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Pharmacology and Therapeutics 2 Y2 > Adverse Drug Reactions > Flashcards

Adverse Drug Reactions Flashcards

1
Q

ADRs can be classified by … (3)

A

ONSET, SEVERITY and TYPE

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2
Q

Onset ADR classifications?

A
  • Acute Within 1 hour (anaphylaxis)
  • Sub-acute 1 to 24 hours
  • Latent > 2 days
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3
Q

Severity ADR classifications?

A
  • Mild Requires no change in therapy
  • Moderate Requires change in therapy, additional treatment, hospitalization
  • Severe Disabling or life-threatening
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4
Q

Severe ADR result in…

A
  • Results in death/Life-threatening
  • Requires or prolongs hospitalization
  • Causes disability
  • Causes congenital anomalies
  • Requires intervention to prevent permanent injury
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5
Q

Adverse drug reaction types? (ABCDE)

A 
A = Augmented pharmacological effect
B = Bizarre
C = Chronic
D = Delayed
E = End-of-treatment
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6
Q

Type A drug reactions are?

A

Extension of the pharmacologic event

  • Usually predictable and dose dependent
  • Responsible for at least two-thirds of ADRs
  • E.g. atenolol and heart block, anticholinergics and dry mouth, NSAIDS and peptic ulcer, paracetamol, digoxin
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7
Q

Type B drug reactions are?

A

Idiosyncratic (particular to certain individuals) or immunologic reactions- Includes allergy and “pseudoallergy”

  • Rare (even very rare) and unpredictable
  • E.g. chloramphenicol and aplastic anemia, ACE inhibitors and angioedema (this is a pseudoallergy)
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8
Q

Type C drug reactions are?

A

Associated with long-term use

  • Involves dose accumulation
  • E.g. methotrexate and liver fibrosis, anti-malarials and ocular toxicity
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9
Q

Type D drug reactions are?

A

 Delayed effects (sometimes dose dependent)

  • Carcinogenicity (e.g. immunosuppressants)
  • Teratogenicity (e.g. thalidomide)
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10
Q

Type E drug reactions are?

A

 End of treatment

  • WITHDRAWAL reactions- opiates, benzodiazepines, corticosteroids
  • REBOUND reactions- clonidine, beta-blockers, corticosteroids
  • ADAPTIVE reactions- neuroleptics (major tranquilisers)
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11
Q

Incidence of type B drug reactions?

A

Rare

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12
Q

Allergic reactions are what type of ADR?

A

B

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13
Q

Example of type A ADR?

A

Paracetamol OD, digoxin OD

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14
Q

Example of type B ADR?

A

chloramphenicol and aplastic anemia, ACE inhibitors and angioedema (this is a pseudoallergy)

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15
Q

Example of type C ADR?

A

methotrexate and liver fibrosis, anti-malarials and ocular toxicity

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16
Q

Example of type D ADR?

A

Carcinogenicity of immunosuppressants

- Teratogenicity (e.g. thalidomide)

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17
Q

Example of type E withdrawal ADR?

A
  • WITHDRAWAL reactions- opiates, benzodiazepines, corticosteroids
  • REBOUND reactions- clonidine, beta-blockers, corticosteroids
  • ADAPTIVE reactions- neuroleptics (major tranquilisers)
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18
Q

Types of type E ADR?

A
  • WITHDRAWAL reactions- opiates, benzodiazepines, corticosteroids
  • REBOUND reactions- clonidine, beta-blockers, corticosteroids
  • ADAPTIVE reactions- neuroleptics (major tranquilisers)
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19
Q

Antibody in type I allergic reaction?

A

IgE

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20
Q

Antibody in type II allergic reaction?

A

IgG, IgM

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21
Q

Antibody in type III allergic reaction?

A

IgG, IgM

22
Q

Immune cell in type IV allergic reaction?

A

T cell mediated, chronic

23
Q

What is type I allergic reaction

A

immediate, anaphylactic

24
Q

What is type II allergic reaction

A

cytotoxic antibody

25
Q

What is type III allergic reaction

A

serum sickness

26
Q

What is type IV allergic reaction

A

delayed hypersensitivity

27
Q

Relationship of pseudo allergies to the immune system?

A

None

28
Q

Examples of pseudoallergies? (2)

A
  1. Aspirin/NSAIDs – bronchospasm, the drugs block COX and the formation of prostanoids so you get a diversion of the pathway to leukotrienes. These are pro-inflammatory bronchoconstrictors.
  2. ACE inhibitors – cough/angioedema. Angioedema is similar to anaphylaxis but not hugely serious. You get a build-up of bradykinins which cause cough and are proinflammatory. Can lead to swelling of lips and tongue and bronchospasm and hypotension.
29
Q

Common causes of ADRs? Why are they most common?(8)

A
  • Antibiotics
  • Anti-neoplastics
  • Anticoagulants
  • Cardiovascular drugs
  • Hypoglycemics
  • Anti-hypertensives
  • NSAID/Analgesics
  • CNS drugs

Common because highly used in population

30
Q

What is a subjective report in ADR?

A

Patient complaint

31
Q

What are the stages of an objective report in ADR? (5)

A
  • Direct observation of event
  • Abnormal findings
  • Physical examination
  • Laboratory test
  • Diagnostic procedure
32
Q

Problem with finding ADR?

A

They are quite rare in many cases, so you’d have to look at massive groups of people to be sure that the drug caused the reaction

33
Q

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

A

Data for drug-related hospital admissions do not separate out drug interactions, focus on ADRs
Lack of availability of comprehensive databases
Difficulty in assessing over-the-counter and herbal drug therapy use
Difficulty in determining contribution of drug interaction in complicated patients

34
Q

3 drug interaction types?

A

Pharmacodynamic
Pharmacokinetic
Pharmaceutical

35
Q

Example of pharmaceutical ADR interaction

A

IV infusions that shouldn’t be put together

36
Q

What are Pharmacodynamic dug interactions

A

Additive, synergistic, or antagonistic effects from co-administration of two or more drugs

37
Q

What drugs have synergistic interaction

A

Antibiotics

38
Q

What drugs have antagonistic interaction

A

Anticholinergic medications

39
Q

What drugs have additive, overlapping toxicities

A

Alcohol and benzos

40
Q

What is chelation

A

drugs given together can form a stable chelate which means you don’t absorb the drugs well:

  • Irreversible binding of drugs in the GI tract
  • Tetracyclines, quinolone antibiotics
41
Q

Phase 1 metabolism reactions?

A

Oxidation, reduction, hydrolysis

42
Q

How does the presence of P450 isozymes impact on drug metabolism

A

If drugs are co-administered with CYP450 inhibitor, some isozymes may “pick up slack” for inhibited isozyme- ‘redundancy’

43
Q

CYP450 inhibitors?

A
  • Grapefruit juice
  • Cimetidine
  • Erythromycin and related antibiotics
  • Ketoconazole etc.
  • Ciprofloxacin and related antibiotics
  • Ritonavir and other HIV drugs
  • Fluoxetine and other SSRIs
44
Q

Speed of CYP450 inhibitors?

A

Rapid

45
Q

Speed of CYP450 inducers?

A

Hours/days

46
Q

CYP450 inducers?

A
  • Rifampicin
  • Carbamazepine
  • (Phenobarbitone)
  • (Phenytoin)
  • St John’s wort (contains hypericin)- available over-the-counter
47
Q

Where do DRUG ELIMINATION INTERACTIONS take place mainly

A

Renal tubule

48
Q

Example of a drug elimination interaction?

A

Lithium and thiazide - thiazides reduce lithium clearance so toxicity is more likely to occur)

49
Q

Deliberate drug interactions? (4)

A
  • Levodopa + carbidopa
  • ACE inhibitors + thiazides Reduce BP by different mechanisms
  • Penicillins + gentamicin Antibiotics
  • Salbutamol + ipratropium Asthma (beta-2 agonist and anticholinergic drug)- both bronchodilators by different mechanisms
50
Q

PHARMACOKINETIC DRUG INTERACTIONS? (4)

A
  1. Alteration in absorption
  2. Protein binding effects
  3. Changes in drug metabolism
  4. Alteration in elimination
51
Q

Example of ALTERATIONS IN ABSORPTION:

A

Chelation- drugs given together can form a stable chelate which means you don’t absorb the drugs well:

  • Irreversible binding of drugs in the GI tract
  • Tetracyclines, quinolone antibiotics - ferrous sulfate (Fe+2), antacids (Al+3, Ca+2, Mg+2), dairy products (Ca+2)
52
Q

Example of PROTEIN BINDING INTERACTIONS:

A

Competition between drugs for protein or tissue binding sites- Increase in free (unbound) concentration of a drug due to competition for binding sites may lead to enhanced pharmacological effect

  • Many interactions previously thought to be PB interactions were found to be primarily metabolism interactions
  • PB interactions are not usually clinically significant but a few are (mostly with warfarin)

Pharmacology and Therapeutics 2 Y2 (24 decks)

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