Drug Movement On The Body

Question 1

What are the determinants of drug disposition in the body?

Answer 1

Absorption
Distribution
Metabolism
Excretion

(Elimination = metabolism + excretion)

Question 2

Describe Absorption?

Answer 2

the process by which a drug enters the body from its site of administration

Question 3

Describe Distribution?

Answer 3

the process by which a drug leaves the site of administration, enters the blood and subsequently the tissues perfused by the blood. Once within a tissue further blood-independent distribution, dictated by a concentration gradient, may occur by diffusion (or carrier-mediated transport)

Question 4

Describe Metabolism?

Answer 4

the process by which tissue enzymes (principally in the liver – hepatic metabolism) catalyze the chemical conversion of a frequently lipid soluble drug to an often less active and more polar form that is more readily excreted from the body

Question 5

Describe excretion?

Answer 5

the processes that remove the drug, or its metabolites, from the body (principally the kidneys – renal excretion), but other routes may be important for specific agents

Question 6

What are the Physicochemical Factors Controlling Drug Absorption?

Answer 6

Solubility – the drug must dissolve (dissolution) in order to be absorbed

Chemical stability – some drugs are destroyed by acid in the stomach, or enzymes in the gastrointestinal tract

Lipid to water partition coefficient - Absorption of a drug commonly occurs by simple diffusion across membranes (importantly, some agents are transported). For a given drug concentration gradient across a membrane, the rate of diffusion increases with the lipid solubility of the drug)

Degree of ionisation - Only unionised forms readily diffuse across the lipid bilayer

Question 7

Describe what and acid and base do in terms of protons?

Answer 7

Acid - donates protons

Base - accepts protons

Question 8

How can the proportions of ionised and unionised drugs be calculated?

Answer 8

Henderson-Hasselbalch equation

Question 9

What is the Henderson-Hasselbalch equation?

Answer 9

pKa =pH+log10([BH+ ]/[B]) - for WEAK base

pKa =pH+log10([AH]/[A-]) - for WEAK acid

Question 10

Do acidic drugs become more or less ionised in an acidic environment?

Answer 10

Less ionised

Question 11

Do Basic drugs become more or less ionised in an basic environment?

Answer 11

Less ionised

Question 12

Where does the majority of absorption occur?

Answer 12

In the small intestines

Question 13

What are the Factors Affecting Gastrointestinal Absorption?

Answer 13

Gastrointestinal motility (the rate of stomach emptying and movement through the intestines). This is modified by some drugs and the presence of food

pH at the absorption site (varies along the gastrointestinal tract)

Blood flow to the stomach and intestines (increased by food)

The way in which the tablet, capsule etc. is manufactured. This can be customised to release drugs at different rates and sites (e.g. intestine versus stomach)

Physicochemical interactions (e.g. the rate of absorption of some drugs is modified by calcium rich-rich foods)

The presence of transporters in the membranes of epithelial cells of the G.I tract which can facilitate drug absorption (e.g. levodopa which is absorbed my amino acid transport mechanisms)

Question 14

What is oral availability?

Answer 14

the fraction of drug that reaches the systemic circulation after oral ingestion

i.e. amount in systemic circulation / amount administered

Question 15

What is systemic availability?

Answer 15

the fraction of drug that reaches the systemic circulation after absorption

i.e. amount in systemic circulation / amount absorbed

Question 16

What is first pass?

Answer 16

When the drug administered oral can be inactivated by enzymes in the gut wall or liver before reaching the systemic circulation and body tissues in general

Question 17

What are the common routes of drug administration?

Answer 17

Oral 
Inhalation
Buccal/Sublingual
Transfermal/Subcutaneous
IV
Rectal
IM

Question 18

What does enteral and parenteral mean?

Answer 18

Enteral - via the GI tract

parenteral - not via the GI tract

Question 19

Describe Adv and Dis of Oral route? (enteral)

Answer 19

adv - simple, convenient, good for absorption of most drugs

dis - inactivation of some drugs, first pass metabolism, GI irritation

Question 20

Describe Adv and Dis of sublingual/buccal route? (enteral)

Answer 20

adv - rapid absorption, by passes portal system, avoids first pass
dis - infrequent route

Question 21

Describe Adv and Dis of rectal? (enteral)

Answer 21

adv - used for nocturnal administration of some drugs, useful when oral compromised
dis - variable absorption, not very nice or common

Question 22

Describe Adv and Dis of IV? (parenteral)

Answer 22

adv - rapid onset, continuos infusion, complete availability

dis - sterile prep needed, risk of sepsis

Question 23

Describe Adv and Dis of IM? (parenteral)

Answer 23

adv - rapid onset of lipid soluble drugs, depot injection for slow prolonged release
dis - painful, tissue damage, absorption variable

Question 24

Describe Adv and Dis of subcutaneous? (parenteral)

Answer 24

adv - ideal for drugs requiring parental administration

dis - few

Question 25

Describe Adv and Dis of inhalation? (parenteral)

Answer 25

adv - lungs good surface area, good for volatile agents, ideal for local effect
dis - when used for local effect (e.g. in asthma as aerosol) requires some degree of manual dexterity

Question 26

Describe Adv and Dis of Transdermal? (parenteral)

Answer 26

adv - slow absorption across skin into circulation

dis - suitable for relatively few drugs, local irritation

Question 27

Describe Adv and Dis of Topical? (parenteral)

Answer 27

adv - ideal for local effecgt

dis -few

Question 28

What are the different body fluid compartments that drugs can be distributed to?

Answer 28

Interstitial water, intracellular water, transcellular water, plasma water and fat

Question 29

What kind of drug can move FREELY between compartments?

Answer 29

Only an unbound (FREE) drug

Question 30

What is the apparent volume in which a drug is dissolved in?

Answer 30

The volume of distribution (Vd)

Question 31

What is the equation for Vd for a drug administered IV?

Answer 31

Vd = amount of drug in body/plasma concentration

Question 32

What does Vd < 10l imply?

Answer 32

that the drug is largely retained in the vascular compartment [occurs for drugs extensively bound to plasma protein (e.g. aspirin, warfarin), or too large to cross capillary wall (e.g. heparin)]

Question 33

What does Vd = 10-30L imply?

Answer 33

suggests that the drug is largely restricted to extracellular water [occurs for drugs with low lipid solubility (e.g. gentamicin, amoxicillin)]

Question 34

What does Vd > 30L imply?

Answer 34

may indicate distribution throughout total body water, or accumulation in certain tissues [occurs for highly lipid soluble drugs (e.g. ethanol, amitriptyline, thiopentone), or those that bind extensively to tissue proteins (e.g. digoxin)]

Question 35

In terms of (drugs within the systemic circulation can be distributed to one, or more, body fluid compartments) describe how ionised and unionised drugs move?

Answer 35

Ionised and unionised drugs that are not bound to proteins (e.g albumin) can move freely by diffusion - THIS CAN ONLY HAPPEN FROM PLASMA TO INTERCELLULAR WATER

ONLY unionised drugs can move readily by diffusion - THIS HAPPENS FROM EXTRACELLULAR FLUID TO INTRACELLULAR FLUID