7.4 Pharmacokinetics Part 2 Flashcards
What is the Steady State?
1) The point in a consistent dosing regimen where serum levels are no longer changing.
2) Time to steady state is a function of the drug’s elimination half-life.
3) Loading doses can can decrease the time needed to achieve steady state.
How many half lives does it take to reach steady state?
4 half lives
What do loading doses do?
-They are larger initial doses to get to the steady state quicker. Then only smaller doses are needed to maintain steady state level.
What is Phase 1 of drug liver metabolism?
Involves cytochrome p450 (CYP) liver enzyme system
What are the two most common drug metabolizing CYP?
CYP 34A and CYP 3A5
When do you draw a peak level?
30 minutes after the drug dose is infused.
What type of relationship does the half life and clearance rate have?
- Inverse relationship.
- Clearance time up, half life down
If a drug has a 8 hour half life how long will it take to reach a steady state?
32 hours
What is Phase 2 of the drug liver metabolism?
- Conjugation step (with glucuronic acid, sulfate)
- Uridine 5’-diphosphat-glucuronosyl transferases are the most dominant enzymes in phase 2.
- Conjugation of drug with glucuronic acid is most common reaction.
What is a prodrug?
- Is an inactive parent drug which requires bio-activation.
- Toxification: toxic metabolite formed from parent drug
- A biologically inactive compound that can be metabolized in the body to produce a drug.
Does the liver have to be involved in the creation of all prodrugs?
Prodrug activation does not have to involve the liver.
What are the 4 possible outcome of liver drug metabolism.
1) Chemical alteration.
2) Bioactivation
3) Toxification
4) Elimination
- Drug metabolism is the process by which drug molecules are chemically ale red, usually to more polar metabolites that exhibit increased water solubility to allow elimination in urine or bile and or increased access to execratory transporters.
- Metabolism: active metabolites can be formed both parent drug and metabolite active, prodrug is an inactive parent drug which requires bioactivation, toxification (toxic metabolite formed from parent drug)
What is an inducer?
A drug that speeds up the metabolism of other drugs.
What is enterohepatic recycling?
- It can prolong drug duration of action
- Drugs eliminate in the bile are available for absorption in the GI tract. This re-entry into the body after elimination via the bile results in the recycling of drug and prolongs the time required for the rig to be irreversibly eliminated from the body.
Role of Kidney in Drug elimination, Drug Out?
- Filtration at glomerulus
- Renal tubular secretion
Role of kidney in drug elimination, drug in?
- Renal tubular reabsorption
- pH effect and ion trapping= therapeutically change ruing pH to alter drug ionization and lipid solubility.
What does the kidneys do during aspirin overdose?
Increases urine pH to increase secretion of aspirin in an overdose situation
How do histamines initiate effects?
- Histamine initiates its effects by stimulating the cel membrane.
- Mast cells release histamine after binding to IgE and antigen.
What are the four different Histamine receptors?
H1R, H2R, H3R, H4R
What are the two main histamine drug targets?
H1 and H2 to stop major biological effects such as acute allergic responses.
What drug is the choice for emergency treatment of severe allergic reactions?
-Epinephrine
What care two clinical advantages that loratadine and fexofenadine have over diphenhydramine?
- CNS depression-sedation (mainly with first generation agents)
- Anticholinergic Effects (mainly with first generation agents)
- Loratadine and fexofenadine are 2nd generation drugs and are basically “non-drowsy” and have a low incidence of anticholinergic effects. These drugs have a decreased ability to cross into the CNS (this explains the “non-drowsy”)
Describe the anticholinergic effects from diphenhydramine?
1) Dry mouth
2) Confusion memory loss
3) Constipation
4) Blurred vision
5) Confusion memory loss
