Term
| Phenytoin is oxidized by which isoenzyme of P450? |
|
Definition
|
|
Term
| Acetaminophen is oxidized by which isoenzyme of P450? |
|
Definition
|
|
Term
| In the MEOS pathway, ethanol is oxidized by which isoenzyme of P450? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What enzyme metabolizes levodopa to dopamine? |
|
Definition
| Aromatic Amino Acid Decarboxylase |
|
|
Term
| Give three examples of prodrugs |
|
Definition
| Levodopa (dopamine), Codeine (morphine), and Prontosil (sulfanilamide) |
|
|
Term
| Give two examples of a drug that asserts an effect by lethal synthesis |
|
Definition
Malathion --> Malaoxon,
Parathion --> Paraoxon |
|
|
Term
| How is Isoniazid metabolized in phase I and phase II? Which one happens first? |
|
Definition
Phase II (occurs first): acetylation;
Phase I: Hydrolysis |
|
|
Term
| Give an example of N-dealkylation. What compound is o-dealkylated but can also be N- dealkylated, and what is the product? |
|
Definition
| Imipramine --> Desipramine; Codeine is normally O-dealkylated, but can be N-dealkylated to give norcodeine |
|
|
Term
| Give an example of O-dealkylation |
|
Definition
|
|
Term
| Give an example of deamination |
|
Definition
| Amphetamine --> Phenylacetone |
|
|
Term
| What drug prevents ageing of cholinesterase in the presence of paraoxon? |
|
Definition
|
|
Term
|
Definition
| It covalently binds to cholinesterase and inhibits its enzymatic activity (ageing) |
|
|
Term
| What is the "minor pathway" for alcohol metabolism? |
|
Definition
| Oxidation via the enzyme CYP2E1 |
|
|
Term
| What causes "Gray Baby Syndrome"? |
|
Definition
Inability to properly metabolize and excrete chloramphenicol.
Babies lack glucuronyl transferase and must metablize chloramphenicol by nitroreduction. The resulting arylamine product is toxic, but babies cannot effectively excrete it
Leads to cardiovascular collapse and cyanosis. |
|
|
Term
| What is an example of desulfuration? |
|
Definition
|
|
Term
| What two compounds compete with ethanol to bind to alcohol dehydrogenase? |
|
Definition
| Ethylene glycol and Chloral Hydrate |
|
|
Term
| In what two ways is chloramphenicol metabolized during phase II transformation? Which of these is defective in babies? |
|
Definition
| Choramphenicol is either glucuronylated or reduced (nitroreduction). Babies lack the ability to transfer glucuronyl to the compound |
|
|
Term
| What is an example of azoreduction? |
|
Definition
| Prontosil --> Sulfanilamide |
|
|
Term
| What activity does sulfanilamide exhibit? Does its precursor exhibit this same activity? |
|
Definition
| Sulfanilamide is a bacteriostatic drug. Prontosil does not exhibit this activity until it is metabolized. |
|
|
Term
| What drug is metablized by amide hydrolysis? Where does this happen? |
|
Definition
| Procainamide; this happens in the liver |
|
|
Term
| You test a blood sample for drugs and find morphine glucuronide. What three drugs could the metabolite have come from? |
|
Definition
| Heroin, morphine, and codeine |
|
|
Term
| What compound could you put in a blood sample to prevent cocaine from being metabolized by blood esterases? |
|
Definition
|
|
Term
| What drugs are glucuronidated during phase II? |
|
Definition
| Morphine, codeine, heroin, chloramphenicol, phenytoin, acetaminophen, and aspirin (20%) |
|
|
Term
| What drugs are acetylated during phase II? |
|
Definition
| Isoniazid and Procainamide |
|
|
Term
| What is an example of a drug that is metabolized by glycine conjugation during phase II? |
|
Definition
|
|
Term
| What drug is methylated during phase II? |
|
Definition
| Norepinephrine --> normetanephrine |
|
|
Term
| What drug is metabolized by glutathione conjugation during phase II? |
|
Definition
|
|
Term
| In what three ways is acetaminophen normally modified during phase II? |
|
Definition
| Glucuronidation (55%), sulfonation (35%), and glutathione conjugation |
|
|
Term
| What causes toxic metabolites to build up after ingestion of acetaminophen? |
|
Definition
| Overdose of acetaminophen depletes glutathione (needed for conjugation during metabolism) and causes build up of the intermediate N-acetyl benzoquinone, which reacts with cell macromolecules. Chronic alcohol usage induces the MEOS pathway and CYP2E1; the alcohol hogs CYP2E1 activity, which is required to metabolize N-acetyl benzoquinone |
|
|
Term
| Give three compounds that act as enzyme inducers |
|
Definition
| Phenobarbital (anti-convulsant), polycyclic aromatic hydrocarbons (charcoal), and rifampin (antibiotic) |
|
|
Term
| Give three substances that act as enzyme inhibitors |
|
Definition
| Disulfiram (used to increase alcohol sensitivity to treat alcoholism); Cimetidine (used to decrease stomach acidity and treat ulcers); Grapefruit juice (furanocoumarins) |
|
|
Term
| Why is Cimetidine prescribed? What enzyme does Cimetidine inhibit, and how can this interact with other drugs? |
|
Definition
| Cimetidine is an H2 blocker that inhibits acid secretion in the stomach. Cimetidine also inhibits CYP3A4, which is responsible for metabolizing calcium channel blockers. |
|
|
Term
| Furanocoumarins inhibit which enzyme? |
|
Definition
|
|
Term
| Which isoenzyme of P450 is responsible for metabolism of 60% of drugs? |
|
Definition
|
|
Term
| What two metabolites continue to exhibit the same activity of their drug precursors? |
|
Definition
| Imipramine (to desipramine) and procainamide (to N-acetylprocainamide) |
|
|
Term
| Why is levodopa administered to Parkinson's patients instead of dopamine? |
|
Definition
| Dopamine is too polar to cross the blood-brain barrier. Levodopa is less polar and will cross the blood-brain barrier. |
|
|
Term
| What drug do you administer with levadopa to ensure that it is not converted to dopamine in the periphery? Why does this drug only act in the periphery? |
|
Definition
| Carbidopa inhibits aromatic amino acid decarboxylase, which metabolizes l-dopa to dopamine. Carbidopa only acts in the periphery because it is too polar to cross the blood-brain barrier. |
|
|
Term
| Why is malaoxon toxic to insects but not to mammals? |
|
Definition
| In humans, malaoxon is broken down quickly by esterases. Insects lack these esterases, and malaoxon is a potent cholinesterase inhibitor. |
|
|
Term
| Why is inhibition of cholinesterase potentially lethal? |
|
Definition
| Cholinesterase breaks down acetylcholine, a neurotransmitter that causes skeletal muscle to contract. If acetylcholine is not cleared from the synaptic space, muscle relaxation is inhibited |
|
|
Term
| What isoenzyme of P450 is prevalent in the gut? What effect is this responsible for? |
|
Definition
| CYP3A4; this enzyme is responsible for the first pass effect, which causes drugs to be metabolized before they enter the systemic circulation |
|
|
Term
Where is the Mixed Function Oxidase system located?
What is present in the system?
Which enzyme constitutes the limiting reaction, and why?
What substrates and coenzymes are required for enzymatic activity? What are the products? |
|
Definition
Cytochrome P450 (all isoenzymes) and cytochrome P450 reductase make up the micrsomal P450 system in the smooth endoplasmic reticulum.
Cytochrome P450 reductase is 10-20 times more prevalent than cytochrome P450 in the membrane.
Enzymatic activity requires Fe, NADpH, O2, and the drug.
Products are NADP, oxidized drug, and water. |
|
|
Term
| What are two examples of non-microsomal oxidation? |
|
Definition
| Alcohol oxididation by alcohol dehydrogenase and acetaldehyde oxidation by acetaldehyde dehydrogenase |
|
|
Term
| Under what conditions will the MEOS pathway for alcohol metabolism be utilized? |
|
Definition
| Blood alcohol of greater than 0.10%, and chronic alcohol usage |
|
|
Term
| After finding morphine glucuronide in a blood sample, you do further testing and find 6 monoacetyl morphine. Did this come from morphine, heroin, or codeine? |
|
Definition
| Heroin--heroin is 3,6 acetyl-substituted morphine, but during metabolism, the acetyl groups are removed in a stepwise fashion. The presence of the acetyl group in the blood indicates that the drug was heroin. |
|
|
Term
| In elderly people with decreased hepatic circulation, which transformation phase (I or II) is effected? |
|
Definition
|
|
Term
| A patient has been prescribed Warfarin as a blood thinner. The patient is a frequent smoker. Why is the patient at risk of developing blood clots if he is prescribed the same dose as a non-smoker? |
|
Definition
| Smoking introduces aromatic cyclic hydrocarbons into the body. These compounds are enzyme inducers that increase the metabolism of the warfarin. |
|
|
Term
| What phase II metabolic transformation of cocaine produces a neurotoxin? |
|
Definition
|
|
Term
| What are two examples of genetic polymorphisms that could contribute to differences in the way two people metabolize drugs? |
|
Definition
Fast and slow acetylators; would affect the metabolism of isoniazid
Absence of alcohol dehydrogenase or acetaldehyde dehydrogenase in Asian populations |
|
|
Term
| What is the purpose of Phase I transformation? Where does it mostly occur? What are the exceptions to this? |
|
Definition
| Phase I transformation exposes polar groups that increase retention of the compounds in the kidneys for excretion. The transformation takes place mostly in the liver, but can occur in the gut and blood |
|
|
Term
| What is the most abundant synthetic pathway in phase II transformation in mammals? |
|
Definition
|
|
Term
| Which compounds are metabolized to toxic substances (not counting lethal synthesis)? |
|
Definition
| Isoniazid, Benzo(a)pyrene, and chloramphenicol |
|
|
Term
| What two phase II transformations can aspirin undergo? Which is the more prevalent transformation? |
|
Definition
| Glycine conjugation (more prevalent) and glucuronidation |
|
|
Term
| What drugs undergo ester hydrolysis during phase I? Where in the body does this occur? |
|
Definition
| Procaine, cocaine, and aspirin. Esterases are present in the blood. |
|
|
