Pharmacology - Antimicrobial Drugs - Effect on Gene Function in Bacteria

Vocabulary flashcards based on lecture notes about antimicrobial drugs affecting gene function in bacteria.

Antimicrobial Drugs

Drugs that target unique bacterial processes with acceptable selective toxicity, generally well-tolerated by humans.

Examples of drugs affecting gene function in bacteria

Sulfonamides, trimethoprim, quinolones, and nitrofurantoin.

Sulfonamides Mechanism

Inhibits folic acid synthesis; selective toxicity due to humans not synthesizing folic acid.

Trimethoprim Mechanism

Inhibits dihydrofolate reductase; selective inhibition in bacteria.

Synergistic effect of Sulfamethoxazole and Trimethoprim

Sequential blockade of folic acid synthesis.

Mechanisms of Resistance to Sulfonamides and Trimethoprim

Alterations in enzyme structure, drug efflux, overproduction of PABA.

Plasma Concentration Ratio of 20:1

Ratio of sulfamethoxazole to trimethoprim for optimal synergism.

Drug Formulation Ratio is 5:1

Ratio of sulfamethoxazole to trimethoprim in formulations.

Sulfonamide Variations

Structural differences leading to variations in pharmacokinetics.

Sulfonamide Pharmacokinetics

High protein binding, potential for drug interactions.

Sulfonamide Contraindications

Avoid in late pregnancy and early infancy due to risk of kernicterus.

Sulfonamide Metabolism

Acetylation in the liver, metabolites can precipitate in urine causing crystalluria.

Cotrimoxazole Spectrum

Resistance has increased; used for Listeria, Brucella, Pneumocystis jiroveci, Stenotrophomonas maltophilia, and Burkholderia cepacia.

Cotrimoxazole Use

Drug of choice for Pneumocystis jiroveci pneumonia.

Cotrimoxazole alternative use

Alternative for listerial meningitis in penicillin-allergic patients.

Sulfonamide Derivatives

Sulfadiazine (for toxoplasmosis), silver sulfadiazine (topical for burns), sulfadoxine (with pyrimethamine for malaria), sulfacetamide (eye drops), sulfasalazine (for ulcerative colitis).

Cotrimoxazole Side Effects

Skin reactions, GI upset, crystalluria, hemolysis (in G6PD deficiency), kernicterus, drug interactions.

Quinolone Examples

Nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin, gemifloxacin, moxifloxacin.

Generations 2, 3, and 4 of Quinolones are called

Fluoroquinolones

Quinolone Mechanism

Inhibit DNA gyrase and topoisomerase IV, disrupting DNA replication. Bactericidal.

Quinolone Resistance

Mutations in topoisomerase structure.

Quinolone Pharmacokinetics

Good absorption, penetration into tissues including prostate and CNS; renal excretion.

Quinolone Spectrum

Enterobacteriaceae, Pseudomonas aeruginosa (ciprofloxacin), Haemophilus, Moraxella, Vibrio, Brucella, Campylobacter, Meningococcus, Pneumococcus, Mycobacterium tuberculosis, atypical mycobacteria, Helicobacter pylori, Bacillus anthracis.

Quinolone Spectrum con't

Mycoplasma, Chlamydia pneumoniae, Legionella, Chlamydia trachomatis (ofloxacin best).

Nalidixic Acid Spectrum

Limited, E. coli and Shigella only.

Quinolone Uses

UTIs, prostatitis, urethritis/cervicitis, GI infections, respiratory infections, other microbial infections.

Quinolone Side Effects

GI upset, headache, dizziness, rare seizures, cartilage damage (in children), tendonitis, arrhythmia, glucose dysregulation, aortic rupture.

Quinolone Drug Interactions

Avoid use with divalent and trivalent cations; ciprofloxacin inhibits metabolism of theophylline and caffeine.

Nitrofurantoin Mechanism

Activated by bacterial nitroreductases, damages bacterial DNA. Urinary antiseptic.

Nitrofurantoin Spectrum

E. coli, Enterococcus, Staphylococcus, Klebsiella, Proteus. Effective only for cystitis.

Nitrofurantoin Uses

Used for prophylaxis and treatment of cystitis; safe in pregnancy.

Nitrofurantoin Side Effects

Anorexia, nausea, vomiting, rash, hemolysis (in G6PD deficiency), discolored urine, rare pulmonary toxicity, neurotoxicity, hepatotoxicity.