Term
| what are the three consequences of metabolic transformations of drugs? |
|
Definition
| inactivation, activation and maintenance of activity |
|
|
Term
| are hydrophobic or hydrophilic drugs more easily reabsorbed in the renal tubules? |
|
Definition
|
|
Term
| what is the active form of the pro-drug L-dopa? |
|
Definition
|
|
Term
| what is "lethal synthesis"? |
|
Definition
| production of a more toxic metabolite from a non-toxic compound |
|
|
Term
| what is the most important organ for biotransformation? |
|
Definition
|
|
Term
| where are enzymes responsible for phase I reactions mainly located? |
|
Definition
|
|
Term
| where are enzymes responsible for phase II reactions mainly located? |
|
Definition
|
|
Term
| what are phase I reactions? |
|
Definition
| small chemical change makes drugs more hydrophilic and also provides functional group used to complete phase II reactions |
|
|
Term
| what are phase II reactions? |
|
Definition
| conjugation with small, endogenous substance on functional group added during phase I reaction |
|
|
Term
| what is the net effect of phase I and II reactions? |
|
Definition
| a lipophilic drug is converted to a more hydrophilic metabolite that is easily eliminated in the urine |
|
|
Term
| what are phase I referred to as? |
|
Definition
| "functionalization reactions" |
|
|
Term
| what are the four main Phase I reactions? |
|
Definition
1. microsomal oxidations
2. non-microsomal oxidations
3. reductions
4. hydrolysis reactions |
|
|
Term
| what are the 7 types of microsomal oxidations? |
|
Definition
1. aromatic hydroxylation
2. N-dealkylation
3. O-dealkylation
4. S-demethylation
5. sulfoxide formation
6. N-oxidation
7. N-hydroxylation |
|
|
Term
| what cellular compartment is rich in enzymes responsible for oxidative drug metabolism? |
|
Definition
| smooth endoplasmic reticulum |
|
|
Term
|
Definition
| vesicle-like artifacts re-formed from pieces of the ER when eukaryotic cells are broken up in the laboratory |
|
|
Term
| what happens to cells at 100,000g? |
|
Definition
-microsomal fraction!
-ER sediments out of solution as a pellet (microsomes) but the soluble enzymes remain in the supernatant
-cytochrome P450 (CYP) is in the microsomes and is concentrated and isolated |
|
|
Term
| what is the most common in vivo system mediating drug oxidation reactions? |
|
Definition
| mixed-function oxidase (MFO) system |
|
|
Term
| what is a mixed-function oxidase? |
|
Definition
-an enzyme that oxidizes two different substrates simultaneously
-each of the two atoms of oxygen are used for a different function in the reaction |
|
|
Term
| what enzymes are associated with MFO system? |
|
Definition
|
|
Term
| what can companies use to assign P450 enzyme to a particular drug? |
|
Definition
|
|
Term
| how many P450 enzyme isoforms are there? |
|
Definition
|
|
Term
| what is the general equation for microsomal drug oxidation? |
|
Definition
| RH + O2 + NADPH + H+ --> ROH + H2O +NADP+ |
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