Variations in Drug Action and Effect

Question 1

What terms are preferred to be used when talking about the extent to whcih a person takes his/her medication?

Answer 1

Adherence or concordence now preferred terms to compliance as they emphasise a partnership between the person adn the HCP in the process of taking medicaitons, rather than simply following instructions.

Question 2

List 10 reasons for poor drug adherence

Answer 2

• poor knowledge of the illness and medication.
• administering and dosage of the medication.
• independent pausing, stopping or controlling of the medication.
• lack of competence in self-managment
• hiding the drug information (e.g. drugs prescribed by private doctors)
• fear towards drugs
• media and neighbours as source of medication information
• diseases where poor control of medication does not immediately present with symptoms
• challenges with lifestyle changes
• replacing prescription drugs with self-administered drugs

Question 3

List some (5) patient oreinted approaches to improving adherence

Answer 3

• Focus on health outcomes of self-management and drug therapies
• support for patients to better understand their disease and its management
• pharmacists as coaches for drug therapies
  medication counselling for caregivers
  peer groups for chronic conditions and training in peer groups.

Question 4

List some doctor/prescriber orientated approaches to improving adherence

Answer 4

• continuity of care and permanent doctor-patient relationships
• Equal relationships with pts, with a coaching attitude
• setting achieveable goals

Question 5

List some medication oriented approaches to improve adherence (6).

Answer 5

• Medication reconciliation (nurse or pharmacist)
• medicine optimisation (pharmacist)
• medication review (pharmacist)
• Combination of products to minimise the number of medicines
• Checking and teaching the right use of medical devices
• use of calender packs or prepacked dispensing boxes

Question 6

Name 7 things to tell patients or that patients may want to know about the drugs they are taking

Answer 6

1. the name of the medicine
2. the purpose of treatment
3. when, how and for how long to take their medicine
4. what to do if dose is missed
5. unwanted effects and what to do about these
6. any necessary precautions to take, such as effects on driving
7. any problems with alcohol or other drugs

Question 7

What can be used as a measure of health literacy in English speaking populations?

Answer 7

the REALM-R list

Question 8

How does the REALM-R list work? What score suggests poor health literacy?

Answer 8

Ask patient to read the specified list of words. Score for each word pronounced correctly (except first 3, 3-lettered words which don’t get a score and are there to reduce test anxiety).
A score of <7 suggests poor health literacy

Question 9

How does codeine work as an analgesic?

Answer 9

codeine is a prodrug and is metabolised to morphine, the active opiate, by CYP2D6

Question 10

What could you do if a patient suffers with drug toxicity from a dose that is considered normal for that person’s age and weight?

Answer 10

Genotype the gene that codes for the CYP enzyme that breaks down the drug.
the patient may be an ultrarapid metaboliser.

Question 11

What are the implications of being a CYP2D6 ultra-rapid metaboliser and taking codeine?

Answer 11

They will be able to metabolise codeine into morphine quicker so the patient will have higher than expected morphine levels (an initial “overdose”), with more side effects and a shorter than expected duration of pain control

Question 12

If someone has a genotype result of CYP2D6 diplotype (2A/10)3N, what does the 3N mean?

Answer 12

the 3N indicates there are 3 alleles present so there will be an additional copy of either *2A or *10

Question 13

How many phenotypes of CYP2D6 are there?

Answer 13

4

Question 14

What are teh 4 phenotypes of CYP2D6?

Answer 14

ultra-rapid metaboliser (very high activity)
Extensive metaboliser (normal activity)
intermediate metaboliser (lower activity)
poor metaboliser (low or no activity)

Question 15

What is the most common CYP2D6 phenotype?

Answer 15

Extensive metaboliser - normal activity

Question 16

other than codeine, which other opiates are affected by the CYP2D6 genetic polymorphism?

Answer 16

hydrocodone
oxycodone
tramadol

Question 17

Mutations of the gene encoding an enzyme that metabolises thiopurine drugs, such as azathioprine, have been identified in teh population. What is the name of the enzyme?

Answer 17

Thiopurine methyltransferase (TPMT)

Question 18

TPMT metabolises thiopurine drugs such as azathioprine, mercaptopurine, tioguanine) so what is the effect if a patient has a mutation in the gene encodeing TPMT that means its activity is reduced?

Answer 18

Increased risk of myelosuppression because drug is in system for longer.

Question 19

What should you do before starting someone on a thiopurine drug?

Answer 19

consider measuring TPMT activity.

Question 20

Can you give thiopurine drugs to pts with absent TPMT activity?

Answer 20

No - should be avoided

Question 21

can you give thiopurine drugs to pts with reduced TPMT activity?

Answer 21

only under specialist supervision.

Question 22

What is the difference between pharmacogenetics and pharmacogenomics

Answer 22

Although both terms relate to drug resposne based on genetic influences, pharmacogenetics focuses on single drug-gene interactions, while pharmacogenomics encompasses a more genome-wide association approach, incorporating genomics and epigenetics while dealing with the effects of multiple genes on drug response.

Question 23

What does the Medicines Act, 1968, define a medicinal product to be?

Answer 23

any substance or article intended to be taken by or administered to, a person or animal, which contains a compound or compounds with proven biological effects, plus excipients, and may also contain contaminants

Question 24

When a licenced medicine is prescribed and administered in accordance with teh SPC, then generally there will be no liability attached to the prescriber if what 3 things are stated:

Answer 24

1. correct diagnosis
2. correct choice of medicine
3. pt warned of potential adverse events

Question 25

what does it mean when a drug is used ‘off-label’

Answer 25

licenced drug is being used for a unlicensed indication or by an unlicensed route

Question 26

What is it meant if a medicine is on the general sale list (GSL)?

Answer 26

You can buy it off the shelf in a shop

Question 27

Name 4 classifcations of medicinal products from a purchasing point of view

Answer 27

• General Sale list (GSL)
  Pharmacy only Medicines (P)
  Prescription only Medicines (POM)
  Controlled Drugs (CD)

Question 28

What is the prescription form used at GPs called?

Answer 28

FP10

FP10MDA-SS for addicts

Question 29

What are the POM legal requirements that should go on an FP10? (10)

Answer 29

Be signed
In ink or otherwise indelible (ink that can't be removed)
repeat once only if repeatable
dispensed within 6 months
address of practitioner
indicate role (e.g. doctor)
date
name and address of pt
age, if under 12-yres
dose in numbers AND words if a CD

Question 30

what does ac and pc mean as abbreviations on a prescription?

Answer 30

ac = ante cibum = before food
pc = post cibum = after food

Question 31

What does PRN stand for and what does it mean?

Answer 31

pro re nata

Means take drug when required.

Question 32

What does TDS mean?

Answer 32

3 times daily

Question 33

What abbreviation would you use for a drug that needed to be taken 4 times daily?

Answer 33

qds (quater die sumendum)

Question 34

What is the aim of therapeutic drug monitoring?

Answer 34

To gain useful information that may be used to modify treamtent

Question 35

There are two ways of monitoring drug therapy effectiveness, what are they?

Answer 35

clinical monitoring e.g. BP resposne to antihypertensives
Blood test monitoring e.g. INR in monitoring warfarin anticoagulation, or serum creatinine for assessing response to ACEi

Question 36

What are the criteria for therapeutic drug monitoring? (3)

Answer 36

• absence of good clinical markers of drug effect
• poor correlation between dose and clinical effect
• narrow concentration interval between toxic and therapeutic effects

Question 37

what is meant by therapeutic index?

Answer 37

the margin between the therapeutic dose and the toxic dose - the larger, the better

Question 38

What is the criteria that need to be considered when requesting therapeutic drug monitoring? (6)

Answer 38

appropriate clinical question
accurate clinical info
appropriate sample
accurate analysis
relevant clinical interpretation
effective action taken

Question 39

What are the two main reasons for performing therapeutic drug monitoring?

Answer 39

• to ensure effective therapy (why is pt not responding to therapy - could this be due to inadequate plasma concentrations of the drug?)
• To avoid drug toxicity

Question 40

how many half lives does it take, on average, to reach steady-state

Answer 40

4-5 half-lives

Question 41

Knowing that the steady-state level of a drug can only be measured after 4-5 half-lives of the drug, how many days would have to pass to check the steady-state of digoxin which has a half life of 37.5hrs?

Answer 41

6 days
37.5 x 4 = 150
150/24 = 6.25 days

Question 42

why is it important to measure steady-state correctly?

Answer 42

failure to evaluate correct steady-state level can lead to significant errors in estimates of elimination rate and in prediction of the appropriate dosage.