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Overview of Anti-microbials and Target Site of Activity 22/8/10 Yung, A. et al (2004) “Infectious Disease: A Clinical Approach” Second Edition, IP Communications Ltd Anti-microbial = kill or suppress the growth of micro-organisms. ANTI-BACTERIALS (i) Inhibition of cell wall synthesis - Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) - Glycopeptides (vancomycin, teicoplanin) - Others (cycloserine, bacitracin) (ii) Inhibition of protein synthesis - Macrolides (ethyromycin, roxithromycin, azithromycin) Aminoglycosides (gentamycin, tobramycin) Tetracyclines (doxycycline) Chloramphenicol Clindamycin Fusidic acid (iii) Inhibition of nucleic acid synthesis - Trimethoprim Sulphonamides (sulphamethoxazole) Fluoroquinolones (ciprofloxacin, norfloxacin) Rifamycins (rifamipicin) (iv) Inhibitors of cell membrane function - Colistin ANTI-VIRALS - are all virustatic rather than virucidal - they all suppress virus and allow the host immune system to irradicate disease - majority = nucleoside analogues -> gain access to the infected cell and then are phosphorylated by viral and/or cellular enzymes. (1) Drugs for HSV and VZV – inhibition of DNA polymerase - Acyclovir - Famciclovir - Valaciclovir (2) Drugs for CMV - Ganciclovir – inhibition of CMV DNA polymerase Jeremy Fernando (2011) - Foscarnet – inihibitor of virion DNA polymerase - Cidofovir - Formivirsen – antisense oligonucleotide that inhibits CMV replication (3) Drugs for HIV HAART = highly active anti-retroviral therapy - Nucleoside reverse transcriptase inhibitors (NRTI’s - zidovudine, didanosine, stavudine, lamivudine) - Nucleotide reverse transcriptase inhibitors (RTI’s - tenofovir) - Non-nucleoside reverse transcriptase inhibitors (NNRTI’s – nevirapine, efavirenz) - Protease inhibitors (PI’s - saquinavir, ritonavir, indanvir, nelfinavir, amprenavir, lopinavir) - Others (enfuvirtide) (4) Drugs for Influenza - M2 Channel Inhibitors (amantadine and rimantadine) – disrupts the process of dissociation of matrix and ribonucleoprotein - Neuraminidase inhibitors (oseltamivir and zanamivir) – impairs release of virus from infected cells (5) Drugs for other viruses - Ribavirin – mechanism uncertain - Alpha-interferon – very complex - Pleconaril – prevent virus binding and viral uncoating ANTI-FUNGALS (i) Interference with ergosterol (sterol in fungal cell membrane) - Azoles (ketoconazole, fluconazole, itraconazole, voriconazole) - Allylamines (terbinafine) (ii) Disruption of fungal cell wall - Polyenes (amphotericin B, nystatin) - Echinocandins (caspofungin, micafungin) ANTI-PARASITICS Protozoan Parasites Nitroimidazoles – inhibiting DNA synthesis - metronidazole - tinidazole Other agents: - Paromomycin - Nitazoxanide Jeremy Fernando (2011) Metazoan Parasites (nematodes and cestodes = worms) Benzimidzoles – prevents formation of microtubules and cell division - albendazole - mebendazole Diethylcarbamazine – mechanism unknown Praziquantel – mechanism unknown Ivermectin – causes influx of Cl- into cells -> muscular paralysis Jeremy Fernando (2011)