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Powerpoint 6- Metabolism AND excretion
Terms in this set (44)
• Drugs are eliminated from the body by the aid of two processes?
- Metabolism (Biotransformation)
and Excretion (Elimination)
For renal excretion drugs should:
- have small molecular mass
- be polar in nature
- not be fully ionized at body pH
Most drugs are complex and do not have these properties and thus have to be broken down to simpler products.
true or false?
Drugs strongly bound to plasma proteins stops them from getting eliminated
true or false?
Drugs (xenobiotics) don't have to be converted to simpler hydrophilic compounds so that they are eliminated and their action is terminated.
true or false?
false, they do have to
Biotransformation can also result in ?
bioactivation, which involves the production of reactive metabolites that are more toxic, mutagenic, or carcinogenic than their parent compound(s).
Drugs may be converted to?
- less toxic materials
- more toxic materials
- materials with different type of effect or toxicity
Biotransformations occur between?
absorption and elimination from kidneys.
Biotransformation reactions can be?
- Phase I reactions
- Phase II reactions
Phase 1 rxns are?
Oxidation, Reduction, Hydrolysis
Phase I metabolites may be?
Activated - "prodrug"
All tissues have the ability to biotransform drugs
true or false
Drugs given orally can also get metabolized, where?
- in intestine
- by intestine wall enzymes
- by microorganisms in lower GIT
Cytochrome P450 (CYP450)
is the major drug metabolizing enzyme system in the body.
what three families are responsible for drug metabolism?
CYP1, CYP2 and CYP3
Induction of CYP450s
Results from repeated exposure to certain xenobiotics including drugs.
• Increased rate of synthesis of enzyme or reduced rate of breakdown.
what xenobiotics cause induction?
- Polycyclic hydrocarbons-Epoxide formation
- Smoke- Tobacco
- Charcoal - barbecued food
what drugs can cause induction?
Inhibition of CYP450s
• May increase serum concentrations of second drug
• Can lead to toxicity
- Alcohol dehydrogenase
- Xanthine oxidase
- Monoamine oxidase - catecholamines
• Reduction reactions
• Hydrolytic reactions
• Not all Phase I reactions are CYP450 based
true or false
Reduction reactions-Phase I
• Bacterial reductases
• Aldo-keto reductases
Remove O, add H, decrease valence
Hydrolysis Reactions-Phase I
• Epoxide Hydrolase
Add water-expose groups for Phase II
Phase II rxns:
Glucuronidation, Sulfation, Methylation, Acetylation, Amino acid conjugation, Glutathione Conjugation
- Major pathway
- Catalyzed by UDP glucuronosyltransferase
- Requires UDP co-factor
- Glucuronides are water soluble
-Sulfate conjugation products are water soluble
-Catalyzed by sulfotransferase
- Transfer of sulfonate group to xenobiotic
- Important but minor pathway
- Catalyzed by methyltransferases
- May r may not be more water soluble
- Increases renal excretion
- Catalyzed by N-acetyltransferase
• Amino acid conjugation
- Glycine conjugates
- Taurine conjugates
• Glutathione Conjugation
- Reaction catalyzed by glutathione S-transferase using glutathione thiolate
Most patients are treated on similarities rather than as individuals. what are they?
Sources of variation:
• Environmental factors
• Drug-drug interactions
- Enzyme induction
- Enzyme inhibition
• Genetic factors
In pediatric age group biotransformation:
Premature infants, neonates, children and adolescents cannot be treated like small adults.
All these groups have special metabolic parameters.
Neonates virtually no Phase-2 enzymes. Hepatic biotransformation and enzyme activity is reduced in the early neonatal stages.
There is decreased biotransformation of drugs and increased plasma levels and prolonged half life.
Less developed excretory mechanisms.
Malnutrition in children can impair metabolism.
In humans a difference in metabolism of a few drugs has been reported, what are they?
- Some antiinflammatory drugs
- Propranolol oxidation M>F.
• N-Demethylation of erythromycin F>M.
• Cigarette smoke leads to enzyme induction and increases the breakdown of drugs.
• Exposure to industrial chemicals, pollutants also alters metabolism.
• Clinical outcome:
- Increase dose in smokers
- Drugs with narrow safety margins should be given carefully.
When two or more drugs are coadministered
Routes of excretion
1- Renal Excretion
It is the result of three processes:
1.Passive glomerular filtration
2.active tubular secretion in proximal tubules
3. passive tubular re-absorption.
1. Salivary glands: e.g., iodides, rifampicin and acidic drugs as salicylates.
2. Stomach: e.g., morphine (free and conjugated).
3. Large intestine: e.g., tetracycline, streptomycin.
4. Liver through bile, e.g.
rifampicin, vitamin B1
gases and volatile anesthetics.
basic drugs are trapped and excreted in acidic milk, e.g., morphine, amphetamine.
(chloramphenicol and oral anticoagulants can be excreted in milk.)
-Non Absorbed Ingesta: A fraction of what is ingested is not absorbed and contributes to fecal excretion.
-Biliary Excretion: Is the most significant source contributing to fecal excretion, as a result of liver biotransformation activity.
results: contraceptive failure
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