Adverse Drug Reactions Flashcards Preview

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Flashcards in Adverse Drug Reactions Deck (30)
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1
Q

What is an ADR?

A

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

2
Q

How can the onset of an ADR be classified?

A
  • Acute= within 60 minutes and presents with bronchoconstriction
  • Sub-acute= 1-24 hours and presents with rash, serum sickness
  • Latent= >2 days and presents with eczematous eruptions
3
Q

How can the severity of an ADR be classified?

A
  • Mild: bothersome but requires no change in therapy i.e metallic taste with metronidazole
  • Moderate: requires change in therapy, additional treatment, hospitalisation i.e amphotericin induced hypokalemia
  • Severe: disabling or life-threatening i.e kidney failure
4
Q

How can ADRs be classified?

A
  • Type A: Augmented
  • Type B: Bizarre
  • Type C: Chronic
  • Type D: Delayed
  • Type E: End of Treatment
  • Type F: Failure of Treatment
5
Q

Describe type A ADRs.

A
  • dose related
  • predictable
  • easily reversible
  • most common
  • not usually life threatening
6
Q

Describe type B ADRs

A
  • idiosyncratic
  • unpredictable
  • rare
  • cause serious illness/death
  • unidentified fro months/years
  • unrelated to dose
  • not readily reversible
7
Q

What are the predisposing factors relating to ADRs?

A
  • multiple drug therapies
  • renal/hepatic impairment
  • Race and genetic polymorphisms
  • age
  • sex
8
Q

What causes type A reactions?

A
  • Excess pharmacological action

- they may be due to the secondary pharmacology of a drug unrelated to the therapeutic effect

9
Q

What are the 2 types of type A ADRs?

A
  • augmentation of the primary effect

- secondary effect

10
Q

Reasons for Type A ADRs

A
  • too high a dose
  • pharmaceutical variation
  • pharmacokinetic variation
  • pharmacodynamics variation
11
Q

What factors affect pharmacokinetic variation?

A

Absorption (dose, formulation, GI motility, first pass metabolism)

  • distribution
  • metabolism (enhanced/impaired)
  • elimination (renal disease, reduced GFR)
12
Q

Describe pharmacogenetics in ADRs.

A
  • a number of drugs are metabolised via acetlyation which is under genetic control
  • 1 in 10 have slow metabolism
  • prone to drug toxicity
  • peripheral neuropathy with isoniazid
13
Q

How can disease impact ADR?

A
  • renal and hepatic impairment can lead to increased toxicity if drug is not excreted
  • Cardiac failure reduces the drug absorption from the gut due to oedema. There is poor renal perfusion and decreased GFR which leads to hepatic congestion.
14
Q

When are type B ADRs more likely to occur?

A

-more common with macromolecules such as proteins, vaccines and polypeptides
-patients with asthma or eczema
Presence of particular HLA increases risk

15
Q

What is the mechanism of type B?

A

-drug allergy or hypersensitivity
-immunological
-no relation to the pharmacological action of the drug
-delay between exposure and ADR
no dose response curve
manifests as rash, asthma, serum sickness

16
Q

Define idiosyncratic

A
  • inherent abnormal response to a drug

- due to genetic abnormality such as enzyme deficiency or abnormal receptor activity

17
Q

How can differences in response to a drug be considered?

A
  • genetic

- immunological

18
Q

Describe an enzyme abnormality

A

Erythrocyte glucose 6-phosphate dehydrogenase (G6PD) deficiency
-individuals with sex-linked inherited deficiency of this enzyme are susceptible to red cell haemolysis when given drugs such as primaquine or sulphonamides

19
Q

Describe a receptor abnormality.

A

malignant hyperthermia with general anaesthetics

20
Q

Describe hypersensitivity reactions.

A
  • due to antigen-antibody interaction
  • first dose acts as the antigen
  • body produces the antibody
  • subsequent antigen-antibody reaction
21
Q

Describe type C ADRs.

A
  • related to duration of treatment
  • does not occur with a single dose
  • semi-predictable
22
Q

Give examples of Type C reactions.

A
  • Iatrogenic Cushings disease
  • Steroid induced osteoporosis
  • opiate dependence
  • tardive dyskinesia with neuroleptic drugs
  • analgesic nephropathy due to paracetamol or NSAIDa
23
Q

Describe type D reactions.

A
  • adverse effects occur a long time after treatment
  • teratogenesis- the children of treated patients
  • carcinogenesis- treated patients years after treatment has stopped
24
Q

Give examples of type D reactions.

A
  • second cancers in those treated with alkylating agents or immunosuppressive agents (cyclophosphamide, alkylating agents)
  • craniofacial malformations in children whose mothers were treated with isotretinoin
25
Q

What is teratogenesis?

A

abnormal congenital malformations in the fetus following in utero exposure due to maternal medication use during 1st trimester of pregnancy

26
Q

Name 5 teratogenic agents.

A
  • cytotoxics
  • vitamin A
  • antithyroid drugs
  • steroids
  • oral anticoagulants
27
Q

Give examples of type E reactions.

A
  • unstable angina and MI when beta blockers are stopped
  • Addisonian crisis when long term steroids are suddenly stopped
  • Withdrawal seizures when anti-epileptics are stopped
  • alcohol
28
Q

When does rebound phenomena occur?

A

-when a drug is suddenly stopped

29
Q

Describe type F reactions.

A

-failure of therapy
-common
-dose related
frequently caused by drug interactions
-failure of the OCP when administered with hepatic enzyme inducers/antibiotics

30
Q

How are ADRs diagnosed?

A
  • differential diagnosis
  • medication history
  • assess time of onset and dose relationship
  • lab investigations inc. plasma conc. measurement and allergy tests