Pharmacokinetics

Question 1

Routes of drug administration

Answer 1

Enteral (oral, rectal, sublingual, buccal), paranteral (IV, subcutaneous, intramuscular and intradermal), topical, transdermal, inhalation, intrathecal

Question 2

Where do most drugs end up after absorption

Answer 2

Systemic circulation

Question 3

Drug distribution

Answer 3

Process by which the drug is transferred reversibly from the systemic circulation into the tissues as concentrations in the blood increase, and from the tissues into blood when the blood concentrations decrease during elimination
Distribution of the drug into vascular, interstitial and intracellular compartments

Question 4

How does distribution occur

Answer 4

Most drugs transfer by passive diffusion
Across capillary walls down a concentration gradient
Into interstitial fluid until concentration of free drug molecules in interstitium is equal to that in plasma

Question 5

Plasma protein binding

Answer 5

Drugs bind non-specifically to albumin in plasma
Reversible and saturable
Unbound or free fraction distributes
Unbound portion is responsible for clinical effect

Question 6

Highly protein bound drugs

Answer 6

Warfarin, phenytoin, aspirin, thyroxine, ibuprofen, heparin, furosemide

Question 7

Factors that influence drug distribution

Answer 7

Drug physicochemical properties: lipid solubility, water solubility
Drug particle size
Drug protein binding
The environment - blood flow; pH

Question 8

Apparent volume of distribution (Vd)

Answer 8

A concept that seeks to predict how extensively a drug is distributed throughout the body
Volume into which a drug appears to be distributed with a concentration equal to that of plasma.
Vd=Dose (mg)/Concentration (mg/L)

Question 9

Body Fluid Compartments

Answer 9

Total body water volume = 40L, 60% body weight
Intracellular fluid volume = 25L, 40% body weight
Extracellular fluid volume = 15L, 20% body weight - interstitial + plasma volume
Interstitial fluid volume = 12L, 80% of ECF
Plasma volume = 3L, 20% of ECF

Question 10

Vd equation

Answer 10

= Dose/plasma concentration

Question 11

Vd is 2.5 L

Answer 11

Low volume of distribution

Drug remains largely in plasma

Question 12

Vd as 50L (25/0.5)

Answer 12

Large volume of distribution

Drug has largely left the plasma as plasma volume in humans is about 2.5-3L

Question 13

Apparent volume of distribution (2)

Answer 13

Volume into which a drug appears to be distributed with a concentration equal to that of plasma.
Drugs that have a large Vd will need to be administered in larger doses to achieve a target concentration in the plasma.

Question 14

What does it mean if a drug has a low Vd

Answer 14

Vd<10L (warfarin)

Highly protein bound drug so retained in plasme

Question 15

Middle value Vd

Answer 15

Water soluble drugs, low lipid solubility
Distributes into interstitial fluid but not cells
Dose on ideal body weight, to avoid toxicity

Question 16

Drugs with high Vd

Answer 16

Vd>100L (amiodarone)

Fat soluble drug, distributes into tissues

Question 17

Pharmacokinetics

Answer 17

Facilitates safe and effective use of medicines
Determines optimal dosage regimen (dose, route, dose interval, duration of treatment)
Predicts potential drug interactions

Question 18

Factors that influence enteral absorption

Answer 18

Gastrointestinal (GI) motility/blood flow
Absorptive area
Drug particle size and formulation
Drug physicochemical properties & binding
pH:
Acidic Drugs (aspirin) are better absorbed in acidic media, eg in stomach; Basic Drugs (Diazepam) are better absorbed in basic media, in intestines;
Acidic drugs are better excreted in basic media, vice versa

Question 19

Bioavailability

Answer 19

= Oral AUC/IV AUC

Question 20

Bioavailability vs Bioequivalence

Answer 20

Bioequivalence = Two drugs are considered bioequivalent when there is no significant difference in the rate or extent of bioavailability at the same molar dose and under the same conditions