Adverse Drug Reactions Flashcards
(106 cards)
1
Q
What are four goals of successful drug therapy?
A
-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
2
Q
What must drug therapy include in order to be rational?
A
drug, host and disease factors
3
Q
What are most drug therapies based on?
A
Fixed dosage regimens
4
Q
What are some host physiologic factors
A
Neonatal pt, geriatric pt, pregant/lactating pt, species/breed
5
Q
what are some disease pathophysiologic factors
A
renal dz, hepatic dz, cardiovascular dz
6
Q
What are some drug factor “interactions”
Which one is most important?
A
pharmaceutical interactions
pharmacokinetic interactions (most important one)
pharmacodynamic interactions
7
Q
What is an ADR?
A
-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)
8
Q
What is the estimated incidence of ADRs in hospitalized patients?
A
Approximately 3-5% of all hospitalized human patients are admitted due to an ADR.
9
Q
What are the most common drug classes to produce ADRs?
A
NSAIDs, vaccines (not classified as drugs), and antimicrobial drugs
10
Q
What is the most common type of ADR?
A
Type A
11
Q
What type of adverse drug reaction (ADR) is Type A?
A
Type A (Augmented) ADRs are avoidable
12
Q
Are Type A ADRs dose-dependent and predictable?
A
Yes
13
Q
Can Type A ADRs occur in all patients?
A
Yes
14
Q
Are Type A ADRs experimentally reproducible?
A
Yes
15
Q
What can alter plasma drug levels in Type A ADRs?
A
Changes in drug disposition can alter plasma drug levels.
16
Q
What are the potential outcomes of altered plasma drug levels in Type A ADRs?
A
Elevated plasma drug levels can lead to toxic effects, while reduced plasma drug levels can result in therapeutic failure.
17
Q
What do pharmacological ADRs involve?
A
Exaggerated pharmacological effects of a drug (or metabolite) on a cellular receptor.
18
Q
Where do pharmacological ADRs typically occur?
A
They occur “on the intended target receptor.”
19
Q
Give an example of an ADR involving propranolol.
A
Propranolol (Inderal®, generic) can induce bradycardia.
20
Q
Give an example of an off-target receptor ADR caused by NSAIDs.
A
NSAIDs (like Aspirin) can induce gastrointestinal ulcers.
21
Q
What is an example of an off-target receptor ADR caused by xylazine?
A
Xylazine can induce emesis (vomiting).
22
Q
How can propranolol affect respiratory function?
A
Propranolol can induce bronchospasm as an off-target receptor effect.
23
Q
What determines intrinsic adverse drug reactions (ADRs)?
A
They are determined by the drug’s physico-chemical properties and non-specific binding to targets.
24
Q
What is frequently necessary for intrinsic ADRs?
A
They are often dependent on bioactivation of the drug.
25
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.
26
What happens when a reactive metabolite binds to non-specific targets?
It can disrupt membranes and organelles in susceptible cells.
27
Which cellular components can reactive metabolites affect?
They can affect nucleic acids and proteins.
28
What type of targets do reactive metabolites bind to?
Non-specific targets in susceptible cells.
29
What type of adverse drug reaction (ADR) is Type B?
Type B (Bizarre) ADRs are considered unavoidable.
30
Are Type B ADRs dose-dependent?
No, Type B ADRs are dose-independent and unpredictable.
31
What factor makes Type B ADRs host dependent?
Genetic predisposition of the individual can influence Type B ADRs
32
Why can classification of Type B ADRs be challenging?
Due to their unpredictable nature and variability among individuals.
33
What is the major form of Type B adverse drug reactions (ADRs)?
Immunological ADRs.
34
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
35
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.
36
Give an example of an immunological ADR in animals.
Penicillin induced allergies in dogs
37
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.
38
What similarity do idiosyncratic ADRs share with intrinsic ADRs?
Both depend on the chemical properties of the drug and typically involve bioactivation.
39
Give an example of an idiosyncratic ADR involving oral medication in cats.
Oral diazepam in cats
40
Provide an example of an idiosyncratic ADR in dogs.
Carprofen
41
What is important to consider when diagnosing an ADR?
The strength of association between the drug and the reaction
42
What does temporal association refer to in diagnosing ADRs?
The timing of the reaction in relation to drug administration.
43
Why is specificity and plausibility important in ADR diagnosis?
It assesses whether the observed reaction is consistent with known effects of the drug.
44
What does repeatability and consistency refer to in the context of ADRs?
The ability to reproduce the reaction upon re-exposure to the drug.
45
What does the biological gradient imply in diagnosing ADRs?
It suggests that the severity of the reaction may correlate with the dose of the drug.
46
What role do predisposing patient factors play in diagnosing ADRs?
They can influence an individual's susceptibility to adverse reactions.
47
What is the most important step in therapy for ADRs?
Drug withdrawal
48
How should treatment be approached for an ADR?
Treatment should be based on the clinical manifestation of the ADR, along with supportive care.
49
What do clinical signs of ADRs depend on?
the affected organ
50
What type of effects are often seen with Type B ADRs?
Systemic effects
51
What should animals manifesting neutropenia be treated with?
They should be treated with a broad-spectrum prophylactic antibiotic.
52
How are ADRs reported in Canada?
voluntary basis
53
Which agency oversees drug reporting in Canada?
The Veterinary Drug Directorate
54
Which agency is responsible for reporting biologics in Canada?
CFIA
55
What agency handles reporting for veterinary pesticides in Canada?
The Pest Management Regulatory Agency
56
Why was there failure to report ADRs in human medicine?
-Belief that they were infrequent and that common ADRs werent worth reporting
-Apathy
-Too busy to fill out the paperwork
57
What is a major cause of clinically significant ADRs?
Altered drug disposition in the target species.
58
What are some species differences that we need to consider with ADRs?
-Maked extrapolating dosage regimens across species challenging
-GIT
-Body composition
-Blood volume
59
What are the two main phases of drug metabolism?
Phase I reactions (oxidation, reduction, hydrolysis) and Phase II reactions (conjugation).
60
What are some examples of conjugates in Phase II reactions? (5)
-Glucuronide
-Glutathione
-Sulfate
-Acetyl group
-Amino acids
61
Give an example of a drug that produces toxic metabolites in cats
Acetaminophen
62
What can metabolism of some drugs produce?
Toxic metabolites
63
Why are elderly patients more likely to experience problems with drug disposition?
They often have significant reductions in organ function and/or suffer from organ disease
64
How does organ disease affect the likelihood of drug toxicity?
Drugs capable of organ toxicity are more likely to cause issues if organ disease or significantly reduced organ function exists
65
What is the most profound change in drug disposition related to renal disease?
Decline in renal function.
66
How does age affect nephron function?
Functioning nephron mass declines with age
67
Why is chronic renal failure significant in aging individuals?
It is common among aging individuals, affecting drug metabolism and disposition
68
Why are the kidneys particularly vulnerable to ADRs?
-They receive 20-25% of the cardiac output
-They concentrate drugs and toxicants
-They have high metabolic activity
69
Where is damage more commonly observed in the kidneys?
Proximal tubule damage is more common due to high renal cortex blood flow.
70
What is chronic renal failure associated with? (3)
-Reduced clearance of drugs by the kidney
-Uremia can reduce protein binding and hepatic metabolism some drugs
-Renal protein loss and dehydration affecting drug distrubution
71
What should be avoided when CRF is present?
-Avoid using the kidney for drug elimination if possible.
-Choose drugs that are not eliminated by the kidney and are not toxic to the kidney.
-Use therapeutic drug monitoring (TDM) and make dosage adjustments when possible.
72
What are some drugs capable of renal ADRs?
-Aminoglycosides (gentamycin, amikain)
-NSAIDs
73
What do primary or compensatory disturbances in renal function lead to?
-Renal and sodium retention
-The sympathetic nervous system responds by increasing output and causes blood redistribution to the brain and heart.
74
How should drugs be given in a cardiac patient?
-Critical drugs should be given IV
-Potentially toxic drugs should be given IV slowly
-TDM and dosage adjustments when possible
75
Why is the liver highly vulnerable to ADRs? (4)
-Liver also receives a high cardiac output %
-It is the “portal of entry” of most drugs
-It is the major site of metabolite formation
-It has very high metabolic activity
76
What are some possible consequences of liver disease? (3)
-Reduced enzyme function
-Increased fraction of plasma unbound drug (Hypoalbumemia, bilirubinemia)
-Reduced hepatic blood flow
77
How can ADRs arise in the context of liver disease?
ADRs can arise from reactive metabolites causing hepatocellular injury.
78
Why is it difficult to predict changes in drug disposition with hepatic disease?
Because the effects of liver disease on drug metabolism can be complex and variable.
79
What happens to drugs that are inactivated by the liver when hepatic function is reduced?
Their levels could increase due to decreased metabolism.
80
What level of hepatic disease is generally required for clinically relevant changes?
Significant hepatic disease is usually needed before clinically relevant changes occur.
81
What should be avoided in cases of significant liver disease?
Avoid using drugs that rely on hepatic metabolism if possible.
82
What type of drugs should be chosen for patients with liver disease?
Choose drugs that are primarily eliminated by extra-hepatic mechanisms.
83
What management practices should be used for drug therapy in patients with liver disease?
Use therapeutic drug monitoring (TDM) and make dosage adjustments when possible.
84
Two types of drugs that cause hepatic ADRs
-Corticosteroids
-Anticonvulsants
85
What is a drug interaction?
A change in the magnitude or duration of a pharmacologic effect of a drug due to the presence of another drug, food, or environmental factor.
86
What affects the incidence of drug reactions?
-Increases with number of drugs; polypharmacy
-Increases with duration of use
87
When can drug interactions occur in relation to drug absorption?
Interactions can occur before or after the drug is absorbed by the host
88
What are the primary sequelae of drug interactions?
Toxic adverse drug reactions (ADRs) and subtherapeutic (failure) pharmacologic effects, which are also considered ADRs.
89
How are drug interactions classified?
Drug interactions are classified as pharmaceutical, pharmacokinetic, or pharmacodynamic in nature
90
What does "subtherapeutic pharmacologic effects" mean in the context of drug interactions?
It refers to the failure to achieve the desired therapeutic effect due to the interaction, resulting in inadequate treatment.
91
What are pharmaceutical interactions?
Interactions that occur in vitro before the drug is absorbed by the host, usually in the GI tract lumen following oral administration
They affect the total dose of drug available for absorption.
92
What do pharmaceutical interactions rely on?
Alterations in the physicochemical properties of the affected drug.
93
What is a common type of drug-drug interaction?
Drug incompatibilities, often seen with the addition of drugs to IV fluids.
94
What are less common types of pharmaceutical interactions?
rug-environment and drug-diet interactions, which can involve syringes or containers, light, and temperature.
95
Why should caution be exercised when compounding drugs?
To prevent pharmaceutical interactions that could alter drug efficacy or safety.
96
What are pharmacokinetic interactions?
Interactions that affect the disposition of a drug, often leading to significant changes in pharmacokinetics.
97
What factors can cause absorption interactions?
-GI pH (some drugs rely on acid pH to be activated)
-GI motility and regional blood flow (slows down rate of absorption)
-P-glycoprotein (MDR-efflux pump) and GI CYP450 enzymes
98
What are distribution interactions?
Interactions that involve changes in plasma protein binding or tissue protein binding, as well as blood flow.
99
What factors are involved in excretion interactions?
-Urine pH
-Tubular secretion
-Renal blood flow
100
What are two metabolism interaction?
-Hepatic blood flow (can affect rate of metabolism)
-Metabolizing enzymes; CYP450 enzymes, involved in phase I mixed-function oxidation, affecting drug metabolism.
101
Why is urine pH important in drug excretion?
It can affect the solubility and ionization of drugs, thereby influencing their reabsorption and excretion.
102
What are pharmacodynamic interactions?
Interactions that occur when one drug directly alters the physiological or cellular response to another drug.
103
What are receptor interactions in pharmacodynamic interactions?
They occur at the same target site, where drugs may act as agonists, antagonists, or partial agonists
104
What are post-receptor interactions?
second messengers (e.g., cAMP levels).
105
5 practices to avoid an ADR
-Choose drugs with wide therapeutic indices; use TDM when possible
-Adjust dose according to the stage of life and health of the patient
-Use drugs approved for target species in the disease of interest
-Try to limit polypharmacy
-Realize that most drugs do cause adverse effects; all drugs can potentially be associated with immunological ADRs
-Never prescribe a drug without being aware of its potential adverse effects
105
How can physiological response interactions manifest?
They can result in differing or additive effects on the same physiological response.
