Antibacterials and Tuberculosis PDF

Antibacterials, tuberculosis Dr Georgia Mitrousia  Learning outcomes Describe the bacterial cell structure. Explain the key terms concerning antibacterial drugs. Discuss the antibacterial drug targets. Describe the pathophysiology, risk factors,...

Antibacterials, tuberculosis Dr Georgia Mitrousia  Learning outcomes Describe the bacterial cell structure. Explain the key terms concerning antibacterial drugs. Discuss the antibacterial drug targets. Describe the pathophysiology, risk factors, signs and symptoms, and pharmacotherapy of tuberculosis.  Chemotherapy and antibiotics Erlich – early 20th century Chemotherapy: synthetic chemicals Alexander Fleming in 1928 – Penicillinum, penicillin Selectively toxic Not harmful to host Antibiotics: substances produced by some microorganisms or synthetical chemicals Bacterial cell Cell wall: peptidoglycan (except Mycoplasma) Plasma membrane: phospholipid bilayer, proteins Cytoplasm No presence of mitochondria or nucleus Single chromosome Outer membrane: Gram’s stain (methyl violet) – Gram-positive or Gram-negative  Selective toxicity Cell wall Cytoplasmic membrane Protein synthesis Nucleic acid metabolism (direct/indirect)  Antibacterials - terms Bacteriostatic: inhibits bacterial multiplication (e.g. sulfonamides, tetracyclines, chloramphenicol) Bactericidal: kills bacteria (e.g. penicillins, aminoglycosides, rifampicin) Minimum inhibitory concentration (MIC): minimum concentration of an antimicrobial capable of inhibiting the growth of an organism Minimum bactericidal concentration (MBC): lowest concentration that kills the pathogen Drug targets  Drug targets: class I, II and III Class I: energy from glucose/carbon source→ATP→basic carbon compounds Class II: basic carbon compounds from Class I + ENERGY→small molecules: amino acids, nucleotides, phospholipids, amino sugars, carbohydrates and growth factors Class III: small molecules from Class II→macromolecules: proteins, RNA, DNA, polysaccharides, peptidoglycan Drug targets: class I, II and III (continued) Class I Not so good target Class II Better target Class III Good target Drug targets: class II Selective toxicity. Folate biosynthetic pathway Folate synthesized in many bacteria species Humans cannot synthesize folate Sulfonamides: inhibits folate synthesis Trimethoprim: inhibits folate utilization Sulfonamide + trimethoprim=co-trimoxazole→active against Pneumocystis jirovecii (Pneumocystis carinii)