Pharmacokinetics

Question 1

what is pharmacokinetics?

Answer 1

what the body does to the drug following administration
(movement of drug into, through and out the body)

Question 2

what are the 4 phases of pharmacokinetics?

Answer 2

absorption, distribution, metabolism, excretion

Question 3

explain pharmacokinetic absorption

Answer 3

the drug enters the body and reaches system circulation

Question 4

explain pharmacokinetic distribution

Answer 4

drug moves from systemic circulation to reach target (+ possibly non-target) tissues

Question 5

explain pharmacokinetic metabolism

Answer 5

drug is chemically altered by the body (usually alters drug characteristics to facilitate excretion)

Question 6

explain pharmacokinetic excretion

Answer 6

drug is removed from body (most commonly through urine/bile)

Question 7

what are the main principles of pharmacokinetics?

Answer 7

rationale of recommended dosing regimens
time blood sampling correctly in relation to dosing and interpret drug conc. for therapeutic drug monitoring
how to adjust dose regimens rationally
identify/evaluate possible drug interactions

Question 8

what is pharmacokinetic bioavailability?

Answer 8

the fraction of an administered drug that reaches systemic bloodstream intact

Question 9

what is pharmacokinetic volume of distribution?

Answer 9

volume of plasma necessary to account for the total amount of drug in patients body

Question 10

what is first pass metabolism?

Answer 10

where a medication undergoes metabolism in a specific body location leading to a reduction in active drug conc. before it reaches action site or systemic circulation
must pass stomach, intestine and liver

Question 11

define the enteral route of drug delivery and give examples

Answer 11

delivery via GI tract with a system wide effect
- oral (antibiotics)
- rectal
- naso-gastric
- sub-lingual

Question 12

define the parental drug route delivery and give examples

Answer 12

bypasses GI tract with system wide effect:
- intravenous (pain relief)
- intramuscular (vaccines)
- subcutaneous (insulin)
- inhalation (anaesthetics)

Question 13

define local drug entry and give examples

Answer 13

delivers drugs to specific tissues with local effect:
- cutaneous (topical steroid creams)
- ocular (eye ointments)
- repiratory (asthma)
- luminal (laxatives)

Question 14

what factors would determine the best route of entry for a drug?

Answer 14

if drug is digested/absorbed poorly
if rapid onset is required
if drug irritates stomach lining
minimise adverse effects
must be patient acceptable

Question 15

list the main routes of drug administration

Answer 15

topical
subcutraneous
rectal
intramuscular
inhalation
intravenous
oral

Question 16

list some advantages of why a drug route may be suitable

Answer 16

• self-administration (suitable for prolongued administration)
• absorption/onset speed controlled
• bypasses first pass metabolism
• safe/predictable route or concentration

Question 17

list some disadvantages to why a drug route may be unsuitable

Answer 17

• vunerable to thrombosis (IV)
• vunerable to first pass metabolism
• delayed/unreliable onset/absorption
• limited volume (intramuscular)
• tissue damage
• rectal inflammation (rectal)

Question 18

explain how drugs can cross cell membranes to reach systemic circulation

Answer 18

paracellular (between cells)

transcellular (membrane permeation)
- passive/facilitated diffusion
- active transport
- pinocytosis

Question 19

what are some intestinal specialisations in the SI that regulate drug intestinal absorption?

Answer 19

influx transporters (SLC family) transports drugs down electrochemical gradient (penicillin, ACE inhibitors)

efflux transporters (ABC family) uses ATP to actively transport drugs against electrochemical gradient (digoxin, cyclosporine)

Question 20

what drug factors affect rate/extent of drug absorption?

Answer 20

molecular size (low)
lipid solubility (high)
pKa/pH (non-polar/uncharged)

Question 21

what patient factors affect rate/extent of absorption?
what increases them?

Answer 21

age (variable, often reduced in elderly)
blood flow (increased)
gastric acid secretion (increased in acidic drugs, reduced in basic or acid degraded drugs)
gastric emptying (increased)
gastric content (fasting)

Question 22

how does a patients GI disease status affect drug absorption?

Answer 22

GI transit time (diarrhoea) - reduced
GI fluid pH (gastritis/GORD) - reduced
GI membranes (crohn’s) - reduced

Question 23

what drug factors affect (increase) the rate of drug distribution?

Answer 23

drug protein binding (low)
blood flow (high)
lipid solubility (high)

Question 24

what patient factors affect rate of drug distribution? (increase Vd)

Answer 24

kidney/liver function (reduced)
age (younger = increase in water soluble drugs)
obesity (increased)
dehydration (reduced)

Question 25

what are the 4 main compartments a drug can distribute to?

Answer 25

plasma water (3L)
interstitial water - between cells (11L)
intracellular water - in cells (28L)
transcellular water - water in epithelial lining

Question 26

explain how volume of distribution can affect a drugs ability to occupy different water compartments

Answer 26

low Vd (<10L) - only plasma
medium Vd - plasma/interstitial fluid
high Vd (>15L) - all compartments

high Vd likely low molecular weight/lipophilic

if Vd exceeds total water volume (42L) it enters tissues