list the four stages of drug disposition
- Absorption
- Distribution (plasma/tissue distribution)
- Metabolise (biotransformation)
- Excretion = out of body (different to elimination which means not active anymore)
list the three basic movements of substances across a cell membrane
- passive movement
- paracellular transport
- diffusion
- facilitate diffusion (carrier)
- active transport
- movement against gradient
- uses carriers & energy
- pinocytosis
- fluid endocytosis
- also internalise small particles suspended in extracellular fluids
define SLC
= solute carriers co-transporter = use gradient not energy to co-transport solutes e.g. inorganic ions, amino acids, lipids. Sugars, neurotransmitters, drugs
define absorption of drug
= movement from site of administration into plasma
factors that effect absorption of drug x9
- lipid solubility (molecular weight & structure pKa)
- surface area
- gut content
- GI transit time (food, dioheara, vomiting)
- blood flow at site of administration
- drug interaction
- age
- health status
- genetic polymorphisms
what type of molecules can freely cross a membrane
molecules in which electrons are uniformly distributed = unionised
if the pKa of acetic acid is 5 and the pH of the environment is 1 is the environment basic or acidic
protonated = acidic - drug can cross the membrane
if the pKa of acetic acid is 5 and the pH of the environment is 8 is the environment acidic or basic
deprotonated = basic - drug can’t cross membrane
if the drug is more basic is it able to travel through the membrane
no
why do weak acids get trapped in the cell
because it means they usually have a pKa of around 4.4 meaning the environment pH is usually higher at around 7 which means they are trapped because it is in the ionised form as a basic acids
the higher the pH
facilitates dissociation
the lower the pH
reduces dissociation
what does the Henderson-Hasselbalch equation allow us to predict
we can calculate the unionised amount of the drug which means we can predict the absorption of the drug, and where the drug can be trapped depending on the pH of the environment
routes of administration
o Oral o Sublingual o Rectal o Application to other epithelial surfaces (e.g., skin, cornea & vagina) o Inhalation (pulmonary) o Injection o Subcutaneous (SC) – insulin o Intramuscular (IM) – covid o Intravenous (IV) o Intra-arterial o Intrathecal & intravitreal
define parameter
a measurable factor forming one of a set that defines a system or sets the conditions of its operation
what are the parameters in pharmacokinetics
- C max
- T max
- peak absorption phase
- peak elimination phase
- above therapeutic range
- bioavailability
- volume of distribution
define area under a curve
provides a measure of drug exposure
define bioavailability
important parameter to inform the fraction of the drug that has reached the systemic circulation = blood plasma = NOT THE ACTUAL SITE = drug unaltered from entering the site of administration
if 100% of the does of drug enters the systemic circulation the bioavailability is
1.0
the fraction is equal to
the quantity of drug reaching the systemic circulation divided by the quantity of drug administered
factors that may affect drug bioavailability
- first-pass metabolism = broken down/altered before destination, enzymes released from bacteria could break down drugs
- neglects rate of absorption
- gastic pH
- intestinal motility
how can absorption characteristics change even though the same drug is administrated
the formation of the drug e.g. oral or intravenous
factors that affect drug distribution x9
- large drug
- polar drug
- drug enriched in fat
- permeability across tissue barriers
- binding within compartments
- pH partition
- fat: water partition
- blood flow to the tissue = takes more to get to toes
- protein binding
how much of our body is water (percentage)
50-70%
