azas-azas umum toksikologi (nasib racun dalam tubuh)

Azas-azas umum Toksikologi

Azas-azas umum ToksikologiNikmatul Ikhrom EJ, MFarmKlin., Apt.Prodi Farmasi Fakultas Ilmu KesehatanUniversitas Muhammadiyah MalangPROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

PROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

A common course is when a toxicant delivered to itstarget reacts with it, and the resultant cellular dysfunction manifestsIt self in toxicity.Potential stages in the development of toxicity


Development a toxicitypuffer fish poisonPoison reaches the voltage-gated Na+channels of motoneuronstetrodotoxiningestionresults in blockade of Na+ channels, inhibition of the activity of motor neurons and ultimately skeletal muscle paralysis. No repair mechanisms can prevent the onset of such toxicity


Development a toxicityentering the mitochondrial matrix space ingestioncollapses the outwardly directed proton gradient across the inner membrane by its mere presence there (step 2b)2,4-dinitrophenolmitochondrial dysfunction (step 3) : hyperthermia and seizuresSometimes a xenobiotic does not react with a specific targetmolecule but rather adversely influences the biological (micro) environment, causing molecular, organellar, cellular, or organ dysfunction leading to deleterious effects.

. Chemicals that precipitate in renal tubules and block urine formation represent another example for such a course (step 2b).4


Bagaimanakah nasib racun ketika masuk dalam tubuh??

Nasib Racun dalam TubuhPROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG


Although a distinction is made in Figure 2.1 between the target tissue and the central compartmentthat includes the blood, in some instances the blood itself represents the target tissue. Carbon monoxide,for example, combines with hemoglobin to form carboxyhemoglobin, whose presence in the bloodreduces the availability of oxygen to the tissues. Hemolytic agents such as arsine are also active in theblood compartment, and blood is their target tissue. But most often the target tissue is a tissue otherthan the blood.7

Biological membranesa phospholipid bilayerAmphipatic : nonpolar (liphophilic) + polar (hydrophilic)Semipermeable PROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

Daerah lipofilik mrp rantai asam lemak dan daerah hidrofilik merupakan fosfat atau kolin dan etanolamin

8


senyawa racun melewati membran sel bergantung pada :sifat fisika-kimia racunukuran partikellipofilitaskemiripan dengan molekul endogen kepolaran/muatan 9


Molecules can traverse membranes by three principal mechanisms:Passive diffusionFacilitated diffusionActive transport10


AbsorbtionAbsorption is the transfer of a chemical from the site of exposure, usually an external or internal body surface (e.g., skin, mucosa of the alimentary and respiratory tracts), into the systemic circulationBiology membraneK absorbsiMenentukan toksisitas sebuah racunK absorbsi adalah :11

GITThree main factors affect absorption within the various sites of the gastrointestinal tract:type of cells at the specific site;period of time that the substance remains at the site; pH of stomach or intestinal contents at the site.PROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

Absorption from the GI tract is strongly site-dependent, since the pH varies from the very acidicrange of about 13 in the stomach (depending on the amount and quality of the food and when it waseaten) to around 58 in the small intestine and colon (depending on location, food, and intestinalmicroflora). The intestinal contents can therefore be neutral or even slightly basic12

GITAdanya pengaruh dari asam lambung, enzim yang ada dalam lambung serta flora usus dapat mempengaruhi potensi ketoksikkan suatu racun yang diabsorbsi melalui saluran cerna.Ex : bisa ular yang diberikan secara oral tidak akan menunjukkan efek toksik sebagaimana yang ditunjukkan bila diberikkan secara intravena.


Respiratory Absorption can occur at any place within the upper respiratory tractThere are three basic regions to the respiratory tract:nasopharyngeal region;tracheobronchial region;pulmonary region.


most important site for absorption is the pulmonary region consisting of the very small airways (bronchioles) and the alveolar sacs of the lung14

Respiratory Chloroform and ether are examples of lipid-soluble substances with high blood solubility Non-absorbed foreign material can also cause severe toxic reactions within the respiratory system chronic bronchitis, alveolar breakdown (emphysema), fibrotic lung disease, and even lung cancer. In some cases, the toxic particles can kill the alveolar macrophages, which results in a lowering of the bodies' respiratory defense mechanism.


The nature of toxicity of inhaled materials depends on whether the material is absorbed or remains within the alveoli and small bronchioles15

Skinskin is a complex, multilayertissue. For this reason, it is relatively impermeable to most ions as well as aqueous solutions.passive diffusionEx : organophosphate pesticides, carbon tetrachloride causes liver injury, Hexane nerve damagePROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

Any process that removes or damages the stratum corneum can enhance penetration of a xenobiotic. Abrasion, scratching, or cuts to the skin will make it more penetrable. Some acids, alkalis, and corrosives can injure the stratum corneum and increase penetration to themselves or other agents. The most prevalent skin conditions that enhance dermal absorption are skin burns and dermatitis.16


DistribusiDuring distribution, toxicants reach their site or sites of action. Mechanisms Facilitating Distribution to a Target Distribution of toxicants to specific target sites :(1) the porosity of the capillary endothelium, (2) specialized membrane transport,(3) accumulation in cell organelles, (4) reversible intracellular bindingPROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

DistributionHow do chemicals move through the body?Does distribution vary with the route of exposure?Is a chemical distributed evenly to all organs or tissues?How fast is a chemical distributed?Why do some chemicals stay in the body for a long timeWhereas others are eliminated quickly?PROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

DistributionTotal volume of body fluids which a toxicant is distributed is known as thevolume of distribution(VD)Protein plasm if toxicant bind protein DEPO High lipid DEPO toxicant nonpolarPROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

MetabolismBiotransformationis the process whereby a substance is changed from one chemical to another(transformed)by a chemical reaction within the body.PROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

MetabolismPROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG

XenobioticsenzymsmetabolitesactiveNon active< polar> toxicredistributionToxic effect> polar< toxicExcretion detoxification ??? bioactivation ???Fase IFase II

MetabolismPROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG


Excretionexcretion and : the same process whereby a substance leaves the body.Toxicants or their metabolites can be eliminated from the body by several routes. The main routes of excretion are via urine, feces, exhaled air and otherPROGRAM STUDI FARMASIFAKULTAS ILMU KESEHATANUNIVERSITAS MUHAMMADIYAH MALANG



Thanks ^^

azas-azas umum toksikologi (nasib racun dalam tubuh)

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