What is pharmacokinetics?
what the body does to the drug
(interpreting data on changing concentrations or amounts of drug and its metabolites in blood, plasma, urine and other body tissues and fluids)
How does a drug reach the systemic circulation?
What is the name of the process by which a drug moves between the systemic circulation and tissues?
What is the name of the process by which a drug it metabolised or excreted from the body?
What are pharmacodynamics?
the effect of drugs and their mechanism of action
(balance between therapeutic effect and toxicity)
Which drugs are the worst absorbed?
strong acids or bases
(they are mostly ionised = cannot cross membranes!)
Why are pharmacokinetics important (4)?
1. important to know if a drug is going to be absorbed if given by a particular route (e.g. orally)
2. need to know the plasma concentration as a function of time (its dynamic)
3. to know where the drug goes once inside the body (distribution) -> determines if histamine is drowsy or non drowsy
4. drug metabolites (are they active or toxic)
Name 3 different enteral (via GI tract) routes of drug administration:
Name 7 different parenteral (not via GI tract) routes of drug administration:
What is bioavailability a measure of?
How well a drug gets into the systemic blood circulation
An oral bioavailability (f) value of 1 means how much of the drug gets into the systemic circulation?
An oral bioavailability (f) value of 0 means how much of the drug gets into the systemic circulation?
Can a drug still be used if it has poor bioavailability?
Why/ why not?
Some will still get into the systemic blood circulation but the rest is lost (excreted)
-> n.b. not very practical to use a drug with v. low bioavailiability
What is an alternative way of measuring bioavailability?
Comparing plasma concentration of drug (Cp) following oral and IV administration, comparing the area under the curves gives a direct experimental measure of bioavailiability
n.b.if area under curves is very similar then the bioavailability is close to 1
n.b. to calculate oral bioavailiability... F = area under curve oral/ area under curve IV
Which 3 factors affect the oral bioabailiability of a drug?
1. poor absorption from gut
2. breakdown of drug in gut
3. first pass effect
What is the first pass effect?
- any drug first absorbed in stomach/ small intestine -> portal circulation -> drug must first pass through liver before it gets into the circulation
- liver = bag of enzymes = metabolise drug to different extents in liver = loss of some of the drug
Where are most drugs absorbed?
The small intestine due to its huge surface area
Through which method do drugs usually cross membranes (e.g. GI mucosa) to be absorbed?
Some drugs are absorbed by alternative routes... give two examples and state how these are absorbed...
L-dopa = transporter in membrane
Iron = transporter
List the 4 different factors that affect drug absorption at a membrane:
1. pKa of drug (lipid solubility)
2. pH at absorbing surface (lipid solubility)
3. GI motility/ food (decreased rate of gastric emptying e.g. opioids = decreased rate of absorption)
4. Drug preparation (e.g. enteric coated aspirin = takes a while to break down = stomach wall not exposed)
Which factor contributes directly to lipid solubility?
pKa of a drug pH at absorbing surface = changes depending on body compartments = ion trapping
What is the pKa of a drug?
the pH at which the drug is 50% ionised
What is the name of the equation relating pH, pKa and ration of ionised to unionised drug?
The henderson hasselbalch equation
What two things does the degree of distribution of a drug (amount in blood or tissues) depend on?
1. Lipid solubility (more likely to get into brain if lipid soluble)
2. plasma protein binding
What does the rate of drug distribution often depend on?
Rate of blood flow to different tissues (particularly for lipid soluble drugs)= especially high to brain!
What is the total body water volume in the average adult?
What is the plasma water volume in the average adult?
What is the blood volume in the average adult?
What is the extracellular water volume in the average adult?
What causes a person to wake up after general anaesthetic is no longer administered via IV?
The brain concentration decreases as the drug redistributes out of the brain back into the blood