Pharmocokinetics Flashcards
pharmacokinetics meaning?
investigation into how the body acts/reacts to the drug
literally means drug movement
stages of pharmacokinetics?
absorption
distribution
metabolism
elimination
administration routes?
the rate of absorption is affected by the route of administration
intravenous (IV) - vein
intramuscular (IM) - muscle
subcutaneous (S/C) - under skin
oral (Per Os or PO) - GI tract
bioavailability?
the amount of drug that reaches the circulation intact
affected by:
- administration route
- rate and ease of absorption
- blood supply
if entire dose reaches systemic circulation intact the bioavailability will be 100% or 1
oral medication absorption?
have to pass through GI tract to be absorbed into the circulation
- can be solid or liquid = liquid quicker
some are formulated to delay or interfere with absorption
sustained-release
- slows down dissolution and absorption
- reaches correct part of gut - done by capsule
enteric coated
- protective coating
- prevents drug being destroyed in stomach
- o passes out stomach then starts dissolving
the first-pass effect?
oral preparations are absorbed and directed to the liver
- via the hepatic portal vein
the main function of the liver is to remove toxins
- so some drugs are partially or fully destroyed
if drugs are absorbed directly to system circulation they may enter brain and organs causing damage
any remaining drugs after entering the liver can then enter systemic system
so higher doses of oral drugs are normally required
distribution meaning?
movement of drug from systemic circulation to target tissue
distribution process?
protein bounding occurs when drugs are in circulation
- refers to how drugs move through circulation
- render drug molecules inactive
an equal number of drug molecules are bound and unbound
the unbound molecules diffuse into the target tissue
some of the bound molecules are then released
creates a three-way equilibrium
three-way equilibrium?
bound drug molecules in circulation = unbound drug molecules in circulation = unbound drug molecules in target tissue
prevention of distribution?
occur using natural barriers
- eg the blood brain and placental barrier
they act to protect themselves against toxicity (drugs)
- eg drugs entering the brain can impact consciousness
redistribution?
occurs when drugs redistribute back into circulation to move to other areas where tissues are less perfused
to keep equilibrium
- too many drugs in target tissue so diffuse/redistribute
- due to high affinity
lipophilic drug molecule?
distribute process same as usual drug molecules
- with three way equilibrium
but can cross lipid barriers (eg blood brain barrier)
metabolism?
process where drugs are chemically changed
- from required for absorption and distribution
- to hydrophilic form suitable for excretion
phase 1 of metabolism?
drug molecules are altered chemically
- by oxidation, reduction or hydrolysis
molecules become pharmacologically inactive
- known as a metabolite
phase 2 of metabolism?
metabolite is combined with endogenous substrate
- solution from body
to form an inactive conjugate
this conjugate much more very hydrophilic
- so can be excreted by urine
ways of elimination?
urine faeces/bile exhalation saliva sebum on sweat milk
elimination through urine?
the hydrophilic conjugate will then enter the bloodstream and will be filtered by the tubules in the kidney and not be reabsorbed
- so are extracted in urine
molecules with low molecular weight (small and not heavy) may already be hydrophilic and will be excreted in urine without needing to be metabolised
elimination through faeces?
metabolites with a large molecular weight
travel to the liver and leave via bile ducts to enter the small intestine
- pass down the intestine and expelled in faeces
enterohepatic circulation?
some metabolites remain lipophilic when in the GI tract
so can be absorbed through the gut wall and into circulation
- so exert an additional therapeutic effect
then enter liver and GI tract again
half life?
the amount of time it takes for concentration of drug in blood to decrease by 50% due to metabolism and elimination
used to determine when to administer repeat doses
- to ensure concentration is maintained within therapeutic range
long half-life = small therapeutic range
- eg half life is two days = dose after two days will cause overdose
therapeutic range?
measured by the therapeutic index
= toxic dose % effective dose
the higher the index the safer the drug
drugs with a wide therapeutic range require a large overdose to cause toxicity
- vice versa
steady state?
rate of administration = rate of elimination
on a graph peak and troughs are constant
- and within therapeutic range
what we are aiming for when administering
loading doses?
some drugs are ineffective due to taking a long time for the drug to reach therapeutic steady states
- so may give a higher than normal initial dose
- so can quickly reach therapeutic value then reach a steady-state
