Pharm of Asthma and COPD - Fitzy lecture Flashcards Preview

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Flashcards in Pharm of Asthma and COPD - Fitzy lecture Deck (58):
1

Bronchodilators: Shorter acting selective beta-2 adrenergic receptor agonists

Albuterol
Levalbuterol
Metaproterenol
Terbutaline

2

Bronchodilators: Longer acting selective beta-2 adrenergic receptor agonists

Salmeterol
Formoterol
Indacaterol (COPD)

3

Bronchodilators: Muscarinic receptor antagonists

Ipratropium
Tiatropium

4

Bronchodilators: Methylxanthines

Theophylline
Roflumilast (COPD)

5

Leukotriene modulators - LTC4/D4 receptor antagonists

Montelukast
Zafirlukast

6

Leukotriene Modulators - 5-lipoxygenase inhibitor

Zileuton

7

Anti-inflammatory drugs: corticosteroids

Budesonide
Fluticasone
Beclomethasone
Flunisolide
Mometasone
Prednisone (systemic)

8

Anti-inflammatory drugs: biologicals

Omalizumab (anti- IgE antibody)

9

Asthma controller use

Inhaled and oral agents: used chonically/daily during asymptomatic periods

Limit frequent, severe asthma attacks. Do not replace relievers which must till be used during asthmatic attack

10

Asthma Relievers

Bronchodilators - short acting beta-2 adrenergic receptor agonists, used alone or with controllers

Theophylline

11

Asthma Controllers

Anti-inflammatory - corticosteroids, leukotriene modifiers, anti-IgE antibody

+/- bronchodilators - long-acting beta-2 agonist, anti-cholinergic agent

theophylline

12

Mild intermittent asthma

Attacks: less than 2 per week
Peak Flow: near normal
Long-term control: n/a
Relief: SABA

13

Mild persistent asthma

Attacks: >2/wk
Peak Flow: near normal
Long-term control: Low dose ICS
Relief: SABA

14

Moderate persistent asthma

Attacks: daily
Peak Flow: 60-80% of predicted
Long-term control: Low med dose ICS with LABA
Relief: SABA

15

Severe persistent asthma

Attacks: continual
Peak Flow: less than 60% of predicted
Long-term control: high dose ICS with LABA + others
Relief: SABA

16

Inhaled SABA prn for mild intermittent asthma (Step 1)

Take prn for relief of symptoms.

Onset 5-15 min, lasting 4-6 hr

Use 10 minutes prior to predicted trigger (cold, exercise) to prevent onset of symptoms

17

SABA (inhaled)

Relievers:
Albuterol
Levalbuterol
Metaproterenol
Terbutaline

18

LABA (inhaled)

Salmeterol
Formoterol

Controllers, not relievers

19

Location of action of inhaled B2 agonists

B2 selective adrenergic receptor agonists preferentially act on pulmonary smooth muscle, compared to cardiac smooth muscle

Relax smooth muscle and dilate airways

20

B2 receptor antagonists

harmful on airway, negate any beneficial effects on the heart in asthma patients with heart conditions

Propranolol
Nadolol
Timolol
Pindolol

21

Low dose daily inhaled corticosteroid in mild persistent asthma (Step 2)

Budesonide - high potency
Fluticasone - high potency
Beclamethasone
Mometasone
Flunisolide
Prednisone (systemic, non inhaled)

22

Action of corticosteroids

CSR corticoid receptor when occupied --> dimerization, nuclear transport and gene transcription

Suppress inflammatory genes
Express anti-inflammatory genes
ICS not quick acting

Maximal effect on FEV1 may take 1 week or more

23

Benefits of daily inhaled corticosteroids

Fewer symptoms
fewer severe exacerbations
reduced use of SABA bronchodilators
Improved lung function (improve FEV1 >80% predicted)
Reduced airway inflammation (decline in leukocytes, LTs, cytokines, NO exhalation will decline

24

Complications of corticosteroids

Impair growth in children

oral candidiasis in adults due to localized mucosal immunosuppression

Post-menopausal systemic dosing can aggravate osteoporosis, overuse can confer risk of osteoporosis

25

Systemic glucocorticoids used in asthma

Oral or IV

Prednisone
Prednisolone
Dexamethasone

Taper off after control of severe asthma attacks established

associated with impaired wound healing, psychosis, osteoporosis, HTN, glaucoma

26

Medium dose ICS plus LABA plus SABA prn for moderate persistent asthma (Step 3)

daily attack with FEV1 60-80%

Corticosteroid and B2 receptor agonists

Budesonide/formoterol
Fluticasone/salmeterol

27

Effects of beta adrenergic receptor agonists: SABA and LABA

Decreased blood potassium levels

increases blood sugar levels

28

LABA agonists

Salmeterol, formoterol

not for immediate leave or substitution for anti-inflammatory drugs

beneficial with ICS

Don't use alone as associated with increased risk of death in asthmatic patients

29

Salmeterol black box warning

increased risk of asthma related death, reserve for patients who are not controlled on low-to-medium dose corticosteroid + rescue inhaler

30

Leukotrienes

lipid mediates of inflammation

LTC4 and LTD4 promote inflammation, edema, mucus formation, bronchospasm

Phospholipase A2 converts phospholipids to arachidonic acid

5-lipoxygenase converts AA to LTA4.

Tissue specific isomerases convert to LTB4 and LTC4, LTD4, LTE4

31

Zileuton

LT modifier

inhibits 5-lipoxygenase
inhibits LT biosynthesis

2x daily
approved for children older than 12

32

Zafirlukast

LT modifier

Antagonist of cysteinyl LT receptors

2x daily, approved for children older than 5

33

Montelukast

LT modifier

antagonist of cysteinyl LT receptors

1 x daily, approved for children older than 1

34

LT receptor antagonists in mild persistent asthma (step 2)

alternative to ICS

35

LT receptor antagonists/inhibitor in moderate persistent asthma (step3)

alternative or additive to ICS + LABA

36

Adverse effects of Zileuton

Liver toxicity - elevated ALT

Flu like symptoms - chills, fever, fatigue, myalgias

37

Adverse effects of zafirlukast and montelukast

Liver toxicity - discontinue therapy (Zafirlukast only)

Hypersensitivity - angioedema, rash, eosinophilia

38

Clinical indication for Leukotriene modifiers

first line for patient who will not take or cannot tolerate inhaled corticosteroids

39

Aspirin sensitive asthma

excessive leukotriene production

tend to benefit from leukotrienes modifiers are added to inhaled and/or oral glucocorticoids

40

Exercise induced asthma

zileuton, montelukast, zafirlukast all prevent exercise-induced bronchospasm

41

Omalizumab

recombinant humanized monoclonal antibody targeted against IgE

IgE bound to omalizumab cannot bind to IgE receptor on mast cells and basophils

Used to blunt allergic reaction only when environmental or occupational allergens provoke asthma

42

Omalizumab boxed warning

anaphylaxis as early as 1st dose also beyond 1 year after beginning treatment

43

Theophylline in asthma

oral

If asthma not adequately controlled with conventional doses of ICS + LABA

If pt adheres to oral drug, but not inhaled and montelukast is ineffective

Inhalation difficult (toddlers) and montelukast ineffective

Additive in ICU patients failing to respond to IV corticoids, etc

44

Cellular actions of theophylline

inhibition of PDE4 thus inhibiting breakdown of cAMP

Blockade of adenosine receptors

45

Adverse effects of theophylline

CNS stimulation, nervousness, restlessness, insomnia, tremors, anorexia

Cardiovascular: palpitations, arrhythmias, convulsions

46

COPD vs asthma

alveolar disruption and much worse fibrosis in COPD

Smokers - COPD
younger than 35 - asthma
chronic productive cough - COPD
Breathlessness - persistent and progressive = COPD, variable = asthma

Nocturnal breathlessness - asthma

Diurnal or day-to-day variation of symptoms - asthma

47

Ipatropium and tiatropium MOA

inhibit muscarinic M1-M3 receptors

relieve parasympathetic tone, relieving bronchoconstriction, decrease mucus discharge

foundation for treatment of COPD

Can be used in asthma, but less effective than B2 adrenergic receptor agonists (SABA or LABA)

48

Vagus nerve

innervates airways, releases ACh causing pulmonary sm. m. constriction and increase mucus discharge

49

Ipratropium

inhaled
short acting - 6 hrs, dose 3-4 x/day
quick onset - 15 min

Less selective M1-M3 antagonist

Quaternary amine +
peripheral effects
NOT CNS due to charge

50

Tiotropium

Inhaled
Long acting, once per day dose
Onset 30 min

More selective, M1 and M3

Quaternary amine +
Peripheral effects
NOT CNS due to charge

51

Gold stages for COPD

I - intermittent symptoms
II - persistent symptoms
III - frequent exacerbations
IV - respiratory failure

52

Stage I bronchodilators for COPD

Short acting
Ipratropium, albuterol or combination

53

Stage II bronchodilators for COPD

Long acting and short acting

Tiotropium and albuterol

Salmeterol or formoterol + ipratropium, albuterol, or combination

54

Stage III bronchodilators for COPD

Long acting - 2 mechanisms

Tiatropium + salmeterol or fomoterol

55

Stage IV bronchodilators for COPD

Add inhaled corticosteroid to long acting

Tiatropium
Budesonid/formoterol
Fluticasone/salmeterol

56

Roflumilast

PDE4 inhibitor

reduce risk of COPD exacerbation in patients with frequent exacerations

57

Leukotriene modifiers in COPD

No role of leukotriene modifiers and mast cell stabilizers in management of COPD

58

Glucocorticosteroids in COPD

chronic treatment with systemic glucocorticosteroids avoided because of unfavorable benefit to risk ratio