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  Chemotherapeutic Agent, Biology tutorial

Introduction:

Antimicrobial chemotherapeutic agents are oldest known form of chemotherapy, usually referred to as antibiotics. Antibiotics refer to substances of biological origin, whereas chemotherapeutic agents are substances derived from chemical components. Though, most new antibiotics are chemically altered or chemically synthesized biological products, so unique differences have been lost over time. Common name for antibiotics and chemotherapeutic agents is antimicrobial agents. Naturally, chemotherapeutic agents work in 2 different ways; they either kill microbes or interfere with its growth. The efficient chemotherapeutic agent is one that poisons pathogens, with little side effects to host. Antimicrobial chemotherapeutic agents come in different forms, and are distinguished by their source, mode of action, toxicity and spectrum of activity.

Antibacterial Chemotherapeutic Agents:

The known different antibacterial chemotherapeutic agents are derived directly or indirectly mainly from microbes and plants. Antibacterial chemotherapeutic agents can be bactericidal or bacteriostatic. The bactericidal effect occurs when the chemotherapeutic agent binds irreversibly to bacteria, while bacteriostatic effect takes place when chemotherapeutic agent badly binds to bacteria, therefore binding is reversible. Bactericidal agents demolish bacteria to which they bind, whereas bacteriostatic agents slow down growth of the bacteria to which they bind. Bactericidal agents are more efficient, whereas bacteriostatic agents allow host defense mechanism to eradicate bacteria. In spite of the method of binding, antibacterial chemotherapeutic agents act against bacteria in different ways.

i) Inhibition of Bacteria Cell Wall Synthesis:

Inhibition modifies bacteria growth as most bacteria need peptidoglycan cell wall to avoid osmotic lysis. Bacitracin, an antibiotic inhibits the second stage of cell wall synthesis in eubacteria. β lactam antibiotics such as penicillin, cephalosporins, thienamycins and aztreonam, inhibit the attachment of peptidoglycan to the bacteria cell wall. Vancomycin interrupts cell wall synthesis, and is useful in treatment of bacteria that have grown resistance to β lactam antibiotics.

ii) Disruption of Cell Membrane Functions:

Polymyxin B and polymixin E are known chemotherapeutic agents that disorganise the cell membranes of gram negative bacteria.

iii) Protein Synthesis Inhibition:

Ability of these chemotherapeutic agents to inhibit protein synthesis is based on structural difference between bacteria ribosome and eukaryotic ribosome. Aminoglycosides like gentamicin and streptomycin bind irreversibly to 30S ribosome. While tetracycline bind irreversibly to 30S ribosome.

iv) Nucleic Acid Synthesis Inhibition:

Antibacterial chemotherapeutic agent's which inhibit nucleic acid synthesis act at various levels. Rifampin inhibits bacteria RNA synthesis.

v) Antimetabolites:

Bacteria can't use preformed folic acid for growth; therefore they have to synthesize their own. Chemotherapeutic agents like sulfonamides inhibit synthesis of folic acid.

Antifungal Chemotherapeutic Agents:

Over time, several antifungal chemotherapeutic agents have been developed, but only few are active. Some can't be utilized in humans as they don't diffuse in tissues, are inactivated by induced enzymes, or are too toxic. Factors which affect permeability of fungi to chemotherapeutic agents are; structure of fungal cell wall and cytoplasmic membranes. Consequently, most antifungal chemotherapeutic agents are developed to break cell wall of fungi, by inhibiting synthesis of chitin that is component of fungi cell wall, or inhibiting synthesis of ergosterol which is major component of fungi cell membranes. Three main categories of antifungal chemotherapeutic agents are; azoles, polyenes and allylamine/ thiocarbamates.

Azoles: This group of chemotherapeutic agents inhibits synthesis of ergosterol and is active against dermatophytes group of fungi. E.g. are ketoconazole, clotrimazole, tioconazole and miconazole.

Polyenes: This group binds to fungal membrane sterols, causing it to leak, and as a result small molecules are lost. E.g. are nystatin, and amphotericin B.

Allylamines: This group inhibits fungal sterol synthesis, by obstructing the main part of ergosterol production pathway. E.g. are Terbinafine, amorolfine, butenafine and naftifine.

Another significant chemotherapeutic agent is flucytosine that is very significant in treatment of yeast, by interfering with nucleic acid synthesis.

Antiviral Chemotherapeutic Agents:

Most antiviral chemotherapeutic agents have been proven to have little or no use, as this virus they intend to eliminate uses host cell metabolic reactions, therefore these agents in long run attack cells they are developed to protect. Though few have been proven to be of clinical useful;

Receptor Binding: AMD-3100 and maraviroc disrupts HIV- co receptor interactions by binding to receptors.

Fusion of viral and host cell membrane: Enfuvirtide is chemotherapeutic agent also essential in treatment of HIV infection, by blocking conformational change of some of peptides needed in interaction.

Uncoating: Few antiviral chemotherapeutic agents act by inhibiting uncoating of virus. Examples are arildone and pleconaril. Other very significant antiviral chemotherapeutic agents are Amantadine and its derivative rimantadine. They act by blocking protein which functions as ion channels in disease influenza. Acyclovir inhibits herpes DNA polymerase in herpes simplex virus infections.

Antiprotozoan chemotherapeutic agents: There has been little progress made in search for new chemotherapeutic drugs to combat protozoan. Though because of the number of deaths caused by AIDS, it has become urgent to grow drugs with novel features, since most AIDS patients die as a result of other opportunistic diseases that are majorly protozoan in origin. Few examples of antiprotozoan chemotherapeutic agents are metronidazole, chloroquine against malaria and iodoquinol against amebiasis.

ntihelminth chemotherapeutic agents: These are agents utilized to treat infections with parasitic worms. Despite high prevalence of parasitic worms, rate of drug discovery or therapy is low, as most countries affected by these infections have little or no money to fund research in the areas. As a result, number of antihelminth chemotherapeutic agents available for human treatment is extremely small and most originates from veterinary medicine. It was also seen that success related with growth of drug ivermectin over the last 20 years, further decreased motivation in search for antihelminth chemotherapeutic agents. Other antihelmint chemotherapeutic agents are praziquantel, mebendazole and albendazole.

Over time, microbes have grown resistant mechanisms against chemotherapeutic agents, and as a result drug development is the ongoing research. Also research on drug discovery is going on to decrease unfavorable effects of the agents on host.

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