Pharmacology of Vancomycin

Study Notes

Cell Wall Synthesis Inhibitors

Vancomycin:
- Bactericidal, inhibits cell wall synthesis
- Effective against Gram-positive organisms
- Pharmacokinetics:
  - Administered by IV infusion, but given orally for antibiotic-induced pseudomembranous colitis
  - Excreted renally, dosage adjusted in renal dysfunction
- Therapeutic uses:
  - Oxacillin-resistant Staph aureus (ORSA)
  - Serious allergy to penicillins
  - Pseudomembraneous colitis following antibiotic use
- Adverse effects:
  - Fever, rigors, and phlebitis
  - Shock with rapid infusion (Red Man Syndrome) due to histamine release
  - Hearing affection or loss
  - Renal dysfunction
Bacitracin:
- Effective against Gram-positive organisms
- Restricted to topical application due to potential nephrotoxicity

Protein Synthesis Inhibitors

Tetracyclins (Tetracyclin, Doxycyclin, Minocyclin, Demeclocyclin):
- Mechanism of action: binding to 30S ribosomal subunit, inhibiting protein synthesis
- Therapeutic uses:
  - Chlamydial infections
  - Cholera
  - Amoebiasis
  - Acne vulgaris
  - Mycoplasma pneumonia
  - Meningococcal carriers
  - Brucellosis
- Adverse effects and contraindications:
  - Epigastric pain due to gastric irritation
  - Teeth discoloration and bone hypoplasia (contraindicated in pregnancy, lactation, and children < 8 years)
  - Hepatotoxicity
  - Phototoxicity
Macrolides (Erythromycin, Clarithromycin, Azithromycin, Roxithromycin):
- Mechanism of action: inhibition of protein synthesis by binding to 50S bacterial ribosomal subunits
- Spectrum and uses of erythromycin:
  - Drug of choice in patients with spirochetes or Gram-positive coccal infections with allergy to β-lactam antibiotics
  - Drug of choice in urogenital chlamydial infection in pregnancy and mycoplasma pneumonia in children
- Adverse effects of erythromycin:
  - Epigastric pain and intestinal colic
  - Cholestatic jaundice (contraindicated in liver disease)
  - Ototoxicity and transient deafness
  - Thrombophlebitis if injected IV
Clindamycin & Chloramphenicol:
- Mechanism of action: binding to 50S ribosomal subunit, inhibiting protein synthesis
- Clindamycin:
  - Used specifically against anaerobic infections
  - Effective against Gram-positive organisms (Staph and Strept.)
  - Used in bone infections due to good penetration into bones
- Adverse effects of clindamycin:
  - Pseudomembraneous colitis
  - Skin rash
  - Diarrhea
  - Liver dysfunction
- Chloramphenicol:
  - Therapeutic uses:
    - Typhoid fever (replaced by fluoroquinolones)
    - Bacterial meningitis (H.influenza) + penicillin
    - Topical use in eye infections (e.g., conjunctivitis)
    - Anaerobic infections (e.g., anaerobic brain abscess)
  - Adverse effects of chloramphenicol:
    - GIT upset and superinfection
    - Bone marrow depression (dose-independent or idiosyncrasy)
    - Grey baby syndrome in neonates
    - Optic neuritis
    - Inhibition of hepatic microsomal enzymes (drug interaction)
Clofazimine:
- Mechanism of action: unknown, possibly DNA binding
- Anti-inflammatory effect
- Absorption: variable from gut, given orally once daily
- Excretion: mainly in feces, storage in reticuloendothelial tissues and skin
- Half-life: 2 months, delayed onset of action (6 weeks)
- Clinical uses:
  - Multidrug resistance TB
  - Lepromatous leprosy
  - Tuberculoid leprosy in patients intolerant to sulfones or with dapsone-resistant bacilli
  - Chronic skin ulcers caused by M.ulcerans
- Adverse effects:
  - Skin discoloration (red-brown to black)
  - Gastrointestinal intolerance
  - Red color urine
  - Eosinophilic enteritis

Treatment of TB in Pregnant Women

INH (with pyridoxine), Rifampicin, Ethambutol
Pyrazinamide only if:
- Resistant to other drugs is documented
- Streptomycin is contraindicated
Breastfeeding is not a contraindication, but caution should be observed

Antiprotozoan Drugs

Protozoa are eukaryotic cells
Many drugs are experimental, and their mode of action is unknown

Amoebiasis

Infection with Entameba histolytica produced by ingestion of cysts
In the intestine, cysts develop into trophozoites (active invasive form) which adhere to colonic epithelial cells
Trophozoites lyse host cells and invade the submucosa, resulting in:
- Bowel lumen amoebiasis: asymptomatic, but cysts pass in the stool, transmitting infection to others
- Treatment is directed at eradicating cysts with luminal amebicidal drugs:
  - Diloxanide
  - Iodoquinol
  - Paromomycin
  - Tetracyclin