Pharmacokinetics (AD[M]E)

Question 1

ADME?

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

7 ways to administer a drug?

Answer 2

Dermal i.e. through the skin
Intramuscular
Subcutaneous
Intraperitoneal
Intravenous
Inhalation
Ingestion

Question 3

Two circulations a drug can be in?

Answer 3

Systemic and local

Question 4

Parenteral vs. Enreral?

Answer 4

Enteral - refers to the gut so travels GI tract

Parenteral - refers to outside the GI tract (only ingestion is this)

Question 5

How do drugs enter the systemic circulation?

Answer 5

Drugs move around the body in 2 ways:
Bulk-flow transfer i.e. in bloodstream
Diffusional transfer i.e. molecule by molecule over short distances

Question 6

What two environments do drugs have to transverse?

Answer 6

Aqueous i.e. bloodstream, lymph, ECF and ICF (compartments)

Lipid i.e. cell membrane (barriers)

Question 7

How can drugs cross barriers?

Answer 7

1. Diffuse straight across lipid membrane
2. diffuse across aq pores
3. Carrier proteins
4. Pinocytosis (rarer)

Question 8

Lipid soluble vs. water soluble drugs?

Answer 8

Lipid soluble drugs can readily diffuse across the membrane BUT water soluble need proteins to move through

Question 9

Which barrier route is least relevant?

Answer 9

Diffusion through aq pores - as need to very small to be able to BUT most are water-soluble which need transporter proteins

Question 10

How do drugs normally exist?

Answer 10

Most drugs are either weak acids or weak bases SO exist in either an ionised or non-ionised forms

Question 11

What factor determines the ratio in which drugs exist?

Answer 11

pH

Question 12

Analgesic drugs?

Answer 12

Treat pain

e.g. aspirin and morphine

Question 13

In what form does aspirins and morphine exist

Answer 13

Aspirin - a weak acid so donates protons
Morphine - a weak base so accepts protons

They can exist in either form BUT this depends on pH

Question 14

Equation for finding out the ratio of the drug in each compartment?

Answer 14

10^(pKa - pH) = [AH]/[A-]

OR

[BH+]/[B]

Question 15

Properties of pKa and pH?

Answer 15

pKa DOES NOT change

pH DOES change as dependent on the different body compartments

Question 16

Effect of pH and pKa values on acidic and basic drugs?

Answer 16

Acid:
pH BELOW pKa = more UNIONISED
pH ABOVE pKa = more IONISED

Base:
pH BELOW pKa = more IONISED
pH ABOVE pKa = more UNIONISED

Question 17

In what form are drugs readily absorbed?

Answer 17

Unionised form!

Question 18

Ion-trapping?

Answer 18

If the environment pH is ABOVE the drugs pKa, the drug is ion-trapped as it is mainly ionised and thus isn’t passively diffused much

Question 19

E.g. of ion-trapping

Answer 19

Aspirin - unionised in stomach so diffuses easily out

Blood - ionised so does NOT diffuse well into lipid membranes/tissues

Question 20

Why might treatment with IV sodium bicarbonate increase aspirin excretion?

Answer 20

IV sodium bicarbonate will increase urine pH SO will have MORE IONISED aspirin which are readily excreted as cannot diffuse into membrane as easily

Question 21

4 factors influencing drug distribution?

Answer 21

Regional blood flow
EC binding (PPB)
Capillary permeability
Localisation in tissues

Question 22

Regional blood flow?

Answer 22

Increased blood flow to more metabolically active tissues as denser capillary networks so more drugs there

Question 23

EC binding?

Answer 23

PPB - acidic drugs tend to bind more readily
Issue as only a proportion is free and another drug could displace altering % in the blood
e.g. aspirin and warfarin

Question 24

Capillary permeability?

Answer 24

If lipid-soluble does not matter as diffuses across

Continous vs. discountinous vs. fenestrated vs. B-BB

Question 25

Localisation in tissues?

Answer 25

Some drugs remain/stored in certain tissues e.g. fat soluble drugs in adipose tissue - so can still release the drug slowly even after main effect e.g. LAs

Question 26

2 major routes of drug excretion?

Answer 26

Kidney and Liver

Question 27

Kidney?

Answer 27

Not alot of drugs have LMW so move back to blood but diffuse into kidney via active diffusion.

Question 28

An issue with kidneys and excretion?

Answer 28

If drug is lipid-soluble, can diffuse back out into blood SO urine pH and drug metabolism (make drug more water-soluble) very imp here.

Question 29

Liver?

Answer 29

Larger MW drugs excreted into the bile as has discountinous capillary structure and active transport systems (for water-soluble drugs)

Question 30

An issue with liver and excretion?

Answer 30

Enterohepatic cycling - drug excreted into gut via bile then reabsorbed back into the HPV as gut bacteria breakdowns drug-conjugate complex and into the liver
Leads to drug persistence

Question 31

Other routes of excretion?

Answer 31

Lungs (e.g. alcohol breath), skin, GI secretion, saliva, sweat etc.

Question 32

Q: Why might treatment with IV sodium bicarbonate increase aspirin excretion?

Answer 32

A: Increased urine pH ionises the aspirin making it less lipid soluble and less reabsorbed from the tubules, increasing its rate of excretion – remember IONISED drugs DO NOT pass through barriers easily!

Question 33

Bioavailability?

Answer 33

Linked to absorption

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

Question 34

Apparent volume of distribution?

Answer 34

Linked to distribution

The volume in which a drug appears to be distributed - an indicator of the pattern of distribution

Question 35

Biological half-life?

Answer 35

Linked to metabolism/excretion

Time taken for [drug] in blood/plasma to fall to half its original value

Question 36

Clearance?

Answer 36

Linked excretion

Blood/plasma clearance is the volume of blood/plasma cleared of a drug (i.e. from which the drug in completely removed) in a unit time