CPT S1 - Pharmacokinetics 1 Flashcards
Define pharmacodynamics
The study of the drug mechanisms of action and effects on the body. “What the drug does to the body”
Define pharmacogenetics
The effect of genetics on the kinetics and dynamics of the drug on an individual
Define pharmacokinetics
The study of the movement of a drug into and out of the body. “What the body does to the drug”
What are the key factors of pharmacokinetics?
Bioavailability Half life Drug elimination Intra-subject variability Drug to drug interactions
What are the processes of pharmacokinetics?
Absorption
Distribution
Metabolism
Elimination
Define bioavailability
The proportion of a dose which finds itself in a body compartment, usually circulation. IV plasma bioavailability is 100% so other routes of administration are compared to this.
What factors affect bioavailability?
Drug formulation (sustained release etc.) Age Malabsorption (eg in Crohn's disease) Food - (lipid soluble?) First pass metabolism
Where can first pass metabolism occur?
The gut lumen
The gut wall
The liver
Define first pass metabolism
Any metabolism occurring before the drug enters systemic circulation
Give an example of first pass metabolism in the gut lumen
Denature due to gastric acid, proteolytic enzymes, grapefruit juice.
Give an example of first pass metabolism in the gut wall
Efflux pumps to move the drug back into the gut lumen from the enterocytes.
Give an example of first pass metabolism in the liver
Many enzymes including the CYP450 family metabolise drugs extensively and contribute to the first pass effect
Define drug distribution
The ability of a drug to dissolve in the body
What key factors affect the distribution of a drug?
Protein binding
Volume of distribution (Vd)
Give examples of proteins that drugs can bind to in circulation
Albumin (acidic drugs)
Globulins (hormones)
Lipoproteins (basic drugs)
Glycoproteins (basic drugs)
Why is protein binding an important factor?
Most drugs have to be free/unbound to have their desired pharmacological effect.
Multiple drugs in circulation may bind to the same proteins, causing changes in drug distribution. In what circumstances is this clinically relevant?
There is high protein binding
Low Vd
A narrow therapeutic ratio
What are some factors affecting protein binding?
Hypoalbuminaemia
Pregnancy
Renal failure
Displacement by other drugs
What can affect tissue distribution?
Specific receptor types within the tissue Regional blood flow Lipid solubility Active transport Disease States Drug interactions
What are active metabolites?
The products of the phase I enzymes of the drug metabolism in the liver. Sometimes, the active compound which has the desired pharmacological effect is produced from a precursor or pro-drug, eg codeine, losartan.
Give examples of foods and OTC medications which can interact with prescription drug metabolism
Charcoal grilled food consumption is a CYP inducer
Grapefruit juice is a CYP inhibitor
St. John’s Wort is another inhibitor
What can affect drug metabolism?
Ethnicity (genetic variability)
Age (lower doses for the very old and very young)
Sex (women slower ethanol metabolisers)
Species (drug development)
Clinical or physical condition (eg hypo/eralbuminaemia)
Where is the biggest route of drug elimination?
The kidney
Which processes determine the renal excretion of drugs?
Glomerular filtration
Passive tubular reabsorption
Active tubular secretion
Define 1st order kinetics
Rate of elimination is proportional to the drug level.
Constant fraction of the drug is eliminated per unit time.
Half life can be defined.
Define zero order kinetics
Rate of elimination is a constant.
Almost all drugs exhibit zero order kinetics at high enough doses as receptors become saturated
Why is zero order kinetics more dangerous?
More likely to result in toxicity Fixed rate of elimination Small dose changes can produce large changes in plasma concentration No half life is calculable Drug monitoring is essential
In what circumstances might you monitor a patient’s plasma drug concentration?
Zero order kinetics Long half life Narrow therapeutic window High drug to drug interaction profile Known toxic effect In order to monitor therapeutic effect (BP, glucose)
How long does it take for a new drug to reach a steady state in the plasma?
3-5 half lives, irrespective of dose frequency or administration
