Pharmocokinetics

Question 1

pharmacokinetics meaning?

Answer 1

investigation into how the body acts/reacts to the drug

literally means drug movement

Question 2

stages of pharmacokinetics?

Answer 2

absorption
distribution
metabolism
elimination

Question 3

administration routes?

Answer 3

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

Question 4

bioavailability?

Answer 4

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

Question 5

oral medication absorption?

Answer 5

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

Question 6

the first-pass effect?

Answer 6

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

Question 7

distribution meaning?

Answer 7

movement of drug from systemic circulation to target tissue

Question 8

distribution process?

Answer 8

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

Question 9

three-way equilibrium?

Answer 9

bound drug molecules in circulation 
= 
unbound drug molecules in circulation 
= 
unbound drug molecules in target tissue

Question 10

prevention of distribution?

Answer 10

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

Question 11

redistribution?

Answer 11

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

Question 12

lipophilic drug molecule?

Answer 12

distribute process same as usual drug molecules
- with three way equilibrium

but can cross lipid barriers (eg blood brain barrier)

Question 13

metabolism?

Answer 13

process where drugs are chemically changed

• from required for absorption and distribution
• to hydrophilic form suitable for excretion

Question 14

phase 1 of metabolism?

Answer 14

drug molecules are altered chemically
- by oxidation, reduction or hydrolysis
molecules become pharmacologically inactive
- known as a metabolite

Question 15

phase 2 of metabolism?

Answer 15

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

Question 16

ways of elimination?

Answer 16

urine 
faeces/bile 
exhalation 
saliva 
sebum on sweat 
milk

Question 17

elimination through urine?

Answer 17

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

Question 18

elimination through faeces?

Answer 18

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

Question 19

enterohepatic circulation?

Answer 19

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

Question 20

half life?

Answer 20

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

Question 21

therapeutic range?

Answer 21

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

Question 22

steady state?

Answer 22

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

Question 23

loading doses?

Answer 23

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