Prodi Farmasi Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
A common course is when a toxicant delivered to its target reacts with it, and the resultant cellular dysfunction manifests It self in toxicity. Potential stages in the development of toxicity
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Development a toxicity puffer fish poison Poison reaches the voltage- gated Na + channels of motoneurons tetrodotoxin ingestion results 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 PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Development a toxicity entering the mitochondrial matrix space ingestion collapses the outwardly directed proton gradient across the inner membrane by its mere presence there (step 2b) 2,4- dinitrophenol mitochondrial dysfunction (step 3) : hyperthermia and seizures PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Nasib Racun dalam Tubuh PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Biological membranes a phospholipid bilayer Amphipatic : nonpolar (liphophilic) + polar (hydrophilic) Semipermeable PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
senyawa racun melewati membran sel bergantung pada : 1. sifat fisika-kimia racun 2. ukuran partikel 3. lipofilitas 4. kemiripan dengan molekul endogen kepolaran/muatan PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Molecules can traverse membranes by three principal mechanisms: 1. Passive diffusion 2. Facilitated diffusion 3. Active transport PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Absorbtion Absorption 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 circulation Biology membrane K absorbsi Menentukan toksisitas sebuah racun GIT Three main factors affect absorption within the various sites of the gastrointestinal tract: 1. type of cells at the specific site; 2. period of time that the substance remains at the site; 3. pH of stomach or intestinal contents at the site. PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
GIT Adanya 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.
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Respiratory Absorption can occur at any place within the upper respiratory tract There are three basic regions to the respiratory tract: 1. nasopharyngeal region; 2. tracheobronchial region; 3. pulmonary region.
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
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.
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Skin skin is a complex, multilayer tissue. For this reason, it is relatively impermeable to most ions as well as aqueous solutions. passive diffusion Ex : organophosphate pesticides, carbon tetrachloride causes liver injury, Hexane nerve damage PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Distribusi During 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 binding PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Distribution 1. How do chemicals move through the body? 2. Does distribution vary with the route of exposure? 3. Is a chemical distributed evenly to all organs or tissues? 4. How fast is a chemical distributed? 5. Why do some chemicals stay in the body for a long time 6. Whereas others are eliminated quickly? PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Distribution Total volume of body fluids which a toxicant is distributed is known as the volume of distribution (V D ) Protein plasm if toxicant bind protein DEPO High lipid DEPO toxicant nonpolar PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Metabolism Biotransformation is the process whereby a substance is changed from one chemical to another (transformed) by a chemical reaction within the body. PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Metabolism PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Xenobiotics enzyms metabolites active Non active < polar > toxic redistribution Toxic effect > polar < toxic Excretion detoxification ??? bioactivation ??? Fase I Fase II Metabolism PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
Excretion excretion 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 other PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG