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Block 9 Week 4 > Singer: Bronchodilator Therapy > Flashcards

Singer: Bronchodilator Therapy Flashcards

1
Q

What is the cellular mechanism of asthma?

A

allergen –> activates mast cells, dendritic cells, TH2 cells –> inflammation

vagal stimulation from sensory nerves causes vasoconstriction

epithelial shedding

mucous hypersecretion

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2
Q

The vagal nerve is involved in (blank)

A

bronchoconstriction

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3
Q

Why might you have an increased FEV1 in mild asthma?

A

you actually get hypertrophy and hyperplasia, which gives you more muscle to exhale forcefully

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4
Q

What then happens to FEV1 in moderate and severe asthma?

A

it decreases

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5
Q

Asthma is an inflammatory disease coupled with changes in (blank)

A

airway smooth muscle

**hypertrophy, hyperplasia

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6
Q

There is very little inflammation involved in COPD. Really what is happening is bronchioles are losing their shape and becoming clogged with mucous. So are anti-inflammatory therapies useful?

A

no - patients are largely resistant to corticosteroids

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7
Q

3 reactions in COPD

A

fibrosis of small airways
alveolar wall destruction
mucus hypersecretion

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8
Q

There is some evidence that (blank) may play a role in the development of asthma

A

epigenetics (allergens, antibiotics, pollution, diet)

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9
Q

Routes of drug delivery to the lungs

A

inhaled - direct effect on lungs

swallowed - thru GI tract, liver, can get into systemic circulation and cause side effects

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10
Q

3 bronchodilators used to treat asthma

A

Beta2 adrenergic agonists
theophylline
anti-cholinergics

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11
Q

List some beta 2 agonists

A 
NE
epi
isoproterenol
albuterolol
salmeterol
formoterol
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12
Q

How do beta agonists work?

A

bind to Beta-2 receptors –> activate Gs –> increase in cAMP –> increase protein kinase A –> LOWER INTRACELLULAR Ca+ –> less constriction

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13
Q

Beta-2 agonists have other effects, too. Name a few.

A

Prevent mediator release from mast cells
Prevent microvascular leakage and edema
Increase mucous secretion from submucosal glands and ion transport across airway epithelium
Reduction in neurotransmission in human airway cholinergic nerves by an action at presynaptic b2 receptors to inhibit acetylcholine release.

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14
Q

Short acting beta agonist

Drug of choice of acute attacks

A

albuterol

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15
Q

Long acting beta agonists

Always used in combo with corticosteroids in asthma

A

Salmeterol

Formoterol

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16
Q

Negative side effects of Beta 2 agonists

A

Muscle tremor

Tachycardia

Hypokalemia

Restlessness

Hypoxemia

**Increased mortality with LABA

Seizures with theophyilline

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17
Q

How do methylxanthines work?

A

inhibit phosphodiesterases and adenosine

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18
Q

What methylxanthine should we remember?

A

theophylline

**like caffeine in structure

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19
Q

What is one thing we should remember about theophylline?

A

it causes seizures

20
Q

What effects do methylxanthines (theophylline) have on the lung?

A

decreases inflammatory cells
causes bronchodilation
decreased leak

21
Q

Other effects of methylxanthines?

A

CNS – increased alertness, reduced fatigue, tremor, insomnia, anxiety

Cardiovascular – increased cardiac contractility, reduced peripheral vascular resistance

Metabolic –diuresis, increased basal metabolic rate

**think of the effects of coffee

22
Q

How is theophylline administered?

A

orally or IV

23
Q

Why is theophylline not used often?

A

increased clearance in children and marijuana smokers **induces CYP12

reduced clearance in liver disease, heart failure, pneumonia

reduced clearance w co-administration of anti-heart burn meds

24
Q

Side effects of theophylline?

A 
nausea
vomiting
gastric discomfort
diuresis
behavioral disturbances
cardiac arrhythmias
epileptic seizures
25
Q

What muscarinic receptors are involved in the airway?

A

M1, M2, M3

26
Q

prototypical nonselective inhibitor of cholinergic transmission
tertiary ammonium derivative that has system effects

A

atropine

27
Q

nonselective inhibitor of cholinergic receptors
quaternary ammonium derivative
can be combined with albuterol (Combivent)

A

Ipratropium (Atrovent)

28
Q

Inhibits M1, M2, M3 receptors but dissociates quickly from M2
Also quaternary ammonium derivative

A

Tiotropium (Spiriva)

29
Q

What do muscarinic receptor antagonists do for pts with COPD?

A

contol vagal tone –> decrease constriction of airways

30
Q

What are some side effects of anti-cholinergics?

A

Ipratropium –> bitter taste, can precipitate glaucoma

Triotropium –> dry mouth

31
Q

Inhaled corticosteroids we should know

A

Beclomethasone
Budesonide
Fluticasone

32
Q

How do corticosteroids work?

A

repress gene transcription –> via deacetylation –> less inflammatory response

33
Q

Corticosteroids not only decrease inflammatory immune cells, what else do they do?

A

act on epithelial cells to decrease cytokines and mediators
decrease leak
increase Beta receptors
decrease mucous secretion

34
Q

Formulated as a pro-drug, which is activated once it’s inhaled

A

beclomethasone

35
Q

These corticosteroids have greater first pass metabolism

They have less systemic effects and less adverse effects

A

Fluticasone

Budesonide

36
Q

Local side effects of inhaled corticosteroids?

A

oropharyngeal candidiasis

cough & dysphonia

37
Q

Systemic side effects of inhaled corticosteroids?

A 
Adrenal suppression and insufficiency	
Growth suppression	
Bruising	
Osteoporosis	**esp w long term treatment
Cataracts	
Glaucoma	
Metabolic abnormalities (glucose, insulin, triglycerides)
Psychiatric disturbances (euphoria, depression)	
Pneumonia
38
Q

Which leukotriene antagonist should we be aware of?

A

Montelukast

39
Q

How to leukotriene antagonists work?

A

block leukotriene receptors –> prevent bronchoconstriction, eos recruitment, mucus secretion, plasma leakiness

40
Q

How is Montelukast administered? Who is it commonly used in?

A

orally;
widely used to treat children
good for mild/moderate asthma and aspirin-sensitive asthma

41
Q

The newest therapy for asthma?

A

anti-IgE

42
Q

What anti-IgE drug should we be aware of?

A

Omalizumab

43
Q

When should Omalizumab (anti-IgE antibody) be used for asthma?

A

severe asthma that doesn’t respond to inhaled corticosteroids or long-acting beta agonist

**expensive, and must be injected every 2-4 weeks

44
Q

For a pt with mild, well controlled asthma, what should you prescribe?

A

albuterol

45
Q

If the asthma is a little worse than mild, what should you prescribe?

A

low dose ICS

leukotriene antagonist

46
Q

If asthma is really severe, what should you use?

A

Omalizumab

or

long-term oral corticosteroid

47
Q

Newer option for asthma, which burns open airways essentially

A

bronchial thermolplasty

Block 9 Week 4 (8 decks)

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