7.6. PDF task. Drugs that inhibit the synthesis of bacterial cytoplasm proteins and DNA

1.1 Classify the drug list into: Tetracyclines / Glycylcyclines / Aminoglycosides / Lincosamides / Macrolides / Ketolides / DNA gyrase inhibitors. Also: which bind 30S vs 50S?

Answer:

Tetracyclines - Doxycycline, Tetracycline, Minocycline (page 3).

Glycylcyclines - Tigecycline (page 8).

Aminoglycosides - Amikacin, Gentamicin, Kanamycin, Neomycin, Streptomycin, Tobramycin (page 3, 9) - CORRECTION: original sheet's "Streptotobramycin" merged two separate drugs, both belong here individually.

Lincosamides - Clindamycin (page 23). Macrolides - Azithromycin, Erythromycin, Clarithromycin (page 17).

Ketolides - Telithromycin (page 17). DNA gyrase inhibitors - CORRECTION: should include Norfloxacin and Ofloxacin too, missing from original list (page 26 names ofloxacin), plus Ciprofloxacin, Levofloxacin, Moxifloxacin, Oxolinic acid.

NOTE: Colistin and Fidaxomicin don't fit any of these 7 categories - colistin is a polymyxin (different lecture), fidaxomicin is a separate RNA-polymerase inhibitor (Q25). 30S binders: Tetracyclines, Glycylcyclines, Aminoglycosides. 50S binders: Macrolides, Ketolide, Lincosamide, Oxazolidones (page 2).

1.2 From which drug were they derived: Telithromycin, Tigecycline?

Answer: Telithromycin from Erythromycin (macrolide), page 17. Tigecycline from Minocycline (tetracycline), page 8.

2. Which groups of broad-spectrum antibiotics act on the steps of protein synthesis shown in the figure (1-4)? Explain mechanism.

Answer: 1) Tetracycline - binds REVERSIBLY (not irreversibly) to 30S subunit, prevents aminoacyl-tRNA from binding to mRNA-ribosome complex (page 4 - IMPORTANT CORRECTION, this is a classic exam distinction vs irreversible-binding drugs). 2) Aminoglycosides - binds irreversibly to 30S, disrupts initiation complex, mRNA misread, erroneous amino acids incorporated (page 10). 3) Chloramphenicol - inhibits peptidyl transferase, blocks peptide bond formation (page 2 groups it under 50S binders; this specific mechanism is standard pharmacology not spelled out verbatim in the lecture). 4) Macrolides - binds irreversibly to 50S, inhibits translocation by suppressing peptidyl transferase (page 17, near-verbatim match).

2. Properties of tetracyclines (underline the correct option in each pair).

Answer: Wide spectrum; Bacteriostatic; Act on chlamydia and mycoplasma; Usually NOT used in renal insufficiency, EXCEPT Doxycycline (excreted via bile, not metabolized); NOT used in hepatic insufficiency; FORM chelates with divalent/trivalent ions; ACCUMULATE in developing bone. All confirmed, pages 3, 5, 6, 8.

4. Most common tetracycline adverse effects and why?

Answer: GI disturbance (mucosal irritation, altered gut flora); Effects on calcified tissue (accumulation in bone/teeth - discoloration, hypoplasia, growth inhibition); Phototoxicity (free radicals from UV exposure); Fatal hepatotoxicity (pregnancy + high doses); Fanconi syndrome (correct spelling - not "Franconia") from outdated drugs - polyuria, polydipsia, aminoaciduria, proteinuria, glycosuria, acidosis. Matches page 6 closely. Lecture also lists vestibular problems, superinfection, and pseudotumor syndrome as additional adverse effects.

5. Contraindications of tetracyclines, explained.

Answer: Pregnancy/nursing; Children under 8 (no permanent teeth yet); Hypersensitivity; Severe hepatic impairment - all confirmed page 8. A 5th belongs here too: impaired renal function (except doxycycline) - page 8.

6. Name the aminoglycoside with each property: TB treatment/pregnancy contraindicated; best gram(-) activity + synergy + meningitis; oral use for intestinal infections only; inhaled for cystic fibrosis.

Answer: A) Streptomycin - TB second-line, contraindicated in pregnancy (page 15). B) Gentamicin - best Gram(-) activity, synergy with beta-lactams, intrathecal for meningitis (pages 15-16). C) Neomycin - oral use limited to intestinal infections (page 16). D) Tobramycin - inhaled for cystic fibrosis (page 11).

7. Macrolide properties (underline the correct option in each pair).

Answer: Medium-wide spectrum (page 17 says "medium-wide," not just "wide"); Resistant to gastric acid - MIXED: erythromycin is actually acid-labile (needs coated tablets), clarithromycin/azithromycin/telithromycin are acid-resistant (page 18); Act on Gram(+); Act on anaerobes; Bacteriostatic (bactericidal at high doses); Renal insufficiency - page 19 says "dose adjustment," not full avoidance; Hepatic insufficiency - contraindicated (page 19).

8. Mechanisms of bacterial resistance to macrolides? a) Esterases hydrolyze lactone ring b) Efflux pumps c) Methylation of 50S subunit binding region d) Increased oxygen concentration e) Decreased oxygen concentration f) Changes in 30S subunit

Answer: a, b, c are correct. a) Esterase synthesis hydrolyzing the lactone ring (page 21); b) Efflux pumps (page 21); c) Methylation of 23S rRNA near the 50S binding site (page 21). d, e, f are false distractors - not real macrolide resistance mechanisms per this lecture.

9. Why are ketolides and glycylcyclines reserved antibiotics?

Answer given: Serious side effects, used as last resort. PARTIAL MISMATCH: this lecture actually frames their reservation around treating resistant pathogens - tigecycline covers MRSA/VRE/ESBL producers (page 8), telithromycin is used for macrolide-resistant infections (page 21) - rather than emphasizing side-effect severity specifically.

10. Aminoglycoside properties (underline the correct option in each pair).

Answer: Wide spectrum; Act on P. aeruginosa; Bactericidal; NOT metabolized; CAUSE nephro/ototoxicity. All confirmed, pages 11-13.

11. Explain the mechanism of action of fluoroquinolones.

Answer: Near-verbatim match to page 26: "FQs block release of positively coiled DNA, normal transcription and replication cannot proceed." Fuller picture: DNA gyrase (topoisomerase II) normally creates ATP-dependent supercoiled DNA; fluoroquinolones block this, and gyrase inhibitors are bactericidal.

12. Fluoroquinolone properties (underline the correct option in each pair).

Answer: Wide spectrum; Absorbed well; Act on Gram(+); Act on Gram(-); CONTRAINDICATED in pregnant women. All confirmed, pages 25, 27-28.

13. What is the post-antibiotic effect? Which antibiotics have it?

Answer: Persistent suppression of bacterial growth after concentration falls below MIC. This exact definition is from a different lecture (7.1 Introduction), not restated in this deck. Of the three drugs listed, only fluoroquinolones' PAE is explicitly stated in this lecture (page 27: "Possess postantibiotic effect"). Aminoglycosides and macrolides having PAE is accurate general pharmacology but isn't spelled out in this specific deck's text.

14. Which antibiotic groups cause: nephrotoxicity, neurotoxicity, ototoxicity, hepatotoxicity, phototoxicity, teeth hypoplasia, connective tissue growth inhibition, pseudomembranous enterocolitis?

Answer: Nephrotoxicity - Tetracyclines (not doxycycline), Aminoglycosides. Glycylcyclines is likely WRONG here - page 9 states tigecycline can be given in renal insufficiency, suggesting it's renal-safe, not nephrotoxic. Neurotoxicity - Aminoglycosides (neuromuscular paralysis), Fluoroquinolones (pages 13-14, 28). Ototoxicity - Aminoglycosides, Macrolides (pages 13, 19). Hepatotoxicity - Tetracyclines, Macrolides, Glycylcyclines (this one fits, page 9 notes dose adjustment needed for hepatic disorders). Phototoxicity - Tetracyclines, Fluoroquinolones (pages 6, 28). Teeth hypoplasia - Tetracyclines (page 6). Connective tissue growth inhibition - Tetracyclines (bone/teeth growth, page 6) and Fluoroquinolones (tendon rupture, page 28). Pseudomembranous enterocolitis - Lincosamides (page 24).

15. Which antibiotic groups treat osteomyelitis? Why? a) Tetracyclines b) Macrolides c) Lincosamides d) Fluoroquinolones

Answer: Both c) Lincosamides and d) Fluoroquinolones - not just one. Page 24 explicitly lists osteomyelitis as a lincosamide indication; page 29 explicitly lists bone/joint infections from S. aureus or Gram-negative bacilli as a fluoroquinolone indication. Reasoning: good bone penetration, effective against S. aureus.

16. Which antibiotic groups are contraindicated in pregnancy/children? Why? a) Tetracyclines b) Macrolides c) Penicillins d) Fluoroquinolones

Answer: a) Tetracyclines and d) Fluoroquinolones only. Tetracyclines affect developing teeth/bone (page 8); fluoroquinolones are teratogenic, cause articular erosions (page 28). Macrolides (b) shouldn't be included - erythromycin is explicitly used safely in pregnancy for chlamydial UTI (page 20). Penicillins (c) also shouldn't be included - generally safe in pregnancy, no teratogenic effect.

17. Sun avoidance needed with which antibiotics? a) Tetracyclines b) Macrolides c) Lincosamides d) Fluoroquinolones e) Glycylcyclines

Answer: a) Tetracyclines, d) Fluoroquinolones, e) Glycylcyclines. Tetracyclines and fluoroquinolones both explicitly cause phototoxicity (pages 6, 28); glycylcyclines share tetracyclines' adverse effect profile (page 9), so phototoxicity risk carries over.

18. Which antibiotics avoided in arrhythmia? a) Tetracyclines b) Macrolides c) Lincosamides d) Fluoroquinolones e) Glycylcyclines

Answer: b) Macrolides, d) Fluoroquinolones. Macrolides cause QT prolongation (page 19); moxifloxacin specifically is contraindicated in arrhythmia due to QT prolongation (page 28).

19. Young woman treated for chlamydia, painful sunburn despite sunscreen. Which drug? a) Tetracyclines b) Lincosamides c) Aminoglycosides d) Macrolides

Answer: a) Tetracyclines. Classic phototoxic reaction (page 6); doxycycline is a standard chlamydia treatment.

20. Oncology patient, P. aeruginosa UTI, developed hearing + kidney impairment. Which antibiotic? a) Tetracyclines b) Aminoglycosides c) Lincosamides d) Fluoroquinolones

Answer: b) Aminoglycosides. Classic combined oto/nephrotoxicity (page 13), used for P. aeruginosa infections (page 11).

21. 58-year-old, gastric pain/nausea, using milk, physician warns against it. Which drug? a) Tobramycin b) Gentamicin c) Clarithromycin d) Erythromycin e) Tetracycline

Answer: e) Tetracycline. Calcium in milk forms non-absorbable chelates with tetracycline (page 5) - the classic "no dairy with tetracyclines" teaching point.

22. 55-year-old, yellow-brown teeth since childhood. Which drug used in childhood? a) Aminoglycosides b) Lincosamides c) Fluoroquinolones d) Macrolides e) Tetracyclines

Answer: e) Tetracyclines. Classic tooth discoloration/hypoplasia (page 6).

23. 10-year-old, Gram-positive osteomyelitis. Which antibiotic? a) Clindamycin b) Tetracycline c) Tobramycin d) Erythromycin e) Ciprofloxacin

Answer: a) Clindamycin. Good bone penetration, strong Gram(+)/staph coverage, explicitly indicated for osteomyelitis (pages 23-24).

24. 50-year-old with chronic prostatitis, Achilles tendon rupture during exercise. Which drug class caused this?

Answer: Fluoroquinolones - connective tissue problems, tendon rupture (page 28). Fits clinically since fluoroquinolones are classic first-line for chronic bacterial prostatitis (good prostate penetration, page 27).

25. Macrolide-like drug used to treat pseudomembranous enterocolitis?

Answer: Fidaxomicin - inhibits RNA polymerase and protein transcription, used for C. difficile pseudomembranous colitis (page 22, word-for-word match).