Adverse Drug Reactions

Question 1

What is an adverse drug reaction?

Answer 1

Preventable or unpredictable medication event with harm to the patien

Question 2

Describe the classification of ADRs based on onset.

Answer 2

Acute = < 1 hour  
Sub-acute = 1-24 hours
Latent = > 2 days

Question 3

Describe the classification of ADRs based on severity of the reaction.

Answer 3

Mild – requires no change in therapy
Moderate – requires change in therapy
Severe – disabling or life-threatening

Question 4

Define Type A ADR.

Answer 4

Extension of pharmacological effect
This is usually predictable and dose-dependent
This is the most common type of ADR – 2/3
Example: atenolol can slow down heart rate but if you give too much you could cause heart block

Question 5

Define Type B ADR.

Answer 5

‘Bizarre’ type of ADR
Idiosynchratic or immunologic reactions – includes allergy or pseudoallergy
This is very rare and unpredictable
Example: chloramphenicol and aplastic anaemia

Question 6

Define Type C ADR.

Answer 6

Associated with long-term use
Involves drug accumulation
E.g. methotrexate and liver toxicity

Question 7

Define Type D ADR.

Answer 7

Delayed effects – sometimes dose independent

E.g. carcinogenicity and teratogenicity

Question 8

Define Type E ADR.

Answer 8

Withdrawal reactions  (take away a drug that you have been giving for a long time)
Rebound reactions  (if you miss a few dose of eg clonidine, your BP suddenly spikes)
Adaptive reactions ( i dont know what this is)

Question 9

Describe and explain clonidine rebound.

Answer 9

Clonidine is an alpha-2 agonist so it suppresses the release of noradrenaline
Long-term use of clonidine leads to an upregulation in adrenergic receptors on the post-synaptic membrane
If the dose of clonidine is missed once or twice, it will cause an increase in noradrenaline release, which then acts on an increased number of receptors so has a greater effect
This causes a large increase in blood pressure

Question 10

What is the ABCDE classification of adverse drug reactions?

Answer 10

A – augmented pharmacological action   
B – bizarre 
C – chronic  
D – delayed  
E – end of treatment

Question 11

Describe the classification of allergies.

Answer 11

Type 1 – immediate, anaphylaxis (IgE)
Type 2 – cytotoxic antibody (IgG + IgM) ]
Type 3 – serum sickness (IgG + IgM)
Type 4 – delayed hypersensitivity (T cell)

Question 12

Give examples of pseudoallergies.

Answer 12

Aspirin/NSAIDs and bronchoconstriction:
This occurs because aspirin and NSAIDs inhibit the production of prostanoids, which are bronchodilators
 This diverts the synthesis pathway to lead to production of leukotrienes, which are bronchoconstrictors

ACE inhibitors and cough/angioedema:
 ACE inhibitors prevent the breakdown of kinins
 Kinins accumulate in the sensory nerves in the lungs and trigger cough

Question 13

What are the most common causes of ADRs

Answer 13

Antineoplastics
Cardiovascular drugs
NSAIDs/analgesics
CNS drugs

Question 14

What is the yellow card scheme?

Answer 14

A voluntary scheme allowing doctors, dentists, nurses, coroners and pharmacists to report serious adverse drug reactions

Question 15

Why is it difficult to determine the incidence of drug-drug interactions?

Answer 15

There is a lack of availability of comprehensive databases
Difficulty in assessing OTC and herbal drug therapy use
Difficulty in determining contribution of drug interaction in complicated patients

Question 16

What are the three types of pharmacodynamic drug interaction?

Answer 16

Additive effects   (1+1=2)
Synergistic effects   (1+1=3)
Antagonistic effects (effect of 1 cancels the other out)

Question 17

What are the different types of pharmacokinetic drug interaction?

Answer 17

Alteration in drug absorption  
Protein binding effects  
Changes in drug metabolism  
Alteration in elimination 
ADME

Question 18

What is an example of alteration of absorption?

Answer 18

Chelation
eg Tetracyclines, quinolone antibiotics – these drugs can bind to ferrous sulfate (Fe+2), antacids (Al+3, Ca+2, Mg+2), dairy products (Ca+2) when taken together. If bound, they cannot be absorbed in the GI tract

Question 19

Explain what is meant by protein binding effects.

Answer 19

Competition between drugs for protein or tissue binding sites
It can increase free unbound concentration of a drug thus leading to enhanced pharmacological effects (e.g. warfarin)

Question 20

Give a few examples of CYP450 inhibitors.

Answer 20

Drug metabolism inhibited or enhanced by coadministration of other drugs. The following 2 will inhibit drug metabolism enzymes:
Erythromycin
Grapefruit juice

Question 21

Give a few examples of CYP450 inducers.

Answer 21

St. John’s Wort (hypericin)

Phenobarbitone

Question 22

Describe the difference in the speed of inhibition and the speed of induction of CYP450 enzymes.

Answer 22

Inhibition is RAPID

Induction (causing the production of new CYP450 enzymes) takes hours/days

Question 23

Give an example of a deliberate drug interaction.

Answer 23

ACE inhibitors and thiazides = antihypertensive combo

Question 24

In summary, what three parameters can be used to classify ADR

Answer 24

Can be classified in terms of their:
Onset (acute/subacute etc)
Severity (mild/moderate/severe)
Type (ABCDE)

Question 25

In general, are drugs metabolised by one specific subtype of the CYP450 family or can it be metabolised by multiple different isozymes?

Answer 25

Most drugs are metabolized by more than one isozyme of the family
If drug is co-administered with a CYP450 inhibitor, some other isozymes may “pick up the slack” for the inhibited isozyme and metabolise the drug instead of the inhibited enzyme

Question 26

Give an example of a ‘good’ drug elimination interaction (pharmacokinetic interaction)

Answer 26

Happens Almost always in renal tubule. Some drug elimination interactions are good and some are bad

- probenecid and penicillin (good): probenecid reduces rate of penicillin excretion. This allowed a lower dose of penicillin to be used in the patient

Question 27

Give an example of a ‘bad’ drug elimination interaction (pharmacokinetic interaction)

Answer 27

• lithium (mood stabiliser) and thiazides (bad): thiazides also increase lithium circulation in the body but this can cause lethal effects on the patient