principles of pharmokinetics Flashcards
define pharmokinetics
the action of drugs in the body (absorption, distribution, metabolism, excretion)
define absorption
the process of transfer from the site of administration into the general or systemic circulation
what are the routes of administration
Oral
Intravenous
Intra-arterial
Intramuscular
Subcutaneous
Inhalational
Tropical
Sublingual
Rectal
Intrathecal
Most drugs (except IV/IA) must cross at least one membrane from site of generation to general circulation.
what are the methods of passage across membranes?
Passive diffusion through the lipid layer
Diffusion through pores or ion channels
Carrier mediated processes
Pinocytosis
what is ionization
Ionization is a basic property of most drugs that are either weak acids or weak base
why are ionisable groups important?
Ionizable groups are essential for the mechanism of action of most drugs as ionic forces are part of the ligand receptor interaction
is ionised more water or lipid soluble
most water sol
is un-ionised more water or lipid soluble
lipid
what are the obstacles the drug needed to overcome before it reaches the systemic circulation?
drug structure
drug formation
gastric emptying
first pass metabolism
how is the drug structure an obstacle before it reaches the systemic circulation?
Drugs need to be lipid soluble to be absorbed from gut
Some drugs unstable at low pH or in presence of digestive enzymes so have to be given by alternative route
how is the drug formation an obstacle before it reaches the systemic circulation?
The capsule/ tablet must disintegrate and dissolve to be absorbed
Some formulated to dissolve slowly or have a coating that is resistant to the acidity of the stomach
how is gastric emptying an obstacle before it reaches the systemic circulation?
Rate of gastric emptying determines how soon a drug taken orally is delivered to small intestine
Can be slowed (food/drugs) or speeded up (gastric surgery)
how is first pass metabolism an obstacle before it reaches the systemic circulation?
Drugs taken orally have to pass 4 major metabolic barriers to reach circulation;
Intestinal lumen
Intestinal wall
Liver
Lungs
describe Intradermal and subcutaneous absorption
Avoids barrier of stratum corneum
Mainly limited by blood flow
Small volume can be given
when is intradermal and subcutaneous absorption used
Use for local effect or to deliberately limit rate of absorption
describe Intramuscular absorption
Depends on blood flow and water solubility
Increase in either enhances removal of drug from injection site
Can make a depot injection by incorporating drug into lipophilic formulation which releases drug over days or weeks
describe inhalation absorption
large SA and blood flow but limited by risks of toxicity to alveoli and delivery of non-volatile drugs
Largely restricted to volatiles such as general anesthetics and locally acting drugs such as bronchodilators in asthma
Asthma drugs non-volatile so given as aerosol or dry powder
describe protein binding- is it reversible?
Many drugs can bind to plasma or tissue proteins
This may be reversible or irreversible
what Is the most common reversible protein binding?
with the plasma protein albumin
what does binding with the plasma protein ablumin do?
Binding lowers the free concentration of drug and can act as a depot releasing the bound drug when the plasma concentration drops through redistribution or elimination
what happens if a drug bind irreversibly?
Some drugs bind irreversibly and cannot re-enter the circulation and is equivalent to elimination
describe drug distribution
Lipid soluble drugs easily pass from blood to brain
The brain does little metabolizing and drugs are removed by diffusion into plasma, active transport in the choroid plexus or elimination in the CSF
Lipid soluble drugs readily cross placenta
Large molecules do not cross placenta
describe foetal liver drug distribution
Foetal liver has low levels of drug metabolizing enzymes, so relies on maternal elimination
what is elimination
The removal of a drugs activity from the body
