Adverse Drug Reactions Flashcards
1
Q
ADRs can be classified by … (3)
A
ONSET, SEVERITY and TYPE
2
Q
Onset ADR classifications?
A
- Acute Within 1 hour (anaphylaxis)
- Sub-acute 1 to 24 hours
- Latent > 2 days
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
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
5
Q
Adverse drug reaction types? (ABCDE)
A
A = Augmented pharmacological effect B = Bizarre C = Chronic D = Delayed E = End-of-treatment
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
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)
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
9
Q
Type D drug reactions are?
A
Delayed effects (sometimes dose dependent)
- Carcinogenicity (e.g. immunosuppressants)
- Teratogenicity (e.g. thalidomide)
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)
11
Q
Incidence of type B drug reactions?
A
Rare
12
Q
Allergic reactions are what type of ADR?
A
B
13
Q
Example of type A ADR?
A
Paracetamol OD, digoxin OD
14
Q
Example of type B ADR?
A
chloramphenicol and aplastic anemia, ACE inhibitors and angioedema (this is a pseudoallergy)
15
Q
Example of type C ADR?
A
methotrexate and liver fibrosis, anti-malarials and ocular toxicity
16
Q
Example of type D ADR?
A
Carcinogenicity of immunosuppressants
- Teratogenicity (e.g. thalidomide)
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)
18
Q
Types of type E ADR?
A
- WITHDRAWAL reactions- opiates, benzodiazepines, corticosteroids
- REBOUND reactions- clonidine, beta-blockers, corticosteroids
- ADAPTIVE reactions- neuroleptics (major tranquilisers)
19
Q
Antibody in type I allergic reaction?
A
IgE
20
Q
Antibody in type II allergic reaction?
A
IgG, IgM
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
What is type III allergic reaction
serum sickness
26
What is type IV allergic reaction
delayed hypersensitivity
27
Relationship of pseudo allergies to the immune system?
None
28
Examples of pseudoallergies? (2)
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
Common causes of ADRs? Why are they most common?(8)
- Antibiotics
- Anti-neoplastics
- Anticoagulants
- Cardiovascular drugs
- Hypoglycemics
- Anti-hypertensives
- NSAID/Analgesics
- CNS drugs
Common because highly used in population
30
What is a subjective report in ADR?
Patient complaint
31
What are the stages of an objective report in ADR? (5)
- Direct observation of event
- Abnormal findings
- Physical examination
- Laboratory test
- Diagnostic procedure
32
Problem with finding ADR?
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
Why is the true incidence of drug-drug interactions difficult to determine?
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
3 drug interaction types?
Pharmacodynamic
Pharmacokinetic
Pharmaceutical
35
Example of pharmaceutical ADR interaction
IV infusions that shouldn't be put together
36
What are Pharmacodynamic dug interactions
Additive, synergistic, or antagonistic effects from co-administration of two or more drugs
37
What drugs have synergistic interaction
Antibiotics
38
What drugs have antagonistic interaction
Anticholinergic medications
39
What drugs have additive, overlapping toxicities
Alcohol and benzos
40
What is 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
41
Phase 1 metabolism reactions?
Oxidation, reduction, hydrolysis
42
How does the presence of P450 isozymes impact on drug metabolism
If drugs are co-administered with CYP450 inhibitor, some isozymes may “pick up slack” for inhibited isozyme- ‘redundancy’
43
CYP450 inhibitors?
- Grapefruit juice
- Cimetidine
- Erythromycin and related antibiotics
- Ketoconazole etc.
- Ciprofloxacin and related antibiotics
- Ritonavir and other HIV drugs
- Fluoxetine and other SSRIs
44
Speed of CYP450 inhibitors?
Rapid
45
Speed of CYP450 inducers?
Hours/days
46
CYP450 inducers?
- Rifampicin
- Carbamazepine
- (Phenobarbitone)
- (Phenytoin)
- St John’s wort (contains hypericin)- available over-the-counter
47
Where do DRUG ELIMINATION INTERACTIONS take place mainly
Renal tubule
48
Example of a drug elimination interaction?
Lithium and thiazide - thiazides reduce lithium clearance so toxicity is more likely to occur)
49
Deliberate drug interactions? (4)
- 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
PHARMACOKINETIC DRUG INTERACTIONS? (4)
1. Alteration in absorption
2. Protein binding effects
3. Changes in drug metabolism
4. Alteration in elimination
51
Example of ALTERATIONS IN ABSORPTION:
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
Example of PROTEIN BINDING INTERACTIONS:
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)
