Adverse Drug Reactions and Interactions Flashcards

1
Q

What is an adverse drug event

A

preventable or unpredicted medication event with harm to patient

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2
Q

What are adverse drug reactions classified by

A

Onset
Severity
Type

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3
Q

What are the classifications of adverse drug reactions according to onset

A

Acute - within 1 hour
Sub-acute - 1-24 hours
Latent - >2 days

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4
Q

What are the classifications of adverse drug reactions according to severity

A

Mild - requires no changes to therapy
Moderate - requires change in therapy, additional treatment, hospitalisation
Severe - disabling or life-threatening

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5
Q

Describe severe adverse drug reactions

A
Results in death
Life-threatening
Requires or prolongs hospitalisation
Causes disability
Causes congenital anomalies
Requires intervention to prevent permanent injury
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6
Q

Describe type A adverse drug reactions

A

Extension of pharmacologic effect
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

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7
Q

Describe type B adverse drug reactions

A

Idiosyncratic or immunologic reactions
Includes allergy and “pseudoallergy”
Rare (even very rare) and unpredictable
e.g., chloramphenicol and aplastic anemia, ACE inhibitors and angioedema

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8
Q

Give examples of ADR that are totally unexpected

A

Herceptin and cardiac toxicity

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9
Q

Describe type C adverse drug reactions

A

Associated with long-term use
Involves dose accumulation
e.g., methotrexate and liver fibrosis, antimalarials and ocular toxicity

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10
Q

Describe type D adverse drug reactions

A
Delayed effects (sometimes dose independent)
Carcinogenicity (e.g. immunosuppressants)
Teratogenicity (e.g. thalidomide)
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11
Q

Describe type E adverse drug reactions

A

Withdrawal
Rebound
Adaptive reactions

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12
Q

Give examples of drugs that cause withdrawal reactions

A

Opiates
Benzodiazepines
Corticosteroids

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13
Q

Give examples of drugs that cause rebound reactions

A

Clonidine
Beta-blockers
Corticosteroids

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14
Q

Give examples of drugs that cause adaptive reactions

A

Neuroleptics (major tranquillisers)

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15
Q

Describe clonidine withdrawal

A

Hypertensive patient
Treat them and the BP decreases
After stopping the drug, there is a rise in BP to levels that are higher than they were to begin with

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16
Q

What is the ABCDE classification of adverse drug reactions

A
Augmented pharmacological effect
Bizarre
Chronic
Delayed
End-of-treatment
17
Q

Describe type I allergic reactions

A

immediate, anaphylactic (IgE)

e.g. anaphylaxis with penicillins

18
Q

Describe type II allergic reactions

A

cytotoxic antibody (IgG, IgM)

e.g. methyldopa and hemolytic anemia

19
Q

Describe type III allergic reactions

A
serum sickness (IgG, IgM)
antigen-antibody complex

e.g. procainamide-induced lupus

20
Q

Describe type IV allergic reactions

A

delayed hypersensitivity (T cell)

e.g. contact dermatitis

21
Q

Give examples of pseudoallergies

A

Aspirin/NSAIDs – bronchospasm

ACE inhibitors – cough/angioedema

22
Q

Give examples of common causes of ADRs

A
Antibiotics
Antineoplastics
Anticoagulants
Cardiovascular drugs
Hypoglycemics
Antihypertensives
NSAID/Analgesics
CNS drugs
23
Q

What are pharmacodynamic drug interactions

A

Related to the drug’s effects in the body

Receptor site occupancy

24
Q

What are pharmacokinetic drug interactions

A

Related to the body’s effects on the drug

ADME

25
Q

What are pharmaceutical drug interactions

A

drugs interacting outside the body (mostly IV infusions)

26
Q

Describe pharmacodynamic drug interactions

A

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

27
Q

Give examples of pharmacodynamic drug interactions (synergistic, overlapping toxicity, antagonistic)

A

Synergistic actions - antibiotics

Overlapping toxicities - ethanol + benzodiazepines

Antagonistic effects - anticholinergic medications (amitriptyline and acetylcholinesterase inhibitors)

28
Q

What are the types of pharmacokinetic drug interactions

A

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

29
Q

What is chelation and give examples of drugs that may be affected (pharmacokinetic interaction)

A

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)

30
Q

Describe protein binding interactions (pharmacokinetic interaction)

A

Competition between drugs for protein or tissue binding sites
Increase in free (unbound) concentration may lead to enhanced pharmacological effect

31
Q

Describe drug metabolism interactions (pharmacokinetic interaction)

A

Drug metabolism inhibited or enhanced by coadministration of other drugs
Phase 2 metabolic interactions (glucuronidation, etc.) occur

32
Q

Describe the metabolism of CYP 450 substrates

A

Metabolism either by a single isozyme or multiple isozymes

33
Q

Give examples of CYP 450 inhibitors

A

Cimetidine
Erythromycin and related antibiotics
Ketoconazole etc
Ciprofloxacin and related antibiotics

Ritonavir and other HIV drugs
Fluoxetine and other SSRIs
Grapefruit juice

34
Q

Give examples of CYP 450 inducers

A
Rifampicin
Carbamazepine
(Phenobarbitone)
(Phenytoin)
St John’s wort (hypericin)
35
Q

Describe the time scale of inhibition and induction of drug interactions

A

Inhibition is very rapid

Induction takes hours/days

36
Q

Describe drug elimination interactions (pharmacokinetic interaction)

A

Almost always in renal tubule
probenecid and penicillin (good)
lithium and thiazides (bad)

37
Q

Give examples of deliberate interactions

A

levodopa + carbidopa

ACE inhibitors + thiazides

penicillins + gentamicin

salbutamol + ipratropium