Lecture 4 - Intro to Pharmacokinetics

Question 1

what is pharmacokinetics?

Answer 1

the branch of pharmacology concerned with how often a drug needs to be administered, what dose is given, etc.

Question 2

what happens after you administer a drug?

Answer 2

1) the drug needs to be absorbed and travel to its target tissue
2) over time the effects of the drug ‘wear off’ because it is eliminated from the body

Question 3

the range of drug dosages that can effectively treat a disease without having toxic effects

Answer 3

therapeutic window

Question 4

describes a dynamic equilibrium in which drug concentrations stay within therapeutic limits for long, potentially indefinite, periods

Answer 4

steady state concentration

Question 5

where do we want the steady state concentration to fall?

Answer 5

within the therapeutic window

Question 6

what are five factors that can affect steady state concentration?

Answer 6

• dose
• time between doses
• bioavailability
• clearance
• half-time

Question 7

what are the six main routes of drug administration?

Answer 7

• oral
• intravenous
• intramuscular/subcutaneous
• inhalation
• sublingual
• transdermal

Question 8

the most commoun route of administration for prescription drugs, the rate of absorption is slow and affected by food intake, exposure of drug may be influenced by breakdown in the gut and processing in the liver

Answer 8

oral administration

Question 9

drug is delievered directly into the systemic circulation, so very rapid onset of action, however very inconvenient.

Answer 9

intravenous administration

Question 10

injection of drug into the muscle, or just below the skin, rate of absorption is dependent on blood flow to site

Answer 10

intramuscular/subcutaneous administration

Question 11

absoprtion of drug through epithelium in the lungs, and can be very rapid

Answer 11

inhalation

Question 12

drug is taken orally but placed under the tongue, thus it bypasses the liver and digestive system

Answer 12

sublingual administration

Question 13

taken as an ointment or patch, convenient, slow absorption and sustained exposure

Answer 13

transdermal administration

Question 14

what is first pass metabolism?

Answer 14

drugs that are absorbed from the gut first encounter the liver before entering systemic circulation so there can be significant processing/breakdown before entering the systemic circulation

Question 15

what is the equation for extraction ratio?

Answer 15

extraction ratio = (clearance (liver)) / (blood flow)

Question 16

the fraction of unprocessed/unaltered drug that reaches the systemic circulation after administration by a particular route

Answer 16

bioavailability

Question 17

what is distribution in relation to pharmacokinetics?

Answer 17

refers to how a drug/substance is partitioned into different body ‘compartments’ after it is absorbed

Question 18

what are two key factors that inflence drug distribution in the body?

Answer 18

1) binding to plasma proteins
2) drug accumulation in tissues

Question 19

drugs will circulate in an equilibrium between ___ and ___

Answer 19

free, bound

Question 20

usually, only the ‘free’ fraction of a drug is considered to be ___

Answer 20

pharmacologically active

Question 21

accumulation is favoured in drugs that are ___

Answer 21

lipophilic

Question 22

more highly ____ tissues can accumlate a drug more redily than tissues with poor ____

Answer 22

perfused, perfusion

Question 23

provides a relative comparision of how well drugs are distributed into tissues

Answer 23

volume of distribution

Question 24

what is the equation for volume of distribution?

Answer 24

Vol = (total amount of drug in the body) / (drug concentration)

Question 25

true or false: volume of distribution is a ‘concept’ and is not meant to represent a real volume

Answer 25

true

Question 26

for single compartment distribution, if an elimination pathway is present, the drug concentration decreases with ___

Answer 26

exponential decay kinetics (see notes for visual)

Question 27

for multiple compartment distribution, if an elimination pathway is present, the rate of elimination is determined by the ____, but the reservoir of drug in the tissues can ____

Answer 27

drug concentration in the blood, prolong the lifetime of the drug in the body

Question 28

key mechanisms leading to drug elimination are:

Answer 28

• metabolism in the liver (biotransformation)
• excretion in the kidney/gut

Question 29

what is phase one of drug metabolism in the liver?

Answer 29

the mixed function oxidase system (CYP enzymes) generates oxidative modification of drugs (ex: dehydrogenation)

Question 30

what is phase two of drug metabolism in the liver?

Answer 30

conjugation of phase one product with large polar adducts to make the product more prone to excretion (ex: methylation)

Question 31

true or false: phase one and two of drug metabolism in the liver must occur in sequence

Answer 31

false

Question 32

true or false: there is often more than one pathway for drug metabolism, and multiple CYP enzymes can metabolize a drug

Answer 32

true

Question 33

what is the most widely expressed CYP enzyme in the liver what percent of therapeutic drugs does it metabolize?

Answer 33

CYP3A4, ~75%

Question 34

sometime metabolizing drugs can cause the formation of toxic/reactive intermediates, which can lead to ____

Answer 34

heptotoxicity

Question 35

what are the two main routes of drug elimination?

Answer 35

1) bile/feces
2) urine

Question 36

overall drug elimination is typically described by ____, meaning that the enzymes and systems mediating drug elimination are ____

Answer 36

half-life, not saturated

Question 37

what type of equation can be used to desribe drug elimination?

Answer 37

exponential decay

Question 38

if the enzymes involved in elimination are saturated and rate limiting, then a constant rate of decay can be observed, this is known as ____

Answer 38

capacity-limited elimination