pharm 22: adverse drug effects Flashcards
By what 3 methods is Adverse drug Reactions classified by?
a) onset
- acute / subacute / latent
(< 1hr) (1 - 24hrs) (> 2days)
b) severity
- mild / moderate / severe
c) type
- A / B / C / D / E
What is meant by adverse drug event?
- preventable or unpredicted medication event with harm to the patient
What might be some consequences of Severe ADR ?
- death
- life threatening
- causes disability
- requires intervention to prevent permanent injury
- requires / prolongs hospitalization
What is meant by type A ADR?
- extension of pharmacologic effect
- usually predictable and dose dependent
- -> responsible for at least two-thirds of ADRs
e.g atenolol –> heart block
NSAIDS –> Peptic ulcer
What is meant by type B ADR?
- idiosyncratic or immunologic reactions
- includes allergy and “pseudoallergy”
- Unpredictable
- rare
e.g ACE i –> Angioedema
What is meant by type C ADR?
- associated with long-term use
- involves dose accumulation
e.g., methotrexate –> liver fibrosis
(dependent on amount of drug given)
What is meant by type D ADR?
delayed effects
What is meant by type E ADR?
- Withdrawal reactions (e.g opiate)
- Rebound reactions (e.g corticosteroids/ beta blockers )
- “Adaptive” reactions (neuroleptics - abnormal movements )
What are the 4 classifications of allergies:
Type 1 =
Type 2 =
Type 3 =
Type 4 =
Type 1 = immediate, anaphylactic (IgE)
Type 2 = cytotoxic antibody (IgG, IgM)
Type 3 = serum sickness (IgG, IgM)
Type 4 = delayed hypersensitivity (T cell) - e.g dermatitis
What is meant by pseudo allergies ?
Aspirin/NSAIDs – bronchospasm
- leukotrienes = proinflammatory –> causes bronchospasm
ACE inhibitors – cough/angioedema
What are common causes of ADR?
- Antibiotics
- Antineoplastics*
- Anticoagulants
- Cardiovascular drugs*
- Hypoglycemics
- Antihypertensives
- NSAID/Analgesics*
- CNS drugs*
How does ACE inhibitors cause angioedema?
angioedema = less severe anaphylaxis
- occurs due to build up of bradycardia –> pro inflammatory –> cause swelling in some patients )
How would you detect adverse drug reactions?
- subjective report (Patient complaint)
- objective report (Abnormal findings in tests or examinations / direct observation of event e.g in ward)
What is the yellow card scheme with regards to adverse drug effects?
-
Note:
- Usually rare events will probably not be detected before drug is marketed
-
define
- Pharmacodynamic
- Pharmacokinetic
- Pharmaceutical
Pharmacodynamic = the drug’s effects in the body
Pharmacokinetic = Related to the body’s effects on the drug
Pharmaceutical = drugs interacting outside the body
What are examples of Pharmacodynamic Drug Interactions?
- Additive
- synergistic (e.g antibiotics)
- antagonistic effects
- -> from co-administration of two or more drugs
What is meant by Pharmacokinetic Drug Interactions?
- Alteration in absorption (e.g chelation –> binding of drugs to GIT)
- Alteration of Protein binding effects ( Competition btw drugs for protein or tissue binding sites e.g warfarin - highly protein bound)
- Changes in drug metabolism
- Alteration in elimination
note:
determining drug interaction is:
- Difficult in determining contribution of drug interaction in complicated patients
- Lack of availability of comprehensive databases
- difficult to determine true incidence
-
what are the 3 main methods of drug metabolism + elimination?
- straight through kidney –> out
- phase 1 reaction –> out
- Phase 1 –> phase 2 –> out
- phase 2 reaction –> out
note: CYP 450 =
most drugs metabolized by more than 1 isozymes
- so interruption to CYP450 –> not very important clinically
-
What are some of the usual suspects for 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
–> inhibition = very rapid
What are some of the usual suspects for CYP 450 INDUCERS?
induction = production of genes
- Rifampicin
- Carbamazepine
- St John’s Wort
–> induction = takes hours/ days
Drug elimination interaction usually occurs in :
renal tubule !
- thiazide increase excretion of sodium at the expense of lithium (BAD)
- Probenecid when given with penicillin –> Increases pharmacological effect –> so you can use lower dose / prolongs effect etc.
What are the 4 major deliberate drug interactions?
- levodopa + carbidopa
- ACE inhibitors + thiazides
- penicillins + gentamicin
- salbutamol + ipratropium
How is giving probenecid with penicillin a good thing?
Probenecid when given with penicillin –> Increases pharmacological effect –> so you can use lower dose / prolongs effect etc.
How is giving lithium with thiazide a bad thing?
- thiazide increase excretion of sodium at the expense of lithium (BAD)
