CAFFEINE AND TOXICOLOGY

Questions on Caffeine

1. Why caffeine can lead to addiction?
 Answer :
Because caffeine is a CNS stimulants! That's make you addict to it. You love it. It makes you become more aware, more confidents - because you stimulate the neourons in the brain. That's why people like to misuse and abuse of the caffeine.

2. What are toxicokinetics of caffeine in the body?
Answer :
Caffeine have higher absorption characteristics. Because caffeine is both water- and lipid-soluble. Because of this also, it readily crosses the blood–brain barrier that separates the bloodstream from the interior of the brain. Apart from that, Caffeine has pressor and mild diuretic effects.

In this case, in toxicokinetics, the parameters is what we need to consider. We can talk about the half-life. Half-life is the time of the [caffeine] to drop to half of it. If the caffeine have shorter half-life, it have better clearance. You faster you clear them, the more you eliminate them.

For caffeine, the half-like would be higher after you take them, and then it will slowly down after about 4-5 hours. That's why I advise you to take caffeine in the morning and not at the night. And also, take drinks water with caffeine. It would make concentration better. So that at 4 and 5 pm you already eliminate out most of the caffeine. Thus, at the night you will have a good sleep.

3. What effects of caffeine on pregnant mother and smoker?
Answer :
For cigarette smoker, they tends to addicts with caffeine. why? because cigaratte smoker will reduce the half-life of the caffeine. The half-life that actually about 4-5 hours will be reduced to less than that. When the half-life become lesser, the caffeine will eliminate out fast. When caffeine eliminate out fast, they will not happy. The stimulation not last long. Thus, they will tends to take the caffeine more.

To pregnant mother, the caffeine half-life will become 18 hours or more. It will not easily to be eliminated out and if the pregnant mother take caffeine on the next day, it will lead to accumulation of caffeine in the body. Accumulation of caffeine is very dangerous. Since it can pass through blood-brain-barrier, it can also pass through the placenta easily.

People who take oral-contraceptive will also longer the half-life of the caffeine in the body. It affects will same as the pregnancy mother.

HOUSEHOLD PRODUCT : SOLVENT TOXICOLOGY

Solvent = dissolved substance.

When we said 'dissolved substance', its a volatile (meruap) substance, aerosol substance. Thus, most of them are an inhalation substance. Here I put a picture of dissolved substance that have widely used and misused. Amyl Nitrate :

Amyl Nitrate have not much of medical therapautic. It was growing widely in the west, and now has spread to Malaysia. In Malaysia, for the past three years, it have being misused and abused. Initially it was used as vasodilating material, can dilate the blood vassels. People then used them as socially and recreationaly. Men love them. They used them for sexually activity function to get the erection and make their penis to become longer. Amyl Nitrate sold in a name of poopers in a bottle. Brown bottle. Its very pungent and smelly (like stinky socks. yukks). But, when you are the one that opened it, you will not feel the smell of the stinky socks, but only by people around you. It have become notorious in Malaysia.

For a household product, it have at your house, your exposure to it are increased, people who works at factory very exposed to them, since the factory need to be always clean, sterile. 

BENZENE

When we talk about heterocyclic amines and polyaromatic hydrocarbons, do the benzene is an aromatic compounds? Yes. Why? Because of their cyclic molecular structure. it have single bonds, double bonds. When it is benzene rings, and its name itself aroma,  it have distinct smell, where people love the smell especially kids. So, aromatic compounds is dangerous or not? As a dissolved substance it have functions. But, to be exposed to humans, it have toxic effects. For the Polycyclic aromatic hydrocarbon (PAH) and amines, did they have only one benzene ring? No. They have POLYaromatic hydrocarbons. Thus,the higher its toxicity effects.

So, why they are toxic. Go back to the mechanism of toxicity of PAH or the benzene rings. Its a story how the double bonds being metabolized. When double bonds being metabolized, it is going to be broken (this happen in a body since it need to be metabolized) to an oxidize products. The intermediate products will give you the epoxide.  When the double bond breaks, the rings still there, and at the top of the molecule have oxygen, then it is called Epoxide.

Epoxide is a reactive product. It need to react or bind with other molecules, ASAP. Fineee if it want to react fast BUT, in benzene, is there only one double bond? No. it have three double bonds. After one double bond break, the others can break or not? Yes. Meaning here, your body need to work up more to metabolize and excrete one benzene. But, in one solvent compound, is there only one benzene? No. it have a lot of benzene!

Tell you what, Sate and BBQ, have POLYbenzene rings! So, MORE double bonds need to break out. One PAH did not finished yet, another ring have been broken down. That's why its very difficult to actually excrete the polyaromatic hydrocarbons. PAH have a lot in grill foods and vehicles and factory emissions. 

Ok, lets go to first activity. Look this picture :

This is a picture about glue sniffing. The world most widely recorded in glue sniffing activities is in the southern asian countries typically in Filiphines. In Filiphine, even you go to Manilla, by the roadsides, you can always see a lot of these people. They are called Glue, Kick, Bang, Sniff, Huff, Poppers, Whippets, Texas Shoeshine. They are sounds as a blows things. Its all about the solvents. The solvents is the volatile things, evaporate. They put the glue in a plastics and then they sniff them. Why people addicted to it? Why they cannot be controlled? Why glue sniffer pronds to be among childrens? (90% children. For adults, they start to take ecstacy etc.) Socioeconomic factor also one of the reasons. Mostly glue sniffer among low socioeconomic people.

In factory, you want to dissoved something, to get something. Then you can extracted the things, this dissolved extract also need to used solvents. Solvents also widely used for sterility functions. Same with household product, that used for cleaning purposes. So, exposure to general populations, can easily happen. 

So, why the uses of solvents can easily to be misused and abused and addicting? Especially to children, poor people? Especially to glue, why not chlorox? (people do not addict to chlorox eventhough it also a solvents)

1. AROMA

Chlorox, chlorine etc have pungent or distinct smell. With the benzene solvents with the aromatic rings is why the people love them. The smell also have to do with why children loves them more than the adults. You can see when you fill in petrol, they love to came close to smell the petrol, when you in a house that had just being paint, modelling car etc. children like to come closer. (You need to move them away from it) So, why children more susceptible, why children will start with glue sniffer first? It have to do with the smell. The different smell, new smell, children love it more than the adults. When they love it, they want to smell them more and more. When it become continues/addicts, that's how the dangerous come. Those dangerous we didn't see them at first, but the dangerous came when the children in growing stage,  they did not want those glue anymore, they start to take prohibited substance that can give the same effects. Then they will get coccaine, ecstacy, and at the end of the day they end up with heroine. That's why prevention is better than cure. Need to avoid the children from all of this.

2. EASY ACCESSIBILITY.

Thats why its popular among to low socioeconomic people. Thats why also this problem is difficult to control. When you buy heroine, its easily to being detected and arrested. But, when you go to market/shop. you buy a glue, you can just simply said I want to glue papers for homework or something like that. Others will not have a reason to arrested you. Easy accessibility. Children can get those glue easily. 

3. TOXICOKINETICS OF SOLVENTS - EASILY TO BE ABSORB

Why children easily to addict to them? Easily to be absorbed. Because they are in form of gas, volatile, small molecules --> easily to be absorbed, easy to distributed, easily go into CNS. Other factors? lipid solubility of solvents. If not at CNS, first organ that it will attack would be the LUNGS (pulmonary). Then your CNS.

These is the general for all solvents.

Lot of solvents have difference in target organ toxicity. Not all will give effects on pulmonary and CNS. Solvents have their own target organ toxicity. It means, when it gets into your body, absorption and distributions, then, why they go to difference organ? That one at blood, others at nerve, here at pulmonary, liver, eyes and also reproductive?

Why not all same? while all are lipid soluble, small size but at the end they give difference effect? Why? The first reason would be due to the toxicokinetics. No longer just about absorption and distributions, now you have to considor also the metabolism and extractions also.

So, I give you another activity.

This activity is about Toluene. An alkylbenzene. I already had explained about benzene. Now we have benzene attached with methyl group. The alkylbenzene have effects on CNS. But Benzene on blood?.Benzene that without alkyl group effects on blood, you become anemic. Why difference in target toxicity??

Reasons have to do with ADME.

Toluene also can break double bond like benzene. But for benzene, it need to be broken to produce epoxide to give toxicity effects. So, the breaking up of double bond should be conducted at what place? by what? Before answering that, lets answer "Why need the breaking up of the double bonds at the first place?" The answer is "for metabolism and and metabolism is needed for extractions". The problem is, when it being metabolized, it become epoxide, which is very reactive compounds. So, if it have toxic effect, actually it reactivity is not in ASAP mode. and its not balance at all. Since metabolism mostly in liver, the reactions may be balancing because there are a lot of compound that it can binds to. The problem is when they have higher affinity, they love at the bone marrow. When they go to the bone marrow, is it a major organ for metabolism? Not really. But body still can metabolize. Is there enough compounds for them to binds to? Not enough. Balance or not? Not balance, reactive compounds are much higher then the compounds that they need to react to,  so, they will attack the bone marrow, binds to the blood cells progeny, then blood cells cannot be produced: damage, low in numbers, and that's why you get metaplastic anemia.  

Compared to alkylbenzene, did not need metabolism already since it is already a very reactive compound, direct toxic effect, directly go to CNS, directly get the effect.

NOW, Activity three.

CHLORINATED HYDROCARBONS. Where is their target organ toxicity? Lungs/pulmonary system. Because you inhaled them. We will talk about Chlorine and Phosgene.

Phosgene = very potent chemical warfare. It smells like musty hay (jerami basah), not a nice smell at all, and pungent. They can failed the pulmonary systems. The problem is, phosgene used as solvents at factory but at the same time, they are also a reactive compounds that you probably also get from other solvents.If they have metabolic activations, they can produce phosgene. And with phosgene, no need metabolim because they are already toxic (as the toluene). For this solvents you get the aerosol and Anasthatic agents

Come to the question, whats the industries do with the level of exposure of the solvents at the work place?

They do the Dose-Responds Measurements. You draw the graph and you will get the NOAEL and LOAEL. Since NOAEL, you are exposed but give you no toxic effects. But the NOAEL is so small since you are exposed to them everyday (I means if you are the workers). If not NOAEL, take the LOAEL. If LOAEL, it have the toxic effect but then you need to do the MANAGEMENT OF THE RISK. 

MANAGEMENT OF THE RISK. 

Yeah, if you dot wear goggles, lab jacket, all others safety attire, of course you will get at least LOAEL. But, you can change LOAEL to NOAEL. Occupational toxicologist call of this as TLV = Threshold Limit Value.

Solvents, also can give effects also to the enviroment when you not dispose them properly or at right method. A lot of this have been happening. Escpecially with the chlorinated hydrocarbons. Do not how to dispose them, you buried them in soil. What the Fishhhhhhhhhh??? If you do that, at first, it seems nothing wrongs, but after a while, if rain come, it will become volatile NOT at the place where you buried them, but it will to be elsewhere. In ecotoxicology, distributions from one place to another due to winds, rains. It can go to another place, such as residential place, where there would be mother, pregnant mother, young children (because the father go to work)

Another activity - the ALCOHOL, METHANOL, ETHYLENE GLYCOL

They have different organ target toxicity. Alcohol at liver, methanol at the eyes, and ethylene glycol at the kidney and reproductive organs. WHYYYYYY? Again, it have to do with toxicokinetics, it have to do with metabolism. First, we go to alcohol.

Alcoholism mostly a subject of the Fetal Alcohol Syndrome (FAS). The mother is an  alcoholic and her child have a characteristics of FAS. So, the questions is, why the effect goes to the child, not the mother? 

This is due to several factors, 

1. Age

    *Undeveloped fetus cannot do the metabolism. 

2. Alcohol - volatile, small - good diffusion and distributions. Anything that can go through BBB can go through also the placenta

When you take alcohol, in your body there is already enzyme that recognize the alcohol. (If they not recognize, alcohol need to through Phase 1 and Phase 2).  Alcohol will be directly metabolized by enzymes. The enzymes is called as alcohol dehydrogenase (ADH). They already in our body, more price, in the liver. They can metabolize alcohol ASAP. People who are intoxicated with alcohol, their metabolism are NOT COMPLETE. Because when alcohol being metabolised by ADH, it will become aldehyde. Aldehyde still cannot be extrected out from the body because its water solubility is not high enough. Aldehyde need to be changed to carboxylic acid to become water soluble. But aldehyde to become carboxylic acid, it need to metabolise with aldehyde dehydrogenase (ALDH) enzyme. 

The problem is, when you are expose to alcohol too much. The enzyme are not that much acually. So, they will metabolize the alcohol but they cannot extract them out. Aldehyde dehydrogenase not enogh and aldehyde will build up in the body, and that's how you get aldehyde intoxication. But the body loves you!, Your body, eventhough there are no ADH and ALDH, it will switch to catalyste, an antioxidant enzyme that can metabolize the alcohol. But, then, you drink a lot of alcohol again. What will happen, they will switch on to the conventional metabolism, Phase 1 and Phase 2. It will used the Cytochrome 2P42E1. This is what we called as Microsomal Ethanol Oxydizing System (MEOS). Microsomal because they will send to liver --> oxidize --> conjugate --> excrete out. Why there will be liver toxicity? Your ADH, ALDH, Catalyse, compound that it need to be conjugate already finished, whats remained are the reactive compounds produced by the Cytochrome 2P42E. This remaining active compounds will attack your own nearest cells in the liver -->  LIVER TOXICITY

Genetic polyphorism also can occur. Caucasian people do not easily drunks, but Oriental (Estern) people easily to be drunks. Girls easily to be drunk than the guys. These have to do with your own enzymes. 

METHANOL

Methanol attack the eyes. Methanol is a contaminants or it is an alcoholic drink that are not pure. (Alcohol, the cheaper it is, the more impurities in it, the more not pure they are). Methanol is one carbon.

Metabolism : Methanol enters the body, directly metabolize by ADH and ALDH and causes an increase in aldehyde. Aldehyde is very retinotoxic, attack retina, thus make you blind. 

ETHYLENE GLYCOL

They attack kidney and reproductive systems. Why? Due to incomplete metabolism. (Complete metabolism : alcohol -> aldehyde -> carboxylic acid). Incomplete metabolism make you drunk fast. That's make you hangover till the next day. Because the level of aldehyde is too much. With the ethylene glycol, you get them from coolant, lubricant for the vehicles. Sometimes children drink them because they think the coolant is a drinking water. They die due to accidental exposure. 

ETHYLENE GLYCOL -- > Glycol aldehyde (oxalate) --> Oxalic Acid

Aldehyde wanted to be extrected out but did not have time to be excreted. Thus it will send to the kidneys and at the wrong reproductive organs and form a crystals. Sharp crystals will injured the organs and hence the Target Organ Toxicity only at the reproductive systems and the kidneys.

KUCING MATI MASUK SYURGA ATAU TIDAK?

Ustaz Azhar Idrus :

Kucing ini Allah jadikan sejenis binatang eksotik, binatang peliharaan yang bermain dengan orang dan duduk dalam rumah. Dua jenis binatang yang main dalam rumah orang, sampai atas katil naiknya. Iaitu kucing dan anjing. Untuk orang kafir adalah anjing, untuk orang Islam adalah kucing. Adil dah di situ. Tapi ada sesetengah kita yang tidak puas dengan kucing, nak juga anjing dibela di dalam rumah. Aa tu yang pelik tamak nih. Bukan kata tidak boleh bela anjing pada orang Islam, tetapi ada kegunaannya. Contohnya, nak jaga kebun, kita duduk rumah, kebun kita nun sana di dusun, takkan nak suruh anak kita duduk dalam hutan? Letaklah anjing, maka itu dibolehkan untuk dibela atas tujuan yang betul.

Dua-dua orang putih ke memang sayang anjingnya, orang Islam pula sayang kucingnya. Kene dah dengan tempat tu. Itu makanya bijaknya Allah. Binatang yang boleh duduk dalam rumah orang. Allah tak buat badak sumbu dalam rumah orang, gajah duduk dalam bilik, tido. Ha, orang tak buat gitu.

Disebut oleh ulama-ulama tafsir, binatang-binatang dibangkitkan di padang Masyhar, kemudia juga diadili oleh Allah. Supaya Allah melihat keadilan Allah bahawa binatan pun diadili. Kemudan ia dijadikan tanah. Pada masa inilah orang-orang kafir bercita-cita ingin menjadi tanah. "Lau kun taturoba" Andainya elok aku juga menjadi tanah macam binatang. Tak masuk neraka. Jadi, tidak ada binatang yang masuk di dalam syurga menurut pendapat yang sahih. Walaubagaimanapun, ada pendapat yang lemah yang mengatakan beberapa jenis binatang yang masuk di dalam syurga.

Tidak perlu berbalah mengenai perkara ini. Perkara yang khilafiyah. Yang kita perlu yakin, ada banyak binatang yang berada di dalam syurga. Kerana ia disebut di dalam hadis. Seorang laki-laki berkata "Ya, Rasulullah, saya ini minat bermain kuda. Maka, adakah di dalam syurga itu adanya kuda?" Nabi menjawabnya "Ya. Bahkan kuda itu boleh terbang" Menunjukkan di sini adanya kuda di dalam syurga. Melalui hadis inilah, dilukis kuda-kuda terbang di dalam dinding-dinding gereja. Kebanyakannya di Sepanyol. Jika di Rome, banyaknya lukisan Nabi Isa dengan Maryam. Di Sepanyol banyak gambar-gambar syurga. Di antaranya kuda putih yang terbang. Itu yang nabi sebut di dalam hadis. Kuda ada dua sayap yang boleh terbang.

Jadi, apa yang kita minat, binatang apa yang kita minat, ada di dalam syurga. Jika minat burung titit, mung masuk syurga, ada tak burung dalam syurga? Ada. Tetapi istimewa. Ada hadis lain yang mengatakan, kita melihat comelnya ayam itu, comelnya burung. Ayam itu bertanya semula kepada kita "Nak makan?"  Kita pun mengatakan "Nak". "Masak lagu mana?" tanyanya balik kepada kita. Kita pun jawab "3 Rasa". Kemudian, burung pun sendiri berguling-guling masuk dalam kuali dan menjadi makanan. Lalu ia kita makan. Di sini menunjukkan adanya binatang di dalam syurga.

Yang tidak ada di dalam syurga, benda-benda seperti hotdog.

HYPONATREMIA

Is a condition when Sodium (Na) levels is less than 135 milliequivalents of solute per litre (meq/L).

Remember that Na is the must abundant electrolyte in the extracellular fluids. It is a good indicator for the body water balance.

"Water Follows Sodium"

This helps you to understands when there is changes in shift due to inadequate amount of sodium. The other key point to remember about sodium is;

"The Kidney is responsible for the excreting the sodium from the body"

So, any changes in kidneys are going to affect your Na balance. So, here is a case;

We have someone who have a very fatigue look, and overall body appearance in terms of hydration were very depending on - if we talking about a depletional or dilutional hypernatremia. There's a confusion, and we also see a sense of noxious, not hungry and sometimes vomiting, which again when you think about what happens about fluids during vomiting is a problems. There's also muscle cramps, weakness, and changes in blood pressure - which again depends on depletional or dilutional, which may end up being increased or decreased.

Dilutional hyponatremia

There is excess of water in the systems. You have a dilutional low sodium level. So, so much water in ratio of to the sodium that produces the dilutional hyponatremia. The situation here would be a high BP, weight gain, typically a bounding, rapid pulse and a high urine specificity gravity.

Depletionl Hyponatremia

This is often seen with hypobulimia - in other words, there is so much fluids loss, that it have been occurs in corresponding with sodium loss. The patient have a low BP, dry skin, and  a low urine specificity gravity. So, they really excreting a lot of fluids - eg vomiting.

So, two different causes that produce the same imbalance of hyponatremia

Apakah itu fitnah dajjal?

Macam-macam fitnah dajal yang wujud di dalam hadis-hadis Nabi saw. Diantaranya;

Dajjal mengaku sebagai Tuhan. Maka, orang yang menerima dan membenarkan, maka ia orang yang tersesat jalan. Cara kita nak menjaga ialah dengan mengkuatkan akidah kita pada masa sekarang. Kerana kalau kita tak sempat, dengan ketua dajjal, kita akan tersempak dengan anak cucu dajjal yang banyak sekarang ini. Cara nak kenal tentera-tentera dajjal, dia mengajak kita membuat perkara yang dilarang oleh Allah. Tak kra kamu seorang raja, menteri, kawan, kerana ia mengajak kepada perkara-perkara jahat, maka ia adalah tentera-tentera dajjal

Adakah naga wujud? Bagaimana rupa naga begitu?

Baik, apa yang pelik, boleh jadi ada, boleh jadi tidak. Tidak mustahil Allah swt boleh cipta naga. Namun kerana tiada bukti, usah kita bercerita tentangnya. Jadi, naga itu tiada, maka kita mengatakan ia mitos, cerita orang-orang dahulu kala sahaja. Tapi, kalau sekali benda (bukti) itu ada - tulang contohnya, maka, adalah benda itu. Tulang-tulang besar selalu dijumpai, seperti di Australia etc. Bila ada tulang itu, maka adalah isinya - dulu. La sekarang ini tinggal tulang sahaja. Jadi, jika ada tulang, maka adalah binatangnya beribu tahun dahulu, zaman dinasour, zaman Nabi as, tapi dia besar. Kenapa dia besar? Kerana sebelum zaman turun Nabi Adam dia duduk dengan kaum Jin. Ni cameron highland ni dulu Jin yang duduk. Selepas itu Allah pula berkata ingin ciptakan manusia di bumi, Malaikat bertanya "Ya Allah, adakah kamu akan buat satu lagi makhluk yang akan melakukan penumpahan darah dan berbunuhan, kemaksiatan, kemungkaran?" Ada tafsir yang mengatakan ianya bermaksud "Adakah nak buat jin lagi yang macam yang ada di bumi sekarang ini?" Disebut pula di dalam hadis, apabila diturunkan pula Nabi Adam as, maka dihalau jin-jin ke laut dan ke gunung-ganang. Sehingga dalam kitab-kitan hadis pula, "Siapa yang ingin ke laut atau gunung-ganang, hendaklah membaca ayat-ayat perlindungan daripada Jin. Jadi, sekarang masih belum diketemui tulang naga. Adanya tulang besar, tulang gajah yang besar sahaja. Jadi maka jawapan yang paling tepat ialah "apa yang pelik, boleh jadi ada, boleh jadi tidak"

What we really looks like - wake up human!

If we all tear out off our skins, do not surprise, we all just look the same.. You just look like me, muscle all over the body.. Its just the skin that makes the difference, but still, if you get a nice skin, which make you look so beautiful, think again. Tear off your skin, we all just look all the same. That's scary look without the skin, accept it - that's us. That's what our body made of. Don't too proud of yourself. However, please do to love your body, accept how you are, accept how you look. Do not take a cosmetic surgery just because you think you're not beautiful. Nobody are beautiful! or Everyone are beautiful - because we are all the same!

REACTIVE METABOLITES - SHORT NOTES

Surat Mohon Cuti Raya Haji dan penangguhan hari

Dr. HANITA BT OTHMAN,

Ketua

Jabatan Perkhidmatan Makmal Diagnostik,

Pusat Perubatan Universiti Kebangsaan Malaysia.

 

GOH EU WEI,

Ketua Pelajar ,

Sains Bioperubatan Tahun 3,

Universiti Kebangsaaan Malaysia                                                                                        2 Oktober 2013

                                                                                              

Puan,

PERMOHONAN CUTI RAYA HAJI SELAMA SEHARI

Merujuk kepada perkara diatas, Saya  Goh Eu Wei/Mo.Matrik (IC no.),mewakili pelajar Sains Bioperubatan Tahun 3 Universiti Kebangsaan Malaysia (UKM)  untuk memohon cuti selama sehari, iaitu pada 14 Oktober 2013 bersamaan hari Isnin sehari sebelum Raya Haji yang akan bertarikh 15 Oktober 2013.

2.   Tujuan kami  memohon cuti pada hari Isnin tersebut kerana ingin memberi peluang kepada pelajar yang beragama Islam untuk pulang ke kampung terutama yang tinggal berjauhan untuk menyambut Hari Raya Haji. Sehubungan itu, kami memohon cuti sehari dan ditangguhkan Kursus Diagnosis di Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) yang bertarikh pada 14 Oktober 2013.

3.  Dengan ini saya lampirkan senarai nama pelajar yang memohon cuti pada hari tersebut. (LAMPIRAN 1)

4. Sehubungan dengan itu, saya berharap agar pihak puan dapat mempertimbangkan dan meluluskan permohonan cuti tersebut.

Sekian, terima kasih.

Yang benar,

 

(GOH EU WEI)

Ketua Pelajar ,

Sains Bioperubatan Tahun 3,

Universiti Kebangsaaan Malaysia              

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. 

INTRODUCTION TO TOXICOLOGY

When you see a symbol of Skull and Bone logo, what can you actually think from it? Straight away come from your mind?

-err, your boyfriend..? ahaks, just kidding

- Death

-Harmful effect

-Hazardous

-Cautions

-Poison

Basically, when you see it, you know it is a bad thing, that can give a harmful effect. That's why you need precautions in handling it. If you not, you will get death and harmful effect. Thus, toxicology is the study to do that have to do with harmful effect. Its associated with Pharmacology. Logia = study, Pharmaco = Drugs. Drugs is not a a magic bullet, which means it have a side effect that you do not want. Thus, toxicology is a continuous from Pharmacology. 

Arsenic = something good, or something bad? Its a heavy metal. Its a poison. It is a notorious that have been used from along time and STILL have been used especially in murder cases, killing people politician etc. But, arsenic formerly used as a cosmetic ingredient. Because people look at the benefit of arsenic, that can give them look white, smooth and polished their face, but, at the end of the day, its very harmful. They don't know.

Heroin = is a drug, group Morphine. A painkiller. To release cough. Of course their cough being suppressed but they will become addicted to it. Because heroin very lipid soluble. People that start with heroin there will be no turning back. They can never come back to their origin. No roundabout. No U turn even, roundabout no. You stuck there. That's why its very difficult to treat heroin addicts.

Cocaine = you used to put on the head to treat dandruff. Yes, there will be no dandruff, but it will go into your head and then you will become addicts to it. Many celebrities death case due to cocaine addicts. Amy Whitehouse is one of them. Not just she take heroin, she also take cocaine. Those people take cocaine for recreational used but when they take other things, they always end up with death.

What I'm trying to said here, with Skull and Bone, it something adverse, something toxic. They can be used as drugs, they have medicinal benefits, but more importantly if people do not know their adverse effect, people do not know reason of their toxicity, it will become more severe. Very Potent!

So, Toxicology have been start from the old times. Old people do research about it. The first documentation about poison, is when people wrote on a Pirates, paper made from straw, they wrote, all poison. documented all are poison. More importantly it have to do with one person that has widely-used many toxic;

Cleopatra, always people relate her with beauty, as a woman, she's the prettiest, but, deep down inside, she is very evil,  because she only seen beautiful people only. Beauty is not important, but inside is very important. But, she was very evil. Why? Because she was a toxicologist. You see, a lot of poison to kill people, to gain power and to rule the land. Cleopatra is the last Pharaoh. She is the only female Pharaoh. That's why, to rule the lands, to gain power, she had using a lot of toxic material, poison. That's why she is considered a very good toxicologist. Even during her death. Her death is like a ritual. In history, during her death, what she did, she put a desert snake on her chest, the snake pecked her, then she died. But, that's history. In 2011, there was a research on toxicology that associated with history, They said Cleopatra did not died because of the snake venom, what she did was actually, since she is a good toxicologist, she already concocted, she already drink the mixture of poison to died. She put the snake on her chest only just as a ritual. What actually that lead to her death is due to that poison, not due to the venom of the snake. That's why Toxicology is important. 

Then you have in 17000 also, this person Catherine De Medici, this Italian women married to the French King and become a French queen. Thus, people do not like her. Thus, when she become a queen, become an Italian, she want a power. Its about power and about politics. When you read about sleeping beauty, snow white, you have the evil step-mother, evil queen, she was based for that character, because she was also a good toxicologist. What she did was, if you heard about the snow white, she give an apple, that what Catherine did also. She had that apple, she put vapor of cyanide into the apple, people eat and they all died. She was the one who make the apple. She actually the evil. She also learn about the toxicology, she was very good in mixing of poison. Why? To get into a French loyalty is very hard and the same time for the 1st ten years she did not have children to continued the power. But after 10 years she did have children. I don't know how, but she was a good toxicologist. She have 10 children. But, 2 of the last girls died because they not safe in her womb. She broke off their feet. If you read about her history, you see that she is very cruel and evil. Then she had 3 first son, and all of them capable to become a king in France on three consecutive sections. Although all her children all in 40 of age, 10 of age can become a king, but, they all are very weak and sickly, people did not like it, because the successor unable to defend their county. But, she managed to make her three son become a king. Why? Because she was a good toxicologist, when people have bad hidden agenda, hidden conspiracy, she killed all them. That's why, she is very evil. And if now, if you want to see the luxury and go to France, try to visit De Chateau where you will see 200 hundred cabinets which look like a wall, that contains full of her poison collection. She is a very good scientist She very interested in science, astronaut, and all chemical. She made all of this poison. To get into this rooms of the De Chateau, is like when you read Elizabeth story, when you see a door that can be pushed but it bring you into another rooms. It's ;like that. She made that to concurred all of her mixed poison herself.

More importantly is about a man, Sir Percivall Pott, this one not a bad guy. She made a research on chimney sweepers. These people go from house to another house to clean the trapped soot in the chimney. Usually chimney sweepers is a group of people of small children, thinner people and poor people. Thin and smaller people easily can go into the chimney to do this job. Sir Percivall Pott, the first person do research and linked epidemiology with toxicity by relate chimney people with scrotal cancer. Because most of chimney people are men. And what you will see how they can get scrotal cancer. Why not lung cancer? Why not dermal cancer while it is the site where exposed to chimney material more. Chimney material are very toxic, you have tar, soot, polyaromatic hydrocarbon that all are very carcinogenic. Why not they got lung cancer since they breath in the chimney? Why not skin cancer? How come they can get scrotum cancer? Chimney people look black people because they have black skin, but they actually are white people! Shock are we? But, think, why scrotal cancer?? Take that as your homework, put that in your head.

What is very important here also, is that what had happen in 17000 also still happen now. And, I'm not talking about Western people, I'm talking about our local people, our local farmers, I'm talking about person who his work is spray pesticides. What have we done and research, people who exposed to pesticides, pesticides sprayer also develop scrotal cancer. So, think. Why all of these people, chimney sweeper, exposed to pesticide sprayer get scrotal or reproductive cancer?  It's not happen just in 17000 only, its also happen now. That why we have group community research, we go to see farmers, tell them and educated them how to use pesticides cautiously . Even in our own backyard, its quit rampant. Means, there is increasing in scrotal cancer. 

Then you have Minamata Disease, in Japan. Where the mother have an adult son, did not have legs, hands and it is very painful. What happen was, in Minamata Bay there is a factory that throw out Mercury. What happen was, the mercury go into the sea, go into the Minamata Bay, people there eat seafood, fish etc that have contaminated with mercury. Its get into the mother. The mercury poisons give effect more to the fetus/the baby than the mother/not the adult people. Why? Think.

The Mother of Environment Movement, Racheal Carson, that wrote on Silent Spring (1962). When you have 4 seasons, spring season should be like birds chirping, flowers blooming, animals err chase each other. But what happen was in her place, during that time, the spring become silence. Then she realized when her childhood day, all the birds chirping, there are beetles sounds etc. But then, all lost. Everything become silence. The spring become silence. This because there is starting in uses of a pesticides to kill insects and to controlled the agriculture products, its not just they can controlled them, but, at the same time all the ecosystem and environmental become exposed to the pesticides which leads to silence spring. Then she wrote the book, and only with that book that lead to released of legislative act, registration, all sorts of controls on pesticides to be used. That why she become The Mother of Environment. 

Tokyo Subway Attack (1995), a bomb is detonated by a man in a subway underground, which there have a lot of people. Bomb explode which lead to gas off into the air and killed all the people in the subway. What have he used is the organophosphate, a sarin, the chemical warfare. He used sarin, people become breathless thus killed them. Whats more severe, its happen now, in Syria war - civil war. What they did was, they used the chemical warfare which is Sarin, to kill the civilian, not the soldier, but the children and women. But largely the children. Because they did not want and allow the children to grow to become vengeance. Thus, they killed the children. This is very illegal in any war! When you have a war, there is some rules and legislation. You cannot disturbed the civilian. Soldier fight with soldier only. What happen in Syria is the opposites. But, we will see. God is Great.

So, toxicology - generally from the old times until now is very important. you need to know not because you want to kill people but you need to know what its effect and how it kill people, how its handling and manage them. At the same time is there any treatment to the adverse effects.

What is you understood about the poison? Its bad, its symbol is Bone and Skull - not means if you eat them you can become slim - Its shows you the adverse effect. So, expand your knowledge with this questions. 

If you see there is a glass of arsenic and a glass of plain water in a laboratory. Directly what would you do?

-separated them. Separated them and put your book in the middle and study. Is that good? No. Why? because you friends can be exposed to them. If being exposed to water maybe nothing, but exposed to arsenic - you dont want. Meaning here what? Means, comparing arsenic than water, arsenic is poison and toxic. 

Firstly in the lab, you can identified them as toxic or not.  Toxic compound we defined them as hazardous. Hazard compound is their potential to become harm is there already. Its can give harm even though you take just a glass of arsenic. 

Then you separated them - toxic and not toxic one. Keep them. How to keep them if it in a glass? Keep it in a proper cabinet with cautiously. Why, because they are Skull and Bone. To manage them, put on label,  then keep it lock in a cabinet. Because its very toxic.

So, its very clearly that arsenic is very poison. So, thus this means water is not toxic? Yeah, if its being contaminated. But, if the water in a bottle? Is the water can be toxic or harmful? Yes. How? Think.

The water can become toxic when you take it a lot! Right? You can die when you consume water in a large quantity. Have you heard there are people who die because water intoxication? One case, in America, there is Hold You Wee to Play Win a Wii Competitions. A women, take water, play, and hold still her wee. Come back home, she died. Postmortem show she died because she holding her wee. In 2011, a man died because water overdose. This man take ecstasy - make you euphoria. He is an ecstasy user. He go to clubs, with techno sound - which very good to ecstasy people. It make them more passionate to dancing. They become high. At the same time, when you are so high you body become lethargy. And died because you did not rest. In this case, this man know the culture in taking ecstasy. Many ecstasy people died because dehydration. Lethargy - not take water - dehydration - then died. This man knows it and he keep on takinh water more and more to avoid dehydration. But then died due to water intoxication.

Meaning here, arsenic is toxic, water also CAN BE toxic. The father of toxicology; Paracelsus said that "Everything is Toxic" What difference between toxic and remedy is the dose.