Adverse Drug Reactions Flashcards

1
Q

What is an adverse drug reaction?

A
  • Preventable or unpredictable medication event with harm to the patient
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2
Q

Describe the classification of ADRs based on onset

A
  • Acute = < 1 hour
  • Sub-acute = 1-24 hours
  • Latent = > 2 days
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3
Q

Describe the classification of ADRs based on severity of the reaction

A
  • Mild – requires no change in therapy
  • Moderate – requires change in therapy
  • Severe – disabling or life-threatening
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4
Q

What is the ABCDE classification of adverse drug reactions?

A
  • A – augmented pharmacological action
  • B – bizarre
  • C – chronic
  • D – delayed
  • E – end of treatment
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5
Q

Define Type A ADR and give an example (3 answers are given but just get any you can)

A
  • Augmented (extension of) pharmacological effect
  • Predictable and dose-dependent
  • This is the most common type of ADR – 2/3
  • Examples:
  1. Atenolol can slow down heart rate but if you give too much you could cause heart block
  2. Anti-cholinergics and dry mouth
  3. NSAIDs and peptic ulcers
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6
Q

Define Type B ADR and give an example

A
  • ‘Bizarre’ type of ADR
  • Idiosynchratic or immunologic reactions – includes allergy or pseudoallergy
  • This is very rare and unpredictable
  • Example:
  • ACEis and angioedema
  • Chloramphenicol and aplastic anaemia
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7
Q

Define Type C ADR and give an example (2 answers given but give any of these)

A
  • Chronic’ - associated with long-term use
  • Involves drug accumulation
  • E.g:
  1. Methotrexate and liver toxicity
  2. Anti-malarial drugs and ocular toxicity
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8
Q

Define Type D ADR and give 2 examples

A
  • Delayed effects – sometimes dose independent
  • E.g:
  1. Carcinogenicity (e.g. immunosuppressants)
  2. Teratogenicity (e.g. thalidomide)
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9
Q

Define Type E ADR and give 3 reactions that constitute this type of ADR

A
  • End-of treatment reactions - WAR acronym
  1. Withdrawal reactions
  2. Adaptive reactions
  3. Rebound reactions
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10
Q

Describe and explain clonidine rebound, starting with what clonidine is and then how it has this ADR rebound effect - also what type of ADR is this?

A
  • 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 - undesired
  • This is a type E ADR
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11
Q

Describe the classification of allergies - the various types, what they are otherwise known as, and the main mediators involved

A
  • All types of hypersensitivity reactions
  1. Type 1 – immediate, anaphylaxis (IgE)
  2. Type 2 – cytotoxic antibody (IgG + IgM)
  3. Type 3 – serum sickness (IgG + IgM)
  4. Type 4 – delayed hypersensitivity (T cell)
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12
Q

What are pseudoallergies and give 2 key examples of pseudoallergies caused by drugs

A
  • Pseudoallergies are when you get conditions where it mimics allergies but it is not actually anything to do with the immune system, i.e. pharmacological not immunological
    1. Aspirin/NSAIDs and bronchoconstriction
  • This occurs because aspirin and NSAIDs inhibit the production of prostanoids, which are bronchodilators
  • They promote the production of leukotrienes, which are bronchoconstrictors
  1. ACE inhibitors and cough/angioedema
  • ACE inhibitors prevent the breakdown of (brady)kinins
  • Kinins accumulate and trigger sensory C-fibre nerves in the lungs to cause coughing
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13
Q

What are the most common causes of ADRs

A
  • Antineoplastics
  • Cardiovascular drugs
  • NSAIDs/analgesics
  • CNS drugs
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14
Q

What is the yellow card scheme?

A
  • A voluntary scheme allowing doctors, dentists, nurses, coroners and pharmacists to report serious adverse drug reactions
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15
Q

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

A
  • 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
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16
Q

What are the three types of pharmacodynamic drug interaction?

A
  1. Additive effects - cumulative effect
  2. Synergistic effects - potentiation of each other’s effects
  3. Antagonistic effects
17
Q

What are the different types of pharmacokinetic drug interaction?

A
  • Alteration in drug absorption
  • Protein binding effects
  • Changes in drug metabolism
  • Alteration in elimination

(Basically changes in adme - one to look out for is the protein binding effects - this is a essentially a change in distribution though)

18
Q

What is an example of alteration of absorption?

Give an example

A
  • Chelation
  • Quinolone and tetracyclines may be given and you can also digest ferrous sulfate (Fe2+), antacids (Al3+, Mg2+, Ca2+) and dairy products (Ca2+)
  • These interact to form a stable chelate which prevents absorption of both the mineral ions and the antibiotics quinolone and tetracycline
19
Q

Explain what is meant by protein binding effects

A
  • 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)
20
Q

Which cytochrome P450 enzymes are responsible for over half of drug metabolism?

A
  • CYP2D6
  • CYP3A4
21
Q

Give a few examples of CYP450 inhibitors

A
  • Erythromycin
  • Ketoconazole
  • Ritonavir and other HIV drugs
  • Cimetidine
  • Fluoxetine and other SSRIs
  • Ciprofloxacin
  • Grapefruit juice
22
Q

Give a few examples of CYP450 inducers

A
  • Rifampicin
  • Phenytoin
  • Carbamazepine
  • St. John’s Wort (hypericin)
  • Phenobarbitone
23
Q

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

A
  • Inhibition is RAPID
  • Induction takes hours/days
24
Q

Give an example of a deliberate drug interaction

A
  • ACE inhibitors and thiazides - synergistic interaction, both work to reduce BP
  • Penicillin and gentamicin - synergistic interaction, both antibiotics
  • Salbutamol and ipatropium - synergistic interaction (salbutamol is a beta-2 antagonist and ipatropium is an anti-cholinergic, therefore both work to treat asthma)