ETX 30-4 - Environmental Toxicology 30 Chemical Use and...

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Environmental Toxicology 30 Chemical Use and Abuse Topic: Pharmacokinetics and Metabolism I. Metabolism and Pharmacokinetics a. How will that stuff get from down there [bottom] up to his [hippo] sore throat? b. The answer is metabolism. II. Blood Level and Concentration at Site of Action a. Response curves and blood level curves i. Response related to concentration of drug at the receptor site. ii. Concentration at receptor site is directly related to blood level. iii. Blood level controlled by processes of absorption, distribution, metabolism and excretion. b. ADME controls blood levels and hence response. i. Elimination = metabolism + excretion III. The Processes of Absorption, Distribution, Metabolism, and Excretion (ADME) a. Absorption-across membranes i. Fluid mosaic membrane model. ii. Body as aqueous compartments separated by lipid membranes. iii. Like dissolves like therefore lipophilic drugs readily cross cell membranes. iv. Passage across membranes 1. Fick s law-diffusion 2. Filtration of small molecules 3. Active transport-against concentration gradient 4. Facilitated diffusion 5. Phagocytosis, pinocytosis v. Barbiturates: Acids 1. Partition coefficient: solubility in oil vs. water. vi. Absorption from the gastro-intestinal (GI) tract 1. Surface area-small intestine surface area x 500-1000 that of stomach. 2. Must be soluble in GI tract contents. 3. Lipid soluble sufficient to pass across membrane. 4. Nonionized at GI tract pH. 5. Not broken down in GI tract. vii. Dermal absorption 1. Topical application 2. 4 transport pathways a. Intercellular-between cells b. Transcellular-across cells c. Follicular-hair d. Sweat glands 3. Nicotine, contraceptives, fentanyl (pain), nitroglycerin (angina) viii. Green tobacco sickness in tobacco workers: nicotine 1. Nausea, vomiting, headaches, difficulty breathing, stomach pains
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2. Unrecognized occupational hazard 3. For severe poisoning: seizures ix. Administration of drugs 1. External, via the GI tract 2.
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