Non-Disease Specific Pharmacology Therapeutics 2018-2020 Flashcards
1
Q
1. What type of receptor is the glucocorticoid receptor? A. G-protein coupled receptor B. Ligand-gated ion channel C. Nuclear receptor D. Receptor tyrosine kinase
A
Chapter 25 Answers:
1. C, Nuclear receptor.
The glucocorticoid receptor is a nuclear receptor.
Chapter 25: Resolution of Allergic Inflammation
Middleton’s Allergy Principles and Practice, 8th Edition
2
Q
1. What term defines the mass of drug emitted per actuation that is actually available for inhalation at the mouth? A. Emitted dose (ED) B. Fine particle dose (FPD) C. Fine particle fraction (FPF) D. Labeled dose (LD)
A
- A, Emitted dose (ED), p. 1067.
The mass of drug emitted per actuation that is available for inhalation at the mouth is the emitted dose or delivered dose.
Chapter 66: Aerosol and Aerosol Drug Delivery Systems
Middleton’s Allergy Principles and Practice, 8th Edition
3
Q
2. Which of the following is the primary determinant of the site of lung deposition, distribution of the drug within the lung, and resulting deposition efficiency? A. Breath hold B. Inspiratory flow rate C. Sedimentation rate D. The size of an aerosol particle
A
- D, The size of an aerosol particle, p. 1068.
The size of an aerosol particle is the primary determinant of the site of lung deposition,distribution of the drug within the lung, and resulting deposition
efficiency.
4
Q
3. As the mass of an aerosol particle decreases and the air stream velocity decreases, particlessmaller than 5 µm tend to deposit on which of the following airways? A. Large conducting airways B. Esophagus C. Oropharynx D. Small airways
A
- D, Small airways, p. 1068.
Particles smaller than 5 µm tend to deposit by sedimentation and diffusion on successively
smaller airways as the mass of an aerosol particle decreases and the air stream velocity
decreases.
5
Q
4. In addition to the particle size, what additional factor may make it possible to target specific regions in the lung for therapy? A. Expiratory flow rate B. Inspiratory flow rate C. Inspiratory to expiratory ratio D. Total lung deposition
A
- B, Inspiratory flow rate, p. 1069.
It may be possible to target specific regions in the lung for therapy by selection of particle
size and inspiratory flow rate.
6
Q
- Nebulizers are used for liquid formulations. Which of the following describes an ultrasonic nebulizer?
A. A piezoelectric crystal vibrates at a high frequency withsufficient intensity to create
standing waves on the surface of the liquid overlying the crystal
B. Compressed air or oxygen breaks up a thin film of fluid into droplets suitable for inhalation
C. Controls the entire inhalation maneuver by applying a positive pressure delivered with a
computer-controlled compressor
D. Vents supplemental air into the nebulizer across the venturi jet in the nebulizer bow
A
- A, A piezoelectric crystal vibrates at a high frequency withsufficient intensity to create standing waves on the surface of the liquid overlying the crystal, 1072-4.
An ultrasonic nebulizer incorporates a piezoelectric crystal vibrates at a high frequency with sufficient intensity to create standing waves on the surface of the liquid overlying the crystal.
7
Q
6. Most current ultrasonic nebulizers producing aerosols operate at frequencies above what MHz? A. 1 B. 10 C. 100 D. 1000
A
- A, 1, p. 1073.
Most current ultrasonic nebulizers operate at frequencies above 1 MHz, producing aerosols withMMADs between 2 and 12 µm, with an output that is two to three times higher than with
most jet nebulizers
8
Q
7. Which HFA inhaled corticosteroid has a built-in spacer? A. Beclomethasone dipropionate B. Ciclesonide C. Flunisolide D. Fluticasone propionate
A
- C, Flunisolide, p. 1076.
The HFA inhaled corticosteroid flunisolide has a built-in spacer.
9
Q
8. Adding which of the following to the standard therapy for cystic fibrosis produces sustained improvement in lung function for up to 52 weeks? A. Atenolol B. Mannitol C. Metoprolol D. Olodaterol
A
- B, Mannitol, p. 1080.
A new study has shown that adding inhaled dry powder mannitol to standard therapy for cystic
fibrosis produces sustained improvement in lung function for up to 52 weeks.
10
Q
- A component of many highly active antiretroviral therapy (HAART) regimens, which
nucleoside reverse transcriptase inhibitor causes a potentially fatal hypersensitivity reaction in
patients, more commonly in HLA B5701-positive individuals?
A. Abacavir
B. Emtricitabine
C. Lamivudine
D. Zidovudine
A
- A, Abacavir, p. 1180.
Abacavir (ABC) causes a potentially fatal systemic illness in up to 8% of patients, typically
within the first 9-11 days of treatment. Manifestations of this illness include high fever, diffuse rash, malaise, nausea, myalgia, arthralgia, and abdominal pain. Treatment-naïve white patients with higher CD8+ T cell counts at treatment initiation are at higher risk, and the HLA B5701 allele is the dominant risk factor for this hypersensitivity with a PPV greater than 70%. Lack of this allele has a NPV of 95-98%. Prescreening for this allele before starting ABC is now recommended. If signs of hypersensitivity occur, this drug must be discontinued and can never be safely reintroduced.
Chapter 73: Human Immunodeficiency Virus and Allergic Disease
Middleton’s Allergy Principles and Practice, 8th Edition
11
Q
- Minor determinants of penicillin are most commonly associated with what type of reactions?
A. Acute generalized exanthematous pustulosis (AGEP)
B. Anaphylaxis
C. Drug rash with eosinophilia and systemic symptoms (DRESS}
D. Urticaria
A
- B, Anaphylaxis, p. 1276.
The minor determinants of penicillin are of major clinical importance because they are generally associated with anaphylaxis.
Chapter 79: Drug Allergy
Middleton’s Allergy Principles and Practice, 8th Edition
12
Q
2. P-i mechanism explains for which of the following bizarre phenomenon? A. Delayed onset drug allergy B. Erythema multiforme C. First encounter drug hypersensitivity D. Toxic epidermal necrolysis
A
- C, First encounter drug hypersensitivity, p. 1276.
The P-i concept by Pichler and colleagues described the direct pharmacologic interaction of
drugs with immune receptors. A chemically inert drug that is unable to covalently bind to
peptides or proteins may activate the immune system by directing binding and reversibly to
HLA molecules on APCs or TCRs on certain T cells.
13
Q
3. Type IVa reactions involve the secretion of large amounts of which cytokine? A. CXCL8 B. IFN – γ C. IL – 5 D. IL – 13
A
- B, IFN- γ. Figure 79-7. P. 1281.
Type IVa reactions involve Th1 type immune reaction that activates macrophages
resulting in large amounts of IFN – γ.
14
Q
- Patients requiring taxanes can be treated for infusion reactions with which of the following?
A. Decreasing the rate of infusion
B. Decreasing the rate of infusion, antihistamines, corticosteroids
C. Increasing rate of infusion
D. Increased rate of infusion, antihistamines, corticosteroids
A
- B, Decreasing the rate of infusion, antihistamines, corticosteroids, p. 1284.
Taxanes can lead to mast cell degranulation by nonimmune mechanisms. Such infusions are
common with the first infusion. Slowing the infusion and pretreatment with antihistamines,
steroids can prevent hypersensitivity reactions.
15
Q
5. The definitive diagnosis of IgE mediated drug allergy involves A. lymphocyte activation testing. B. provocative drug testing. C. skin prick testing. D. intradermal and skin prick testing.
A
- B, Provocative drug testing, Page 1287.
Intradermal and prick skin testing are methods of diagnosing drug allergies however the most
definitive way is provocative drug challenge. Patients are given gradually increasing doses of
the drug. Provocative drug tests should not be done if there was a reaction within 4–6 weeks,
patient used antihistamines, steroids, or has underlying uncontrolled conditions (urticaria,
asthma, URI, etc). Provocative drug testing may not be helpful for non-IgE mediated reactions.
16
Q
6. How long should skin testing be delayed after an acute anaphylactic episode? A. 3 months B. 4 weeks C. 6 months D. 12 months
A
- B, 4 weeks, p. 1288.
Skin testing should be delayed by 4 weeks to avoid the refractory period and falsenegative
testing.
17
Q
7. For patients with a history of severe anaphylaxis, what should be the initial dose for drug sensitization? A. Between 1/1,000 and 1/100 B. Between 1/10,000 and 1/100 C. Between 1/10,000 and 1/1,000 D. Between 1/1,000,000 and 1/10,000
A
- D, Between 1/1,000,000 and 1/10,000, P. 1289.
Desensitization protocols for patients with severe anaphylaxis (hypotension, loss of
consciousness, severe bronchospasm, etc.) should be started at a lower concentration than
patients with milder symptoms.
18
Q
1. Which non-steroidal anti-inflammatory drugs (NSAIDs) hypersensitivity likely involves COX-1 inhibition? A. Fixed drug eruption B. Multiple NSAID induced urticaria C. Single drug induced anaphylaxis D. Single drug induced urticaria
A
- B, Multiple NSAID induced urticaria, p. 1297, Table 80-1.
Cox-1 inhibition is the likely mechanism in urticaria/angioedema induced bymultiple NSAIDs.
Single drug induced urticaria and anaphylaxis are IgE mediated. A fixed drug eruption is a form
of delayed-type hypersensitivity.
Chapter 80: Immune Receptors and Signal Transduction
Middleton’s Allergy Principles and Practice, 8th Edition
19
Q
- A patient presents with urticaria to multiple non-steroidal antiinflammatory drugs (NSAIDs). What is the next step inmanagement?
A. Avoid all NSAIDs
B. Confirmatory oral challenge with COX-1 inhibitor
C. Desensitization to preferred NSAID
D. Oral challenge with non-COX-1 inhibitor
A
- B, Confirmatory oral challenge, p. 1306, Figure 80-3.
The first step is a confirmatory oral challenge with a COX-1 inhibitor. If positive, then an
oral challenge with a non-COX-1 inhibitor should be done next.
20
Q
- A patient presents with angioedema to a single non-steroidal antiinflammatory drug (NSAID). What is the next step in management?
A. Confirmatory oral challenge with same NSAID
B. Desensitization
C. Oral challenge test with chemically unrelated NSAID
D. Oral challenge with non-COX-1 inhibitor
A
3, C, Oral challenge test with chemically unrelated NSAID, p. 1306, Figure 80-3.
The first step is an oral challenge test with a chemically unrelated non-steroidal antiinflammatory drug (NSAID).If positive, patient should be treated as a reactor to multiple
NSAIDs
21
Q
- In the absence of a spacer device, what percentage of inhaled corticosteroid delivered
by a metered-dose inhaler (MDI) or dry powder inhaler (DPI) is delivered to the lungs?
A. 10-20%
B. 30-40%
C. 60-75%
D. 90-100%
A
Chapter 99 Answers:
1. A, 10-20%, p. 1562-1563.
In the absence of a spacer, 10-20% of topical inhaled corticosteroids is delivered to the lungs
by an MDI or DPI with greater than 50% (and up to 90%) of the drug being deposited in the
mouth and pharynx before being swallowed. Use of a spacer and mouth rinsing after
inhaler use can reduce oral deposition by 90%
Chapter 99: Glucocorticoids
Middleton’s Allergy Principles and Practice, 8th Edition
22
Q
2. What is a feature of an inhaled drug (such as an inhaled corticosteroid) with a good therapeutic index? A. High oral bioavailability B. Large particle size C. Low oral bioavailability D. Slow metabolism
A
- C, Low oral bioavailability, p. 1563.
In using inhaled therapies, the goal is to exert effects on local tissue while minimizing
systemic effects and thus side effects. An inhaled drug with a good therapeutic index has
low oral bioavailability, small particle size, rapid metabolism, high clearance, highplasma
protein binding, and low systemic half-life. When designing inhaled corticosteroids,
increasing lipophilicity increases pulmonary tissue retention as well.
23
Q
- Glucocorticoids have which of the following effects on eosinophils?
A. Acutely increase circulating eosinophil numbers
B. Decrease eosinophil chemotaxis
C. Decrease eosinophil degranulation
D. Prevent an increase in blood eosinophil progenitors after antigen challenge
A
- D, Prevent an increase in blood eosinophil progenitors after antigen challenge, p.
1565.
Glucocorticosteroids (GCs) given orally or intravenously cause an acute reduction in
circulating basophils, eosinophils, and monocytes with numbers returning to baseline 24-
48 hours after a single dose. GCs have been shown to prevent eosinophil migration to the
lung and prevent the increase in blood eosinophil progenitors after antigenchallenge. In
vitro studies have shown that GCs also induce eosinophil apoptosis althoughthat has been
difficult to corroborate in vivo. GCs do not modulate eosinophil chemotaxis, adhesion, or
degranulation.
24
Q
- In the airway epithelial cells, glucocorticoids suppress the expression and release of a
number of inflammatory cytokines, chemokines, and growth factors likely by affecting which
transcription factor?
A. FOXP3
B. GATA3
C. NF-κB
D. NOTCH1
A
- C, NF- κB, p. 1566-1567.
Glucocorticoids suppress the expression and release of a host of inflammatory cytokines (eg
IL-1, IL-6, IL-11, GM-CSF, TNF-α,), chemokines (eg CXCL8, CXCL12, CXCL10, growth-regulated
oncogene-α, GRO-γ, CCL2, CCL13, CCL11, 24, 26; CCL17, CCL22, CCL5), and growth factors (eg
TGF-β, PDGF, bFGF, IGF-1) from epithelial cells in vitro and in vivo. This suppression is
thought to be through an effect on NF-κB, whichis reduced in vivo by ICS in some studies. GC
do enhance expression of FOXP3 inducing formation and activation of Tregs but not in
airway epithelium.
25
Q
- A pregnant woman at 31 weeks gestational age presents to the emergency department
with signs of early labor. Measures to stop labor are begun. She is also given
betamethasone and told it will protect her baby’s lungs.
Expression of what protein is enhanced by glucocorticoids, a factor that may be important in
preventing neonatal respiratory distress syndrome?
A. ICAM-1
B. Monocyte chemoattractant protein 4
C. Surfactant protein B
D. Zonula occludens-1
A
- C, Surfactant protein B, p. 1567.
Glucocorticoids enhance the expression of surfactant protein B (SP-B) and SP-C to reduce
airway surface tension which may be important in preventing neonatal respiratory distress
syndrome. Glucocorticoids also induce the expression of SP-A and SP-D, important host
defense collectins.
26
Q
- Inhibitorstargeted at which enzyme have been able to restore glucocorticoid sensitivity
inpatients with steroid refractory asthma?
A. DNase I
B. HDAC6
C. IκB kinase
D. P38 MAPK (MAPK14)
A
- D, P38 MAPK (MAPK14), p. 1573-75.
IL-2, IL-4, and IL-13 can induce glucocorticoid receptor (GR) phosphorylation under the
MAPK14 pathway although the precise mechanisms that result in enhanced activation or
increased expression of MAPK14 in the airways of refractory asthma are unclear.
Phosphorylation of GR in a specific location induced by pro-inflammatory insults and
mediated by the MAPK14 pathway leads to a conformational change in GR which
downregulates GR responses. Patients with severe asthma have inappropriate
overexpression of MAPK14 compared to patients with non-severe asthma, and MAPK
inhibitors have been shown to restore glucocorticoid sensitivity in some of these patients
27
Q
- Which interleukin, associated with neutrophilic asthma, is elevated in sputum and
serum samples from patients with severe asthma and has been shown experimentally
to inhibitcorticosteroid responsiveness in human bronchial epithelial cells?
A. IL-2
B. IL-12
C. IL-10
D. IL-17
A
- D, IL-17, p. 1572-1574.
Neutrophilic asthma, a subset of corticosteroid-refractory asthma, is associated with the
presence of IL-17 and Th17 cells. Many chemokines and neutrophil survival factors are
elevated in response to IL-17, and this chemokine also enhances the production of profibrotic
cytokines and extracellular matrix proteins. In one study, IL-17A pretreatment of cells
attenuated the ability of budesonide to inhibit TNF-α-induced CXCL8 production. IL-17 levels
are elevated in sputum and serum from patient with severe asthma, and sputum IL-17 levels
correlate with sputum neutrophilia.
28
Q
- Supplementation of which vitamin may augment responsiveness to glucocorticoids in
patients with steroid-refractory asthma by increasing steroid-induced T-cell secretion of IL10?
A. Vitamin A
B. Vitamin B2 (Riboflavin)
C. Vitamin B12 (cobalamin)
D. Vitamin D3 (calcitriol)
A
- D, Vitamin D3 (calcitriol), p. 1566, 1573.
Glucocorticosteroids induce the anti-inflammatory gene IL-10 (particularly in Treg cells),
thus inhibiting secretion of cytokines by Th2 cells. Vitamin D3 has been shown to increase
the secretion of IL-10 from Treg cells isolated from patients with steroid-refractory asthma
to comparable levels in patients with non-severe asthma who were treated with
dexamethasone alone. Pediatric patients with severe therapy-resistant asthma have lower
levels of Vitamin D than children with mild or no asthma, and Vitamin D level is inversely
correlated with exacerbations, ICS use, ASM mass, and bronchodilator response, so
supplementation may be beneficial in pediatric patients.
29
Q
9. Which type of receptor is the glucocorticoid receptor? A. Cell surface receptor B. G-protein coupled receptor C. Nuclear receptor D. Tyrosine kinase receptor
A
- C, Nuclear receptor, p. 1569.
The glucocorticoid receptor (GR) is a nuclear hormone receptor and is divided into distinct
functional modules including a ligand-binding domain, a nuclear translocation domain, and
transactivation domains, the latter of which enables GR to associate with transcriptional
coactivators or repressors
30
Q
- 5-lipoxygenase inhibitor zileuton:
A. blocks the production of arachidonic acid.
B. blocks the production of LTB4 and LTC4.
C. promotes the degradation of cysteinyl leukotrienes.
D. promotes the degradation of LTA4.
A
Chapter 100 Answers:
1. B, blocks the production of LTB4 and LTC4, p. 1604.
Since it blocks 5-LO, it also decreases production of LTB4 and this may contributeto the antiinflammatory effect. It is not involved in degradation.
Chapter 100: Antileukotriene Therapy in Asthma
Middleton’s Allergy Principles and Practice, 8th Edition
31
Q
- After allergen challenge, leukotriene receptor antagonists prevent:
A. eosinophil number in the late response.
B. immediate and late response.
C. immediate response only.
D. mucus production.
A
- B, immediate and late response, p. 1605.
Zafirlukast given prior to allergen challenge inhibited the immediate response by80% and the
late response by 50%. It has no effect on eosinophil number after challenge or mucus
production. It does decrease the cellular influx of basophils and lymphocytes.
32
Q
3. Montelukast is FDA approved for use in which of the following atopic conditions: A. allergic rhinitis. B. atopic dermatitis. C. eosinophilic esophagitis. D. food allergy.
A
- A, allergic rhinitis, p. 1610.
Although less efficacious than intranasal steroids, montelukast is approved for both seasonal
and perennial rhinitis in the US. It is also approved for asthma. It has no role in atopic
dermatitis, food allergy or EoE
33
Q
4. The primary toxicity associated with zafirlukast and zileuton affect which organ? A. GI tract B. Heart C. Kidney D. Liver
A
- D, Liver, p. 1610.
Elevated liver enzymes have been seen with zileuton and zafirlukast. Montelukast does not
have this effect. These agents have also been associated with neuropsychiatric changes
