Drug absorption & distribution (L5) Flashcards
what is pharmacokinetics (PK)?
what the body does to the drug
ADME • absorption • distribution • metabolism • excretion
what is pharmacodynamics (PD)?
what the drug does to the body
time course and mechanism of therapeutic effects
how the drug works
what happens in absorption?
transfer of an exogenous compound from site of administration into the systemic circulation
- usually needs to pass cell membranes
- passive diffusion doen conc gradient
- active transport
what are the 3 types of administration routes for a drug?
IV
oral
dermal
how do you decide which route is best?
- physiochemical properties
- therapeutic aims
- patient preferences
- pharmacokinetic properties
when is parental delivery needed?
- when drug is poorly absorbed
- drug is unstable or metabolised in GI tract
- rapid onset of action is needed
- high dose control is needed
parental delivery includes…
intravenous - bolus or infusion
intramuscular - injected dose is stored in the muscle and diffuses over time
subcutaneous - bolus or infusion
how is the small intestine involved in absorption?
site of absorption of most orally administered exogenous compounds
large, highly permeable SA
excellent blood supply
enterocytes of epithelium contain metabolic enzymes and transporters
what is first pass metabolism?
a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation
what are other absorption routes?
- sublingual
- inhalation
- rectal
- vaginal
- transdermal
absorption in the sublingual route
under the tongue
films and sprays
excellent network of capillaries under the tongue - drug delivered directly into the blood stream
absorption by inhalation
inhalation of powders, gases and suspensions
excellent network of capillaries under the tongue - drug delivered directly into the blood stream
absorption in the rectal route
suppositories and enemas
useful for treating illnesses where vomiting is a symptom
good blood supply
absorption in the vaginal route
gels, pessaries and rings
can ensure local drug efficacy with reduced systemic side effects
good blood supply
pH variances through the menstruation cycle may affect absorption
absorption in the transdermal route
even highly lipid soluble chemicals are slow to enter the bloodstream through the skin
what factors affect absorption via the skin?
- size of drug molecule
- membrane permeability of drug delivery system
- skin hydration
- pKa of drug
- drug metabolism by skin flora
- lipid solubility
what are class I drugs?
high permeability and high solubility
often these drugs are absorbed faster than excreted due to their high solubility
e.g. propranolol
what are class II drugs?
high permeability and low solubility
bioavailability and distribution is limited by the time taken for the drug to dissolve
e.g. naproxen
what are class III drugs?
low permeability and high solubility
a very solvent drug that is limited by its ability to pass through membranes
e.g. ranitidine
what are class IV drugs?
low permeability and low solubility
drugs with very low bioavailability - not good at crossing membranes or being dissolved
e.g. paclitaxel
what factors affect absorption?
- blood flow
- absorptive SA
- contact time at absorptive surface
- gastric emptying
what is Cmax?
maximum concentration of compound after dosing
what is Tmax?
time taken to reach maximum drug conc
what is the area under the curve (AUC)?
considered a measure of systemic exposure
what is bioavailability (F)?
the extent of absorption - how much is available to have an effect on the body
comparison using IV dosing
what do you need to know to work out bioavailability?
- how much exposure using IV route
- how much exposure using oral route
- IV dose administered
- oral dose administered
equation for bioavailability
F = (AUCoral/AUCiv) x (DOSEiv/DOSEoral)
lower bioavailability means more of the oral dose is lost
how is IV and oral bioavailability different?
IV administration - whole dose goes straight into the bloodstream
oral administration - some drug lost to first pass metabolism, lower overall exposure (lower AUC)
