Bacterial Protein Synthesis Antibiotics Flashcards by Cassidy West-Santos

Which drugs inhibit the formation of the initiation complex?

Aminoglycosides (30s) and Linezolid (50s)

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Which drugs inhibit amino acid incorporation?

Tetracyclines (30s)

Dalfopristin/quinupristin (50s) aka Streptogramins

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Which drug inhibits formation of the peptide bond?

Chloramphenicol (50s)

Specifically, it inhibits the enzyme peptidyl transferase

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Which drugs inhibit translocation?

Macrolides and Clindamycin (50s)

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What reads mRNA?

Ribosomes

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Where does tRNA bind during bacterial protein synthesis?

The “P” or “A” site (the P site is only bound to once, during initiation)

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What is the initiating AA (aka which AA contains the AUG codon)?

Formyl methionine

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What is a unique property of formyl methionine?

Chemokine for neutrophils and macrophages

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Why are aminoglycosides bacteriocidal while Linezolid is bacteriostatic?

Aminoglycosides cause a shift in the reading frame and the incorporation of the wrong AA (think steric hindrance)

Linezolid inhibits the formation of the initiation complex by preventing the formation of the N-formylmethionyl-tRNA-ribosome-mRNA ternary complex

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Activity of Aminoglycosides

Bactericidal, accumulated intracellularly in microorganisms via an O2-dependent uptake (anaerobes are innately RESISTANT)

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What are Gentamicin, Tobramycin, and Amikacin used for?

Useful against gram-negative rods

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Synergistic actions of aminoglycosides

Enterococci = aminoglycosides + penicillin G

P. aeruginosa = aminoglycosides + extended spectrum penicillin or 3rd generation cephalosporin

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Streptomycin

Aminoglycoside used in TB and is DOC for bubonic plague

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Resistance to aminoglycosides

Innate = anaerobes

Production of conjugating enzyme = eliminated too fast

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Pharmacokinetics of aminoglycosides

Glyco = Sugar = Water soluble

Polar compounds (i.e., not absorbed orally or widely distributed into tissues)

Renal elimination (major dose reduction needed in renal dysfunction)

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Side effects of aminoglycosides

Nephrotoxicity
Ototoxicity
Neuromuscular blockade (decreased ACh)

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What are the components of triple antibiotic ointment?

Neomycin
Polymyxin
Bacitracin

*Neomycin is the component that leads to contact dermatitis

Explain One-Daily Dosing of Aminoglycosides

Antibacterial effects depend mainly on “peak drug level” and not “time”

The effects of aminoglycosides continue even when blood levels of the drug drop below the MIC (aka PAE)

(Toxicity depends on blood level and the time that such levels are > than a specific threshold)

MIC = minimum inhibitory concentration

PAE = post-antibiotic effect

Activity and clinical uses of tetracycline

Bacteriostatic drugs, actively taken up by susceptible bacteria

“broad spectrum” antibiotics with good activity versus chlamydial and mycoplasmal species, H pylori, Rickettsia, Borrelia burgdorferia…

Backup drug for treponema

Doxycycline

DOC in lyme disease (Borrelia burgdorferi)

Lipid soluble

Useful in prostatitis (from chlamydia or n. gonorrhea) because it reaches high levels in prostatic fluid

Minocycline

Water soluble Tetracycline

In saliva and tears (good for gingivitis) at high concentrations and used in the meningococcal carrier state

Demeclocycline

Tetracycline used in SIADH (blocks ADH receptor function)

Why can’t you take tetracyclines with your meals?

They are Chelators

aka they bind divalent cations (Ca²⁺, Mg²⁺, Fe²⁺) which decreases their absorption

aka DO NOT take with food

Resistance to tetracyclines

Pumps (p. glycoprotein)

Side effects of **tetracyclines**

1. **Tooth enamel dysplasia** 2. **Phototoxicity** 3. GI distress 4. Vestibular dysfunction (minocycline) 5. Liver dysfunction during pregnancy \*\*\*Contraindicated in children (b/c it decreases bone growth) and in pregnant women

Activity and clinical uses of **Chloramphenicol**

Bacteriostatic with a wide spectrum of activity "phen" = lipid soluble = (1) crosses BBB, (2) metabolized in the liver, (3) not contraindicated in renal dysfunction

pharmocokinetics of **chloramphenicol**

Orally effective with good tissue distribution (including CSF) Metabolized by hepatic glucuronidation (dose reduction required in liver dysfunction and in neonates) Inhibition of cP450

Side effects of **chloramphenicol**

Dose-dependent bone marrow suppression (aplastic anemia) -similar to anticancer agents "gray baby" syndrome in neonates (decreased glucuronosyl transferase) -toxic and diplaces bilirubin

Which drugs are contraindicated in pregnancy?

1. **Aminoglycosides** 2. **Fluoroquinolones** 3. **Sulfonamides** 4. **Tetracyclines** Pregnant people are F.A.T.S.

Which 3 drugs are notorious for phototoxicity?

1. **Tetracylines** 2. **Sulfonamides** 3. **Quinolones** **T**oxic **Su**n **Qui**lts Skin

What type of drugs are **Erythromycin**, Azithromycin, and clarithromycin? How do they work? (HINT: all have "thro" in their name)

Macrolides: wide-spectrum antibiotics that inhibit translocation Gram (+) cocci [not MRSA], **atypical organisms**, campylobater, **MAC (*need a "mac" for MAC)***, H pylori **DOC for legionella pneumophilia** Atypicals = Chlamydia, Mycoplasma, and Ureaplasma

**Telithromycin**

a ketolide active against macrolide-resistant S. pneumonia

Side effects of **macrolides**

1. Stimulate motilin receptors and cause GI distress 2. Reversible deafness 3. Increased QT interval (Eat a big MAC = **GI distress**...if you **don't listen** to how bad fast food is = **heart attack**)

Resistance to **Macrolides**

Methyltransferases (cannot recognize 50s binding site)

Why are **macrolides** commonly used to treat community acquired pneumonia (atypical)

Most common organisms responisble are m. pneumoniae and c. pneumoniae (in smokers, pneumococcus are more frequently the pathogen) **Macrolides** have activity against most strains of these organisms (other than viruses)

**Clindamycin**

Not a **macrolide**, but has the same MOA and resistance Narrow spectrum: **gram (+) cocci [including MRSA]**, anaerobes [backup drug for B fragilis] Clinical value in **osteomyelitis** (which is often caused by Staph aureus)

Side effect of **Clindamycin**

Pseudomembranous colitis (treated with metronidazole)

Spectrum for **Linezolid**

Treatment of VRSA, VRE, and drug-resistant pneumococci

Side effect of **Linezolid**

BM suppression (platelets)

MOA of **quinupristin-dalfoprisitin**

**Streptogramins** that act in concert via several mechansims: BLUF = block AA incorporation 1. binding to sites on 50s, they prevent interaction of amino-acyl-tRNA with acceptor site and stimulate its dissociation 2. decrease the release of completed polypeptide by blocking its extrusion

Spectrum for **streptogramins**

Used parenterally in severe infections caused by VRSA and VRE, as well as other drug-resistant gram (+) cocci

Difference between **streptogramins** and **linezolid**

**Streptogramins** are used for E faecium but not for E faecalis **Linezolid** is used for both types of enterococci