Pharmacokinetics & Drug Metabolism Flashcards
What is the journey of a drug through the body?
A ADME V(R)
Administration Absorption Distribution Metabolism Excretion Voided (removal)
What are the positives and negatives of IV administration of drugs?
Positive - Very rapid onset of action. If we want systemic exposure very quickly IV is the way to go.
Negative - Invasive and requires training
Why is intraperitoneal administration of drugs not very common?
This is because the peritoneal cavity has a very rich blood supply so you can get a drug through that blood supply
Define systemic, local, enteral and parenteral
Systemic - where the entire organism is exposed to the drug
Local - restricted to one area
Enteral - via the GI tract
Parenteral - everything but the GI tract
Enteral and parenteral are routes of administration
Which route of administration is easiest to achieve?
Enteral - parenteral requires more skill
List the routes of administration
Dermal, subcutanous, intravenous, intramuscular, inhalation, ingestion, intraperitoneal
In terms of an enteral route of administration describe the movement of a drug when ingested
The drug enters the GI tract where it is absorbed and taken to the liver via the hepatic portal system. From the liver it then enters the systemic circulation
How do drug molecules move around the body?
Bulk Flow Transfer - bloodstream
Diffusion Transfer - short distances molecule by molecule
What kind of environment do drugs have to traverse?
Aqueous and Lipid environments
What are compartments and barriers?
Compartments - Aqueous e.g Blood, lymph, extra-cellular fluid, intra-cellular fluid
Barrier - Lipid e.g Cell membanes
In what state do drugs exist in?
Most drugs are either weak acids or weak bases. Therefore they exist in their non-ionised (non-polar) and ionised (polar) forms - the ratio of ionised to non-ionised forms depends on the pH and pKa of the molecules
What is the pKa of a drug?
The H+ concentration/pH at which 50% of the drug exists in its ionised polar form.
IMPORTANT to understanding pH partition hypothesis
Explain the pH partition hypothesis
See Notes
What does the ratio of ionised to non-ionised forms of a drug depend on?
It depends on the pH of the environment and the pKa of the drug
What is ion trapping?
Once the drug goes to the liver and into the systemic circulation, any ionised drug becomes trapped in an aqueous environment. Lipid barrier that prevents absorption
What is the pH of the stomach and the pKa of Asprin? What does that mean in terms of the pH partition hypothesis?
pH 1
pKa 3.4
See notes
What are the factor influencing drug distribution?
Regional blood flow
Extracellular binding (PPB)
Capillary permeability
Localisation in tissues
What percentage of acidic drugs tend to be bound to plasma proteins?
50-80% - bound to albumin (can bind to ionised and non-ionised forms of the drug)
What type of environment is fat?
Lipophilic environment because it isn’t highly perfused - drugs that are lipophilic will localise in fatty tissue (brain + testes)
What are the two major routes of excretion?
Kidney - responsible for the elimination of most drugs (most drugs are made water soluble)
Liver - some drugs are concentrated in the bile and secreted into the intestines
What kind of drugs are excreted by the liver?
Large molecular weight drugs
What is the main method of the excretion of drugs from the kidneys?
Secretion not ultrafiltration
What happens at the glomerulus, proximal tubule, proximal and distal tubules?
Glomerulus - Drug-protein complexes are NOT filtered
Proximal tubule - Active secretion of acid and bases
Proximal and distal tubule - Lipid soluble drugs are reabsorbed
Why are lipid soluble drugs reabsorbed?
Urine is an aqueous environment - How does lipid material change pH. Lipid soluble means it will be reabsorbed
Why might IV sodium bicarbonate increase asprin excretion?
CHECK notes - ask question to lecturer
Describe the excretion by the liver
See notes
What leads to drug persistence?
Enterohepatic cycling and biliary excretion
What pharmacokinetic characteristics can be used to predict time-course of drug action?
Bio availability (linked to absorption)
Apparent volume of distribution (linked to distribution)
Biological half-life (linked to metabolism/excretion)
Clearance (linked to excretion)
Define: Bio availability Apparent volume of distribution Biological half-life Clearance
See notes
Define first order kinetics
The rate of elimination of a drug where the amount of drug decreases at a rate that is proportional to the concentration of drug remaining in the body
Draw a graph and label the axis for first order kinetics
See diagram
How do you calculate volume distribution?
The dose divided by the initial concentration of drug in the plasma
