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Drug Detoxification Dr. Howaida Supervised by : Prepared by:

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1 Drug Detoxification Dr. Howaida Supervised by : Prepared by:
Asma Al Malek Khloud Al Mutairi Norah Al Jebrin Sara Al Dowsari Shamma Al Hawawi

2 Treatment Prevention Diagnosis

3 Drug: Drug is a chemical substance used in: Treatment Cure Prevention
Diagnosis of diseases For limited duration or for long time

4 How Drug go out from body ?

5 The main routes by which drugs and their metabolites leave the body are:
-Kidney -Hepatobiliary system -Lungs Most drugs leave the body in the urine, either unchanged or as polar metabolites Some drugs are secreted into bile via the liver But most are reabsorbed from the intestine .

6 Drug metabolism Drug metabolism involves two kinds of biochemical reaction known as phase I and phase II reactions Phase II reactions: Conjugation (e.g. glucuronidation) of a reactive group (often inserted during phase I reaction ) usually forms inactive and readily excretable products. Phase I reactions: Oxidation Reduction Hydrolysis Induction of enzymes by other drugs and chemicals can greatly accelerate hepatic drug metabolism (Drug interaction)

7 Detoxification Def: Bio-transformations which eliminate the toxicant or prevent its formation In some cases, detoxification may compete with toxication for a chemical Detoxification can take several pathways, depending on the chemical nature of the toxic substance

8 Detoxification of toxicants with no functional groups:
In general, chemicals without functional groups, such as benzene and toluene, are detoxicated in two phases -initially, a functional group such as hydroxyl or carboxyl is introduced into the molecule, most often by cytochrome P-450 enzymes. -subsequently, an endogenous acid such as glucuronic acid, sulfuric acid, or an amino acid is added to the functional group by a transferase. With some exceptions, the final products are in active, highly hydrophilic organic acids that are readily excreted.

9 Detoxification of nucleophiles:
Nucleophiles generally are detoxificated by conjugation at the nucleophilic functional group. Hydroxylated compounds are conjugated by sulfation or glucuronidation. Thiols are glucuronidated Amines and hydrazines are acetylated. These reactions prevent peroxidase-catalyzed conversion of the nucleophiles to free radicals biotransformation of phenols, aminophenols, catechols, and hydroquinones to electrophilic quinines and quinoneimines.

10 Detoxification of electrophiles:
A general mechanism is conjugation with the thiol nucleophile glutathione Specific mechanisms for the detoxication of electrophilic substances include epoxide hydrolyase-catalyzed biotransformation of epoxides and arene oxide to diols and dihydrodiols, respectively

11 Detoxification of free radicals:
Peroxidase-generated free radicals are eliminated by electron transfer from glutathione. This results in the oxidation of glutathione, which is reversed by NADPH-dependent glutathione reductase. Thus, glutathione plays an important role in the detoxication of both electrophiles and free radicals

12 When detoxification fails:
1-Toxicants may crush detoxification processes, leading to exhaustion of the detoxication enzymes, consumption of their co-substrates or depletion of cellular antioxidants such as glutathione, ascorbic acid, and a-tocopherol. This results in the accumulation of the ultimate toxicant. 2- Liver Diseases. 3- Some conjugation reactions can be reversed. For example: 2-naphthylamine, a bladder carcinogen, is N-hydroxylated and glucuronidated in liver, with the glucuronide excreted

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