M&R 9.1 - Pharmokinetics

Question 1

What is pharmokinetics?

Answer 1

What the body does to a drug

Question 2

What is drug formulation?

Answer 2

A mixture in a particular state supplied to a patient

Question 3

What needs to be considered when supplying a drug?

Answer 3

• Solid? - Solubility and acid stability in stomach
• Liquid? - Quickly absorbed in the gut
• Compliance? - Is it simple e.g. 1 per day is easier
• Drug-drug interactions

Question 4

What can happen if the wrong drug formulation/administration is given?

Answer 4

Adverse effects e.g. poisoning, unnecessary treatment etc

Question 5

What is drug administration?

Answer 5

The path in which a drug is taken into the body

Question 6

What are the benefits of using a specific site of drug administration?

Answer 6

• Concentrates drug at site of action
• Limits absorption in other areas
• Limits side affects

Question 7

Give some sites of drug administration (7)

Answer 7

• Sublingual (under the tongue)
• Oral
• Inhalation
• Transdermal patch
• Rectal
• Topical )on skin)
• Intravenously, intramuscularly, subcutaneously

Question 8

What needs to be considered when administering a drug?

Answer 8

• Safety of route
• Health of patient e.g. unable to swallow = no oral
• Prevention of complications

Question 9

What is oral bioavailability?

Answer 9

The proportion of a drug given orally (or any other way except IV) that reaches circulation without changing

Question 10

How is oral bioavailability measured?

Answer 10

• Amount (1st pass metabolism, gut absorption)

- Rate (Pharmaceutical factors e.g. tablet, liquid)

Question 11

What is the therapeutic ratio?

Answer 11

• Maximum tolerated dose/ minimum tolerated dose

- Shows how dangerous a drug is

Question 12

What does a narrow therapeutic index indicate? Why?

Answer 12

• Drug is more dangerous

- Concentration to get unwanted adverse side effects is close to the concentration to get desired therapeutic ratio

Question 13

How can the therapeutic ratio be changed? Why?

Answer 13

• Change in formulation

- Absorbs/dissolves more slowly so doesn’t peak in toxic concentration range

Question 14

What is first pass metabolism?

Answer 14

• Drug is administered orally
• Absorbed by the digestive system
• Transported by hepatic portal system and portal vein
• Reaches liver FIRST before being metabolised

Question 15

What is the significance of first pass metabolism?

Answer 15

Due to being metabolised in the liver first, the concentration of the drug is decreased greatly before reaching systemic circulation

Question 16

Which methods of administration do not undergo the first pass effect? Why?

Answer 16

• Sublingual
• Intramuscular etc
• Inhalation
• Rectal
• Travel around the rest of the body before reaching the liver

Question 17

How can liver cirrhosis affect oral bioavailability?

Answer 17

• Decreases hepatic clearance
• Not broken down in liver so more is unchanged
• Increases bioavailability

Question 18

What does a high hepatic extraction signify?

Answer 18

Low bioavailability

Question 19

What is volume distribution?

Answer 19

The theoretical volume that the drug is distributed into if done instantly

Question 20

How can volume distribution be measured?

Answer 20

• Extrapolate plasma concentration to 0 time

- Amount given/ plasma concentration at 0 time

Question 21

How does albumin act as a reservoir for drugs?

Answer 21

• Binds to albumin
• Dissociation = increased free drugs
• Is eliminated/ goes to target receptor and produces an effect

Question 22

What does drug displacement cause? When is this important?

Answer 22

• Protein binding drug interactions

When:

• High binding to albumin
• Small volume of distribution (increases concentration)
• Low therapeutic ratio

Question 23

What is the relationship between dose and albumin binding sites during at class 1 (object)?

Answer 23

Dose is SMALLER THAN albumin binding sites

Question 24

What is the relationship between dose and albumin binding sites during at class 2 (precipitant)?

Answer 24

Dose is GREATER THAN albumin binding sites

Question 25

How can class 1 and class 2 be used simultaneously?

Answer 25

• Class 2 displaces class one
• Class 1 concentration increases
• Increases toxicity of class 1

Question 26

Give some examples of object and precipitant drugs

Answer 26

• Warfarin = O, aspirin = P
• Tolbutamide = O, Sulphonamides = P
• Phenytoin = O, Valproate = P

Question 27

What is meant by a first order drug?

Answer 27

• Rate of elimination is proportional to drug level per unit time
• Increased concentration = increased rate of removal
• Can predict therapeutic ratio when dose is increased
• Can have a half life

Question 28

How can you tell if a drug is first order?

Answer 28

• Linear scale = not a straight line it’s an inverted downwards curve thing
• Log scale = straight line

Question 29

What is meant by a zero order drug?

Answer 29

• Rate of elimination is constant

- Therapeutic ratio can suddenly increase when elimination mechanisms saturate (different in different people)

Question 30

How can you tell if a drug is zero order?

Answer 30

Line is straight when scale is linear

Question 31

What is the equation for rate of metabolism?

Answer 31

Vmax [C] / Km + [C]

same as for enzymes

Question 32

When does metabolism of drug lead to a steady state?

Answer 32

• After 5 half lives

- A loading dose (initial high dose) is needed if an immediate effect needs to happen

Question 33

What happens during phase 1 of drug metabolism?

Answer 33

• Hydrolysis
• Reduction
• Oxidation
• Exposes a reactive group so drug can be conjugated

Question 34

What happens during phase 2 of drug metabolism?

Answer 34

• Forms a conjugation product (usually inactive)

- More polar and water soluble so is easier to excrete in bile

Question 35

What is required in the liver for drug metabolism?

Answer 35

• Cytochrome p450 enzyme system

- NADPH (high energy cofactor)

Question 36

What features of a drug are needed for it to be able to interact with other drugs?

Answer 36

• Inducible

- Inhabitable

Question 37

What conditions lead to drug interactions?

Answer 37

• Low therapeutic ratio
• Used at a minimum effective concentration e.g. OC pill
• Follows 0 order kinetics (once enzyme is saturated, small change in concentration = large change in plasma concentration)

Question 38

Give some examples of inducers and effectors

Answer 38

• Phenobarbitone induces Warfarin
• Rifampicin induces OC pill (metabolised more quickly so decreases dose)
• Cimetidine inhibits Warfarin (excessive anticoagulation)

Question 39

When can drugs ONLY be renally excreted?

Answer 39

Only when unbound (free fraction) can they be filtered in the golmerulus as it is not permeable to proteins

Question 40

Describe the process of active secretion. Where does it happen?

Answer 40

• Transfer from the peritubular capillaries to the renal tubular lumen
• Proximal tubule

Question 41

What is the function of active secretion?

Answer 41

Removes toxins etc. from the blood to be excreted in the urine

Question 42

What is active secretion?

Answer 42

The passive reabsorption of lipid soluable, unionised drug, influenced by pH

Question 43

How are weak acids removed from the blood?

Answer 43

• Make urine more alkaline

- Ionises drug so decreases tubular absorption

Question 44

How are weak bases removed from the blood?

Answer 44

• Make urine more acidic

- ionises drug so decreases tubular absorption