Lecture Notes on Antimicrobial Agents (if we run short on time)
Pay attention to the various classes or types of drugs and know how these types of drugs work; know
some drugs in each class.
Parameters of an Effective Drug : selective toxicity, low degree of inducing hypersensitivity, soluble in
body fluids, and low degree of inducing resistance.
Activity of Agents: Spectrum of Activity: range of cell types for which an antimicrobial agent is effective.
Action of Agents:
Cell wall synthesis inhibitors (bacteriocidal): penicillin and derivatives, cephalosporins, bacitracin,
vancomycin prevent peptidoglycan crosslinking.
Protein synthesis inhibitors (bacteriostatic): choramphenicol, tetracycline, streptomycin,
erythromycin block peptide bonds, tRNA binding, indexing, and mRNA reading respectively.
Plasma membrane damagers (bacteriocidal): polymytxin B (changing permeability of membrane),
nystatin , aphotericin B, ketoconazole (come with sterols in fungi to distrub membrane).
Nucleic acid synthesis inhbitors: idoxurine, AZT, acyclovir (block DNA, RNA synthesis).
Metabolic enzyme inhibitors: folic acid synthesis inhibitors: sulfamethoxazole, trimethoprim
Commonly used drugs
Antibacterial synthetics: isoniazid and ethambutol (tuberculosis) inhibit mycolic acid production;
sulfonamides like sulfamethoxazole (sulfa drug) inhibits sythesis of DHF from PABA -->nucleotides;
nitrofurans (cause breakage of DNA. Naladixic acid blocks DNA replication.
Antibiotics are naturally produced drugs: penicillin G and its variants using the beta lactam ring
(ampicillin, amoxicillin, carbenicillin) from Penicillium notatum, some bacteria have penicillinase; other
cell wall inhibitors like cepahlosporin, carbapenems, vancoymin, bacitracin, polymixin B; and protein
synthesis inhibiotors like streptomycin, tetracyliine, chlroamphenicol, and erythromycin.
Antifungals include flucytosine (blocks protein synthesis); nustatin and amphotericin B (attaching
to ergosterol --> lysis); miconazole (blocks sterol synthesis).
Antivirals: nucleotide analogues (blocking replication) are ribaviriun, acyclovir, ganciclovir, AZT.
Antiprotozoan and Antihelminthics: include quinine for malaria (causes mutation of DNA);
metronidazole for giardia and amoebic dysentery; niclosamide (blocks ATP production) in tapeworms.
Resistance: Forms as bacteria develop genes-->enzymes against drugs, genes easily passed by conjugation
or transformation of plasmids called resistance factors. Big problem in hospitals where selection for
resistance great due to constant drug environment.
Synergism: combined effect of two or more drugs yielding a greater effect (alcohol and sleeping pills);
Antagonism: negative or cancelling interactions of drugs, like birth control pills and certain antibiotics
(surprise pregnancies) and pencillin plus tetracycline yields no lysis as pencillin's action is blocked by
bacteriostasis.