Pharm 33 Bacterial Infections: DNA Rep, Trascription, Translation

Question 1

Quinolone Mechanism

Answer 1

• 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.

Question 2

Quinolones, also called Fluoroquinolones

Answer 2

“FLOXACIN”
Ciprofloxacin
Ofloxacin
Levofloxacin

Question 3

Quinolone Side Effects and Contraindications

Answer 3

• 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.

Question 4

Rifamycin Derivative Mechanism

Answer 4

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.

Question 5

Rifamycin Derivatives

Answer 5

Rifampin (Rifampicin)

Rifabutin

Question 6

Rifamycin Derivative Side Effects and Contraindications

Answer 6

• 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

Question 7

Rifamycin Considerations

Answer 7

• 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.

Question 8

Aminoglycoside Mechanism

Answer 8

Bind to the 16S rRNA of the 30S ribosomal subunit to cause missense mutations and misreads during elongation. Bactericidal.

Question 9

Aminoglycosides

Answer 9

Streptomycin
Neomycin
Kanamycin
Tobramycin
Paromomycin
Gentamycin
Netilmicin
Amikacin

Question 10

Most Widely Used Aminoglycosides

Answer 10

Gentamicin, Tobramycin, and Amikacin because of lower toxicity and broader coverage of target organisms.

Question 11

Aminoglycoside Side Effects and Contraindications

Answer 11

• SE: Ototoxicity (most important!), acute renal failure (nephrotoxicity), neuromuscular blockade, respiratory paralysis.
• Cons: Hypersensitivity to Aminoglycosides.

Question 12

Aminoglycoside Consideration and Resistance Mechanisms

Answer 12

• 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.

Question 13

Spectinomycin Mechanism

Answer 13

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.

Question 14

Spectinomyin Side Effects and Contraindications

Answer 14

• SE: Injection site pain, nausea, dizziness, insomnia

- Cons: Hypersensitivity to Spectinomycin.

Question 15

Tetracycline Mechanism

Answer 15

• 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.

Question 16

Tetracyclines

Answer 16

"CYCLINE"
Chlortetracycline
Oxytetracycline
Methacycline
Demeclocycline
Tetracycline
Doxycycline (Safer for patients with kidney disease and minimally alters intestinal flora)
Minocycline

Question 17

Tetracycline Side Effects and Contraindications

Answer 17

SE: kidney toxicity and GI distress with nausea and vomiting.

Question 18

Glycylcyclines

Answer 18

Tigecycline: similar to Tetracyclines, has been approved for intravenous administration for treatment of serious skin and abdominal infections and for community acquired pneumonia.

Question 19

Macrolides and Ketolides Mechanism

Answer 19

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.

Question 20

Macrolides and Ketolides

Answer 20

• “Mycins”

- Erythromycin, Azythromycin, Clarithromycin and Telithromycin (formerly a Ketolide, binds with greater affinity to 23S)

Question 21

Azythromycin and Clarithromycin

Answer 21

• Broader in spectrum and better tolerated than Erythromycin

Question 22

Chloramphenicol Mechanism

Answer 22

• Binds the 23S of the 50S Subunit.

- Active against both aerobic/anaerobic Gram-positive and Gram-negatives.

Question 23

Chloramphenicol Side Effects and Contraindications

Answer 23

• 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.

Question 24

Lincosamide Mechanism

Answer 24

• Blocks peptide formation through interactions with both the A site and the P site.
• Used for treatment of serious anaerobic infections caused by Bacteroides.

Question 25

Lincosamides

Answer 25

Clindamycin: implicated in causing pseudomembranous colitis by Clostridium difficile.

Question 26

Streptogramins Mechanism

Answer 26

• Inhibits protein synthesis by binding to the peptidyl transferase center of bacterial 23S rRNA. Bactericidal against some, but not all bacteria.

Question 27

Streptogramins

Answer 27

Dalfopristin: Group A, binds A and P sites in the transferase center
Quinupristin: Group B, blocks emergence of nascent peptides.

Question 28

Oxazolidinone Mechanism

Answer 28

• Binds the 23S of the 50S subunit in the A site to block tRNAs.

Question 29

Oxazolidinones

Answer 29

Linezolid: excellent acitivty against MRSA and VRE.

Question 30

Pleuromutilins Mechanism

Answer 30

• 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.

Question 31

Pleuromutilins

Answer 31

Retapamulin

Question 32

Drugs that bind the 30S ribosomal subunit

Answer 32

Aminoglycosides, Spectinomycin, and Tetracyclines

Question 33

Drugs that bind the 50S ribosomal subunit

Answer 33

Macrolides, chloramphenicol, lincosamides, streptogramins, oxazolidinones, and pleuromutilins

Question 34

Quinolones, or Fluoroquinolones are used to treat

Answer 34

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.

Question 35

Major Use of Rifampin

Answer 35

Treatment of tuberculosis and other mycobacterial infections.

Question 36

Side Effects of Erythromycin

Answer 36

• 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.