adverse drug reactions 1 Flashcards

1
Q

4 goals of rational/successful drug therapy

A

The goal of successful drug therapy is to….
-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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

rational drug therapy includes consideration of:

A

drug, host, and disease factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

most drug therapies are based on what type of regimens?

A

fixed dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what types of factors can influence plasma drug levels and the likelihood of therapeutic success, or an ADR, thus necessitating dosage regimen adjustments

A

host “physiologic” factors
drug factors- “interactions”
disease “pathophysiologic” factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what Host “physiologic” Factors can influence plasma drug levels (and thus the likelihood of therapeutic success, or an ADR)

A

Neonatal patient
Geriatric patient
Pregnant/Lactating patient
Species/Breeds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what drug “interaction” Factors can influence plasma drug levels (and thus the likelihood of therapeutic success, or an ADR)

A

Pharmaceutical interactions
Pharmacokinetic interactions
Pharmacodynamic interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what Disease “pathophysiologic” Factors can influence plasma drug levels (and thus the likelihood of therapeutic success, or an ADR)

A

Renal disease
Hepatic disease
Cardiovascular disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is an ADR? what is their incidence?

A

adverse drug reaction
-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)

o What is the incidence of ADRs ??
- Estimated 3-5% of all hospitalized human patients admitted due to an ADR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Certain usage patterns are associated with higher incidences of ADRs, such as:

A

-Use of human-labeled drugs with little/no drug safety or efficacy data
-Irrational or trivial drug use
-Failure to set therapeutic goals or end-points
-Use of multiple drugs concurrently in a patient
-Failure to weigh the risk/benefits of drug use
-Use of drugs with a low therapeutic index
-Failure to educate owners on drug usage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

o What are the most common drug classes to produce ADRs (6)

A

qNSAIDs
qVaccines (not classified as drugs)
qAntimicrobial drugs
qEctoparasiticides
qAnthelmintics
qAnesthetic agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

types of adverse drug reactions (7)

A

o Type A (Augmented)…..is avoidable!
> Pharmacological….”receptor-mediated”
> Intrinsic

o Type B (Bizarre)…..unavoidable!
> Immunological
> Idiosyncratic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the most common type of ADR?

A

type A (augmented)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

characteristics of type A ADR

A

o Type A (Augmented)…..is avoidable!
n Most common type of ADR

n Dose-dependent and predictable
o Can occur in all patients

n Experimentally reproducible

n Mechanism responsible is known

n Altered plasma drug levels due to change in drug
disposition
o Elevated plasma drug levels and toxic effects
o Reduced plasma drug levels and therapeutic failure possible also !

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the characteristics of a pharmacological “receptor mediated” ADR? what are the subcategories and what is an example?

A

n Exaggerated pharmacological effects of drug (metabolite)
on a cellular receptor
n “on intended target receptor”
- Propranolol (Inderal®, generic) induced bradycardia
- BZD/barbituate induced sedation

n “off target receptor”
- NSAIDs (Aspirin®, generic) induced GI ulcers
- Xylazine-induced emesis
- Propranolol-induced bronchospasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

examples of “on intended target receptor” pharmacological ADRs

A

-Propranolol (Inderal®, generic) induced bradycardia
-BZD/barbituate induced sedation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

examples of “off intended target receptor” pharmacological ADRs

A

-NSAIDs (Aspirin®, generic) induced GI ulcers
-Xylazine-induced emesis
- Propranolol-induced bronchospasm

17
Q

what do intrinsic ADRs depend on?

A

n Determined by drug’s physico-chemical
properties; non-specific binding to targets

n Frequently dependent on bioactivation

18
Q

site of effects of an intrinsic ADR depends on what?

A

-cells tissues that accumulate drug
-localization of metabolizing NZs (enzymes?)
-susceptibility of various tissues

19
Q

what happens in an ADR when a reactive metabolite binds non-specific targets in susceptible cells?

A

-disrupt membranes, organelles
-nucleic acids, proteins

20
Q

characteristics of a type B ADR

A

o Type B (Bizarre)…..unavoidable !
n Dose-independent and unpredictable
n Host dependent > Genetic predisposition
n Usually not experimentally reproducible > Mechanism???
n Classification can be challenging

21
Q

what are the characteristics of an immunological ADR? what is a common example?

A

-Major form of Type B ADR
-Drug (metabolite) can act as “haptens” binding to larger endogenous molecules—immunological response
> TypeI-IV reactions possible
> “Anaphylactic versus anaphylactoid” ADRs
n Penicillin-induced allergies in dogs

22
Q

what are the characteristics of an idiosyncratic ADR? What are some important examples?

A

n Involvement of the immune system is not confirmed in all Type B ADRs
n Mechanism of action is usually not related to the drugs pharmacologic action, or is unknown
n Like intrinsic ADRs……
> Depends on chemical property of drug
> Typically involves bioactivation of the drug

n Oral diazepam in cats
n Carprofen in dogs

23
Q

what are the signs of an ADR?

A

Clinical signs are often non-specific and rarely pathognomonic

24
Q

what signs do we look to to diagnose an ADR?

A

o Temporal association
o Specificity and plausibility
o Repeatability and consistency
o Experimental evidence
o Biological gradient
o Predisposing patient factors

25
Q

What therapies can we use to alleviate an ADR?

A

Drug withdrawal is the most important step!! Can we use the drug or agent again?

Treatment based on the clinical manifestation of the ADR, along with supportive care
-Clinical signs will depend on the affected organ
-Systemic effects often seen with Type B ADRs
-Specific antidotes possible!!
-Hastening elimination also recommended

Use of corticosteroids for idiosyncratic ADRs is poorly documented

Animals manifesting with neutropenia should be treated with a broad-spectrum prophylactic antibiotic

26
Q

why do people fail to report ADRs in human medicine?

A

-Belief that ADRS were infrequent and that common ADRS were not worth reporting
-Apathy
-Too busy to fill out the paperwork!