ADVERTISEMENTS:
In this article we will discuss about:- 1. Meaning of Chemotherapeutic Agents 2. General Characteristics of Chemotherapeutic Agents 3. Factors that Influence the Effectiveness.
Meaning of Chemotherapeutic Agents:
Microbial pathogens grow on and within the body of other living beings and their colonization may lead to disease, disability, and death. Thus the control or destruction of microbial pathogens within the bodies of humans and other animals to prevent them from causing a disease is of great importance.
The treatment of a disease with a chemical substance is called chemotherapy and the chemical substance used for the purpose is known as a chemotherapeutic drug/agent (generally called therapeutic drug/agent). Chemotherapy has been practiced by man for centuries, but it was early in the present century that chemical treatment of diseases revolutionized the field of medicine.
ADVERTISEMENTS:
This turn in event is attributed to two discoveries. The first was the discovery of sulfa drugs (sulfonamides) that could be used successfully for the treatment of certain diseases caused by bacteria, whereas the second was the finding of a new and potent class of antibacterial drugs/agents, namely, antibiotics.
General Characteristics of Chemotherapeutic Agents:
Following are the important general characteristics of the antimicrobial agents or therapeutic drugs:
1. Selective Toxicity and Therapeutic Index:
A therapeutic agent must have selective toxicity, i.e., it must kill or inhibit the microbial pathogen while damaging the host as little as possible. The degree of selective toxicity may be expressed in terms of the therapeutic index. The therapeutic index is the ratio of the toxic dose to the therapeutic dose.
The toxic dose refers to the drug level at which the agent becomes too toxic for the host, while the therapeutic dose represents the drug level required for clinical treatment for a particular infection. However, the larger the therapeutic index, the better the chemotherapeutic agent (all other things being equal).
ADVERTISEMENTS:
A drug that disrupts a microbial function not found in eucaryotic animal cells often has a greater selective toxicity and a higher therapeutic index. For example, penicillin inhibits peptidoglycan synthesis in bacterial cell wall but has little effect on host cells because they lack cell walls; therefore penicillin’s therapeutic index is high.
2. Side Effects:
A drug may have a low therapeutic index because it inhibits the same process in host cells or damages the host in other ways. These undesirable effects on the host, called side effects, are of many kinds and may involve almost any organ system (Table 45.1). Because side effects can be severe, chemotherapeutic agents should be administered with great care.
3. Range of Effectiveness:
Drugs vary considerably in their range of effectiveness. Many are narrow- spectrum drugs, i.e., they are effective only against a limited variety of pathogens (Table 45.2). Others are broad-spectrum drugs that attack many different kinds of pathogens.
Drugs may also be classified based on the general microbial group they act against antibacterial, antifungal, antiproiozoan, and antiviral. Some agents can be used against more than one group, for example, sulfonamides are active against bacteria and some protozoa.
4. Natural or Synthetic:
Chemotherapeutic agents can be synthesized by microorganisms or manufactured by chemical procedures independent of microbial activity. A number of the most commonly employed antibiotics are natural, i.e., totally synthesized by certain bacteria or fungi.
In contrast, several important chemotherapeutic agents are completely synthetic. (Table 45.3). The synthetic antibacterial drugs are the sulfonamides, trimethoprim, chloramphenicol, ciprofloxacin, isoniazid, and dapsone.
Many antiviral and antiprotozoan drugs are synthetic. An increasing number of antibiotics are semisynthetic. Semisynthetic antibiotics are natural antibiotics that have been chemically modified by the addition of extra chemical groups to make them less susceptible to inactivation by pathogens. Ampicillin, carbenicillin, and methicillin are good examples.
5. Microbicidal or Microbistatic:
Therapeutic agents, like disinfectants, can be either microbicidal or microbistatic (Table 45.4) Micro-biostatic agents reversibly inhibit growth; if the agent is removed, the microorganisms will recover and grow again.
Although a microbicidal agent kills the target pathogen, its activity is concentration dependent and the agent may be only microbistatic at low levels. The effect of an agent also varies with the target species: an agent may be microbicidal for one species and microbistatic for another.
Because microbistatic agents do not directly destroy the pathogen, elimination of the infection depends on the host’s own resistance mechanisms. A microbistatic agent may not be effective if the host’s resistance is too low.
6. Determination of Effectiveness:
ADVERTISEMENTS:
Some idea of the effectiveness of a therapeutic agent against a pathogen can be determined from the minimal inhibitory concentration (MIC). The MIC is the lowest concentration of a drug that prevents growth of a particular pathogen.
The minimal lethal concentration (MLC) is the lowest drug concentration that kills the pathogen. A microbicidal drug kills pathogens at levels only two to four times the MIC, whereas a microbistatic drug kills at much higher concentrations (if at all).
Factors that Influence the Effectiveness of Chemotherapeutic Agents:
Treatment of diseased bodies by administering therapeutic drugs or antimicrobial agents is not a simple matter. We know that there are variety of ways by which the drugs are administered in the body, and also the drugs do not always spread rapidly throughout the body or immediately kill all invading pathogens. During all these practices, a complex array of factors influence the effectiveness of therapeutic drugs.
The important factors are the following:
1. Mode of Administration of Drug:
ADVERTISEMENTS:
The drug must actually be able to reach the site of infection. The mode of administration plays an important role. A drug such as penicillin G is not suitable for oral administration because it is relatively unstable in stomach acid. Some antibiotics—for example, gentamycin and other aminoglycosides—are not well absorbed from the intestinal tract and must be injected intramuscularly or given intravenously.
Other antibiotics (neomycin, bacitracin) are applied topically to skin lesions. Nonoral routes of administration often are called parenteral routes. Even when an agent is administered properly, it may be excluded from the site of infection.
For example, blood clots or necrotic tissue can protect bacteria from a drug, either because body fluids containing the agent may not easily reach the pathogens or because the agents is absorbed by materials surrounding it.
2. Pathogen’s Susceptibility to Drug:
The pathogen must be susceptible to the drug. Bacteria in abscesses may be dormant and therefore resistant to chemotherapy, because penicillins and many other agents affect pathogens only if they are actively growing and dividing.
ADVERTISEMENTS:
A pathogen, even though growing, may simply not be susceptible to a particular agent. For example, penicillins and cephalosporins, which inhibit cell wall synthesis, do not harm mycoplasmas, which lack cell walls.
3. Pathogen’s MIC Value:
The therapeutic drug must exceed the pathogen’s MIC value for its greater effectiveness. The concentration reached will depend on the amount of drug administered, the route of administration and speed of uptake, and the rate at which the drug is cleared or eliminated from the body. It makes sense that a drug will remain at high concentrations longer if it is absorbed over an extended period and excreted slowly.
