?
Fever, cough, and difficulty breathing.
p.5
Mechanism of Action of Antifolates and Quinolones
What is the role of bacterial folate synthesis in relation to drugs?
It is a target for drugs that inhibit the same enzyme.
p.2
Preclinical Pharmacology of Antifolate Medications
What is the purpose of Sulfacetamide?
It is used as an antibiotic in eye drops.
p.18
Clinical Uses of Fluoroquinolones
Name some fluoroquinolones mentioned in the text.
Ciprofloxacin, Lomefloxacin, Levofloxacin, Ofloxacin.
p.7
Pharmacokinetics of Sulfonamides
What is the effect of fast acetylators on drug therapy?
Reduced therapeutic effect but lower risk of side effects.
p.3
Mechanism of Action of Antifolates and Quinolones
What enzyme do antifolate medications inhibit to affect folate production?
Dihydropteroate synthase.
p.20
Clinical Uses of Fluoroquinolones
What is Nitrofurantoin used for?
Treatment of uncomplicated UTIs and prophylaxis against UTIs in people prone to recurrent UTIs.
p.4
Mechanism of Action of Antifolates and Quinolones
What type of inhibitors are trimethoprim and sulfamethoxazole classified as?
Dihydrofolate reductase inhibitors.
p.25
Clinical Case Studies Related to Antifolate and Quinolone Use
What is the patient's hemoglobin level?
9.5 g/dL (normal 12 - 15 g/dL).
p.13
Mechanism of Action of Quinolones
How do quinolones interfere with bacterial function?
By inhibiting DNA synthesis.
p.2
Preclinical Pharmacology of Antifolate Medications
What role does Trimethoprim play in medicine?
It is an antibiotic that inhibits bacterial folic acid synthesis.
p.7
Pharmacokinetics of Sulfonamides
What are the two classifications of individuals based on acetylation rates?
Slow acetylators and fast acetylators.
p.11
Adverse Effects of Sulfonamides and Trimethoprim
What is a potential toxicity associated with trimethoprim-sulfamethoxazole?
Rash, fever, bone marrow suppression, hemolytic anemia in G6PD deficiency, kernicterus.
p.17
Adverse Effects of Sulfonamides and Trimethoprim
Why are these medications contraindicated in pregnancy and in children?
They may inhibit chondrogenesis and damage growing cartilage, causing arthropathy.
p.6
Resistance Mechanisms in Antifolate Medications
What is a physical mechanism of resistance to sulfonamides?
Impairment of permeability to the sulfonamide.
p.8
Pharmacokinetics of Sulfonamides
What causes crystalluria in certain medications?
Renally excreted metabolites.
p.14
Mechanism of Action of Quinolones
What does topoisomerase IV do after DNA replication?
Nicks and separates daughter DNA strands.
p.8
Adverse Effects of Sulfonamides and Trimethoprim
When should certain medications be avoided in pregnant women?
During the third trimester.
p.13
Mechanism of Action of Quinolones
Which topoisomerases do quinolones inhibit?
Topoisomerase II (DNA gyrase) and topoisomerase IV.
p.7
Pharmacokinetics of Sulfonamides
How are sulphonamides metabolized in the body?
They are metabolized in the liver by N-acetyltransferase.
p.21
Adverse Effects of Sulfonamides and Trimethoprim
What are some common toxicities associated with fluoroquinolones?
Neurotoxicity, tendonitis, and cartilage damage.
p.26
Clinical Case Studies Related to Antifolate and Quinolone Use
What symptoms did the 21-year-old woman present with?
Burning on urination and increased urinary frequency.
p.10
Adverse Effects of Sulfonamides and Trimethoprim
What are common hypersensitivity reactions to sulfonamides?
Photosensitivity, skin rashes, exfoliative dermatitis, urticaria, and Stevens-Johnson syndrome.
p.19
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
Name three aminoglycosides.
Gentamicin, amikacin, and tobramycin.
p.1
Mechanism of Action of Antifolates and Quinolones
What effects do antifolates have on DNA synthesis?
They inhibit DNA synthesis.
p.1
Resistance Mechanisms in Antifolate Medications
What are common resistance mechanisms to trimethoprim plus sulfamethoxazole?
Altered target sites and increased efflux.
p.15
Resistance Mechanisms in Antifolate Medications
What is one mechanism of resistance related to cell structure?
Altered cell wall permeability.
p.4
Mechanism of Action of Antifolates and Quinolones
What is the effect of combining trimethoprim-sulfamethoxazole with Pteridine?
It decreases resistance and provides synergy.
p.18
Clinical Uses of Fluoroquinolones
What are the clinical uses of fluoroquinolones?
Treatment of urinary tract infections (UTIs) and other gram-negative infections, especially in cases of drug resistance.
p.13
Mechanism of Action of Quinolones
What is the role of topoisomerase IV in bacteria?
Responsible for separation of replicated DNA during cell division.
p.7
Pharmacokinetics of Sulfonamides
What does N-acetyltransferase do to sulphonamides?
It adds an acetyl group to the drug, forming an N-acetylated derivative.
p.7
Pharmacokinetics of Sulfonamides
What is the risk associated with slow acetylators?
Higher risk of drug toxicity due to prolonged drug presence.
p.17
Adverse Effects of Sulfonamides and Trimethoprim
What are some central nervous system effects associated with these medications?
Insomnia, dizziness, and headache.
p.24
Adverse Effects of Sulfonamides and Trimethoprim
What type of medication did the woman start a week ago for her urinary tract infection?
Sulfamethoxazole-trimethoprim.
p.24
Adverse Effects of Sulfonamides and Trimethoprim
What physical examination findings were noted on the woman's skin?
Erythematous, well-demarcated patches on sun-exposed areas.
p.9
Clinical Uses of Fluoroquinolones
Which Gram-negative infections can sulfonamides treat?
E. coli, Salmonella, Shigella, H. influenzae.
p.1
Mechanism of Action of Antifolates and Quinolones
What is the mechanism of action of trimethoprim plus sulfamethoxazole?
They work synergistically to inhibit folate synthesis.
p.23
Mechanism of Action of Antifolates and Quinolones
What is the mechanism of action of co-trimoxazole in inhibiting bacterial growth?
Inhibition of nucleotide synthesis.
p.15
Resistance Mechanisms in Antifolate Medications
What type of mutations are associated with efflux pump proteins?
Plasmid-encoded mutations.
p.14
Mechanism of Action of Quinolones
How does topoisomerase IV function?
It creates transient double-strand breaks in DNA, allowing strands to pass through each other and relieving supercoiling tension.
p.2
Preclinical Pharmacology of Antifolate Medications
What is Sulfamethoxazole?
A type of sulfonamide antibiotic.
p.27
Clinical Case Studies Related to Antifolate and Quinolone Use
What does the chest x-ray reveal in this patient?
Diffuse, bilateral, interstitial infiltrates.
p.21
Mechanism of Action of Quinolones
What is the mechanism of action of fluoroquinolones?
They inhibit DNA replication by binding to DNA gyrase and topoisomerase IV.
p.21
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
Which types of bacteria are affected by fluoroquinolones?
Both Gram-negative and Gram-positive bacteria.
p.11
Mechanism of Action of Antifolates and Quinolones
What do folate antagonists block in the body?
Purine production and nucleic acid synthesis.
p.16
Pharmacokinetics of Sulfonamides
What substances impair the oral absorption of fluoroquinolones?
Divalent and trivalent cations, such as iron and calcium.
p.16
Pharmacokinetics of Sulfonamides
What effect does probenecid have on fluoroquinolone elimination?
It inhibits their elimination.
p.19
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
Name two ureidopenicillins.
Piperacillin and mezlocillin.
p.10
Adverse Effects of Sulfonamides and Trimethoprim
What is kernicterus and how can it be caused by sulfonamides?
Kernicterus is the displacement of bilirubin in newborns, which can be caused by sulfonamides.
p.9
Clinical Uses of Fluoroquinolones
Which Gram-positive infections can sulfonamides treat?
Staphylococcus (including community-acquired MRSA) and Streptococcus.
p.1
Adverse Effects of Sulfonamides and Trimethoprim
What are the most common adverse effects of trimethoprim plus sulfamethoxazole?
Rash, nausea, and hematologic reactions.
p.14
Mechanism of Action of Quinolones
What is the role of bacterial DNA gyrase?
It introduces negative supercoils in DNA and helps compact DNA while relieving torsional stress during replication.
p.25
Clinical Case Studies Related to Antifolate and Quinolone Use
What is the patient's reticulocyte count?
5.8% (normal 0.6 - 2.7%).
p.18
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
What type of bacteria do fluoroquinolones primarily target?
Gram-negative bacteria, with moderate to good activity against Gram-positive bacteria.
p.27
Mechanism of Action of Antifolates and Quinolones
What is the mechanism of action of Trimethoprim-sulfamethoxazole?
Dihydrofolate reductase inhibition.
p.17
Adverse Effects of Sulfonamides and Trimethoprim
What is a serious complication of tendinitis in adults?
The risk of tendon rupture.
p.17
Adverse Effects of Sulfonamides and Trimethoprim
What skin-related adverse effect can occur?
Phototoxicity and rashes.
p.16
Pharmacokinetics of Sulfonamides
When should oral fluoroquinolones be taken in relation to cation-containing products?
2 hours before or 4 hours after.
p.16
Pharmacokinetics of Sulfonamides
What should be done with fluoroquinolone dosage in patients with renal dysfunction?
The dose should be reduced.
p.10
Adverse Effects of Sulfonamides and Trimethoprim
What urinary issues can sulfonamides cause?
Crystalluria, hematuria, or even obstruction, especially at neutral or acid pH.
p.10
Adverse Effects of Sulfonamides and Trimethoprim
What adverse effect can trimethoprim or pyrimethamine cause?
Bone marrow suppression leading to leukopenia.
p.19
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
What are polymyxins?
Polymyxin B and colistin.
p.1
Mechanism of Action of Antifolates and Quinolones
What is the role of medications acting on bacterial ribosomes?
They affect mRNA translation.
p.1
Resistance Mechanisms in Antifolate Medications
What are common resistance mechanisms to quinolones?
Mutations in target enzymes and efflux pumps.
p.6
Resistance Mechanisms in Antifolate Medications
What is one mechanism of resistance to sulfonamides?
Mutation in bacterial dihydropteroate synthase.
p.15
Resistance Mechanisms in Antifolate Medications
What type of mutation is associated with resistance in DNA gyrase and topoisomerase IV enzymes?
Chromosome-encoded mutation.
p.4
Mechanism of Action of Antifolates and Quinolones
What is the combination of trimethoprim and sulfamethoxazole used for?
To enhance antimicrobial effectiveness and reduce resistance.
p.20
Mechanism of Action of Quinolones
Is Nitrofurantoin a type of fluoroquinolone?
No, it is not a fluoroquinolone.
p.14
Mechanism of Action of Quinolones
What are the actions performed by DNA gyrase?
Nicks double-stranded DNA, introduces negative supercoils, and reseals the nicked ends.
p.2
Preclinical Pharmacology of Antifolate Medications
What is Sulfadoxine commonly used for?
It is often used in combination therapies for malaria.
p.25
Clinical Case Studies Related to Antifolate and Quinolone Use
What medication did the patient recently complete a course of?
Trimethoprim-sulfamethoxazole.
p.27
Clinical Case Studies Related to Antifolate and Quinolone Use
What is the treatment given to the patient?
Trimethoprim-sulfamethoxazole (TMP-SMX).
p.11
Mechanism of Action of Antifolates and Quinolones
What is the synergistic combination of folate antagonists mentioned?
Trimethoprim - sulfamethoxazole.
p.13
Resistance Mechanisms in Antifolate Medications
What is a concerning trend regarding quinolones?
Resistance is increasing.
p.2
Preclinical Pharmacology of Antifolate Medications
What is Pyrimethamine primarily used for?
It is used to treat and prevent malaria.
p.11
Mechanism of Action of Antifolates and Quinolones
What is sulfadiazine used for?
It is another folate antagonist used in combination therapies.
p.7
Pharmacokinetics of Sulfonamides
Why is it clinically relevant to know a patient’s acetylator status?
It helps in adjusting drug doses to avoid toxicity and ensure efficacy.
p.26
Clinical Case Studies Related to Antifolate and Quinolone Use
What was the urine dipstick positive for in this patient?
Leukocyte esterase and nitrites.
p.24
Adverse Effects of Sulfonamides and Trimethoprim
What symptoms did the 32-year-old woman present with after starting a new medication?
A painful, red rash on her arms and face, worsened by sun exposure, associated with itching and burning.
p.19
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
What are carboxypenicillins?
Carbenicillin and ticarcillin.
p.19
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
What are examples of third-generation cephalosporins?
Ceftazidime and cefoperazone.
p.9
Clinical Uses of Fluoroquinolones
What is sulfasalazine used for?
It is a prodrug used in ulcerative colitis and rheumatoid arthritis.
p.9
Clinical Uses of Fluoroquinolones
What is the drug of choice (DOC) for Nocardia?
Sulfamethoxazole combined with Trimethoprim.
p.9
Clinical Uses of Fluoroquinolones
Which protozoan infection can be treated with sulfadiazine?
Toxoplasma gondii (with pyrimethamine).
p.1
Adverse Effects of Sulfonamides and Trimethoprim
What are the most common adverse effects of quinolones?
Gastrointestinal disturbances, CNS effects, and tendon rupture.
p.16
Pharmacokinetics of Sulfonamides
How are fluoroquinolones primarily eliminated from the body?
Mainly by the kidneys through filtration and active secretion.
p.1
Preclinical Pharmacology of Antifolate Medications
What are the main classes of medications discussed in PHM7?
Antifolate medications, quinolones, and inhibitors of protein synthesis.
p.1
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
What is the antimicrobial spectrum of trimethoprim plus sulfamethoxazole?
Broad-spectrum activity against various bacteria.
p.24
Adverse Effects of Sulfonamides and Trimethoprim
Which medication is most likely responsible for the woman's rash after sun exposure?
Sulfamethoxazole-trimethoprim.
p.24
Adverse Effects of Sulfonamides and Trimethoprim
What is a common adverse effect of sulfonamides like sulfamethoxazole?
Photosensitivity leading to rashes.
p.9
Mechanism of Action of Antifolates and Quinolones
When do sulfonamides become bactericidal?
When combined with Trimethoprim (e.g., sulfamethoxazole).
p.9
Clinical Uses of Fluoroquinolones
What fungus can be treated with sulfonamides?
Pneumocystis jiroveci (with backup drugs pentamidine and atovaquone).
p.1
Mechanism of Action of Quinolones
What is the mechanism of action of quinolones?
They inhibit bacterial DNA gyrase and topoisomerase IV.
p.26
Clinical Case Studies Related to Antifolate and Quinolone Use
What was the outcome after starting trimethoprim?
Rapid resolution of her symptoms.
p.9
Clinical Uses of Fluoroquinolones
Why are sulfonamides limited in use?
Due to multiple resistance.
p.19
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
What are two examples of quinolones?
Ciprofloxacin and levofloxacin.
p.1
Mechanism of Action of Quinolones
How do quinolones affect DNA integrity?
They disrupt DNA integrity.
p.1
Antimicrobial Spectrum of Trimethoprim and Sulfamethoxazole
What is the antimicrobial spectrum of quinolones?
Effective against a wide range of Gram-negative and some Gram-positive bacteria.
