M&R Session 9

Question 0

What four things does the pharmaceutical process consider?

Answer 0

Formulation
Compliance
Site of administration
Bioavailability of drug

Question 1

What question does the pharmaceutical process consider?

Answer 1

Is drug getting into patient?

Question 2

What is the advantage of using a specific site of administration?

Answer 2

Concentrates drug at site of action
Decreases systemic absorption
Decreases off-target effects

Question 3

What is the bioavailability of a drug?

Answer 3

The proportion that makes it to the circulation unchanged

Question 4

What does the bioavailability of a drug depend on?

Answer 4

1st pass effect
Gut absorption
Pharmaceutical factors

Question 5

How is bioavailability calculated?

Answer 5

(AUC oral)/(AUC injected) x 100

Question 6

What question does the pharmacokinetic process consider?

Answer 6

Is drug getting to site of action?

Question 7

What is the therapeutic ratio?

Answer 7

max. tolerated dose/min. effective dose

= LD50/ED50

Question 8

What is LD50?

Answer 8

Toxic dose in 50% of the population

Question 9

Give an example of a drug with a small therapeutic index.

Answer 9

Warfarin

Question 10

Give an example of a drug with a large therapeutic index.

Answer 10

Penicillin

Question 11

What does a small therapeutic index indicate?

Answer 11

A large overdose is needed before adverse effects occur

Question 12

What is the disadvantage of a fast release prep?

Answer 12

May be above [toxic] for a short amount of time

Question 13

What is the disadvantage of a slow release prep?

Answer 13

May not remain in the therapeutic window for long

Question 14

What question does the pharmacodynamic process consider?

Answer 14

Is drug producing desired effect?

Question 15

What question does the therapeutic process consider?

Answer 15

Is this translated to a therapeutic effect?

Question 16

What is first pass metabolism?

Answer 16

When drugs administered orally undergo oxidation and conjugation in the liver before reaching systemic circulation

Question 17

What alternative administration routes can be used to avoid first pass metabolism?

Answer 17

Parenteral (IV, IM, SC)
Rectal
Sublingual

Question 18

What is the volume of distribution?

Answer 18

Theoretical volume into which drug is distributed if this occurred instantaneously

Question 19

Why do hydrophobic drugs appear to have a huge volume of distribution?

Answer 19

Absorbed by fat so don’t enter bloodstream

Question 20

What property of a drug does the volume of distribution indicate?

Answer 20

Hydrophobicity

Question 21

What determines the action of a drug at its receptor and its elimination?

Answer 21

Protein binding

Question 22

What are protein binding interactions?

Answer 22

2nd hydrophobic drug binds displacing 1st and causing it to reach toxic levels

Question 23

When are protein binding drug interactions important?

Answer 23

When object drug is:
>90% bound to albumin
Has a small volume of distribution
Has a low therapeutic ratio

Question 24

Give two examples of object drugs and their precipitant drugs.

Answer 24

Warfarin - sulphonamides, aspirin, phenytoin | Tolbutamide - sulphonamides, aspirin

Question 25

How low is the dose of Class I (object) drug used to keep [free drug] low?

Answer 25

A dose lower than the number of albumin binding sites

Question 26

What doses are Class II (precipitant) drugs used at?

Answer 26

Doses higher than the number of binding sites so object drug is displaced

Question 27

Why are drug binding interactions transient?

Answer 27

Elimination rate rises as it is dependent on free drug levels which have risen

Question 28

How quickly is a new steady state restored in brung binding interactions?

Answer 28

Within a few days

Question 29

What is first order kinetics?

Answer 29

Rate of elimination is proportional to drug level

Question 30

What is special about the half life of a drug that follows first order kinetics?

Answer 30

It is defined

Question 31

How does first order kinetics appear on a linear scale?

Answer 31

Exponential decrease

Question 32

How does first order kinetics appear on a log scale?

Answer 32

Linear

Question 33

At what drug doses are first order kinetics seen?

Answer 33

Low

Question 34

How is the therapeutic response from a dose increase of a first order kinetic drug described?

Answer 34

Predictable

Question 35

What is zero order kinetics?

Answer 35

Rate of elimination is a constant

Question 36

Why is the rate of elimination constant in zero order kinetics?

Answer 36

The reaction is saturated

Question 37

Are first or zero order kinetic drugs more long lived?

Answer 37

Zero order

Question 38

How do zero order kinetics appear on a linear scale?

Answer 38

Straight line

Question 39

At what drug doses are zero order kinetics seen?

Answer 39

High

Question 40

What happens to the therapeutic response as the elimination mechanism is saturated?

Answer 40

Suddenly escalates

Question 41

How many half lives does it take to reach a new steady state in repeated drug administration?

Answer 41

5

Question 42

Does the number of half lives needed to reach a steady state in repeated drug administration depend on dose of frequency of administration?

Answer 42

Nope

Question 43

If the half life of a drug is long and a rapid effect is desired, what kind of dose is used?

Answer 43

Loading dose

Question 44

What often determines a loading dose?

Answer 44

Volume of distribution

Question 45

What is used to top up a loading dose?

Answer 45

Maintenance doses

Question 46

Give two examples of drugs which utilise loading doses.

Answer 46

Digoxin - AF | Heparin - anticoagulation

Question 47

By what two methods can drug elimination take place?

Answer 47

Metabolism | Excretion

Question 48

Briefly describe the process of drug metabolism.

Answer 48

Enters through portal/systemic circulation --> phase I --> oxidation +/- hydrolysis --> phase II --> conjugation products

Question 49

What enzymes are used in the liver to metabolise drugs?

Answer 49

Mixed function oxidases consisting of cytochrome P450 reductase

Question 50

What property of cytochrome P450 allows it to act on a range of drugs?

Answer 50

Low substrate specificity

Question 51

What kind of drugs does P450 reductase have an affinity for?

Answer 51

Lipid soluble

Question 52

What alters P450 levels?

Answer 52

Diet/drug interaction can induce or inhibit

Question 53

When in P450 susceptible to drug interactions?

Answer 53

Low therapeutic ratio Drug at minimum effective concentration Zero order metabolism

Question 54

Give three examples of P450 inducers.

Answer 54

Phenoarbitone Rifampicin Cigarette smoke

Question 55

What determines if a drug is ionised or not when excreted by the kidney?

Answer 55

pH of filtrate

Question 56

Which moiety of drug is lipid soluble and can easily cross membrane for excretion?

Answer 56

Non-ionised

Question 57

Which fraction of the drug is filtered?

Answer 57

Free fraction

Question 58

Can drugs be actively secreted by the tubules?

Answer 58

Yes

Question 59

Give an example of a drug which can be secreted by tubules and its location of secretion.

Answer 59

Penicillin by PCT

Question 60

Which drugs are seen most rapidly in the urine?

Answer 60

Ionised, lipid-insoluble

Question 61

What does passive reabsorption depend on?

Answer 61

pH

Question 62

What effect does acid and alkaline urine have on the absorption of weak acid drugs?

Answer 62

Acid urine = increased absorption | Alkaline urine = decreased absorption

Question 63

What effect does acid and alkaline urine have in the absorption of weak bases?

Answer 63

Acid urine = decreased absorption | Alkaline urine = increased absorption

Question 64

How is aspirin poisoning treated?

Answer 64

Weak acid so forced alkaline diuresis to decrease absorption

Question 65

How should the maintenance dose of a drug with a longer half life due to kidney excretion be altered?

Answer 65

Decreased

Question 66

How does half life relate to time taken to reach steady state?

Answer 66

Longer half life = longer time to reach steady state

Question 67

In prescription in renal disease, what two things can be altered?

Answer 67

Loading dose | Protein binding

Question 68

How is protein binding altered when prescribing in renal disease?

Answer 68

Application of a co-molecule