Pharmacokinetics Flashcards
What must considered of drug is solid?
Solubility and acid stability in stomach
Give sites of administration
Focal- eye,skin,inhalation
Enteral-sublingual, oral, rectal
Paraenteral- subcutaneous, intramuscular, intravenous, inhalation, transdermal
Define oral bioavailability
The proportion of a drug dose taken orally that reaches the circulation in an unchanged form
How can oral bioavailability be expressed?
Amount - area under curve of blood drug level vs time
Rate - rate of rise of drug level in blood
Area under curve oral over
Area under curve IV
What is LD50
The maximum tolerated dose.
Lethal dose in 50% of the population
What is ED50
The minimum effective dose
The drug concentration that produces an effective response in 50% of the population
What is the therapeutic ratio
ED50
What does a large therapeutic ratio indicate
Larger therapeutic window
Safer drug
Advantage of slow release prep
Spend longer time in the therapeutic window.
Describe first pass metabolism
Drug absorbed from the gut enters hepatic portal system.
Liver is main site of drug metabolism and contains main enzymes, metabolising drug before it gets to systemic circulation.
How can first pass metabolism be avoided
Paraenteral route
Sublingual route
Rectal route
What is The volume of distribution
The theoretical volume into which the drug has distributed assuming this is instantaneous
What is the erect of a clasS II precipitant drug
When taking an object drug the precipitant drug will displace it on albumin and plasma proteins causing a greater free concentration of object drug
Give two forms of drug elimination and organs
Metabolism liver
Excretion kidneys
Describe metabolism of drugs
Phase I - oxidation, reduction and hydrolysis to expose reactive group cytochrome p450 and NADPH
Phase II - conjugation to form water soluble complex with glucoronide, sulphate,
Describe kidney excretion
Only free unbound drug can be filtered
Drugs actively secreted into PCT
Passive resorption of lipid soluble, unionised drug in DCT
For weak acids, how do you increase excretion
Make urine alkaline
This will ionise the drug causing less resorption and more excretion
How do you increase excretion of weak base
Make urine acid
This will ionise the base and result in less resorption and more excretion.
How many half lives does it take to reach steady state
5
How does drug plasma level change with dose in 1st order kinetics
Constant increase
Straight line
Elimination is proportional to drug plasma concentration.
Half life is constant.
How does las a drug level change with dose in 0 order kinetics
Curve upwards as at high dose ther is very high plasma drug conc as elimination does not increase, it remains at same rate.
Steady state reached in 5 half lives
How does warfarin act?
Vitamin K antagonist
Cut K required for carboxylate on of glutamate residues on prothrombin
Gla residues allow for congregation of clotting factors.
Warfarin prevents this
Give 2 parts of the pharmaceutical process
Formulation of drug
Site of administration
