Adverse drug reactions mw %+ Flashcards Preview

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Flashcards in Adverse drug reactions mw %+ Deck (25)
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1

ADR Definition

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

2

Classification of- Onset

  • Acute- within 1 hour
  • Sub-acute- 1 to 24 hours
  • Latent- >  48 hours

3

Classification of severity

• Mild

» bothersome but requires no  change in therapy

» Metallic taste with metronidazole

• Moderate

» requires change in therapy,  additional  treatment,    hospitalization

» Amphotericin induced hypokalemia

• Severe

» disabling or life-threatening

» kidney failure

4

Classification of ADRs

  • Type A   Augmented
  • Type B  Bizarre
  • Type C  Chronic
  • Type D  Delayed
  • Type E  End of treatment  
  • Type F  Failure of treatment  

5

Type A and Type B

Augmented pharmacologic effects:

  • Dose related
  • Predictable

Type B Bizarre effects

  • Idiosyncratic and unpredictable

6

Predisposing Factors

  • Multiple Drug Therapy: incidence increase exponentially with the number of medicaments
  • Inter-current Disease:renal and hepatic impairment
  • Race and Genetic Polymorphisms
  • Age -elderly and neonates
  • Sex- more common in women

7

Type A Reactions

Due to excess pharmacological action:

  • Bradycardia with beta-blockers
  • Hypoglycaemia with sulphonylureas or insulin
  1. Easily reversible on reducing the dose or stopping the drug.
  2. Not usually life threatening.
  3. Most common of all ADRS accounting for 80% of all ADRs.

8

Types of type A ADRs 

  • Augmentation of the primary effect
  • Secondary effect-  due to the secondary pharmacology of a drug unrelated to the therapeutic effect.

However the ADR is still rationalisable from the known pharmacology of the drug.

9

Reasons for Type A ADRs

  • Too high a dose
  • Pharmaceutical variation
  • Pharmacokinetic variation
  • Pharmacodynamic variation

The last two commonly occur as a result of disease

10

Pharmacokinetic Variation

1.Absorption:

  • Dose
  • Formulation
  • GI motility
  • First pass metabolism

The majority of ADRs which arise through absorption problems result in  therapeutic failure.

2.Distribution

3.Metabolism

4.Elimination

 

11

Pharmacogenetic

A number of drugs are metabolised via acetylation which is under genetic control:

  • 10% of the population are slow metabolisers
  • Prone to drug toxicity
  • Peripheral neuropathy with isoniazid

12

Disease

1. Renal and hepatic impairment

  • If a drug is excreted by the kidneys toxic drug levels may build up

2.Cardiac Failure

  • Reduce drug absorption from the gut due to oedema
  • Poor renal perfusion and decreased GFR
  • Hepatic congestion

13

Pharmacodynamic Variation

  1. Most type A ADRs are pharmacokinetic in nature
  2. Some are due to altered Pharmacodynamic action:
  • Natural variability in pharmacodynamic response
  • Disease states can significantly alter response

14

Type B ADRs

Type B reactions are:

  • Bizarre
  • Unpredictable
  • Rare
  • Cause serious illness or death
  • Unidentified for months or years
  • Unrelated to the dose

 

15

Important factors in type B

  1. More common with macromolecules
  • proteins
  • vaccines
  • polypeptides

     2. Patients with history of asthma, excema,

     3. HLA (human leukoctye antigen) status

  • Presence of particular HLA increases risk of a type B reaction

16

Mechanisms of type B

  1. Idiosyncratic
  2. 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

17

Idiosyncratic

  • Inherent abnormal response to a drug
  • Due to genetic abnormality such as enzyme deficiency
  • Or abnormal receptor activity.

18

Pharmacogenetic

Differences in response to drugs may be considered as:

  • Genetic-enzyme abnormality and receptor abnormality
  • Immunological

19

Drug Allergy –Hypersensitivity Reactions

  • Due to antigen- antibody interaction
  • The first dose acts as the antigen
  • Body produces the antibody
  • Subsequent antigen-antibody reaction

20

Type C Chronic/Long Term Effects

  • Related to the duration of treatment as well as the dose and does not occur with a single dose.
  • Semi-predictable

21

Type D Delayed Effects

  • These adverse effects occur a long time after treatment
  • Teratogenesis
  • Carcinogenesis- In treated patients years after treatment has stopped.

22

Teratogenesis

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

 

23

Type E End of Treatment Effects

  • Adverse effects which occur when a drug treatment is stopped especially suddenly following long-term use.
  • Alcohol

24

Type F ADRs

  • Failure of therapy
  • Common
  • Dose related
  • Frequently caused by drug interactions
  • Failure of the OCP (oral contraceptive pill) when administered with hepatic enzyme inducers/ antibiotics

25

Diagnosis

Step 1: Differential diagnosis

Step2: Medication History [past & present]

Step 3: Assess time of onset and dose relationship

Step 4: Laboratory investigations

  • Plasma concentration measurement
  • Allergy tests