Adverse Drug Reactions and Interactions Flashcards
What is an adverse drug event
preventable or unpredicted medication event with harm to patient
What are adverse drug reactions classified by
Onset
Severity
Type
What are the classifications of adverse drug reactions according to onset
Acute - within 1 hour
Sub-acute - 1-24 hours
Latent - >2 days
What are the classifications of adverse drug reactions according to severity
Mild - requires no changes to therapy
Moderate - requires change in therapy, additional treatment, hospitalisation
Severe - disabling or life-threatening
Describe severe adverse drug reactions
Results in death Life-threatening Requires or prolongs hospitalisation Causes disability Causes congenital anomalies Requires intervention to prevent permanent injury
Describe type A adverse drug reactions
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
Describe type B adverse drug reactions
Idiosyncratic or immunologic reactions
Includes allergy and “pseudoallergy”
Rare (even very rare) and unpredictable
e.g., chloramphenicol and aplastic anemia, ACE inhibitors and angioedema
Give examples of ADR that are totally unexpected
Herceptin and cardiac toxicity
Describe type C adverse drug reactions
Associated with long-term use
Involves dose accumulation
e.g., methotrexate and liver fibrosis, antimalarials and ocular toxicity
Describe type D adverse drug reactions
Delayed effects (sometimes dose independent) Carcinogenicity (e.g. immunosuppressants) Teratogenicity (e.g. thalidomide)
Describe type E adverse drug reactions
Withdrawal
Rebound
Adaptive reactions
Give examples of drugs that cause withdrawal reactions
Opiates
Benzodiazepines
Corticosteroids
Give examples of drugs that cause rebound reactions
Clonidine
Beta-blockers
Corticosteroids
Give examples of drugs that cause adaptive reactions
Neuroleptics (major tranquillisers)
Describe clonidine withdrawal
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
What is the ABCDE classification of adverse drug reactions
Augmented pharmacological effect Bizarre Chronic Delayed End-of-treatment
Describe type I allergic reactions
immediate, anaphylactic (IgE)
e.g. anaphylaxis with penicillins
Describe type II allergic reactions
cytotoxic antibody (IgG, IgM)
e.g. methyldopa and hemolytic anemia
Describe type III allergic reactions
serum sickness (IgG, IgM) antigen-antibody complex
e.g. procainamide-induced lupus
Describe type IV allergic reactions
delayed hypersensitivity (T cell)
e.g. contact dermatitis
Give examples of pseudoallergies
Aspirin/NSAIDs – bronchospasm
ACE inhibitors – cough/angioedema
Give examples of common causes of ADRs
Antibiotics Antineoplastics Anticoagulants Cardiovascular drugs Hypoglycemics Antihypertensives NSAID/Analgesics CNS drugs
What are pharmacodynamic drug interactions
Related to the drug’s effects in the body
Receptor site occupancy
What are pharmacokinetic drug interactions
Related to the body’s effects on the drug
ADME
What are pharmaceutical drug interactions
drugs interacting outside the body (mostly IV infusions)
Describe pharmacodynamic drug interactions
Additive, synergistic, or antagonistic effects from co-administration of two or more drugs
Give examples of pharmacodynamic drug interactions (synergistic, overlapping toxicity, antagonistic)
Synergistic actions - antibiotics
Overlapping toxicities - ethanol + benzodiazepines
Antagonistic effects - anticholinergic medications (amitriptyline and acetylcholinesterase inhibitors)
What are the types of pharmacokinetic drug interactions
Alteration in absorption
Protein binding effects
Changes in drug metabolism
Alteration in elimination
What is chelation and give examples of drugs that may be affected (pharmacokinetic interaction)
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)
Describe protein binding interactions (pharmacokinetic interaction)
Competition between drugs for protein or tissue binding sites
Increase in free (unbound) concentration may lead to enhanced pharmacological effect
Describe drug metabolism interactions (pharmacokinetic interaction)
Drug metabolism inhibited or enhanced by coadministration of other drugs
Phase 2 metabolic interactions (glucuronidation, etc.) occur
Describe the metabolism of CYP 450 substrates
Metabolism either by a single isozyme or multiple isozymes
Give examples of CYP 450 inhibitors
Cimetidine
Erythromycin and related antibiotics
Ketoconazole etc
Ciprofloxacin and related antibiotics
Ritonavir and other HIV drugs
Fluoxetine and other SSRIs
Grapefruit juice
Give examples of CYP 450 inducers
Rifampicin Carbamazepine (Phenobarbitone) (Phenytoin) St John’s wort (hypericin)
Describe the time scale of inhibition and induction of drug interactions
Inhibition is very rapid
Induction takes hours/days
Describe drug elimination interactions (pharmacokinetic interaction)
Almost always in renal tubule
probenecid and penicillin (good)
lithium and thiazides (bad)
Give examples of deliberate interactions
levodopa + carbidopa
ACE inhibitors + thiazides
penicillins + gentamicin
salbutamol + ipratropium
