Pharm 33 Bacterial Infections: DNA Rep, Trascription, Translation Flashcards
Quinolone Mechanism
- Inhibit Type II Topoisomerases (Gyrase in Gram Negative) and Type IV Topoisomerases (In Gram Positive) after they have broken the DNA strand, thus keeping the DNA from being repaired. Bactericidal.
Quinolones, also called Fluoroquinolones
“FLOXACIN”
Ciprofloxacin
Ofloxacin
Levofloxacin
Quinolone Side Effects and Contraindications
- SE: Nausea, vomiting, diarrhea, rash, cartilage damage, tissue rupture, peripheral neuropathy, intracranial pressure, seizure and hypersensitivity.
- Cons: Concomitant Tizanidine with Ciprofloxacin and Hypersenstivity to Quinolones.
Rifamycin Derivative Mechanism
Binds to the Beta subunit of the bacterial RNA polymerase to form a highly stable complex which inhibits elongation of RNA synthesis after initiation. Some evidence shows that it blocks the path by which the nascent RNA emerges from the enzyme. Bactericidal.
Rifamycin Derivatives
Rifampin (Rifampicin)
Rifabutin
Rifamycin Derivative Side Effects and Contraindications
- SE: Throbocytopenia, hepatotoxicity, saliva, tear, sweat, and orange urine discoloration, elevated liver function tests, rash, flu-like illness (fever, vomiting), and jaundice.
- Cons: Active Neisseria Meningitis Infection
Rifamycin Considerations
- Rifampin is not used alone because of increased resistance.
- Rifampin may reduce cyclosporine concentration and efficiency.
- Don’t use Rifabutin and Clarithromycin together because C increases concentration of R and R decreases concentration of C.
Aminoglycoside Mechanism
Bind to the 16S rRNA of the 30S ribosomal subunit to cause missense mutations and misreads during elongation. Bactericidal.
Aminoglycosides
Streptomycin Neomycin Kanamycin Tobramycin Paromomycin Gentamycin Netilmicin Amikacin
Most Widely Used Aminoglycosides
Gentamicin, Tobramycin, and Amikacin because of lower toxicity and broader coverage of target organisms.
Aminoglycoside Side Effects and Contraindications
- SE: Ototoxicity (most important!), acute renal failure (nephrotoxicity), neuromuscular blockade, respiratory paralysis.
- Cons: Hypersensitivity to Aminoglycosides.
Aminoglycoside Consideration and Resistance Mechanisms
- Use mainly for Gram-Negative Bac.
- Works well with Beta lactam antibiotics (cell wall synthesis inhibitor)
- Resistance occurs by:
- — Production of a transferase enzymes that inactivates the Aminoglycoside
- — Impaired Drug entry
- — Mutation of the Drug Target on the 30S Ribosomal subunit.
Spectinomycin Mechanism
Binds to the 16s rRNA of the 30S ribosomal subunit and permits formation of the 70S complex but inhibits translocation.
- Does not induce codon misreading and is NOT bactericidal.
- Administered parenterally.
- Only used for gonorrheal infections.
Spectinomyin Side Effects and Contraindications
- SE: Injection site pain, nausea, dizziness, insomnia
- Cons: Hypersensitivity to Spectinomycin.
Tetracycline Mechanism
- Binds reversibly to the 16s rRNA of the 30 S subunit and inhibits protein synthesis by blocking the binding of tRNA to the A site of the mRNA-ribosome complex.
- Enter Gram-Negative bacteria through passive diffusion through porin proteins in the outer membrane, followed by active transport through the inner membrane.
Tetracyclines
"CYCLINE" Chlortetracycline Oxytetracycline Methacycline Demeclocycline Tetracycline Doxycycline (Safer for patients with kidney disease and minimally alters intestinal flora) Minocycline
Tetracycline Side Effects and Contraindications
SE: kidney toxicity and GI distress with nausea and vomiting.
Glycylcyclines
Tigecycline: similar to Tetracyclines, has been approved for intravenous administration for treatment of serious skin and abdominal infections and for community acquired pneumonia.
Macrolides and Ketolides Mechanism
Block translocation of protein synthesis by binding the 23S rRNA of the 50S subunit and blocking the exit tunnel from which nascent peptides emerge. Bacteriostatic.
Macrolides and Ketolides
- “Mycins”
- Erythromycin, Azythromycin, Clarithromycin and Telithromycin (formerly a Ketolide, binds with greater affinity to 23S)
Azythromycin and Clarithromycin
- Broader in spectrum and better tolerated than Erythromycin
Chloramphenicol Mechanism
- Binds the 23S of the 50S Subunit.
- Active against both aerobic/anaerobic Gram-positive and Gram-negatives.
Chloramphenicol Side Effects and Contraindications
- SE:Serious toxicity by inhibition of mitochondrial protein synthesis manifesting as Gray Baby Syndrome when administered to newborns. Causes vomiting, faccidity, hypothermia, gray color, resp distress, and met. acidosis. Also causes depression of erythropoiesis, GI distress, and Aplastic Anemia.
- Cons: Cannot be taken with P450 drugs.
Lincosamide Mechanism
- Blocks peptide formation through interactions with both the A site and the P site.
- Used for treatment of serious anaerobic infections caused by Bacteroides.
Lincosamides
Clindamycin: implicated in causing pseudomembranous colitis by Clostridium difficile.
Streptogramins Mechanism
- Inhibits protein synthesis by binding to the peptidyl transferase center of bacterial 23S rRNA. Bactericidal against some, but not all bacteria.
Streptogramins
Dalfopristin: Group A, binds A and P sites in the transferase center
Quinupristin: Group B, blocks emergence of nascent peptides.
Oxazolidinone Mechanism
- Binds the 23S of the 50S subunit in the A site to block tRNAs.
Oxazolidinones
Linezolid: excellent acitivty against MRSA and VRE.
Pleuromutilins Mechanism
- Binds to the A site of the peptidyl transferase active center where tRNA binds and extends into the P site. Once elongation is under way, they are no longer useful.
- Used as a topical treatment for bacterial skin infections.
Pleuromutilins
Retapamulin
Drugs that bind the 30S ribosomal subunit
Aminoglycosides, Spectinomycin, and Tetracyclines
Drugs that bind the 50S ribosomal subunit
Macrolides, chloramphenicol, lincosamides, streptogramins, oxazolidinones, and pleuromutilins
Quinolones, or Fluoroquinolones are used to treat
Common urogenital, respiratory, and GI infections caused by Gram Negative microbes: E. Coli, Klebsiella pneuomoniae, Campylobacter Jejuni, Pseudomonas Aeruginosa, Neisseria gonorrhoeae, and Enterobacter, Salmonella, and Shigella.
Major Use of Rifampin
Treatment of tuberculosis and other mycobacterial infections.
Side Effects of Erythromycin
- Most frequent: GI intolerance. Directly stimulates gut motility, causes nausea, vomiting, diarrhea, and sometimes anorexia.
- Metabolites can inhibit certain P450 isoenzymes in the liver, increasing drug concentrations.
