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24 Cards in this Set
- Front
- Back
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What is drug biotransformation?
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Conversion of a molecule to a more water soluble (readily excretable) metabolite.
Drug companies want to make drugs that are resistant to biotransformation |
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Why is detoxification no longer an appropriate term?
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Since some drugs may be converted into more toxic forms
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What do enzyen kinetics involve?
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Elimination half life (T1/2B)
Zero order reaction First order reaction |
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What is elimination half life?
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how long it takes for plasma level to drop by 50%
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What is zero order reaction?
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Rate of enzymatic biotransformation is CONSTANT, does not depend on amoount of drug present.
Few drugs processed this way, one example is alcohol |
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What is first order reaction?
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Rate of enzymatic biotransformation is PROPORTIONAL to the amount of drug present
Most drugs processed this way |
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General Changes Produces by biotransformation
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Active drug > Inactive metabolite - most desired
Active Drug > Active metabolite Active Drug > Toxic Metabolite - ex Tylenol (hepatotoxic out of therapeutic range) Inactive Drug > Active Drug First 2 most common |
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What is a prodrug ie Inactive > active metabolite?
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Drug designed not to be active until they are trinsformed in the liver, otherwise they'd be toxic to gut.
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What is the difference between an active metabolite and original?
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Active metabolite has the same effect of original but less strong
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Phase I Reactions
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Production of metabolite that are more polar thatn parent drug and usually inactive. Many lack degree of water solubility necessary for rapid elimination and therefor undergo cinjugation (phase II rxn)
Most drugs go through intially usually produce inactive Undergo oxidation (live most common), Hydrolysis, Reduction (minimal) |
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Phase II Reactions
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Involves conjugsting a drug with an endogenous substance
Resulting product is polar (ionized), readily excretable, usually inactive |
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What does conjugation rxn involve (phase II)?
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Acetylation (valium), Glucuronidation (morphine), Methylation (epinephrine)
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When does Phase II rxn occur?
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Usua;;y after Phase I but can occur prior to it.
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Where does biotransformation take place?
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Takes place in the SER of the GI, Lungs, Kidneys, and Liver where more biotransformation occurs.
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What are microsomes?
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Vesicles formed by fractionation and ultracentrifugation of cells.
There contain lots of SER which have enzyems that participate in oxidative drug metabolism. |
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What are the two important microsomal enzymes involved in oxidation-reduction?
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NADPH - cytobrome c reductase
Cytochrome P-450 |
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Cytochrome P-450
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12 variants
different types biotransform different drugs Some drugs increase enzyme activity and some decrease enzyme activity |
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What is enyme induction and what is the result?
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Increase in cytochrome synthesis, which is a protective mechanism resulting in more rapid break down of drugs which causes a shorter half life and less pharmcoactivity.
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What are the causes of enzyme induction?
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Drugs: Barbiturates; thiopental & phenobarbituate, Anticonvulsants, Rifampin (RIMACTANE antibiotic)
Environmental Carcinogens: Benzyprene; found in cigs if PT smokes may need more anesthesia b/f surgery, PCB's Increased Physical Activity; increase blood flow therefore increasing drug delivery |
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What is enzyme inhibtion and what is the result?
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Reduced biotransformation capacity which results in longer half life increased pharmacological activity and blood levels of drug go up
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What is enzyme inhibtion produced by?
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Drugs: Cimetidine; antacid & ciprofloxacin antiobiotic (antiobiotic's can be BOTH)
Hepatic Disease Grapefruit Juice (give this and reduce biotransformation) |
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How do you measure changes in oxidative metabolism/hepatic biotransformation?
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measurement of liver enzyme levels, measure serum bilirubin levelsm, look for jaundice. NOT very reliable and limited capacity
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What is the Antipyrine Test?
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It measures the hepatic oxidative capacity (liver function) Not a standard clinical test.
Can be used to figure out enzyme induction also |
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What do you measure after aminister of antipyrine?
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Salivary content of antipyrine (not biotransformed) and urinary levels of its meabolity (biotransformed.
If liver failure then salivary conc. increases and urinary levels decrease |
