Adverse Drug Reactions Flashcards
Type A ADR
makes up about 80% of ADR
- predictable and dose dependent
Ex: toxicity with overdose like Acetominaphen and liver failure
Side effects: antihistamine sedation
2* effects: Diarrhea and Abx
Drug interaction: theophylline toxicity in presence of erythromycin
4 types of Adverse Drug Reactions
Type A = explainable
Type B = unexplainable
Type C = Chronic Effects
Type D = Delayed Effects
Type B
Idiosyncratic effects, dose independent, unpredictable
Ex: Intolerance: aspirin and tinnitis
Hypersensativity and penicillin
Pseudoallergic: radiocontrast dye RXN
Idiosyncratic: anemia with oxidant drugs in G6PD deficient patients
Type C
Chronic long term therapy finds these
Well known and can be anticipated
Ex: Benzodiazepine dependence
Analgesic nephropathy
Type D
Carcinogenic and teratogenic effects
Delayed in onset and very rare
Mechanisms of Drug toxicity
- On target Adverse effects
- Off target adverse effects
- Production of toxic metabolites
- production of harmful immune responses
- Idiosyncratic responses
On Target adverse effects
*couple scenarios
1) exaggeration of desired pharmacological effect
-increase of effective drug concentration on receptor
-deliberate or accidental dosing errors
-altered pharmacokinetics of the drug
-altered pharmacodynamic of the drug
Ex: Insulin - coma, heparin - bleeding, diazepine - sedation
2) drug also acts on nontarget tissue on correct receptor
Ex antihistamine crossing BBB causing somnolence
Off target Adverse effects
*hit correct receptor but also hit incorrect receptors
Ex: terfenadine: antihistamine also inhibits cardiac K channels causing arrhythmia
*Enantiomers
Ex Thalidomide R-helps morning sickness by causing sedation
S-potent teratogen
*Activation of multiple subtypes Ex Beta receptors
*production of toxic metabolites : acetominaphen -> NAPQI
*harmful immune response: Penicillin -> Hypersensativity
Methyldopa: Autoimmune rxn against Rh factor
*Idiosyncratic toxicity: Type B
Pharmacokinetic interactions
some drugs can chane the absorption, distribution, metabolism or excretion of another drug altering the concentration of the active drug.
*Think about CYP450 induction and inhibition since it metabolizes most drugs
Pharmacodynamic Interactions
When onedrug changes the response of target or nontarget tissues to another drug
*2 drugs can complement eachother
Think about sildenafil (viagra) and nitroglycerin
- both cause vasodilation by increasing cGMP or prolonging its life
Drug herb interaction
Herbs can have potent chemicals too.
Ex: Gingko biloba inhibits platelet aggregation and taken with NSAIDs can increase risk of bleeding
Ex: St John’s Wort with SSRI can lead to serotonergic syndrome
Pregnancy Drug Classifications
Type A - Proven to be safe for fetus
Type B - Proven to be safe for human/badfor animals or safe for animals and notenough info for humans
Type C - Proven bad for animals/not enough info for human or not enough info for animals or humans
Type D- high risk for fetus but benefits may outweigh the risks
Type X - never give to pregnant or wanting to be pregnant women. Proven to be bad
