Week 2: Pharmacokinetics Flashcards
What is pharmacokinetics?
What the body does to the drug
- absorption
- distribution
- metabolism
- excretion
What is absorption
The rate at which a drug leaves the site of administration and passes into systemic circulation
What is distribution
The transport of drugs in body fluids from the site of absorption to the receptor site on the cell, a storage site, and the elimination site
How is the drug broken down after distribution?
Metabolism - the drug may be biotransformed through metabolism by the liver or the tissues
How does the drug leave the body?
Excretion - the drug and its metabolites are eliminated from the body in urine, bile, or feces
What are some factors that can impact pharmacokinetics
Age, preganancy, hepatic or renal disease, drug interactions, ethnicity, the rate of metabolism, GI surgeries, nutritional status
Factors that can affect bioavailability of a drug
- how a drug is transported across the membrane
- how a drug interacts with the gastric acid and enzymes in the GI tract
- drug formulations - particle size, the salt form, the crystal polymorphisms, enteric coatings, what binders were used by the manufacturer - influences how a drug dissolves in the system
- *#1 factor that affects bioavailability of a drug - route of administration**
The rate at which the drug leaves the site(s) of administration and passes into systemic circulation
absorption
What is bioavailability?
measure of how much of the drug gets absorbed and into systemic circulation (blood)
F value = fraction of unchanged drug that reaches systemic circulation
F value = 0.25 this means that 1/4 of the dose get to systemic circulation
3 factors that increase absorption and distribution of a drug
1) Lipophilic
2) Low protein binding
3) Low molecular weight
3 factors that decrease absorption and distribution of a drug
1) Hydrophilic
2) High protein binding
3) High molecular weight
A molecule that is un-ionized, uncharged, non-polar is considered:
lipophilic - are more lipid soluble allowing for increased absorption
A molecule that is ionized, charged, polar is considered:
hydrophilic
Where is a basic drug absorbed?
In the more basic environment of the small intestines
Where is an acidic drug absorbed?
In the more acidic environment of the stomach
What is the first pass effect?
Drugs taken orally are absorbed and goes into portal circulation/liver where is may be extensively metabolized before reaching systemic circulation - decreased the bioavailability of oral drugs - limits the efficacy of many oral medications
What affects distribution of a drug?
- cardiac output & local blood flow
- capillary permeability
- Tissue volume
- amount of the drug that become bound to plasma and tissue proteins
- relative lipophilicity of the drug
What is Volume of Distribution (Vd)?
The measure of the apparent space in the body available to contain the drug - theoretical - lipophilic drugs will have a larger Vd (larger concentration in the tissues) - hydrophilic drugs will have a smaller Vd (higher concentration in the plasma because it cannot pass as readily into the tissues/cells)
Properties affecting distribution
- molecular size (large MW - lower distribution; small MW - greater distribution)
- Lipid solubility
- pH of the environment - acidic stays ionized in a basic environment - basic stays ionized in an acidic environment
- Ionization - polar molecules are hydrophilic
- Protein binding - albumin - drug bound to protein is inactive - only unbound drug is active and can exert an effect
Your patient has had HTN for 5 years and has been taking an anti-hypertensive that is 90% protein bound since his diagnosis without any ADR. Recently, he was diagnosed with a DVT and started on Warfarin which is 99% protein bound. What will happen to his blood pressure?
Because Warfarin has a higher affinity to be bound to protein, more of the free antihypertensive medication in the plasma causing the patient’s blood pressure to drop significantly. (went from 10% free HTN medication to 99% free HTN medication)
What enzymes are responsible for Phase 1 drug metabolism?
CYP450 (cytochrome P450)
What is happening during Phase 1 of drug metabolism?
Oxidation (lose an electron), reduction (gain an electron), and hydrolysis (making something hydrophilic more hydrophilic) - oxidation is the most common enzyme reaction in Phase 1
What do oxidation, reduction and hydrolysis do to a drug?
prepares the drug for further metabolism by making it more polar - this can increase or decrease the pharmacologic activity of a drug
What P450 enzyme is responsible for metabolizing close to 50% of drugs?
CYP3A4
