أسئلة_الـ_18_فارما_PPPM_قبل_التعديل_

Protein Synthesis Inhibitors

• Aminoglycosides are bactericidal
• Tetracyclines are bacteriostatic

Aminoglycosides

• These drugs inhibit protein synthesis (30S)
• Effective against Gram-Negative bacilli and Pseudomonas
• Aminoglycosides are poorly absorbed orally, administered parenterally and do not penetrate the blood-brain barrier (BBB).
• Used for serious infections caused by Gram-Negative bacteria, especially Pseudomonas
• Used with Penicillin or Vancomycin for endocarditis (synergism).
• Neomycin is given orally to sterilize the GIT for infection, bowel preparation before surgery, and hepatic coma.
• Side effects include nephrotoxicity, ototoxicity and neuromuscular paralysis with large doses; Note ototoxicity not in pregnancy.
• Examples include: Gentamicin, Streptomycin, Neomycin, Tobramycin (best), and Amikacin.

Tetracyclines (Doxycycline)

• Remain useful as first-line therapy for infections caused by:
  • Rickettsiae, mycoplasmas, chlamydiae, and some MRSA strains
  • Sexually transmitted diseases, Plague, Brucellosis, Cholera
  • Moderate to severe Acne
• GIT upsets could manifest as an adverse reaction
• Other adverse reactions include yellow discoloration of teeth, deformity of bone (chelation of Ca), hepatotoxicity, photosensitivity, and are contraindicated in pregnant or lactating women and children under 8 years.

Nucleic Acid Inhibitors

• Examples include: Quinolones, Metronidazole, and Rifampicin (Anti TB)
• These drugs are bactericidal

Fluoro-Quinolones

• Inhibit DNA gyrase (in Gram-negative bacteria) and topoisomerase IV (in Gram-positive bacteria)
• Nalidixic acid is the first quinolone
• Fluoro-quinolones are produced by the introduction of fluorinated 4-quinolones
• Used for Urinary Tract Infections, Prostatitis, and Respiratory Tract Infections
• Exhibit excellent activity against respiratory pathogens causing pneumonia
• Ciprofloxacin & levofloxacin effective in traveler's diarrhea and typhoid fever
• Treatment of chronic osteomyelitis may require prolonged (weeks to months)
• Can be used as a second-line anti-TB drug (levo & moxi)
• Adverse effects include:
  • GIT Upset: nausea, vomiting & abdominal pain
  • Headache & Dizziness.
  • Seizures may occur
    • Patients with epilepsy are at higher risk for fluoroquinolone induced convulsions
  • Arthralgias (occasionally): Tendinitis or Tendon rupture (Achilles tendon) especially in old patients
    • Should be avoided during pregnancy, lactation & children < 18 years
  • QT prolongation & Ventricular arrhythmia
    • Moxifloxacin carries the highest risk
  • Photosensitivity

Fluoro-Quinolones Generations

• 1st Generation: Nalidixic
• 2nd Generation: Ciprofloxacin
• 3rd Generation: Levofloxacin
• 4th Generation: Moxifloxacin
• Fluorinated Quinolones have good bioavailability, high blood levels, and tissue distribution
• 2nd and 3rd Generations are effective against Gram -ve bacilli (including Pseudomonas), some Gram +ve and atypical bacteria.
• Some anaerobes are susceptible to 3rd generation
• 4th Generation: Less active on Pseudomonas than cipro or levo. More active on Gram +ve, Also effective against atypical bacteria and anaerobes.
• Nalidixic acid was used for UTI
• Ciprofloxacin and Levofloxacin are used for UTI & Systemic Infections
• Levofloxacin and Moxifloxacin called Respiratory Quinolones gives good cover for most organisms causing pneumonia

Metronidazole

• Effective against anaerobic bacteria (Clostridium difficile) and protozoa (entamoeba histolytica, Giardia)
• Converted inside susceptible organisms into an active product that interacts with and disrupts DNA
• Uses: Anti-protozoal (ex: antiamoebic) and treatment of anaerobic bacterial infections, including Clostridium difficile (pseudomembranous colitis) and mouth, dental, abdominal & pelvic infections
• Adverse effects: GIT upset & metallic taste, Headache & Dizziness, Dark coloration of urine, and Leukopenia

Daptomycin

• Active against aerobic & anaerobic Gram-positive bacteria
• Active against VRSA
• Binds to bacterial membranes, resulting in Depolarization, loss of membrane potential, and cell death
• Used for complicated skin & soft-tissue infections

Antibiotic Concepts

• The dose and frequency of antibiotic are determined based on Minimum inhibitory concentration (MIC):
  • The lowest concentration of antibiotic in body tissues and fluids that inhibits bacterial growth.
• Concentration-dependent killing:
  • The higher the antibiotic concentration above MIC, the greater the extent of antibiotic activity.
    • Aminoglycosides a single large dose/day achieves high peak levels and causes rapid killing of bacteria.
• Time-dependent killing:
  • The longer the duration of antibiotic contact to bacteria, the greater the extent of antibiotic activity.
    • Ex: B-lactam antibiotics, macrolides (frequent dosing

Antibiotics & Pregnancy

• Safe Antibiotics:
  • Penicillins & Cephalosporins
  • Metronidazole (in low doses)
  • Trimethoprim (safe after 1st trimester)
  • Nitrofurantoin (best avoided in third trimester)
• Antibiotics Contraindicated:
  • Quinolones, Tetracyclines
  • Aminoglycosides
  • High dose Metronidazole
  • Trimethoprim (if used in first trimester: folate antagonist)
  • Nitrofurantoin (if used at term - risk of neonatal haemolysis)
  • Sulphonamide preparations (near delivery)