Drug-Induced Pulmonary Disease Flashcards Preview

Pharmacology II > Drug-Induced Pulmonary Disease > Flashcards

Flashcards in Drug-Induced Pulmonary Disease Deck (67):
1

How many medications can cause lung injury?

350 and they all manifest in a variety of ways

2

What is the most common drug induced respiratory problem?

Drug-induced bronchospams

Usually seen in patients with pre-existing bronchial hyper-reactivity

3

What are the mechanisms of bronchospams?

Anaphylaxis (IgE-mediated)
Penicillins
Sulfonamides
Serum
Cephalosporins
Can occur with any drug

Cyclooxygenase inhibition
Aspirin/NSAIDs

Pharmacologic effects
β -adrenergic blockers

Direct airway irritation
Smoke
N-acetylcysteine

4

What is the aspirin triad (Samter's syndrome)?

Asthma
Nasal Polyps
And aspirin intolerance

5

Aspirin/NSAID bronchospasm- presentation

Bronchospasm, rhinorrhea, conjunctivitis, flushing
Urticaria, periorbital edema, abdominal pain
Can present separately or blended

6

Aspirin/NSAID bronchospasm- sx resolution

Diminish within 24-48 hours
urticaria may continue 1-2 wks.

7

Aspirin/NSAID bronchospasm- diagnosis

No in vitro diagnostic test to confirm or establish aspirin sensitivity
Provocation challenge
Respiratory reactions
30 -150mg (average 60 mg)
Completed in hospital

8

Aspirin/NSAID bronchospasm- management

Avoid aspirin and nonselective NSAIDs
Cross sensitivity
Ibuprofen (98%)
Naproxen (100%)

9

Aspirin/NSAID bronchospasm- desensitization and leukotriene modifiers

Elimination of reactions by slowly increasing doses of oral aspirin

Leukotriene modifiers
Dose response curve shifted

10

Aspirin/NSAID bronchospasm- therapy options

Therapy options
COX-2 selective NSAIDs (Celecoxib)
Generally can be used safely in patients with ASA induced asthma
Acetaminophen
5% of ASA sensitive patients react
< 1000 mg

11

Aspirin/NSAID bronchospasm- cross-sensitivity

Up to 80% of ASA-sensitive patient had AE to yellow azo dye tartrazine (FD&C Yellow No.5)
Colors food, drinks, drugs, cosmetics
FDA requires labeling

12

The use of ________ might increase the risk of asthma and allergic disease when used early in life?

Acetaminophen

13

Beta blocker bronchospasm

Effects seen with oral, IV or ophthalmic administration
Rarely seen in patients without pulmonary disease
Reaction can be fatal
Primarily with non-selective β-blockers
Patients taking β -blockers without incident for long periods of time may experience fatal asthma attacks

14

Beta blocker bronchospasm- symptoms

Symptoms
Increased pulmonary symptoms
Decreased pulmonary function tests
Decrease in FEV1 or peak expiratory flow
Death

15

Beta blocker bronchospasm- Mechanism

Direct inhibition of β2-receptors may result in bronchoconstriction

16

Beta blocker bronchospasm- management

Inhaled bronchodilator for bronchospasm
Avoidance
If necessary, use selective β-blockers
Use lowest dose possible

17

Will treatmeant with beta blockers in patients with COPD reduce the risk of exacerbations and improve survival?`

It might

18

Sulfite induced bronchospasm

Potassium metabisulfite
Preservative in food and wine
Injectable epinephrine, isoproterenol
Rare in general population
1-5% in patients with asthma

19

Sulfite induced bronchospasm- patient presentation

Severe wheezing, chest tightness and dyspnea after ingestion

20

Sulfite induced bronchospasm- Diagnosis

History
Re-challenge- in a controlled setting

21

Sulfite induced bronchospasm- mechanism

Sulfite converted to sulfur dioxide in acidic or warm environment
Sulfur dioxide causes direct stimulation of parasympathetic receptors
IgE-mediated (anaphylactic reactions)
Reduced concentration of sulfite oxidase enzyme reported in sulfite-sensitive asthma patients
Catalyzes oxidation of sulfites to sulfates

22

Sulfite induced bronchospasm- management

Avoidance
Read labels
Pharmacologic agents
» Manufacturers of drugs for the treatment of asthma have discontinued use of sulfites
Food products
» Labeling required on packaged foods that contain sulfites at 10 ppm or more

23

Sulfite induced bronchospasm- pretreatment

Cromolyn, anticholinergics, cyanocobalamin

24

Inhaled agents bronchospasm

Nonspecific bronchial irritant effect
Usually NOT caused by medication
Propellant, delivery, pH, osmolality, temperature, preservative
Albuterol, cromolyn, inhaled corticosteroids, pentamidine, N-acetyl cysteine

25

Is the bronchospasm from inhaled medications caused by the medication itself?

No its caused by the other chemicals that are in the drug

26

Inhaled agents- bronchospasm- Ethylenediamine tetraacetic acid (EDTA)

Stabilizing agent
Mechanism
Calcium chelation property
Benzalkonium chloride
Bacteriostatic agent
Found in some albuterol nebulization multi-dose vials

Mechanism
Mast cell degranulation

Management
Change therapy

27

Ace Inhibitors-cough- risk factors

Female
Asian descent
Elderly
Heart failure

28

Do patients with asthma or COPD appear to be at an increased risk for development of a cough with ace inhibitor use?

No

29

Ace Inhibitors-cough- symptoms

Cough
Tickle to debilitating cough with insomnia and vomiting
Dry, nonproductive, hacking cough
Patients have normal spirometry and chest xray

30

Ace Inhibitors-cough- mechanism

Not fully known
Usually attributed to accumulation of bradykinin and substance P
Bradykinin
Stimulate cough reflex
Substance P
Cause bronchoconstriction

31

Ace Inhibitors-cough- management

Cough may resolve within a few weeks
Usually stop medication
Cough resolves within a few days to a month after discontinuation
Usually unresponsive to cough suppressants or bronchodilators

32

Fentanyl cough

IV formulation
Unclear mechanism
Associated with young age and absence of smoking
History of asthma/COPD not predictive

33

What is narcotic induced non-cardiogenic pulmonary edema most commonly assoiciated with?

IV heroin use
Also can be seen with morphine, methadone, meperidine, and propoxyphene

34

Narcotic induced non-cardiogenic pulmonary edema- mechanism

Idiosyncratic reaction
Often seen when Moderate and high doses are used
Mechanism is unknown

35

Narcotic induced non-cardiogenic pulmonary edema- sx

May be comatose with depressed respirations, dyspnea and tachypnea
Varies from cough to severe cyanosis and hypoxia
Decreased pulmonary function tests
Appear within minutes of IV administration up to 2 hours

36

Narcotic induced non-cardiogenic pulmonary edema- treatment

Clinical improvement within 24-48 hours
Pulmonary function abnormality may last up to 12 weeks
Treatment
Naloxone, oxygen, ventilatory support
Mortality less than 1%

37

What is the presentation of pulmonary edema?

Persistent cough
Tachypnea
Dyspnea
Tachycardia
Rales on auscultation
Hypoxemia
Decreased lung compliance

38

What is pulmonary edema reported with?

Hydrochlorothiazide
Contrast media
IV bleomycin, cyclophosphamide and vinblastine (oncology agents)
Terbutaline (used as tocolytic)
Salicylate overdose

39

What is the management for pulmonary edema?

DC medication, supportive care

40

What is pulmonary infiltrates with eosinophilia most frequently associated with?

Nitrofurantoin
Para-aminosalicylic acid (not a drug that you will rx to pts, anti-infective topical)

41

Pulmonary esoinophilia- presentation

Fever, nonproductive cough, dyspnea, cyanosis, bilateral pulmonary infiltrates and eosinophilia in blood

42

Pulmonary eosinophilia- nitrofurantoin

Occurs within 1 month of therapy
Complete recovery within 15 days of DC of medication

43

What is excessive amount of connect tissue in the the intersitial spaces of the lung?
Hint- normal airspaces and blood vessels are replaced by fibrotic tissue; lungs become small and stiff and is secondary to chronic inflammatory dz?

Chronic pulmonary fibrosis

44

What can chronic pulmonary fibrosis lead to?

Restrictive airway disease
Can be fatal if process is not stopped

45

Pulmonary fibrosis- causes

Idiopathic pulmonary fibrosis is rare

Drug induced pulmonary fibrosis
~ 50 causative agents

Prevalence increases with increasing cumulative dose

46

What are the chemotherapeutic agents that cause pulmonary fibrosis?

Bleomycin
Busulfan
Carmustine
Methotrexate
Amiodarone- not chemo but causes pulmonary fibrosis

47

Pulmonary fibrosis-acute phase

Non-productive cough
Acute dyspnea
Tachypnea
Lung crackles
PFTs- Initially normally, reduced carbon dioxide diffusing capacity
Arterial blood gases- Hypoxemia

48

Pulmonary fibrosis- chronic phase

Slow progression
Dyspnea on exertion
Fatigue
Non-productive cough
Lung crackles
Clubbing

PFTs
Restrictive disease, decreased vital capacity
Reduced carbon monoxide diffusing capacity

49

Pulmonary fibrosis- time of onset

Acute sx have been seen after 1st dose of bleomycin
Patients have died up to 15 years after receiving therapy.

50

Pulmonary fibrosis- diagnosis

Known exposure to causative drug
No known symptoms, physical findings, laboratory tests or histopathologic findings specific to pulmonary fibrosis

51

Pulmonary fibrosis- management

Discontinuation of medication
+/- prednisone

52

Amiodarone pulmonary toxicity- risk factors

Men
Increases with age
Pre-existing lung disease
Dose/duration- Usually >400 mg/day; seen with 200 mg/day for 6-12 months
Occurs 4 weeks to 6 years after initiating therapy

53

Amiodarone pulmonary toxicity- clinical course

Variable- some patients don’t do that bad and some do really bad
Progressive dyspnea, malaise, nonproductive cough
Rapidly progressive acute respiratory distress syndrome

54

Amiodarone pulmonary toxicity- proposed mechanism

Accumulation of amiodarone and metabolite in lung tissue
Interfere with normal processing of phospholipids
Breakdown of phospholipid-laden macrophages results in pulmonary inflammation and fibrosis

55

Amiodarone pulmonary toxicity- monitoring

Monitor PFTs and CXR at baseline
CXR every year
PFTs if symptomatic

56

Amiodarone pulmonary toxicity- management

Majority of patients improve with DC of medication
Clinical improvement 1-2 months
PFTs and CXR may take up to 18 months
+/- corticosteroids

57

What are the medications that cause pulmonary HTN?

Anorexic agents- used for weightloss
Fenfluramine and dexfenfluarmine (not on the market)
Part of “fen-phen”
Phentermine
20% of diagnosed cases
Onset between 23 days and 27 years

58

Pulmonary HTN- symptoms

Generally non-specific
Exertional dyspnea: most common
Chest pain
Syncope

59

Pulmonary HTN- mechanism

unknown

60

Pulmonary HTN- Management

DC medication
Improvement within 1-3 months

1997: FDA requested withdrawal of fenfluramine and dexfenfluamine (valvular damage)

Phentermine
Case reports of pulmonary hypertension
Association not supported

61

Oxygen toxicity- presentation

Cough, chest pain, dyspnea
Masked in ventilator dependent patients
Lungs become progressively stiffer
Ability to oxygenate is compromised

62

Oxygen toxicity- normal cellular respiration

Oxidants are counterbalanced by antioxidant defense system (prevents tissue destruction)

63

Oxygen toxicity- excess oxygen (hyperoxia)

Produces highly reactive, partially reduced oxygen metabolites
Superoxide anion, hydrogen peroxide, hydroxyl radical, singlet oxygen, hypochlorous acid
Overwhelm antioxidant system

64

Oxygen toxicity- lung damage determinants

Fraction of inspired oxygen--50-100%
Duration of exposure- Inversely proportional to fraction of inspired oxygen

65

Oxygen toxicity- lung damage

Acute phase: edema with alveolar hemorrhage
Subacute or chronic phase: collagen and elastin deposition in alveolar walls

66

What does the lung damage in oxygen toxicity lead to?

Thickening of gas exchange area and fibrosis

67

Oxygen toxicity-course

+/- improvement in lung function
May see improvement months to years following exposure