M&R Session 9

Question 1

What are the four main processes involved in pharmacology?

Answer 1

1) Pharmaceutical process - drug getting to patient?
2) Pharmacokinetic process - drug getting to site of action?
3) Pharmacodynamic process - drug producing the desired pharmacological effect?
4) Therapeutic process - pharmacological effect translated into a therapeutic effect?

Question 2

Regarding the formulation of a drug, what are the two types of drug consistency and what factors should be considered for one of the forms?

Answer 2

Solid or liquid

Solid - solubility and acid stability in stomach must be considered

(Patient compliance!!)

Question 3

Describe the two main and sub types of sites of admin with examples?

Answer 3

Two main: Focal or Systemic

Focal: eye, skin, inhalation etc.

Systemic:

(i) Enteral - sublingual, oral, rectal
(ii) Parenteral - SC, IV, IM, inhl, transdermal

Question 4

What does the term ‘oral bioavailability’ mean?

Answer 4

Proportion of a dose given orally (or by any other route other than IV) that reaches the systemic circulation in an unchanged form.

Question 5

What can bioavailability be expressed as?

Answer 5

Amount - depends on GI abs + 1st pass metab, (gut abs altered by food + disease)

Rate - depends on pharmaceutical factors and rate of gut absorption.

Question 6

How is amount and rate measured for bioavail?

Answer 6

Amount - measured by AUC of blood drug level vs time

Rate - measured by peak height and rate of rise of drug level in blood

OR

BIO = AUC oral / AUC injected x 100

Question 7

What is the therapeutic ratio defined as?

Answer 7

Maximum tolerated dose / minimum effective dose

Defined as LD50/ED50

Question 8

What is the relationship between therapeutic ratio and formulation?

Answer 8

Need a slow release preparation so [Drug] does not exceed toxic dose.

The [drug] should be between the effective conc and toxic conc = therapeutic window

Question 9

What is first pass metabolism?

Answer 9

Blood from the gut reaches the liver by the portal system, where the liver could metabolise the drug before it gets to the systemic circulation (e.g. lidocaine, opiates, propranolol, glyceryl trinitrate)

Question 10

How is FPM avoided?

Answer 10

Parenteral (iv,im,sc)
Rectal (note drainage to both portal and systemic systems)
Sublingual (e.g. use of glyceryl trinitrate in angina)

Question 11

What is volume of distribution of a drug? How is it obtained?

Answer 11

Theoretical volume into which drug is distributed if this occured instantaneously

Obtained by extrapolation of plasma levels to zero time (t=0)

Question 12

What determines the effect of an drug nb what form?

Answer 12

Free drug (most drugs bind to plasma proteins e.g. albumin)

Question 13

Why are protein binding interactions for an object/Class 1 drug?

Answer 13

Is it highly bound to albumin?
Has a small volume of distribution
Has a low therapeutic ratio

e.g. warfarin and tolbutamide

Question 14

What is an object drug/class 1 and precipitant/class 2 drug?

Answer 14

Class 1 - used at doses lower than number of albumin binding sites (therefore [free drug] is low)

Class 2 - drug is used at doses greater than number of binding sites, and thus displaces the Class 1 drug (therefore [free drug] is high)

Question 15

What would occur if a Class I and Class II drug were given simultaneously? Why can this be bad?

Answer 15

Displacement of Class I drug occurs by the class II drug.

Temporarily lead to higher free levels of the object drug, and therefore, higher risk of toxicity.

Question 16

Give examples of object drugs and precipitant drugs?

Answer 16

Object drug : Precipitant drug

Warfarin : Sulfonamides, Aspirin, Phenytoin

Tolbutamide : Sulfonamides, aspirin

Question 17

What is 1st and zero order kinetics for a drug?

Answer 17

1st - rate of elimination is proportional to drug level. Constant fraction of drug eliminated in unit time. Half life can be defined.

Zero - rate of elimination is a constant

Question 18

What occurs at low doses and at high doses of [drug] in relation to rate of drug metabolism?

Answer 18

Low doses - drug metab is first order, that is, proportional to drug dose

High dose - drug metab is zero order, that is, constant and independent of drug dose.

Question 19

What occurs during repeated drug administration? What should be done if a response is needed immediately?

Answer 19

A new steady state is achieved in 5 half lives. Irrespective of dose or frequency of administration.

If an immediate effect is necessary, a loading dose is therefore needed (especially if the half life is long)

Question 20

Where does the major amounts of metabolism and excretion take place?

Answer 20

Metabolism - predominantly liver

Excretion - predominantly renal

Question 21

Describe phase I and phase II reactions in the liver?

Answer 21

Phase I - Oxidation, Reduction and/or hydrolysis by CytP450 enzymes

Phase II - Conjugation (glucuronide, acetyl, methyl, sulphate)

Question 22

What properties do the Cyt P450 enzymes have?

Answer 22

Low substrate specificity
Affinity for lipid soluble drugs
Inducible

Question 23

When are drug interactions in metabolism likely to matter clinically?

Answer 23

1) Drugs with low therapeutic ratio
2) Drug is being used at minimum effective concentration e.g. OC pill
3) Drug metabolism follows zero order kinetics

Question 24

Give examples of drug interactions with enzyme inducers/inhibitors and the affected drugs?

Answer 24

Enzyme inducer : Drug affected

Phenobarbitone : Warfarin, Phenytoin
Rifampicin : OC Pill
Cig smoke - Theophylline

Enzyme inhibitor : Drug affected

Cimetidine : Warfarin, Diazepam

Question 25

What is filtered by the glomerulus in relation to drugs?

Answer 25

Free unbound drug is filtered

Question 26

What can the kidney tubules do to drugs?

Answer 26

Actively secrete drugs e.g. penicillin secreted by prox tub)

Question 27

What types of drugs are reabsorbed into the body in the kidney tubules? What is this dependent on?

Answer 27

Lipid - soluble, unionized drugs

Dependent on pH therefore the pK so only the unionized form is absorbed

Question 28

For weak acids and bases, what conditions are necessary in the urine for reabs?

Answer 28

Weak acid - acidic env for unionzied form e.g. aspirin

Weak base - alkaline env for unionized form e.g. amphetamine

Question 29

What 4 factors are changed in renal disease for drug prescribing?

Answer 29

1) Half lives of drugs are longer - lower the maintenance dose
2) Longer half lives also means longer time to reach a steady state (5 half lives)
3) Loading dose can be altered unless volume of dist is changed
4) Protein binding can be altered