Adverse Drug Reactions and Monitoring Drug Therapy

Question 1

What is an adverse drug reaction?

Answer 1

an unwanted or harmful reaction experienced following the administration of a drug (or drug combination), suspected to be related to drug use

Question 2

What are type A adverse drug reactions?

Answer 2

Augmented adverse drug reactions

• dose related
• largely predictable from known pharmacological/biochemical effects of a drug or its metabolites
• classified as pharmacological or biochemical

Question 3

What are type B adverse drug reactions

Answer 3

Bizzare adverse drug reactions

• not dose related
• idiosyncratic and unpredictable
• often immunological in nature

Question 4

What is an adverse drug event?

Answer 4

an untoward occurrence after exposure to a drug, that is not necessarily caused by the drug
(e.g. patient involved in RTA whilst on specific medication)

Question 5

Describe the 2 types of pharmacological toxicity

Answer 5

1. toxicity relating to the primary therapeutic effect of the drug but the dose is too high
   - e.g. warfarin and bleeding
2. toxicity not relating to the primary therapeutic effect of the drug but still related to other pharmacological properties (i.e. off target effectd)
   - beta blockers causing bronchoconstriction in asthmatics
   - antipsychotics causing parkinsonism

Question 6

1. What is biochemical toxicity?

2. Describe 2 examples of biochemical toxicity

Answer 6

1. tissue damage caused by the interraction of a drug/drug metabolite with cellular compoments
2. toxic metabolite of paracetamol induces hepatic injury
   cyclophosphamide causes haemorrhagic cystitis (as eliminated in the urine, thus causes cell damage in the bladder)

Question 7

1. Why do NSAIDs cause GI irritation?

2. What type of ADR is this?

Answer 7

1. • NSAIDs inhibit the production of prostaglandins
     - prostaglandins are important in the stomach for the maintenance of the mucosal layer and to reduce acid secretion
2. Type A

Question 8

Name 5 examples of Type A ADRs

Answer 8

1. constipation with opioids
2. sedation with antihistamines
3. parkinsonism with dopamine antagonists
4. hyperprolactinaemia associated with dopamine antagonists
5. hepatic failure associated with paracetamol overdose

Question 9

Which type of antibiotics should be avoided if a patient has a hx of allergic reaction to penicillin?

Answer 9

1. penicillin
2. cephalosporin
3. beta lactams

Question 10

1. How should ADRs be reported?

2. What information should be recorded?

Answer 10

1. reported to MHRA using yellow card scheme
2. one piece of patient information
   name(s) of suspected drug(s)
   brief description of ADR
   contact details of reporter

Question 11

What is the result of a drug interraction of ACEi and NSAIDs?

Answer 11

AKI (both reduce renal blood flow by dilating the efferent arteriole (ACEi) and constricting the afferent arteriole (NSAIDs))

Question 12

Name 10 CPY450 inhibitors

Answer 12

1. sodium valproate
2. ciprofloxacin
3. sulfonamide
4. cimetidine
5. antifungals
6. amiodarone
7. isoniazid
8. erythromycin
9. clarythromycin
10. grapefruit juice

Question 13

Name 5 CYP450 Inducers

Answer 13

1. carbamazepine
2. rifampicin
3. barbituates
4. phenytoin
5. st john’s wort

Question 14

Name 4 important interractions relatinf to CPY450

Answer 14

1. combined oral contraceptives and rifampicin
2. warfarin and carbamazepine
3. statins and clarythromycin
4. warfarin and amiodarone

Question 15

1. What is pharmacodynamic variation?

2. What is pharmacokinetic variation?

Answer 15

1. different drug concentrations at sites of action; occurs because of differences in absorption, distribution, metabolsim or excretion
2. differences in responses to drugs at the same concentrations between individuals

Question 16

1. What are the 4 phenotypes of CPY2D6?
2. What is the results of these different phenotypes?
3. Which analgesic drug is affected by CPY2D6 phenotypes?

Answer 16

1. ultrarapid metabolisers; extensive metabolisers; intermediate metabolisers; poor metabolisers
2. patients who are poor metabolisers and ultrarapid metabolisers can have markedly altered responses to drugs that are CYP2D6 substrates
3. coedine - CYP2D6 is responsible for metabolising coedine to morphine
   - ultrarapid metabolisers have higher than expected morphine levels, with more side effects and shorter than expected duration of analgesia

Question 17

which drugs is it important to consider TPMT activity before use?

Answer 17

azathioprine, mercaptopurine, tioguanine

- these drugs shouldn’t be given to people with absent TPMT activity

Question 18

1. Name 2 ways in which pregnancy can influence drug distribution?
2. Why must lipophilic drugs be used with caution in pregnancy?

Answer 18

1. decreased plasma albumin concentration

increased cardiac output → increased renal blood flow → increased renal elimination

Question 19

describe reasons for poor adherence to drug treatment

Answer 19

• poor knowledge of the illness and the medication
• administration and dosage of the medication
• independent pausing, stopping or controlling of medication
• lack of competence in self management
• fear towards drugs
• media and others as a source of medication information
• diseases where poor control does not yet produce symptoms
• challenges with lifestyle changes
• replacing prescription drugs with self administered drugs

Question 20

What tool can be used to assess a patient’s health literacy?

Answer 20

REALM-R list

Question 21

1. What is therapeutic drug monitoring?

2. Name 4 criteria for the use of therapeutic drug monitoring

Answer 21

1. measurement of medication levels in body fluids (usually serum)
2. absence of good clinical markers of drug effect
   poor correlation between dose and clinical effect
   narrow therapeutic window
   good correlation between plasma drug concentration and clinical effect

Question 22

Name examples of drugs which therapeutic drug monitoring is used for

Answer 22

• gentamycin
• vancomycin
• phenytoin
• carbamazepine
• ciclosporin
• tacrolimus
• methotrexate
• digoxin
• lithium
• theophylline

Question 23

What are the legal requirement on a prescription?

Answer 23

• signed
• ink/indelible
• repeat once, only if repeatable
• dispensed within 6 months
• address of practitioner
• indicate if doctor/dentist/nurse/pharmacist
• date
• name and address of a patient
• age of patient if under 12
• dose in numbers and words if a CD

Question 24

1. What occurs in phase 1 trials?

2. What must be obtained before phase 1 trials can be performed?

Answer 24

1. pharmacology of a candidate drug is tested in a small group of health volunteers (confirm safety)
2. clinical trial applications - ensures sufficient preclinical research has been conducted to allow testing in humans to go ahead

Question 25

1. What is done in phase 2 trials?

2. What is the aim of phase 2 trials?

Answer 25

1. examine the efficacy of a compound in volunteer patients who have the condition the drug is intended to treat
2. to determine the most effective dose and method of delivery, the appropriate dosing interval and to reconfirm product safety

Question 26

1. What is done in phase 3 trials?

2. what is the aim of phase 3 trials?

Answer 26

1. drug tested in a much larger patient population, across multiple international sites
2. Aim is to reconfirm phase 2 findings in a larger population and to identify the best dosage regimen

Question 27

What is required following phase 3 trials before a drug can be licensed?

Answer 27

a submission for marketing authorisations is made to the national regulatory authority (MHRA)

Question 28

What is done in phase 4 trials?

Answer 28

post marketing studies/surveillance