Pharmacokinetics

Question 1

What does ADME stand for

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

Why is pharmacokinetics important

Answer 2

Determines the dose of the drug available to tissues

Question 3

compare systemic to local administration

Answer 3

systemic = to entire organism
Local = restricted to one area of the organism

Question 4

Compare enteral to parenteral administration

Answer 4

Enteral = gastro-intestinal admin
Parenteral = outside GI tract

Question 5

What are the main types of administration

Answer 5

Dermal
Intramuscular
Subcutaneous 
Intraperitoneal
Intravenous
Inhalation 
Ingestion

Question 6

What are the two ways that drugs move around the body and give examples

Answer 6

Bulk flow transfer e.g. bloodstream

Diffusional transfer e.g. molecule by molecule

Question 7

What does the form that drugs exist in depend on

Answer 7

Ratio of ionised (polar) to non-ionised depends on the pH as drugs are mostly weak acids or bases

Question 8

How does pH contribute to the absorption of drugs

Answer 8

Determinant of absorption across lipid membranes

Weak acids are more unionised in acidic environment, weak bases are more unionised in alkaline environments

Question 9

Do charged or non-charged molecules diffuse easier across lipid membranes and why

Answer 9

Unionised / non-charged forms are more lipid-soluble so diffuse easier

Question 10

What is the Henderson-hasselbalch equation

Answer 10

pKa = pH + log10 [H+]/[A-]

pKa= pH + log10 [BH+]/[B]

Question 11

What factors influence drug distribution

Answer 11

Regional blood flow
Extracellular binding (plasma-protein)
Capillary permeability
Localisation in tissues

Question 12

Why may capillary permeability differ

Answer 12

Tissue alterations

renal, hepatic, brain/CNS, placental

Question 13

What is the distribution of regional blood flow

Answer 13

liver - 27%
Kidneys - 22%
Muscles - 20%
Brain - 14%
Heart - 4%

Question 14

What is the significance of plasma protein binding

Answer 14

The greater the proportion, the less is free to access to tissue and leave the blood
50-80% of acidic drugs are bound

Question 15

Why are water soluble drugs less well distributed across the body

Answer 15

Poor access to tissues and dependant on saturable carrier proteins for access to tissues

Question 16

Describe and give an example of a discontinuous barrier

Answer 16

Big gaps between capillary endothelial cells

e.g. liver

Question 17

Describe and give an example of a fenestrated barrier

Answer 17

Circular windows within endothelial cells that allow small molecular weight substances through
e.g. kidney glomerulus

Question 18

What are the type of junctions between cells in a continuous capillary

Answer 18

water-filled gap junction (only for small molecules)

Question 19

What are the type of junctions in the blood brain barrier

Answer 19

Tight junctions

Question 20

Why are only small amounts of non-ionised drug delivered to body fat

Answer 20

Blood flow is very low (2%)

Question 21

What is the oil/water partition coefficient

Answer 21

How well the drug deserves in fat vs water.

Question 22

How does oil/water partition coefficient affect how it leaks into the blood

Answer 22

A high coefficient suggests that even a small percentage reaching the body fat will accumulate very effectively and therefore it will leak back slowly due to poor blood flow and preference of the drug to fat e.g. GA

Question 23

What are the two major routes of drug excretion

Answer 23

Kidney - most drugs

Liver - drugs may be concentrated in the bile (usually large)

Question 24

Describe the basic route of drugs through the kidney

Answer 24

Glomerular filtration (usually low mw)
Active secretion into the tubule
Passive reabsorption back into the blood

Question 25

What does the rate at which drugs are excreted through the kidney depend on

Answer 25

GFR dependent on size Active secretion dependent on available transporters Reabsorption is dependent on urine pH and the extent of metabolism

Question 26

What is enterohepatic cycling and what does it lead to

Answer 26

Drugs/metabolites are excreted into the gut (ileum) via bile and then reabsorbed and taken to the liver to be excreted again leading to drug persistence

Question 27

What are some other routes of drug excretion

Answer 27

``` Lungs Skin GI secretions Saliva Swear Milk Genital secretions ```

Question 28

Define bioavailability

Answer 28

Proportion of the administered drug that is available within the body to exert its pharmacological effect

Question 29

Define apparent volume of distribution

Answer 29

The volume in which a drug appears to be distributed (indicator of the pattern distribution)

Question 30

Define biological half-life

Answer 30

Time taken for the concentration of the drug in the blood/plasma to fall to Half its original value

Question 31

Define clearance

Answer 31

Blood clearance is the volume of blood cleared of a drug in a unit of time

Question 32

How do drugs cross lipid barriers

Answer 32

Diffuse across the membrane Diffusion across aqueous pores Carrier mediated transport

Question 33

Which mechanism of crossing a lipid barrier is least relevant and why

Answer 33

Diffusion across aqueous pores as the drug must be small enough to cross

Question 34

At what pH are drugs more ionised

Answer 34

acids - higher than pKa | bases - lower than pKa

Question 35

Why is pH important for drug absorption

Answer 35

Drugs become very localized within body compartments e.g. aspirin will diffuse into the bloodstream easily, but will not diffuse very well across membranes and into tissues