Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

Factors that contribute to controlling concentration of a drug at an action site

Absorption (bioavailability)
Distribution
Metabolism (/clearance)

Question 2

Bioavailaibiilty

Answer 2

Fraction or % of a drug that enters the circulation after the first pass effect

Question 3

Bioavailable dose

Answer 3

mg or mg/kg of a drug that enters the circulation after first pass effect

Question 4

Factors for deciding the appropriate route of administration

Answer 4

Prospects for compliance
Speed of absorption
Potential for therapeutic effects with local delivery

Question 5

Enteral routes

Answer 5

Entering via intestine

Question 6

Parenteral routes

Answer 6

Entering outside the intestine

Question 7

Oral administration

Answer 7

Pros - convenient, safe, economical, higher compliance, can induce vomiting if overdose
Cons - first pass effect, irregular absorption due to pH/food, not practice if patient is vomiting

Question 8

Advantage of sublingual administration

Answer 8

Avoids first pass effect

Question 9

Rectal administration

Answer 9

Pros - can be used for vomiting patient or where oral impractical

Cons - absorption can be irregular, slower (typically)

Question 10

Intravenous administration

Answer 10

Pros - instantaneous, Endothelia more tolerant of irritating solutions

Cons - toxicity?, not readily reversible, requires expertise, repeat injection —> lose patency of veins

Question 11

Subcutaneous administration

Answer 11

Can be manipulated for fast or slow administration

Common for vaccines

Question 12

Intramuscular injection

Answer 12

Often slow

Can be painful

Question 13

Instantaneous administration

Answer 13

IV
Inhalation
Nasal

Question 14

Slow administration

Answer 14

Rectal
transdermal
IM

Question 15

Other routes of administration

Answer 15

Intrathecal, intraocular, intraosseous

Question 16

Factors affecting bioavailability

Answer 16

Route of administration
Physicochemical properties of drug
Physiology of patient

Question 17

Methods of crossing membranes

Answer 17

Passive diffusion (lipid soluble)
Carrier-mediated transport (charged/polar molecules)

Question 18

Weak acids will be absorbed …

Answer 18

In an acidic environment

Question 19

Weak bases will be absorbed …

Answer 19

In a basic environment

Question 20

Factors that affect distribution

Answer 20

Rate of absorption (charge, lipophilicity, pH, amount in circulation, surface area of compartment)

pH gradients

Question 21

Weak acids will accumulate in …

Answer 21

Basic compartments

Question 22

Weak bases will accumulate in …

Answer 22

Acidic compartments

Question 23

Volume of distribution

Answer 23

Hypothetical/apparent volume of plasma into which a drug distributes if drug were only distributed in plasma

= Bioavailabile dose / concentration of drug in plasma

Question 24

Volume of distribution > 0.6 L/kg indicates

Answer 24

Drug accumulated in non-aqueous environment (fat, organs)

Question 25

Volume of distribution << 0.6 L/kg indicates…

Answer 25

Drug is being accumulated in blood compartments; does not have access to non-plasma compartments

Question 26

Majority of drugs are metabolized by …

Answer 26

First order kinetics

Question 27

First order kinetics

Answer 27

Rate of metabolism is proportional to concentration of drug (I.e. the same amount of drug is metabolized over a given interval) No saturation effect

Question 28

Clearance

Answer 28

Metabolism + elimination Volume of plasma that is cleared of a drug per unit time (normalized to body weight - ml/min per kg)

Question 29

Two compartment pharmacokinetic model

Answer 29

A drug may enter a particular compartment quickly —> then redistribute to other areas of the body - this results in an initial rate, followed by a secondary rate Starts out step —> quickly leaves central compartment (most heavily perfused) —> redistributes —> clears more slowly from the system (peripheral compartment) Change in concentration = some of two first order decay processes

Question 30

Repeated administration of a drug

Answer 30

Four doses required to reach steady state Peak/troughs average over plateau concentration

Question 31

To avoid the ramp up to the plateau concentration of a drug

Answer 31

Administer a loading dose (initial high dose)

Question 32

When an enzyme system is saturated elimination follows…

Answer 32

Zero-order kinetics

Question 33

Zero order kinetics

Answer 33

Same amount of drug is eliminated in any time interval (as opposed to same fraction under normal conditions) Common example = alcohol

Question 34

Factors that may impact pharmacokinetics

Answer 34

Age Weight Disease states Drug-drug interactions Polymorphisms Species