Sessin 9 - Pharmacokinetics Flashcards
What is formulation of a drug?
Whether it is in tablet or liquid form
What three factors are considered in the pharmaceutical process?
Formulation, compliance and site of administration
How is compliance improved in the pharmaceutical process?
Produce a drug with simple regimens eg once daily (easier to remember)
What are the various sites of administration?
Inhalation, oral, sublingual, intravenous, intramuscular, subcutaneous, topical, transdermal partly and rectal
What are the advantages of having various routes of administration?
Enables the drug to be concentrated close to the site of action and reduces systemic absorption producing less side effects
Define bioavailability
The proportion of drug given (except iv) that reaches circulation unchanged
How is bioavailability measured?
Based on the amount and rate of availability
What determines the amount of drug available in circulation unchanged?
1st pass metabolism and gut absorption
How is bioavailability calculated?
Area under curve (oral)/area under curve (injected) x100
What is therapeutic ratio?
LD50/ED50 or maximum tolerated dose/minimum effected dose
What is the effective therapeutic window?
The range of drug concentration from the minimum effective dose to the maximum tolerated dose
Why is a small therapeutic window significant?
There is potential to cross into toxic levels when administering the effective dose
What is a maintenance dose?
The dose of drug which keeps the patient above the effective concentration but not reaching toxic levels
Why can slow releasing preparations of drugs be beneficial?
Slow releasing drugs allows the effective concentration to be reached and sustained over a long period of time without entering the toxic concentration
What is meant by first pass metabolism?
When drugs are administered orally, absorption into GI tract results in passage to the liver where it is metabolised and changed before it reaches the circulation.
Why is first pass metabolism problematic?
Only a small proportion of active drug reaches the circulation and thus target tissue unchanged.
How is first pass metabolism avoided?
Parenteral routes, rectal and sublingual routes
What are parenteral routes?
Not orally administered eg, iv, im, sc
When administered rectally, where do drugs drain into?
Both the portal and systemic systems
What is volume of distribution?
Theoretical volume into which the drug is distributed if this occurred instantaneously
What is meant by a low volume of distribution? What type of drug has this?
When the drug is distributed it is at low concentrations/volume
Hydrophilic as it dissolves in the plasma
What is meant by high volume of distribution and what drug type has this?
There is a high concentration/volume as the drug does not dissolve
Hydrophobic which only dissolves in lipid
Why is the concentration of therapeutically active drug lower than circulating conc of drug?
Only the drug which is biologically free is therapeutically active, the bound drug is not
How does drug binding increase the half life of the drug?
Bound drug cannot be excreted
What is an object drug?
The first drug to be administered during treatment
Why are protein binding interactions important when the object drug is highly bound to albumin?
The drug will not reach the effective concentration by itself at a dose lower than albumin binding sites
Why are protein binding interactions important when the object drug has a small volume of distribution?
The drug is widely available in the circulation and thus protein interactions must be taken into account in order to provide a high enough dose
Why are protein binding interactions important when the object drug has a small therapeutic window?
The small therapeutic window means that if a precipitant drug is added, it may exceed the toxic threshold
What is a class I drug and describe the dose in relation to albumin in the presence of a precipitant?
The object drug, given in doses lower than the number of albumin binding sites if being administered with precipitant drug
What are class II drugs and describe the dose in relation to albumin?
The precipitant drugs used in doses greater than the number of albumin binding sites
What is a precipitant drug?
A drug which displaces the object drug from albumin when administered
With the addition of a precipitant drug, why does the steady state of an object drug restore in a few days?
As the free drug levels rise, elimination levels also rise
Name some precipitant drugs of warfarin
Aspirin
Phenytoin
Sulfonamides
Name some precipitant drugs of tolbutamide
Aspirin
Sulfonamides
What is meant by first order kinetics?
Rate of elimination is proportional to drug level
What is meant by zero order kinetics?
The rate of elimination reaches constant with the mechanism becoming saturated
Is it possible to work out the half life of first order or second order drugs?
First order
How many half lives does it take to achieve a new steady state?
5
What is a loading dose and when is it used?
Administration of a dose of drug which will immediately reach the effective window instead of waiting for 5 half lives. This is used when the drug action is needed immediately
What is the da get of using zero kinetic drugs?
The therapeutic response can suddenly escalate as elimination mechanisms saturate
Give an example of zero kinetic drugs
Alcohol
Phenytoin
In what two ways can drugs be eliminated?
Metabolism
Excretion
Where does drug metabolism mainly occur?
Liver
Briefly describe phase I and II of drug metabolism
Phase I - oxidation/reduction/hydrolysis to expose/add reactive group
Phase II - conjugation
What is the main enzyme group used in drug metabolism?
Mixed function oxidises consisting of cyp p450 system
Why are CYP enzymes particularly useful?
Low substrate specificity
Affinity for lipid soluble drugs
Inducible
Inhibitable
Drugs can effect each other’s metabolism, when is it most likely to matter clinically?
When the drugs have a low therapeutic ratio (potential to become ineffective or toxic)
When the drug is being used at its minimum effective concentration(potential to make ineffective)
When drug metabolism follows zero order (potential to cause sudden increase in activity)
Which fraction of drugs are filtered?
Free fraction
During renal excretion, what is passive absorption dependant on?
Urine pH
What effect does pH on weak acid absorption into tubule?
Acidic urine -> increased absorption as the acid remains un-ionised
Alkali urine-> acid is ionised -> decreased absorption
How is aspirin poisoning treated?
Forced alkali diuresis
