Adverse Drug Reactions and Interactions

Question 1

What is an adverse drug event

Answer 1

preventable or unpredicted medication event with harm to patient

Question 2

What are adverse drug reactions classified by

Answer 2

Onset
Severity
Type

Question 3

What are the classifications of adverse drug reactions according to onset

Answer 3

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

Question 4

What are the classifications of adverse drug reactions according to severity

Answer 4

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

Question 5

Describe severe adverse drug reactions

Answer 5

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

Question 6

Describe type A adverse drug reactions

Answer 6

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

Question 7

Describe type B adverse drug reactions

Answer 7

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

Question 8

Give examples of ADR that are totally unexpected

Answer 8

Herceptin and cardiac toxicity

Question 9

Describe type C adverse drug reactions

Answer 9

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

Question 10

Describe type D adverse drug reactions

Answer 10

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

Question 11

Describe type E adverse drug reactions

Answer 11

Withdrawal
Rebound
Adaptive reactions

Question 12

Give examples of drugs that cause withdrawal reactions

Answer 12

Opiates
Benzodiazepines
Corticosteroids

Question 13

Give examples of drugs that cause rebound reactions

Answer 13

Clonidine
Beta-blockers
Corticosteroids

Question 14

Give examples of drugs that cause adaptive reactions

Answer 14

Neuroleptics (major tranquillisers)

Question 15

Describe clonidine withdrawal

Answer 15

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

Question 16

What is the ABCDE classification of adverse drug reactions

Answer 16

Augmented pharmacological effect
Bizarre
Chronic
Delayed
End-of-treatment

Question 17

Describe type I allergic reactions

Answer 17

immediate, anaphylactic (IgE)

e.g. anaphylaxis with penicillins

Question 18

Describe type II allergic reactions

Answer 18

cytotoxic antibody (IgG, IgM)

e.g. methyldopa and hemolytic anemia

Question 19

Describe type III allergic reactions

Answer 19

serum sickness (IgG, IgM)
antigen-antibody complex

e.g. procainamide-induced lupus

Question 20

Describe type IV allergic reactions

Answer 20

delayed hypersensitivity (T cell)

e.g. contact dermatitis

Question 21

Give examples of pseudoallergies

Answer 21

Aspirin/NSAIDs – bronchospasm

ACE inhibitors – cough/angioedema

Question 22

Give examples of common causes of ADRs

Answer 22

Antibiotics
Antineoplastics
Anticoagulants
Cardiovascular drugs
Hypoglycemics
Antihypertensives
NSAID/Analgesics
CNS drugs

Question 23

What are pharmacodynamic drug interactions

Answer 23

Related to the drug’s effects in the body

Receptor site occupancy

Question 24

What are pharmacokinetic drug interactions

Answer 24

Related to the body’s effects on the drug

ADME

Question 25

What are pharmaceutical drug interactions

Answer 25

drugs interacting outside the body (mostly IV infusions)

Question 26

Describe pharmacodynamic drug interactions

Answer 26

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

Question 27

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

Answer 27

Synergistic actions - antibiotics Overlapping toxicities - ethanol + benzodiazepines Antagonistic effects - anticholinergic medications (amitriptyline and acetylcholinesterase inhibitors)

Question 28

What are the types of pharmacokinetic drug interactions

Answer 28

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

Question 29

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

Answer 29

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)

Question 30

Describe protein binding interactions (pharmacokinetic interaction)

Answer 30

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

Question 31

Describe drug metabolism interactions (pharmacokinetic interaction)

Answer 31

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

Question 32

Describe the metabolism of CYP 450 substrates

Answer 32

Metabolism either by a single isozyme or multiple isozymes

Question 33

Give examples of CYP 450 inhibitors

Answer 33

Cimetidine Erythromycin and related antibiotics Ketoconazole etc Ciprofloxacin and related antibiotics Ritonavir and other HIV drugs Fluoxetine and other SSRIs Grapefruit juice

Question 34

Give examples of CYP 450 inducers

Answer 34

``` Rifampicin Carbamazepine (Phenobarbitone) (Phenytoin) St John’s wort (hypericin) ```

Question 35

Describe the time scale of inhibition and induction of drug interactions

Answer 35

Inhibition is very rapid Induction takes hours/days

Question 36

Describe drug elimination interactions (pharmacokinetic interaction)

Answer 36

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

Question 37

Give examples of deliberate interactions

Answer 37

levodopa + carbidopa ACE inhibitors + thiazides penicillins + gentamicin salbutamol + ipratropium