MECHANISM OF TOXICITY

The fate of / how it move in body we called them as kinetics. In order for the drugs to enter the body is the one that we don't want. We want them to being excrete out from the body. We want the drug to be in the body in order for it to have some pharmacological responses. At the same we want it to be excreted and eliminated out. Remember, we do not want to have continues effects because drugs is not a magic bullet , it also have side effects. Thus we want to eliminate it out immediately. 

Problems with toxic material, we cannot controlled it. You going to be exposed to the environmental pollutant,you will be consumes food preservatives and additives all the time. At higher level quantity, it can be toxic when it accumulated. We do not want it to be accumulate in our body and we want it to be eliminated out.

So, how a toxic material can go in and can go out is what we learned in Mechanism Of Toxicity. In a dynamicity, is when it go into our body and it lead to adverse effect. It happen when it produce mutations. We do not want mutations - then we will become X-men. What we want is the mutation can be repaired. 

When you're talking about the movement of the toxic in body - it have 4 phases. (ADME) Absorption, Distribution, Metabolism and Excretion. Since it go into the circulatory system, it can go into the liver, brain and other organs. Hence, you can get toxic effect elsewhere because there is distributions. You do not want this to happen in your body. Thus you want the metabolism and excretion to occur immediately. The metabolism and excretion will help the toxicant to be eliminated out. This is by making it more stables and more water soluble, go to kidneys, eliminated it out immediately. Thus, the toxicant do not accumulate in the body to give toxic effects.

In general, in Absorption and Distributions, the factors involved

- size - large size is hard go through absorption, hard to be distributed. Why?  Because to go through the lipid bilayer of the plasma membrane. Talk about lipid bilayer, other factors involved - solubility

- Solubility - we do not want our toxicants to be lipid-soluble. Since our plasma membrane is lipid bilayer, we do not want toxicant s to be lipid soluble. Because it will make them easily to be absorbed and distributed. Unfortunately, 90% of environmental pollutant are very lipid soluble. Since we always exposed to environmental pollutant, we  need to take care of our body.

General characteristics/movements of toxicants in our body.

When we have xenobiotics - foreign compound, that our body did not recognized - and lipid soluble, it will be absorbed easily. Then, it gets into systemic circulation under our skins. And, when you consume xenobiotics, it also can get into systemic circulation because in our GIT have highly perfused with blood vessels because body want to absorb nutrition, vitamins etc. Then, the toxicant will be distributed in body elsewhere. Since your body loves you, loves you, over. Thus, your body don't like everything that get into your body that can give harmful effects. Then body will excrete it through the liver and kidney.

But, its not will be easy as that. Because things that easily be absorbed, it will hard to excreted out since it is very lipid soluble, it will be distributed in body elsewhere even go through your blood brain barrier, even your nerves. So, its hard to be excreted out. Thus, never ever ever try to take heroins, because it is very lipid soluble, it stuck in your brain, no turning back, no U turn and no roundabouts. That's why its hard to treat heroin addicts.

It have to do with distributions. It is difficult to metabolize all the very lipid soluble compound to be excreted. Thus body will send them into the liver to metabolize the toxicant to become more water soluble compound so that it can easily distributed to the kidney and excreted out from it in urine. If you inhaled vaporize materials, you will exhaled it fast and easily. Because it size are small. But, things that have large size will be send to the liver, and other organs that can do metabolism, but liver is the major one.

When we talk about metabolism also not easy as we said. Things that easily go into liver also easy to be metabolized. Not all enzymes can would recognize xenobiotic. Enzymes activity must need lock-and-key fit, So, when xenobiotic go into, how can lock-and-key fit to be occurred. Hard to metabolize. Thus body will cater the foreign compound. Hence, there will be Phase 1 and Phase 2 metabolizing enzymes.

Phase 1 is when to make the xenobiotic recognized by the body. Phase 2 is when conjugation reaction occurs. This happen by attached the lipid soluble compound with very water soluble compound. The compound then will become water soluble compounds. Thus, will easily be excreted out.

Phase 1 = metabolic activation

Phase 2 = detoxification

But, when you metabolic activating the compounds - it also can become harmful.Why? Because before conjugation occurs, the products that have been formed is very active compound. If there is no conjugation that occurs, it can attack our cells. Attack our protein, attack our DNA. Abnormality can happens. That's why good and healthy diet is very important because from that we can get the conjugater for the active compounds. 

We want detoxification more than the metabolic activation. Unhealthy lifestyle will increase you metabolic activation thus increase active compounds in the body. This will then be distributed and will attack micromolecule such as DNA, cells, lipid or proteins. This can lead to abnormality to the cells and become cancer.