Term
| Elimination processes of biotransformation: |
|
Definition
Hepatic metabolism: Phase I and II
Biliary secretion in stools
Renal elimination in urine
Minor routes in breath, sweat, tears, breast, milk |
|
|
Term
| body's basic strategy for drug elimination: |
|
Definition
| make the parent drug more soluble so that it can be more easily excreted by the kidneys |
|
|
Term
| phase I reactions, especially ____ __, convert or unmask a ___ group such as ___, ___, or ___ via ___, ___, or ____. |
|
Definition
- cytochrome p450s
- functional
- OH
- NH2
- SH
- oxidation
- reduction
- hydroxylation |
|
|
Term
| Phase II are ___ reactions via ____, ____, or ____. |
|
Definition
- conjugation
- glucuronidation, sulfation, acetylation |
|
|
Term
Exceptions to the Rules
Some drugs undergo Phase II before Phase I reactions, e.g., INH
Some drugs are prodrugs (inactive) that are bioactivated through enzymatic action
Some conjugated drugs are more active than the parent, e.g., morphine glucuronide
Many drugs are metabolized to active products |
|
Definition
|
|
Term
| Biotransformation leads to the ___ of L-dopa to dopamine. |
|
Definition
|
|
Term
| Biotransformation of active diazepam goes to active oxazepam. |
|
Definition
|
|
Term
| biotransformation of active sulfanilamide to ____N-acetyl. |
|
Definition
|
|
Term
| Oral administration of drugs all go to the ____. |
|
Definition
|
|
Term
|
Definition
| drug> GI tract> absorbed> portal circulation> liver metabolism |
|
|
Term
| first pass effect can also be __ metabolism before absorption. |
|
Definition
|
|
Term
| Entero-hepatic recycling: |
|
Definition
| - conjugated drug gets excreted in the bile> drug is reabsorbed in the GI tract> drug duration is prolonged |
|
|
Term
| Entero-hepatic recycling occurs with ___ ___. Antibiotics inhibit the entero-hepatic recycling and thus can make ___ less effective. |
|
Definition
oral contraceptives
birth control |
|
|
Term
| Bioavailability signifies how much __ ___ drug reaches the ___ ___. |
|
Definition
in tact
general circulation |
|
|
Term
|
Definition
- p450: drug
- P450 reductase
- NADPH
- O2 |
|
|
Term
P450 – drug
P450 reductase – reduced by NADPH
Reduction of P450 – drug complex
Reduced O2 – P450 – drug complex
Transfer of activated O2 to drug |
|
Definition
|
|
Term
| cytochrome p450 is a ___ of ___ located in the ___ ___ of the ____. |
|
Definition
family of enzyme
endoplasmic reticulum of the liver |
|
|
Term
| cytochrome p450s ___ a wide variety of compounds foreign to the body. |
|
Definition
|
|
Term
There are at least 17 different families of cytochrome P450 identified in humans, each the product of a separate gene.
Approximately 50 different isoforms are present in humans |
|
Definition
|
|
Term
|
Definition
letter= isoform
number= type of isoform |
|
|
Term
| ___ metabolizes 60% of drugs marketed in the US. It recognizes a wide range of substrates. |
|
Definition
|
|
Term
|
Definition
Phenobarbital (and other barbiturates)
Rifampin
Glucocorticoids
Tobacco (benzo[a]pyrene)
Charcoal Broiled Foods
Cruciferous Vegetables
PCBs, dioxin (environmental)
Ethanol (Chronic) |
|
|
Term
| smokers activate their p450s enzymes, so they need higher doses of drugs for asthma. |
|
Definition
|
|
Term
| CY3PA4 enzymes bind ___ ___ receptors which causes coactivators to ____gene expression of CYP3A4. |
|
Definition
rxr retinoid
increase
example of a drug that increases own metabolism |
|
|
Term
| some drugs inhibit metabolizing enzymes. what is a well known one? |
|
Definition
|
|
Term
| Factors affecting drug biotransformation: |
|
Definition
Age and Sex
Very young and very old- slower metabolism
Males have faster rates than females
Disease
Liver disease- reduction of metabolism
CV disease- lower liver perfusion
Lung disease- impaired metabolism of some drugs
Hypothyroidism- reduction of metabolism
Hyperthyroidism- enhancement of metabolism |
|
|
Term
| factors affecting drug biotransformation: |
|
Definition
Genetic polymorphisms- CYP’s, others
Mendelian Inheritance Patterns
Many are autosomal recessive traits
Some inhibit metabolism
Some enhance metabolism |
|
|
Term
|
Definition
| rarely used in clinical practice, except for general anesthesia |
|
|
Term
| polymorphism in pseudocholinesterase: |
|
Definition
| reduces metabolism of succinylcholine, increased skeletal muscle block |
|
|
Term
| individual patients differ in ___ ___ and their ___ of metabolism and elimination. |
|
Definition
- drug distribution
- rates |
|
|
Term
| Metabolism of drugs can lead to generation of ___ ___ __ that damage tissues if present in high concentrations. Example of this. |
|
Definition
free radicals
Acetaminophen overdose (quinone forms, liver failure and death) |
|
|
Term
| acetominophine is mostly metabolized by phase II enzymes, but these enzymes can get saturated, so you get a p450 reaction to a toxic quinone.But if you have enough glutathione, the quinone combines with it to form nontoxic mercapturic acid. But you can deplete glutathione, especially if on empty stomach. So how do they treat an acetominophine overdose? |
|
Definition
| give glutathione so mercapturic acid is formed instead of quinone |
|
|
Term
| overdose of acetaminophen: |
|
Definition
Phase II enzymes are saturated
Acetaminophen is metabolized by p450 enzymes to a toxic quinone
Glutathione (GSH) inactivates this quinone
If GSH is depleted, the quinone interacts with tissues (liver) and causes toxicity |
|
|
