Lecture 7.1 & 7.2: Pharmacokinetics of Drug Administration Flashcards
What is Pharmacology?
Science of drug action on biological systems
What is Pharmacokinetics?
It is the study of what the body does to a drug
What is Pharmacodynamics?
It is the study of what a drug does to the body
ADME in Drug Metabolism
Absorption
Distribution
Metabolism
Elimination
What is Pharmacogenetics?
- Genetically determined variations in
responses to drugs - Role of inheritance in individual
variations in drug responses
What are the 4 questions to be asked when prescribing drugs?
- Is the drug getting into patient
(Pharmaceutical Process) - Is the drug getting to site of action?
(Pharmacokinetic Process) - Is the drug producing desired effect?
(Pharmacodynamic Process) - Is this translated to a therapeutic
effect? (Therapeutic Process)
Sites/Types of Administration of Drugs (7)
- Oral
- IV
- Sublingual
- Inhalation
- Transdermal Patch
- Topical
- Rectal
What is the oral bioavailability of a drug?
Proportion of drug given orally (or any other route except IV) that reaches circulation unchanged
What is the Therapeutic Window of a Drug?
Maximum tolerated dose/minimum effective dose
What is the Therapeutic Index/Ratio?
It the range of doses at which a medication is effective without unacceptable adverse events
Why do oral drugs often have less effect than IV drugs at similar doses?
Drugs administered orally are first exposed to the liver and thus may be extensively metabolised before reaching the rest of the body whereas IV drugs directly enter systemic circulation and reach the rest of the body
How can first pass metabolism be avoided? (4)
- Parenteral (iv, im, sc)
- Rectal (note drainage to both portal and systemic
systems) - Sublingual (e.g. use of glyceryl trinitrate in angina
- Topical (eg transdermal cannabinoids/CBD)
What is First Pass Metabolism?
The first pass effect is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug, specifically when administered orally, before it reaches the site of action or systemic circulation
What is Volume of distribution (Vd)?
- A pharmacokinetic parameter that relates the total
amount of drug in the body to the concentration in
the bloodstream - Vd is defined as the total amount of drug in the body
divided by its concentration in plasma
What does it mean for a drug to have a high volume of distribution?
A drug with a high Vd has a propensity to leave the plasma and enter the extravascular compartments of the body, meaning that a higher dose of a drug is required to achieve a given plasma concentration
What does it mean for a drug to have a low volume of distribution?
A drug with a low Vd has a propensity to remain in the plasma meaning a lower dose of a drug is required to achieve a given plasma concentration
What factors influences Vd?
- Drug properties which affect protein binding and
tissue binding - Molecule Size
- Charge
- pKa
- Lipid/Water Partition Coefficient
Protein binding interactions are important when object drug…? (3)
- Is highly bound to albumin (>90%)
- Has a small volume of distribution
- Has a low therapeutic ratio
Drug Binding to Proteins: Class I
It is used at dose lower than number of albumin binding
sites
Drug Binding to Proteins: Class II
Drug is used at doses greater than number of binding sites, and thus displaces the Class I drug
What organ predominantly metabolises drugs?
Liver
What organ predominantly excretes drugs?
Renal System
Drug Pharmacokinetics: 1st order kinetics
- Rate of elimination is proportional to drug level
- Constant fraction of drug eliminated in unit time
- Half life can be defined
Drug Pharmacokinetics: Zero order kinetics
Rate of elimination is a constant
During repeated drug administration, a new
steady state is achieved in….?
5 half lives
Renal Excretion of Drugs
Liver Enzyme: CYP450
- Enzyme family
- Involved in toxin/drug metabolism
- Highly polymorphic: over 100 allelic variants and
subvariants described
CYP Allele
- Normal
- Decreased
- No function
- Increased
- Unknown function
- Uncertain function
What Chromosome is CYP2D6 on?
Chromosome 22
What does CYP2D6 Metabolise?
- Tamoxifen
- Antidepressants
- Fluoxetine (Prozac)
- Pain management
- Codeine (CPIC Guidelines)
- Antipsychotics
- Inhibitors such as: Bupropion (Wellbutrin), Fluoxetine
(Prozac), Paroxetine (Paxil)
What does CYP2D6 metabolise Codeine into?
Morphine
What is Volume of Distribution?
- Theoretical volume into which drug is distributed if
this occurred instantaneously - Obtained by extrapolation of plasma levels to zero
time - Is the volume of plasma that would be necessary to
account for the total amount of drug in the patient’s
body - If that drug were present throughout the body at the
same concentration as found in the plasma
How to calculate Vd?
D/C0
(amount of drug injected)/(blood concentration extrapolated at t = 0)
