Antiviral drug

What are antibiotics? Antibiotics are medicines that help your body fight bacteria and viruses, either by directly killing the offending bugs or by weakening them so that your own immune system can fight and kill them more easily. The vast majority of antibiotics are bacteria fighters; although there are millions of viruses, we only have antibiotics for half-a-dozen or so of them. Bacteria, on the other hand, are more complex (while viruses must “live” in a “host” (us), bacteria can live independently) and so are easier to kill.

(A note for the purists out there: strictly speaking, an “antibiotic” is a bacteria-fighting medicine that is derived from a biological source (plant, mold, or other bacteria). Since most people use the term “antibiotic” for any anti-infection medicine, I am doing the same here. )Kinds of AntibioticsThere are now so many different antibiotics on the market that it’s hard for us to keep track of them all. Personally, I almost always look up the dose of an antibiotic when I prescribe it, just to make sure that I’m giving the right medicine in the right dose.

I also tend to stick to a few antibiotics in my practice, so that I can stay familiar with their effects and side-effects; most pediatricians I know do the same. Penicillins and CephalosporinsIn the first part of this century, Alexander Fleming discovered that a mold calledPenicillium (the cells are pencil-shaped when you look at them under a microscope) produces chemicals which kills most of the bacteria nearby. (The mold is green when it grows in large amounts, and is often found on bread. This, however, does not mean that eating moldy bread will cure your ear ache — or anything else.

There are other things produced by molds…) He was able to isolate these chemicals, which are now known as “penicillins”. Sometime later, another mold was found which produced a bacteria-killing chemical, and this chemical’s molecule was found to be very similar to the penicillin molecule; this chemical and its cousins were called “cephalosporins” after the mold it came from. The vast majority of antibiotics are either penicillins or cephalosporins; chemical changes have been made to the molecules over the years to improve their bacteria-fighting abilities and to help them overcome breakdown and “immunity” of resistant bacteria. The bacterial cell has a double layer on its outside.

The outermost layer — the “cell wall” — is similar to the outer layer of plant cells, but is missing in human and animal cells. This wall must grow along with the cell, or the growing cell will eventually become too big for the wall and burst and die. Penicillins and cephalosporins kill bacteria by messing up the wall-building system. Since we don’t have cell walls, and plants have a different wall-building system, neither we, nor animals, nor plants are affected by the medicine. There are a very few bacteria that don’t have cell walls, either. These bugs are immune to penicillins and cephalosporins for the same reasons we are.

Most bacteria do have cell walls, but many have changed their wall-building systems so that penicillins can’t interfere, or have come up with ways to break down the medicines before the medicines can work. When we first started using penicillin in the 40’s and 50’s, most bacteria could be killed by plain penicillin. Now, because we have used penicillins and cephalosporins so often (and, in many cases, when we really shouldn’t have), there are many bacteria that can’t be killed any more by plain penicillin or even by the “super-penicillins” and “super-cephalosporins”.

Penicillins and cephalosporins usually don’t cause many problems for a patient. Like all antibiotics, they can cause mild side effects like diarrhea. Less common side effects include rashes (which may or may not imply a true allergy) and hives (which usually means you’re allergic to the medicine). The rarest — and scariest — side effect is “anaphylactic” allergy, in which your airway swells up when you take a dose of the medicine, sometimes to the point where you can’t breathe.

Although the reaction can be treated if you are close to help, the safest thing if you are that allergic to the medicine is never to take it at all. (In cases where you have an anaphylactic allergy to penicillin or cephalosporins and must have it to treat an infection, doctors can “desensitize” you temporarily, using very small doses that are given frequently and in increasing amounts. That is almost always done in a hospital. )Macrolides (Erythromycin and its Relatives)Erythromycin is another antibacterial produced by a mold.

There are a couple of new relatives of erythromycin (azithromycin and clarithromycin) that work the same way, but kill more bugs and have slightly fewer side effects. The erythromycin-like antibiotics are also known as macrolides. Erythromycin works by blocking the bacterial cell’s machinery for making new proteins. Since proteins are both much of the cell’s structure and make the enzymes that direct all the cell’s chemical reactions, this makes the cell unable to function. Erythromycin in low doses will stop bacteria from growing and multiplying, but you need a higher concentration to actually kill the bacteria.

However, if you can stop growth until your immune system kicks in, that will help you get rid of the infection. Since all protein making is affected, erythromycin can slow down or kill any bacteria, even those without cell walls. Because of this, we use the erythromycins for several diseases, including bronchitis, that penicillins and cephalosporins can’t touch. Erythromycin and its cousins don’t have anything like the allergy problems we see with the penicillins and cephalosporins, although there are rare people who have reactions to it.

The biggest problem with these medicines is that they can irritate the stomach. I have seen people who ended up with bleeding stomach ulcers after taking erythromycin — almost always because they didn’t follow the directions and tried to take the medicine on an empty stomach. Always take erythromycin with food or milk. (The same goes for clarithromycin. Azithromycin is supposed to be taken on an empty stomach, and doesn’t irritate the stomach nearly as much as the others, but if you do have stomach irritation on azithromycin, let your doctor know immediately.

)SulfasThe sulfas (more properly “sulfanilamides” or “sulfonamides”) were the first antibiotics to be developed; they are actually completely man-made. They interfere with certain “manufacturing” systems in the bacterial cell, including ones that bacteria use to produce new DNA for new bacteria. Sulfas can stop bacteria from growing, but they cannot actually kill the bacteria. When they were first used, sulfas worked against many kinds of bacteria. Unfortunately, as with penicillin, the more we used the sulfas the more bacteria became resistant to it.

Sulfas also have a tendency to produce allergic reactions — different than those we see with the penicillins, for the most part, but including some that are rare but life-threatening. Because of this we don’t use sulfas nearly as much we used to, and most often when we use sulfas it’s in combination with another drug wihch attacks a different part of the bacteria (an attack on two fronts is usually better than an attack on one). The drugs we usually combine with sulfas are either erythromycin or “trimethoprim” (see below); these combinations usually can kill bacteria rather than just slowing them down.

One frequent use of “plain” sulfas is in antibiotic eyedrops used for conjunctivitis (“pink eye”). Trimethoprim-SulfamethoxazoleTrimethoprim (TMP) is another man-made antibiotic. Like the sulfas, trimethoprim blocks an important step in the bacteria’s system for making new DNA — but it’s a different step. By itself, TMP can kill bacteria, but very slowly. Usually, though, we use TMP in combination with sulfamethoxazole (SMX), and the combination of TMP and a sulfa kills bugs better. In fact, bacteria that are partly resistant to either TMP or SMX can still be killed by the combination of the two.

The side effects of the combination are the same as those of the two separate components. Other AntibacterialsNitrofurantoinNitrofurantoin is another synthetic antibiotic, used mainly for urinary tract infections. (Since it is excreted in the urine, it concentrates in the bladder very nicely. ) Nitrofurantoin stops bacteria from growing, and can kill bacteria with a high enough level, by blocking the bacteria’s ability to use energy it makes by “digesting” nutrients like sugar, and by blocking other chemical reactions that use the same system.

It is not usually used for infections other than UTIs, and there are several side effects (ranging from stomach upset to (very rarely) malfunctioning nerves) which limit its use. AminoglycosidesThe aminoglycosides are drugs which stop bacteria from making proteins; they work by attaching permanently to the protein machinery. Since they attach permanently, the bacterial cell will die if it gets enough of the drug. They can be used by themselves, or along with penicillins or cephalosporins to give a two-pronged attack on the bacteria.

Aminoglycosides work quite well, but bacteria can become resistant to them. The drawbacks are large, though. Since aminoglycosides are broken down easily in the stomach, they can’t be given by mouth and must be injected or given IV (although we can use them as eyedrops for “pink eye”). When injected, their side effects include possible damage (temporary or permanent) to the ears and to the kidneys; this can be minimized by checking the amount of the drug in the blood and adjusting the dose so that there is enough drug to kill bacteria but not too much of it.

Generally, aminoglycosides are given for short time periods, and in the hospital where we can check both the drug levels and the bacteria’s sensitivity easily. Polymyxin BPolymyxin B is an antibacterial that is produced by another bacteria. (We usually take our antibiotics wherever we can find them… ) It kills bacteria by damaging the cell wall chemically — just the way soap does. It can’t be taken internally, but it’s very useful for skin infections (it’s part of “Polysporin”) and for conjunctivitis (“pink eye”).

AntiviralsSince viruses can’t live outside the person or animal they infect, they are much harder to kill off. Our immune system can find and kill many of the viruses that attack us, but sometimes a virus can multiply and overwhelm the immune system before the immune system “comes up to full speed”. We immunize or vaccinate people against diseases — mostly viral — so that their immune systems do have that head start, and that seems to be the most succesful way to kill viruses permanently.

An example is smallpox, which has been eradicated due mainly to the use of vaccines against it — without which the virus killed thousands, if not millions, in epidemics. Some viruses, such as HIV (which specifically attacks the immune system), are very hard to become immune to, but a great deal of research is being aimed at producing a working vaccine for those diseases. Unfortunately, since viruses are completely dormant outside a “host” (an infected human or animal), they can’t be attacked biologically unless they infect someone.

The immune system can’t go after the virus unless it’s in the body, and all of the antiviral medicines we have work only when the virus is trying to reproduce in the body. We can destroy viruses in the environment if we know they are there (an example is using household bleach to kill HIV that might be on equipment contaminated with body fluids — but bleach won’t kill HIV in the body, even if we could get it into the body safely).

Once the virus is in the body, however, all we can do is let the immune system do its work, and in very rare cases (perhaps half-a-dozen viruses at must) give drugs that slow down the infection so that the body can clear it out more easily. AcyclovirOne often-used antiviral medicine is acyclovir, which slows down infections with viruses of a certain family. The family includes both varicella (chickenpox and shingles) and the herpes viruses. Acyclovir slows down the virus’ multiplication and therefore slows down the infection. The problem is that the varicella and herpes viruses are never actually eradicated — they stay in the body forever, and “reactivate” later (sometimes years later).

The recurrent sores of herpes, and the appearance of shingles years after you have chickenpox, are examples of reactivation, and although acyclovir can help you get over the reactivation infection, it can’t actually get rid of the viruses. AZT and other Reverse-Transcriptase InhibitorsAnother very well-known antiviral is triazidothymidine, better known as zidovudine orAZT. This drug, and others like it, are used to inhibit an enzyme called “reverse transcriptase” which HIV uses to “copy” its own genes into the genes of the cells it infects.

Once the HIV genes are copied, the infected cell and all its offspring will be capable of producing more HIV. (This is why an AIDS patient cannot actually get rid of all of the virus once infected: the virus may lie dormant as inactive genes for months or years, and the anti-AIDS drugs cannot get to the gene copies. ) Like bacteria, viruses can mutate, changing their structure so that drugs that used to work no longer help; this explains why AZT and other reverse-transcriptase inhibitors eventually lose their effectiveness in patients.

Protease InhibitorsA newer class of anti-AIDS drugs, the protease inhibitors, work by blocking a different HIV enzyme. HIV uses reverse transcriptase to copy its genes into the cell it’s infecting; it uses “protease” (an enzyme that breaks down protein) to get into the cell in the first place. Many people with AIDS have been able to eliminate the virus from their bloodstream — or almost eliminate it — by using both reverse-transcriptase inhibitors and protease inhibitors at the same time.

The problem is that the virus has copied itself into cells where neither kind of drug can attack it, so a patient must keep taking the drugs forever to keep the virus from reactivating. Note, by the way, that the antiviral drugs, even more than the antibacterials, are tailored to the kind of viruses they are intended to attack. AZT won’t do anything for a cold, and neither will acyclovir. In fact, there are — so far — no antivirals that will do anything for the common cold. And, since there are many different viruses in several different families that can cause colds, we are not likely to have any anti-common-cold drugs in the near future.

The Common ColdSince most colds are due to viruses attacking the mucus membranes of the nose and throat, the only way to get over the cold is to wait for your immune system to get rid of the virus, and for your body to produce a new, virus-free mucus membrane surface. Resurfacing the mucus membranes takes 3-4 days (you automatically resurface the membranes every 3-4 days), but getting rid of the virus takes a week or two, and until the virus is gone the new membranes will keep getting infected. Since we have no medicines that will slow down the cold viruses, we can’t do anything to speed up this process.

Antibacterial antibiotics will do nothing to help get rid of the virus, and giving antibacterial antibiotics when there is a viral cold will like do nothing except help the bacteria in the nose and throat become resistant — which makes the next bacterial infection much harder to treat. I never give antibiotics to someone who has only a cold, unless there seems to me to be a very good chance that he or she may develop a bacterial infection on top of the cold — or unless there is clearly a bacterial infection already.

.. What are antibiotics? .. What kinds are there, and how do they work?.. Antibacterials.. Penicillins and cephalosporins .. Erythromycin and its relatives .. Sulfa drugs .. Trimethoprim and sulfamethoxazole .. Other bacteria killers.. Nitrofurantoin .. Aminoglycosides .. Polymyxin B.. …

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