Chemotherapy I: Basic Concepts

If you saw the title of this post and thought, "Cool, we're going to be learning how to cure cancer!" then you should prepare to be sorely disappointed. Chemotherapy is actually a broad term that refers to treating diseases with drugs that are toxic towards whatever pathogen is making you sick. That means that even stuff like antibiotics and antivirals count as chemotherapy agents. In fact, over the next few posts, I will only be covering antibiotics, antivirals and antifungals. (Apparently anticancer drugs are in later pharmacology units, but I'm currently not intending to specialise in pharmacology.)

Demonstrate awareness of the profound impact antibiotics have had on human health throughout the past century

In a nutshell, antibiotics stopped us from dying of lots of infectious diseases. Now that we don't have as many of these diseases to worry about, we're living long enough to get heart disease and cancer instead. w00t w00t. Oh, and antibiotic resistance is giving us a lot of new challenges. The war on microbes isn't over yet.

Show awareness of key concepts relevant to the action of antibacterial drugs

Spectrum of action

Spectrum of action refers to the range of bacteria that an antibiotic can kill. A narrow spectrum antibiotic will only be able to kill one or two bacteria well (e.g. isoniazid is good against mycobacteria, which causes tuberculosis), whereas a broad spectrum antibiotic (e.g. tetracycline) can act against a range of bacteria.

Mechanism of action (show understanding of difference between bacteriostatic and bactericidal drug action)

Okay, first a quick note on bacteriostatic and bacteriocidal drugs. Bacteriostatic drugs slow down the growth and/or replication of the bacteria, whereas bacteriocidal drugs outright kill them ("-cidal" means kill, as in "suicidal" or "homicidal"), possibly by the generation of free radicals.

As for the specific mechanisms, antibiotics target differences in key pathways between bacteria and human cells so that the bacteria die and we don't. Specifically, antibiotics tend to target cell wall synthesis, folate synthesis, protein synthesis, nucleic acid synthesis and so forth. Most antibiotics target cell wall synthesis (these tend to be bacteriocidal) or protein synthesis (these tend to be bacteriostatic).

Individualization of dosing

One way that drug therapy can be individualised is by taking a microbe sample from the patient and testing to see which antibiotics kill the microbe. This is done by culturing the microbe on an agar gel and putting on some discs that contain different antibiotics. After incubation, you can observe where the organism has grown. Discs that are surrounded by spaces with little or no growth ("zones of inhibition") are likely to contain the effective antibiotics that you need. The larger the "zone of inhibition," the more effective that particular drug. If there is no zone of inhibition, you're probably looking at a resistant organism- eep!

Obviously, this process takes time. Hence, a patient might be started off on a broad-spectrum antibiotic until a more effective drug for that particular organism is found.

Another thing to take into consideration when individualising dosing regimens is pharmacokinetics: y'know, stuff like clearance, volume of distribution and so forth. These may differ from person to person due to differing liver function, kidney function etc.

Drug resistance

As I'm sure you know, the use of antibiotics has gradually led to the emergence of antibiotic-resistant strains of bacteria. There are a variety of ways in which bacteria can acquire resistance to antibiotics:

• They can coat themselves with a "protective slime" or a protective membrane, preventing the drug from reaching the target
• They can inactivate the drug, for example by using β-lactamases (which destroy the β-lactam rings present in some antibiotics- more on this in a later post)
• They can alter the drug target so that the drug can no longer bind
• They can pump the drug out via an efflux pump
• They can develop bypass pathways so that it doesn't matter if the main pathway gets blocked by a drug

In the next pharmacology post, I will talk a bit more about antibiotics.