Micanozole, Ketoconazole, Clotrimazole – Broad spectrum agents. Bind to membrane sterol and disrupt membrane permeability in fungi. Also inhibit sterol synthesis
Tolnaftate is another drug used to treat cutaneous fungal infections
Nystatin obtained from Streptomyces is used for Candidiasis of skin, vagina and alimentary infections. Binds to membrane sterol and disrupts membrane permeability
Griseofulvin obtained from Penicillium disrupts mitotic spindle and inhibits cell division. This prevents multiplication of cells. It may also inhibit protein and nucleic acid synthesis
Systemic mycoses
Amphotericin B, 5-flucytosine, Fluconazole
Amphotericin B is obtained from Streptomyces that binds to membrane sterol and disrupts membrane permeability leading to leakage of cell constituents. Being toxic it is administered only under life-threatening situations
5-flucytosine is converted by the fungus to 5-fluuridine which is incorporated into a growing RNA and the function of the RNA is disrupted
Fluconazole is effective against candidiasis, cryptococcal and coccidioidal meningitis. Because of less adverse effects, it is given prophylactically to prevent fungal infections in AIDS patients and other immunocompromised individuals
Why are antifungal drugs not as effective as the antibacterial ones?
Fungal cell are more similar to host cells than bacteria. Many drugs that inhibit or kill fungi are therefore quite toxic to humans
Most fungi have a detoxification system that modify most antifungal drugs. Thus, they remain fungistatic only as long as repeated application maintains high levels of the unmodified drug
Antiprotozoan drugs
Chloroquine
Used to treat malaria
Increases cytoplasmic pH of the pathogen, clumps plasmodial pigment and intercalates between DNA
Inhibits heme polymerase that converts toxic heme to non-toxic hemazoin resulting in accumulation of the toxin in the cell
Mefloquine
Used to treat Plasmodium falciparum
Swells food vacuole in the cytoplasm of the protozoan by forming toxic complexes. This damages cell membrane and other organelles
Metronidazole
Used to treat Entamoeba
Alters DNA helix resulting in fragmentation of DNA in the pathogen
Atovaquone
Treats Pneumocystis carinii and Toxoplasma gondii
Mimics ubiquinone and functions as its competitive inhibitor. Consequently, ATP synthesis is stopped
Nitazoxanide
Used to treat cryptosporidiosis
Inhibits pyruvate:ferredoxin oxidoreductase
Also generates free radicals which are toxic to the organism
Pentamidine
Used to Pneumocystis
Inhibits various metabolic processes
Pyrimethamine & Dapsone
Pyrimethamine is used against Toxoplasma and dapsone is used against Pneumocystis
The function is same as trimethoprim (metabolite antagonist)
Antiviral drugs
Amantadine
Amantadine and rimantadine are used to prevent influenza A infections
Amantadine blocks penetration and uncoating of the virus (stages of infection)
Vidarabine
Adenine arabinoside or vidarabine disrupts the function of DNA polymerase and many other enzymes involved in nucleic acid synthesis
Used to treat herpes infections
Given intravenously or as a topical ointment
Acyclovir
Used in the treatment of herpes infection
Resembles deoxy-GTP and so gets incorporated into the growing DNA strand. But due to absence of 3’ –OH group elongation of the strand is stopped
Valacyclovir
Prodrug form of acyclovir. Become active only after metabolism
Ganciclovir, penciclovir and famciclovir are used in the treatment of herpes infections
Foscarnet
Binds to the active site of polymerase and blocks binding of pyrophosphate of dNTPs and inhibits replication of DNA and RNA
Used for treating herpes and cytomegalovirus (CMV) infections
Cidofovir
HPMPC or cidofovir is a broad spectrum anti-DNA viral drug
Acts on DNA polymerase as a competitive inhibitor and an alternative substrate of dCTP
Used against HSV and HPV infections
Oseltamivir Phosphate
Oseltamivir phosphate or Tamiflu is a neuraminidase inhibitor
Used to treat avian influenza
Anti-HIV drugs
Reverse transcriptase (RT) inhibitors – azidothymidine or zidovudine, lamivudine, didanosine, zalcitabine and stavudine. These interfere with RT and inhibit genome replication
HIV protease inhibitors – saquinvir, indinavir and ritonavir. The protease enzyme translate many proteins together into proprotein form which is subsequently cleaved into individual proteins for virus replication. Protease inhibitors mimic the peptide bond in the proprotein form and block the actual substrate from binding to the enzyme
Cocktail of drugs such as azidothymidine, lamivudine and ritonavir bring down viral plasma concentration to almost zero. However, it fails to eliminate proviral DNA in memory T cells.
