Pharmacokinetics (my Cards)

Question 1

What is pharmacokinetics? (2)

Answer 1

Pharmacokinetics is the study of:

1) what the body does to the drug

2) how the drug is handled

Question 2

What are the 4 basic principles of pharmacokinetics?

Answer 2

ADME

A - Absorption (how will it get in)
D - Distribution (where will it go)
M - Metabolism (how is it broken down)
E - Excretion (how does it leave)

Question 3

What is absorption and what influences absorption? (2)

Answer 3

1) The movement if a drug into the blood stream

2) The rate of absorption depends on:

a) route of administration
b) permeation (how does the drug get into the systemic circulation)

Question 4

Name 9 different routes of drug administration

Answer 4

1) oral
2) buccal
3) inhalation
4) rectal
5) IV - intravenous
6) transdermal
7) topical
8) IM - intramuscular
9) s/c - subcutaneous

Question 5

What is bioavailability? (4)

Answer 5

1) A term used to describe the proportion of drug reaching the systemic circulation

2) This can vary from person to person

3) This says nothing about the drugs effectiveness

4) IV drugs have 100% bioavailability

Question 6

What factors could effect absorption? (9)

Answer 6

1) Disintegration of dosage form (tablet/liquid)
2) Dissolution of particles
3) Chemical stability (PH) some drugs are not stable in acid
4) Stability of drug to enzyme (physiological factors) insulin can’t be given orally
5) Guy motility
6) presence and type of food
7) passage across GI tract wall (permeation)
8) Blood flow to GI tract
9) Gastric emptying time

Question 7

1) What is bioequivalance?

2) What is bioinequivalance?

Answer 7

1) Bioequivalance: Therapeutic equivalence between 2 drug brands would have the same clinical response

2) Bioinequivalance: Therapeutic equivalence between two drug brands would not have the same response

Question 8

Name the 6 different formulations of oral drugs

Answer 8

1) Solutions (water soluble) are rapidly absorbed

2) Dispersible/effervescent tablets (less water soluble) - changing PH, making it acidic

3) Suspensions and emulations (least water soluble) lipid soluble

4) Film coated and enteric coated tablets - to protect stomach but not evidenced for most drugs

5) Slow release tablets (must not be crushed)

6) Capsules containing slow release pellets (may be opened and added to food or put down NG)

Question 9

What is a drug half life? (T1/2)

(3)

Answer 9

1) Time taken for the concentration of drug in the blood to fall by half (50%) it’s original value

2) The process of drug metabolism and drug excretion will determine the drugs half life

3) standard dosage intervals are based on half life calculations

Question 10

What is steady state? (3)

Answer 10

1) Steady state is when the value of drug input is equal to the rate of elimination

2) It takes 5 half lives to reach steady state

3) If half life is 12 hours, 12x5=60. 60 hours is too long so a loading dose is needed

Question 11

What are the 4 major mechanisms involved in drug permeation?

(Drug transport across cell membrane)

Answer 11

1) Aqueous diffusion (small molecules)

2) Lipid diffusion (most important) - cell membrane contains lipid

3) Facilitated diffusion - needs help (? Carrier molecules) requires ATP

4) Pinocytosis (cell drinking) - in this process the cell membrane folds and creates small pockets, captures cellular fluid and dissolved substances

Question 12

What is Flicks first law? (2)

Answer 12

1) Rate of permeation depends on surface area and concentration gradients

2) Flicks first law of diffusion only works well if:

• small molecules
• short distances
• area of high concentration to low concentration (is concentration dependent)

Question 13

What are the 5 factors to consider in plasma binding of drugs?

Answer 13

1) The degree to which medication attach to proteins within the blood

2) A drugs efficiency may be effected by the degree in which it binds

3) The less bound a drug is, the more effectively it can diffuse through cell membrane

4) Albumin is the most important plasma protein in drug binding

5) Only free drugs/un bound drugs can exert its effect

Question 14

What is meant by distribution of drugs? (4)

Answer 14

1) Involves the transportation of the drug to the target site (where receptors might be)

2) Chemical properties of drugs have little effect on bulk flow (blood flow) transfer

3) Diffusional characteristics and ability to cross hydrophobic barriers varies between drugs

4) Measured as Vd (volume distribution) - how far drugs will distribute

Question 15

What are the 5 most important factors for distribution?

Answer 15

1) Protein binding - drug is inactive while bound to plasma proteins

2) Blood flow (good blood flow = good distribution)

3) Membrane permeation (lipid soluble)

4) Tissue soluble (PH snd ionisation)

5) Molecule size (diffusion only works with small molecules)

Question 16

1) what is large Vd?

2) What is small Vd?

Answer 16

1) Large Volume distribution - 1-10 l/kg
- implies wide/extensive distribution
- lipophilic drugs (ethanol, digoxin, propranolol, meperidine)

2) Small Volume distribution - 0.1-1 l/kg
- implies limited to vascular space (water soluble)
- eg gentamicin, warfarin, phenytoin, heparin

Question 17

What is PKa? (5)

(The lower the PKa, the more acidic a drug is)

Answer 17

1) PKa = PH at which 50% of drug molecules are ionised

2) The more ionised a drug is, the more difficult it is to distribute

3) Weak acids and bases (alkali) exist in both ionised and non ionised forms

4) Ratio of these forms varies with PH

5) Hendoson-Hasselbalch equation measures PH

Question 18

-Lipid solutions attract non ionised molecules
-Aqueous solutions attract ionised molecules

How does this effect acid and alkali drugs? (4)

Answer 18

1) Acidic drugs in acidic environments will be non ionised (move through lipid membranes)

2) Alkali drugs in alkali environments will be non ionised (move through lipid membranes)

3) Acidic drugs in alkali environments will be ionised (won’t move through lipid membranes)

4) Alkali drugs in acidic environments will be ionised (won’t move through lipid membranes)

Question 19

Drugs need to cross cell membrane in order to produce their effect. Such transfer occurs more readily with……(4)

Answer 19

1) Low degree of ionisation
2) Low molecular weight
3) High lipid solubility
4) High concentration gradient

Question 20

What 8 factors influence drug metabolism?

Answer 20

1) Genetics (cytochrome P450 - group of enzymes involved in drug metabolism)
2) Age
3) Gender (males tend to metabolise faster than females)
4) Liver size and function
5) Circadian rhythms (24 hour natural)
6) Body temperature
7) Nutritional weight
8) Environmental factors (smokers metabolise faster)

Question 21

What are Acetolators? (2)

Answer 21

1) Fast acetolators metabolise drugs fast

2) slow acetolators metabolise drugs slowly

Question 22

Describe the 2 phases of the metabolism of paracetamol (3)

Answer 22

Phase l = Enzyme P4502E1 make toxic metabolite NAPQ1, non toxic sulphate and glucuronide

Phase ll = NAPQ1 conjugates with glutathione to make it non toxic

• Glutathione mops up free radicals. Too much paracetamol overrides glutathione

Question 23

What is the enzyme CYP2E1?

Answer 23

Cytochrome P450 enzyme

(CYP2E1)

Question 24

Drug metabolism usually involves 2 phases. What are they?

Answer 24

1) Phase 1 - produce toxic metabolites

2) Phase 2 - turn toxins into soluble metabolites for excretion

Question 25

a) What are inhibitors?

b) What are inducers?

c) What are blockers?

Answer 25

a) Inhibitors PROLONG action of drugs or inhibit action of those bio transformed to active agents (pro drugs) eg: cimetidine, grapefruit juice

b) Inducers SHORTEN action of drugs or increase effect of those bio transformed to active agents (pro drugs)

c) Blockers acting on non microsomal enzymes

Question 26

What are the factors to consider in excretion? (2)

Answer 26

1) Metabolism, biliary and renal excretion, exhalation and transpiration

2) Clearance is the amount of drug leaving the body in a given time (elimination rate)

• also described as the volume of the blood cleared of drug in unit time

Question 27

Name 5 excretion routes

Answer 27

1) Kidneys - Glonerular filtration/Egfr (BP dependent) and tubular secretion

2) Liver - Drugs secreted in bile would be active so can be re absorbed (enterohepatic uptake)

3) GI tract - excreted in faeces

4) Lungs (eg gaseous anaesthetics)

5) Minor routes (sweat, saliva, breast milk)

Question 28

What is Enterohepatic re uptake?

Answer 28

Some drugs are secreted in the bile but are still active so can be re absorbed

This can result in a lagging secondary absorption process and increased drug exposure

Question 29

What is Zero order excretion? (5)

Answer 29

1) The rate of excretion of a drug is independent of its concentration
2) Can’t speed up elimination
3) Only 5 % of drugs are zero order
4) Non linear kinetics
5) Example: ethanol (alcohol)

Question 30

What is first order excretion? (4)

Answer 30

1) The rate of excretion is directly proportional to its concentration
2) Excretion can be influenced
3) 95% of drugs are first order
4) Linear kinetics

Question 31

What is a MAB?

Answer 31

A monoclonal antibody (MAB) is an antibody produced from a cell made by cloning a unique white blood cell