Download Drug elimination

Drug Detoxification
Supervised by :
Dr. Howaida
Prepared by:
Asma Al Malek
Khloud Al Mutairi
Norah Al Jebrin
Sara Al Dowsari
Shamma Al Hawawi
Drug:
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Drug is a chemical substance used in:
Treatment
Cure
Prevention
Diagnosis of diseases
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For limited duration or for long time
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How Drug go out from body ?
Drug Elimination
Metabolism:
conversion of one chemical
entity to another.
Excretion:
Loss of drug or its
metabolites
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 .
Drug metabolism

Drug metabolism involves two kinds of biochemical
reaction known as phase I and phase II reactions
Phase I reactions:
Oxidation
Reduction
Hydrolysis

Phase II reactions:
Conjugation
(e.g. glucuronidation) of a reactive
group (often inserted during phase I
reaction ) usually forms inactive and
readily excretable products.
Induction of enzymes by other drugs and
chemicals can greatly accelerate hepatic drug
metabolism (Drug interaction)
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
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.
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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.
A
general mechanism is conjugation
with the thiol nucleophile glutathione
 Specific
mechanisms for the
detoxication of electrophilic
substances include epoxide hydrolyasecatalyzed biotransformation of
epoxides and arene oxide to diols and
dihydrodiols, respectively

Peroxidase-generated free radicals are
eliminated by electron transfer from
glutathione. This results in the oxidation of
glutathione, which is reversed by NADPHdependent glutathione reductase. Thus,
glutathione plays an important role in the
detoxication of both electrophiles and free
radicals
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 Nhydroxylated and glucuronidated in liver, with
the glucuronide excreted