Adverse Drug Reactions Flashcards
What are four goals of successful drug therapy?
-Achieve effective concentrations of an appropriate drug at the site of drug action in the individual (ie the target site)
-Prevent, ameliorate or cure the disease with our drug therapy
-Avoid an unwanted adverse drug reaction (ADR)
-Avoid violative drug residues in food producing animals
What must drug therapy include in order to be rational?
drug, host and disease factors
What are most drug therapies based on?
Fixed dosage regimens
What are some host physiologic factors
Neonatal pt, geriatric pt, pregant/lactating pt, species/breed
what are some disease pathophysiologic factors
renal dz, hepatic dz, cardiovascular dz
What are some drug factor “interactions”
Which one is most important?
pharmaceutical interactions
pharmacokinetic interactions (most important one)
pharmacodynamic interactions
What is an ADR?
-Unintended and usually noxious response to a drug that is unwanted
-Occurs at drug doses used for prophylaxis, diagnosis or treatment
-Results in injury (toxicity) or lack of efficacy (therapeutic failure)
What is the estimated incidence of ADRs in hospitalized patients?
Approximately 3-5% of all hospitalized human patients are admitted due to an ADR.
What are the most common drug classes to produce ADRs?
NSAIDs, vaccines (not classified as drugs), and antimicrobial drugs
What is the most common type of ADR?
Type A
What type of adverse drug reaction (ADR) is Type A?
Type A (Augmented) ADRs are avoidable
Are Type A ADRs dose-dependent and predictable?
Yes
Can Type A ADRs occur in all patients?
Yes
Are Type A ADRs experimentally reproducible?
Yes
What can alter plasma drug levels in Type A ADRs?
Changes in drug disposition can alter plasma drug levels.
What are the potential outcomes of altered plasma drug levels in Type A ADRs?
Elevated plasma drug levels can lead to toxic effects, while reduced plasma drug levels can result in therapeutic failure.
What do pharmacological ADRs involve?
Exaggerated pharmacological effects of a drug (or metabolite) on a cellular receptor.
Where do pharmacological ADRs typically occur?
They occur “on the intended target receptor.”
Give an example of an ADR involving propranolol.
Propranolol (Inderal®, generic) can induce bradycardia.
Give an example of an off-target receptor ADR caused by NSAIDs.
NSAIDs (like Aspirin) can induce gastrointestinal ulcers.
What is an example of an off-target receptor ADR caused by xylazine?
Xylazine can induce emesis (vomiting).
How can propranolol affect respiratory function?
Propranolol can induce bronchospasm as an off-target receptor effect.
What determines intrinsic adverse drug reactions (ADRs)?
They are determined by the drug’s physico-chemical properties and non-specific binding to targets.
What is frequently necessary for intrinsic ADRs?
They are often dependent on bioactivation of the drug.
What factors influence the site of effects for intrinsic ADRs?
-Cells/tissues that accumulate the drug.
-Localization of metabolizing enzymes (NZs).
-Susceptibility of various tissues.
What happens when a reactive metabolite binds to non-specific targets?
It can disrupt membranes and organelles in susceptible cells.
Which cellular components can reactive metabolites affect?
They can affect nucleic acids and proteins.
What type of targets do reactive metabolites bind to?
Non-specific targets in susceptible cells.
What type of adverse drug reaction (ADR) is Type B?
Type B (Bizarre) ADRs are considered unavoidable.
Are Type B ADRs dose-dependent?
No, Type B ADRs are dose-independent and unpredictable.
What factor makes Type B ADRs host dependent?
Genetic predisposition of the individual can influence Type B ADRs
Why can classification of Type B ADRs be challenging?
Due to their unpredictable nature and variability among individuals.
What is the major form of Type B adverse drug reactions (ADRs)?
Immunological ADRs.
How can a drug or metabolite act in immunological reactions?
It can act as “haptens” that bind to larger endogenous molecules, triggering an immunological response.
Type 1-4 reactions possible
What is the difference between anaphylactic and anaphylactoid ADRs?
Anaphylactic reactions are IgE-mediated, while anaphylactoid reactions do not involve IgE and can occur without prior sensitization.
Give an example of an immunological ADR in animals.
Penicillin induced allergies in dogs
What is a key feature of idiosyncratic adverse drug reactions (ADRs)?
The involvement of the immune system is not confirmed in all Type B ADRs.
What similarity do idiosyncratic ADRs share with intrinsic ADRs?
Both depend on the chemical properties of the drug and typically involve bioactivation.
Give an example of an idiosyncratic ADR involving oral medication in cats.
Oral diazepam in cats
Provide an example of an idiosyncratic ADR in dogs.
Carprofen
What is important to consider when diagnosing an ADR?
The strength of association between the drug and the reaction
What does temporal association refer to in diagnosing ADRs?
The timing of the reaction in relation to drug administration.