9. Xenobiotic Metabolism Xenobiotic Xenobiotic Phase I reactions Hydrolysis Reduction Oxidation Primary metabolite Phase II reactions Glucuronidation Sulfation Methylation Conjugation Secondary metabolite Elimination in urine, bile, or feces Non-toxic metabolite Reactive metabolite Effects on cellular molecules (enzymes, receptors, membranes, DNA) Molecular and cellular repair Toxicity (short- and long-term effects)
10.
11.
12.
13.
14. Cytochrome P-450 enzyme system Inducers Bind to nuclear receptors (aryl hydrocarbon receptor, PPAR, CAR, PXR) Heterodimerize with retinoic X receptor (RXR) Form transcriptional activation complex Associates with promoter elements on CYP genes PPAR – peroxisome proliferator-activated receptors; CAR – constitutive androstane receptor; PXR – pregnane X receptor
81. Multiple cysts were present ( A ) on the face and ( B ) in the auricular areas, which normally are not affected in patients with common acne. Only a few cysts were present on the patient's back in summer 1998 ( C ), whereas 1 year later ( D ) the patient's back was covered with many severely inflamed cysts.
93. SMOKING Direct irritant effect Tracheo-bronchial mucosa Bronchitis Recruitment of leukocytes to lungs Increased local elastase production Injury to lung tissue Emphysema Cigarette smoke Polycyclic hydrocarbons & nitrosamines CYPs Increase water solubility of carcinogens Excretion Electrophilic intermediates of CYPs Form DNA adducts Mutations in K-ras and p53
94. SMOKING Increased platelet aggregation Decreased myocardial oxygen supply Decreased threshold for ventricular fibrillation Significant lung disease Hypoxia due to CO content of cigarette smoke Increased oxygen demand Atherosclerosis and M.I.
123. Acetaminophen Detoxification in liver by phase II enzymes Excreted in urine ~ 95% < 5% CYP2E1 NAPQ1 Covalent binding to hepatic proteins Damage cellular membranes Mitochondrial dysfunction Depletion of glutathione Increased hepatocyte susceptibility to ROS-induced injury
124.
125.
126.
127.
128. Cocaine HCl is the final product exported from South America Crack cocaine is made in the U.S. from several basic household products and cocaine HCl.
181. UVB sunlight is directly absorbed by DNA resulting in single strand breaks and the formation of pyrimidine dimers.
182.
183.
184.
185.
186.
187.
188.
189.
190.
191. Injury to arm of patient. Patient was draped for procedure and physicians did not realize that she had moved her arm so that it was resting on the port of the X-ray tube during the procedure.
![Global Climate Change ,[object Object],[object Object],[object Object]](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)