Questions and Answers
What is the suspected mechanism of action of clofazimine?
What is the half-life of clofazimine?
In which type of leprosy is clofazimine used?
What is the main adverse effect of clofazimine?
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Why is pyrazinamide not used as a first-line treatment for TB in pregnant women?
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What is the purpose of giving pyridoxine to pregnant women with TB?
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What is the mode of action of many antiprotozoal drugs?
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What is the treatment goal for intestinal amebiasis?
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What is the purpose of treatment in asymptomatic intestinal amebiasis?
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Which of the following drugs is used to treat intestinal amebiasis?
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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)
- Therapeutic uses:
-
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
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Description
This quiz covers the mechanism of action, pharmacokinetics, and therapeutic uses of Vancomycin, a bactericidal antibiotic effective against gram-positive organisms.