Adverse drug reactions

Question 1

Define an ‘adverse drug reaction’

Answer 1

Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis (prevention), diagnosis or treatment

Question 2

UK statistics about ADRs

Answer 2

5% of hospital admissions are due to ADRs

Question 3

Types of ADRS (classification)

Answer 3

6 types
Types:-
A- augmented
B- bizarre 
C- chronic
D- delayed
E- end of treatment
F- failure of treatment

Question 4

Type A ADR

Answer 4

augmented ie increases in size

• these pharmacologic effects are dose related and predictable.
• Due to excess pharmacological action ie drug to slow the heart causing excessive slowing of the heart bradycardia and beta- blockers
• easily reversible on reducing the dose or stopping the drug
• not usually life threatening

Question 5

Classification of severity of reaction

Answer 5

Mild
moderate
severe

Question 6

severe reaction

Answer 6

disabling or life-threatening ie results in hospitalisation and death
ie kidney failure

Question 7

moderate reaction

Answer 7

requires change in therapy
additional treatment
hospitalisation
i.e amphotericin (an antifungal drug) induced hypokalemia (low K+ levels in blood)

Question 8

Mild reaction

Answer 8

bothersome but requires no change in therapy

metallic taste with metronidazole (treats bacterial infections)

Question 9

Type B ADR

Answer 9

Bizarre effects
are rare, unpredictable, aggressive and cause serious illness or death.
can be unidentified for months or years.
usually long term or delayed
- It’s unrelated to the dose, and not readily reversed.

They are idiosyncratic (an abnormal physical reaction by an individual).
There is a delay between exposure to drug and ADR.
Manifests as rash asthma, serum sickness

Question 10

Type C ADR

Answer 10

chronic/ long term effects
related to the duration of treatment as well as the dose, and does not occur with a single dose
it is semi-predictable
common with things like steroid use- obvious when patients have been on steroids for a long time- can cause osteoporosis (fragile) and stretch marks etc

Question 11

Type D ADR

Answer 11

delayed- occur a long time after treatment. Secondary cancers in those treated with alkylating agents.

children whose mothers took medication during pregnancy (about 50% of women do)

All drugs should be avoided during pregnancy unless they are safe or the benefit outweighs potential risk

Question 12

Type E

Answer 12

Adverse reactions which occur when a drug treatment is stopped, especially suddenly following long-term use.

E.g unstable angina and beta blockers, rheumatoid arthritis- steroids need to be weened off slowly

if anti-epileptics are stopped suddenly it could cause withdrawl seizures

Question 13

Type F

Answer 13

failure of therapy.
Common (esp in children) and dose related
frequently caused by drug interactions e.g failure of the OCP (oral contraceptive pill) when administered with hepatic enzyme inducers/antibiotics

Question 14

detecting and reporting ADRs

Answer 14

detection: differential diagnosis, medication history (past and present), assess time of onset and dose relationship
- lab investigations (plasma concentration measurement and allergy tests)

Question 15

reporting of ADRs

Answer 15

all significant or unusual drug reactions, as well as unanticipated or novel events that are suspected to be drug related, are meant to be reported using yellow card scheme however only about 10% are and this is why severe ADRs take so long to be known about

Question 16

what is an adverse drug event?

Answer 16

it occurs during treatment, not necessarily caused/linked by/to the drug itself and cannot be proven to be linked to the drug either. A harmful side effect of the drug.
different to reaction as reaction is usually linked to the drug

Question 17

what is an adverse drug reaction?

Answer 17

proven to be caused by the drug

Question 18

What are some of the reasons for having a Type A ADR?

Answer 18

too high a dose
pharmaceutical variation

often caused by disease (ie renal or liver) :-

• pharmacokinetic variaton (how moves through the body ie path it takes etc)
• pharmacodynamic variation (effects of the drug)

Question 19

what is pharmacokinetic variation?

Answer 19

the effect of absorption, distribution, metabolism and elimination on the drug

e.g abs- can be different depending on the dose, formation, GI motility and first pass metabolism
if problems occur with absorption then drugs lose their effect ie there is therapeutic failure

Question 20

pharmacogenetic

Answer 20

acetylation- under genetic control
this process is key for how a number of drugs metabolise
don’t test for links between genetics and drugs so just have to start with a low dose of a drug and increase it.

Question 21

How does cardiac failure reduce drug absorption in the liver?

Answer 21

fluid overflow due to cardiac failure as oedema forms (maybe in the gut, legs, lung etc)- this can reduce the drug absorption from the gut

decreased blood flow to the liver accounts for some of the change in absorption/ clearance of a drug

Question 22

When are Type B ADRs more common?

Answer 22

• with macromolecules (big)- proteins, vaccines, polypeptides
• patients with a history of asthma or excema
  HLA status- presence of particular human leukocyte antigen is a risk of a type B reaction

Question 23

teratogenesis

Answer 23

abnormal cogenital malformations in the fetus

due to mother using medication in 1st trimester of pregnancy

Question 24

How can we diagnose ADRs?

Answer 24

be suspicious
really important to get a thorough medical history of the patient to detect past, current medications, conditions, allergies etc
assess time of onset and dose relationship
lab investigations- allergy tests etc

Question 25

who is most at risk of ADRs?

Answer 25

children- can’t communicate
elderly- comorbidities ie may be on a number of medications for different health conditions
people with prior history of ADRs
genetic predisposition

Question 26

what are antineoplastics commonly involved with treating?

Answer 26

anti cancer drug

Question 27

what percentage of ADRs and ADEs are preventable?

Answer 27

60%

although some effects cannot be avoided e.g nausea in chemo

Question 28

list the non-dose related ADRs

Answer 28

Type B,

Question 29

list the dose related ADRs

Answer 29

Type A, C, F

Question 30

Type B delayed effects

Answer 30

include tardive dyskinesia (disorder that results in involuntary, repetitive body movements) carcinogenesis

Question 31

surveillance of ADRs

Answer 31

a comprehensive adverse drug reaction (ADR) surveillance program is necessary to detect, evaluate, and develop mechanisms to prevent ADRs and their associated morbidity, mortality, and increased costs.