Adverse drug reactions Flashcards
What is an adverse drug reaction?
Preventable or unpredicted medication event, with harm to patient.
How are adverse drug reactions classified?
Onset
Severity
Type
How can the onset of an adverse drug reaction vary?
Acute- within 1 hour
Subacute- 1 to 24 hours
Latent- >2 days
How can the severity of an adverse drug reaction vary?
Mild- requires no change in therapy
Moderate- requires change in therapy, additional treatment, hospitalisation
Severe- disabling or life-threatening
What may be the results of a severe adverse drug reaction?
Results in death Life-threatening Requires or prolongs hospitalisation Causes disability Causes congenital anomalies Requires intervention to prevent permanent injury
What is a type A classified adverse drug reaction?
Extension of pharmacologic effect.
Usually predictable and dose dependent.
What proportion of adverse drug reactions are classified as type A?
At least ⅔.
Give 3 examples of type A classified adverse drug reactions.
Atenolol and heart block.
Anticholinergics and dry mouth.
NSAIDs and peptic ulcer.
What is a type B classified adverse drug reaction?
Idiosyncratic or immunologic reaction.
Includes allergy and ‘pseudoallergy’.
Rare (even very rare) and unpredictable.
Give 2 examples of type B classified adverse drug reactions.
Chloramphenicol and aplastic anaemia.
ACE inhibitors and angioedema.
What is a type C classified adverse drug reaction?
Associated with long-term use.
Involves dose accumulation.
Give 2 examples of type C classified adverse drug reactions.
Methotrexate and liver fibrosis.
Antimalarials and ocular toxicity.
What is a type D classified adverse drug reaction?
Delayed effects (sometimes dose independent). Carcinogenicity (e.g. immunosuppressants). Teratogenicity (e.g. thalidomide).
What is a type E classified adverse drug reaction?
Withdrawal reactions, e.g. opiates, benzodiazepines, corticosteroids.
Rebound reactions, e.g. clonidine, beta-blockers, corticosteroids.
‘Adaptive’ reactions, e.g. neuroleptics (major tranquilisers).
What is the ABCDE classification of adverse drug reactions?
A: augmented pharmacological effect B: bizarre C: chronic D: delayed E: end of treatment
How are allergies classified?
Type I: immediate, anaphylactic (IgE), e.g. anaphylaxis with penicillins.
Type II: cytotoxic antibody (IgG, IgM), e.g. methyldopa and haemolytic anaemia.
Type III: serum sickness (IgG, IgM), antigen-antibody complex, e.g. procainamide-induced lupus.
Type IV: delayed hypersensitivity (T cell), e.g. contact dermatitis.
Give examples of pseudoallergies.
Aspirin/NSAIDs- bronchospasm.
ACE inhibitors- cough/angioedema.
What are the common causes of adverse drug reactions?
Antibiotics Antineoplastics Anticoagulants Cardiovascular drugs Hypoglycaemics Antihypertensives NSAID/analgesics CNS drugs
How are adverse drug reactions detected?
Subjective report- patient complaint.
Objective report through direct observation of event, e.g. abnormal findings, physical examination, laboratory test, or through a diagnostic procedure.
Rare events will probably not be detected before drug is marketed.
What is the ‘yellow card’ scheme?
Entirely voluntary.
Includes blood products, vaccines, contrast media.
Adverse drug reaction suspected, confirmed (high probability), frequency estimated and prescribers informed.
Who can the ‘yellow card’ scheme be used by?
Can be used by doctors, dentists, nurses, coroners and pharmacists, and members of the public.
How is the ‘yellow card’ scheme used for established drugs?
Only report serious adverse reactions (fatal, life-threatening, needing hospital admission, disabling).
How is the ‘yellow card’ scheme used for ‘black triangle’ drugs (newly licensed, usually <2 years)?
Report any suspected adverse reaction.
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 OTC and herbal drug therapy use.
Difficulty in determining contribution of drug interaction in complicated patients.
Sometimes principal cause of ADRs with specific drugs, e.g. statins.
What is a pharmacodynamic drug interaction?
Related to the drug’s effects in the body.
Receptor site occupancy.
Additive, synergistic, or antagonistic effects from co-administration of 2 or more drugs.
Synergistic actions of antibiotics.
Overlapping toxicities- ethanol and benzodiazepines.
Antagonistic effects- anticholinergic medications (amitriptyline and acetylcholinesterase inhibitors).
What is a pharmacokinetic drug interaction?
Related to the body’s effects on the drug. Alteration in absorption. Protein binding effects (distribution). Changes in drug metabolism. Alteration in elimination.
What is a pharmaceutical drug interaction?
Drugs interacting outside the body (mostly i.v. infusions).
What is chelation?
Irreversible binding of drugs in the GI tract.
Alters absorption of a drug.
Tetracyclines, quinolone antibiotics- ferrous sulfate (Fe2+), antacids (Al3+, Ca2+, Mg2+), dairy products (Ca2+).
What are protein binding interactions?
Competition between drugs for protein or tissue binding sites.
Increase in free (unbound) concentration may lead to enhanced pharmacological effect.
Many interactions previously thought to be protein binding interactions were found to be primarily metabolism interactions.
Protein binding interactions are not usually clinically significant but a few are (mostly with warfarin).
What are the reactions of phase I metabolism?
Oxidation
Reduction
Hydrolysis
What are the types of reactions in phase II metabolism?
Conjugation
Glucuronidation
Sulfation
Acetylation
List CYP450 inhibitors.
Cimetidine Erythromycin and related antibiotics Ketoconazole, etc. Ciprofloxacin and related antibiotics Ritonavir and other HIV drugs Fluoxetine and other SSRIs Grapefruit juice
List CYP450 inducers.
Rifampicin Carbamazepine (Phenobarbitone) (Phenytoin) St John’s wort (hypericin)
List drugs that are deliberately given together to react with each other.
Levodopa + carbidopa
ACE inhibitors + thiazides
Penicillins + gentamicin
Salbutamol + ipratropium
How may drugs be excreted from the body?
Excreted unchanged by kidney.
Phase I reaction, then excreted by the liver or more often the kidney.
Phase I reaction, then phase II reaction, then excreted by the kidney.
Phase II reaction, then excreted by the kidney.
Which CYP450 isozymes account for the largest proportion of drug metabolism?
CYP3A4 (36%)
CYP2D6 (19%)
Where do drug elimination reactions usually occur? Give examples.
Almost always in renal tubule.
Probenecid and penicillin (good)- probenecid reduces elimination of penicillin.
Lithium and thiazides (bad)- thiazides reduce clearance of lithium so toxicity is more likely to occur.
