ADME Of Drugs

Question 1

What does ADME stand for?

Answer 1

Absorption

Distribution

Metabolism

Excretion

Question 2

What routes of administration are there?

Answer 2

Oral - most favourable

Sublingual - absorption under tongues “angina spray”

Rectal - diazepam

Injection & inhalation

Other epithelial surfaces:
Skin
Cornea
Vagina
Nasal mucosa

Question 3

What is topical and systemic administration?

Answer 3

Topical is onto the skin

Systemic is into the body

Question 4

What’s the difference between enteral and parenteral administration?

Answer 4

Enteral is via the GI-tract

Parenteral is Non-GI tract route

Question 5

What’re the benefits of oral administration?

Answer 5

Easy for patients to take - high patient compliance

Formulation can be manipulated to alter rate of absorbance

Require gastrointestinal absorption

Question 6

When is rectal administration used?

Answer 6

Used for drugs to produce a local effect

Useful method when patients are unable to take medication orally - post op or due to vomiting

Con - cannot be administered intravenously

Question 7

What’s the benefits of sublingual administration?

Answer 7

Gives rapid response - angina attack

Good for drugs which are unstable at gastric pH or are metabolised rapidly

Question 8

What does the rate of absorption depend on for intravenous administration?

Answer 8

Diffusion through local tissue

Removal by local blood flow

(Want little tissue with good blood flow)

Question 9

What is a Bolus injection?

Answer 9

IV injection, fastest and most certain route

Rapidly produces a high concentration in the right heart, pulmonary vessel and systemic circulation - morphine/adrenaline

Question 10

What is IV infusion?

Answer 10

A steady intravenous infusion avoids peaks of systemic concentrations and uncertainty over absorption

Question 11

What’re the benefits of administration by inhalation?

Answer 11

Achieves high local drug concentration - minimises systemic effects

Administration of volatile and gaseous anaesthetics - nitrous oxide

Large SA and high blood flow in lungs allow rapid changes in systemic concentration

Question 12

What is cutaneous administration?

Answer 12

Used when a local effect on the skin is required - topical steroid creams

Significant absorption can occur leading to systemic effects - transdermal patches / voltarol

Question 13

Why is the small intestine so efficient?

Answer 13

Micorvilli provide very large surface area ≈ 200m^2

High blood flow

Bile help solubilise some drugs

Question 14

What is transcellular absorption?

Answer 14

Passive and facilitated diffusion as well as active transport pathways through the phospholipid bilayer

Question 15

What is paracellular absorption?

Answer 15

For non-lipophilic drugs, pass between cells into blood capillary

Question 16

What factors affect GI absorption?

Answer 16

Physiochemical factors
- water solubility
- lipophilicity
- ionisation

Formulation
- solution > emulsion > suspension > capsule > tablet

Interaction with food - chelation of tetracycline with calcium milk

Drug-drug interactions

Question 17

What is the rate determining step in drug absorption?

Answer 17

Gastric emptying - hence time taken can be used for estimating dose absorption

Question 18

What drug-drug interactions influence GI absorption?

Answer 18

Stomach emptying time - anticholinergics

Gut motility - laxatives

Decreased blood circulation - CV drugs

Adsorption by antacids

Adsorption by ion exchange resins

Question 19

What is partition coefficient P?

Answer 19

Conc in organic solvent / conc in aqueous phase

Question 20

What does Log P indicate? What does a greater Log P mean?

Answer 20

Log of partition coefficient P indicates the lipohilicity of the drug

A greater Log P means greater lipophilicity

Question 21

How does the lipophilicity of a drug affect how it is administered?

Answer 21

A higher lipophilicity means administration absorption should be lower to avoid unwanted effects / toxic build up in fatty tissues

Question 22

What is the definition of pKa?

Answer 22

The pH of an acid/base when it is 50% dissociated

Question 23

What absorbs better weak acid and bases or strong acids and bases?

Answer 23

Weak acids and bases absorb better

pH ≈ 5 is optimal

Question 24

What is pH partition theory?

Answer 24

Ionisation also affects the steady state distribution of drug molecules between two aqueous compartment if a pH difference exists

Question 25

When is aspirin, pKa 3.5, mostly ionised?

Answer 25

When in urine - pH 8

Question 26

When is pethidine, pKa 8.6, mostly ionised?

Answer 26

In gastric juices, pH 3

Question 27

What’re the three main proteins that drugs bind to?

Answer 27

Albumin - acidic drugs

b-globulin - some basic drugs

acidic glycoprotein - some basic drugs

Question 28

What does drug binding result in for ADME?

Answer 28

Reduced excretion

Reduced pharmacological effect

Potential displacement of other drugs already bound

Question 29

What route of administration is preferred when a drug has a high protein affinity?

Answer 29

IV injection

• high single dose
• drug can diffuse out of plasma before protein binding

IV infusion is bad as a low concentration, continuous does results in most of the drug binding in plasma. Hence has no pharmacological effect

Question 30

Why’re many drugs designed to be lipophilic?

Answer 30

To aid with diffusion across membranes

Question 31

What’s the issue with very lipophilic drugs?

Answer 31

Drug can. Accumulate in adipose tissue - body fat - to potentially toxic levels

It can then be trapped in fat for years. Hence it is important to set appropriate dosing regime for each person as fat % varies