Pharmacokinetics Flashcards
What the body does to drugs
ADME
Absorption
Getting the drug into the systemic circulation
Factors affecting absorption
Route of administration
*enteral-oral, sublingual
*parenteral- IV, IM, SC
*other- Inhalation, intranasal, transdermal, topical,rectal, intrathecal
Oral drugs
They are absorbed from the GIT into the portal circulation and from there, they are metabolised in thr liver before reaching the systematic circulation
Modt absorption occurs in the small intestine
Bioavailability
Fraction of administered drug that reaches the systemic circulation
*bioavailability of IV drugs =100%
Factors that affect bioavailability
First pass hepatic metabolism(rate of metabolism in the liver)
Solubility of the drug
Chemical instability
Nature of the drug
Distribution
The drug gets distributed into different compartments of the body after it enters systemic circulation, depending on the properties of the drug
The different compartments
Vascular compartment
Extracellular fluid
Intracellular fluid
Tissue
Volume of distribution
If VD is less than 5l, the drug is retained in the vascular compartment
VD is less 15l, the drug is restricted to extracellular fluid
VD is more than 15l, i indicate distribution throughout total body water
Protein-binding
Drug that is highly bound to plasma proteins is mostly retained in the vascular compartment and not much reaches tissues
Metabolism
Occurs mainly in the liver
Makes the drug more hydrophilic- to be excreted by the kidneys
Stages of hepatic drug metabolism
Phase 1 Reactions- convert the drug into more polar metabolites
Phase 2 Reactions- drug/metabolites that are still not suff hydrophilic are conjugated with endogenous compounds
Metabolites
They are usually less active than the parent drug, but in few cases can be more active
They can be very toxic
Pro drugs must be metabolised to active drugs
Excretion
Getting the drug and its metabolites out of the body
Mainly by the kidneys, in urine
Clearance- the volume of plasma or blood cleared of drug per unit time
It indicates the ability of the liver and kidney to eliminate a drug
Elderly people have decreased renal functioning, thus excretion delayed
Elimination kinetics
Zero order elimination- the same amount of drug is eliminated per unit of time. Regardless of the plasma conc of the drug the rate of elimination is constant
First order elimination- the same proportion of the drug is eliminated per unit time. The conc drops the elimination rate drops as well
