Crr Week 7: Respiratory Pharmacology (Blair)

Front 1

Drugs that are used to treat asthma are divided into which 2 broad categories?

Back 1

1. Short-term relievers
2. Long-term controllers

Front 2

How do "long-term controllers" work?

Back 2

Reduce airway obstruction by reducing inflammatory and immune response

Front 3

What is the primary goal of medical treatment for asthma?

Back 3

To open the airways, either by dilating them or alleviating airway obstruction

Front 4

List 2 responses to inhaled irritants.

Back 4

1. Irritants can excite sensory endings that elicit reflex bronchoconstriction through parasympathetic pathways that constrict airway smooth muscles.

2. Irritants can cause the release of mediators from mast cells that produce immune and inflammatory responses, ultimately narrowing airways.

Front 5

In general, how do "short term relievers" work?

Back 5

They relax smooth muscle in the airways

Front 6

What is the MOA of B2-selective drugs?

Back 6

Relieve bronchoconstriction by relaxing airway smooth muscle via the cAMP pathway

Front 7

List 3 examples of short-acting B2-selective drugs used for asthma.

Back 7

1. Albuterol
2. Terbutaline
3. Metaproterenol

Front 8

How are the short-acting B2-selective drugs administered? (common route of administration)

When does maximum bronchodilation occur and how long does it last?

Back 8

Metered-dose inhalers

*Maximum bronchodilation after 15 - 30 minutes and lasts 3 -4 hours

Front 9

Which B2-adrenergic drugs are available as tablets?

When are these prescribed?

Back 9

1. Albuterol
2. Terbutaline

*Only prescribed if a patient cannot use an inhaler

Front 10

Which B2-adrenergic drug can be administered subcutaneously?

When is this done?

Back 10

Terbutaline

This route is for emergency cases of severe asthma when an inhaler cannot be used

Front 11

What are the most widely used drugs for the relief of acute asthmatic attacks?

Back 11

B2-selective drugs
(Albuterol, Terbutaline, Metoproterenol)

Front 12

The B2-adrenergic drugs contain both R and S isomers, but only one of the isomers binds to the B2 receptor-- which one?

Back 12

R isomer binds to the B2 receptor

Front 13

What is the MOA of antimuscarinic drugs?

Back 13

Block muscarinic receptors, preventing parasympathetic stimulationg (airway constriction and mucus secretion)

Front 14

List 2 antimuscarinic drugs.

Back 14

1. Ipratropium
2. Tiotropium

Front 15

How are the antimuscarinic drugs administered?

Back 15

Both drugs are given by inhalation

Front 16

What does the effectiveness of the antimuscarinic drugs depend on?

Back 16

The degree of parasympathetic bronchoconstriction
(can vary from patient to patient)

Front 17

Even if the initial relief of bronchoconstriction is modest with the use of antimuscarinic drugs, why may the drugs still be useful?

Back 17

Because they can block the reflex constriction elicited by irritants

Front 18

Which group of drugs produces more airway dilation -- B2-agonists or antimuscarinic drugs?

Back 18

B2-agonists produce more dilation

*Antimuscarinics are useful in people who cannot tolerate B2-agonists and they may add to the dilation produced by B2-agonists.

Front 19

Which antimuscarinic drug has a longer half life and can be administered less frequently?

Back 19

Tiotropium

Front 20

What are the adverse effects of antimuscarinic drugs?

Back 20

Typically the effects are minimal with inhalation, but may include anticholinergic effects like:
1. Dry mouth
2. Sedation

Front 21

What is the MOA of methylxanthines?

Back 21

(not established conclusively)
May involve blockade of Phosphodiesterase 4 (PDE4)

*PDE4 hydrolyzes cAMP; thus, inhibition of PDE4 leads to enhanced levels of cAMP with resultant airway dilation

*Also, the blockage of PDE4 reduces the release of cytokines and chemokines from inflammatory cells, inhibiting the immune response

Front 22

List 2 methylxanthine preparations.

Back 22

1. Aminophylline
2. complex of Theophylline

Front 23

What type of drug is Aminophylline?

Back 23

Methylxanthine

Front 24

What type of drug is Theophylline?

Back 24

Methylxanthine

Front 25

What type of drug is Ipratropium?

Back 25

Antimuscarinic

Front 26

What type of drug is Tiotropium?

Back 26

Antimuscarinic

Front 27

What type of drug is Terbutaline?

Back 27

B2-agonist

Front 28

How are the methylxanthines administered?

Back 28

Orally

Front 29

Which asthma drugs have a narrow therapeutic index?

Back 29

Methylxanthines

Front 30

What is the limitation of methylxanthines?

These drugs tend to be prescribed to what kind of patients?

Back 30

1. Serious potential adverse effects (including death)
2. Need to measure plasma levels

*Prescribed to patients who cannot afford other drugs and who live in areas where blood levels can be monitered

Front 31

What are the adverse effects of methylxanthines?

Back 31

1. CNS --> Cortical arousal (insomnia, tremor, nervousness, anorexia, HA, anxiety, seizures)
2. Cardiovascular --> (+)chronotropic and inotropic effects = arrythmias
3. GI --> nausea, vomiting, abdominal discomfort

Front 32

What is the MOA of systemic corticosteroids?

Back 32

1. Inhibit production of inflammatory cytokines
2. Reduce bronchial reactivity to airway irritants
3. *Reduce migration of lymphocytes, eosinophils, and mast cells into the airways <-- MAJOR EFFECT

Front 33

List 2 examples of systemic corticosteroids used for treating asthma.

Back 33

1. Prednisone
2. Methylprednisone

Front 34

Are systemic corticosteroids used as long-term controllers of asthma?

How long are they used?

Back 34

NO.

*Only used in urgent treatment of asthma in patients who do not respond adequately to bronchodilators or who get worse with maintenance therapy

*Used for a maximum of 10 DAYS

Front 35

List 6 groups of long-term controllers of asthma

Back 35

1. Long acting B2-agonists
2. Inhaled corticosteroids
3. Possible chloride channel inhibitors
4. Leukotriene pathway inhibitors
5. Anti-IgE monoclonal antibody
6. Combination therapy

Front 36

Why do the long-acting B2 agonists last longer than the short-acting B2-agonists?

Back 36

Due to high lipid solubility that allows them to anchor to the cell membrane near the B2-receptor.

Front 37

List 2 long-acting B2-agonists.

Back 37

1. Salmeterol
2. Formoterol

Front 38

Can the long-acting B2-agonists be used for acute asthma attacks?

Back 38

NO.

Front 39

Why are long-acting B2-agonists often used with corticosteroid inhalers for long-term management of asthma?

Back 39

Because the B2-agonists do not have anti-inflammatory actions

Front 40

What are the adverse effects of long-acting B2-agonists?

Back 40

1. Skeletal muscles tremors
2. Arrythmias

*In some patients with genetic variations of the B receptor, long-term use of the drugs may increase incidence of asthma mortality

Front 41

What type of drug is Salmeterol?

Back 41

Long-acting B2-agonist

Front 42

What type of drug is Formeterol?

Back 42

Long-acting B2-agonist

Front 43

List 3 types of inhaled corticosteroids used for asthma treatment.

Back 43

1. Beclomethasone
2. Fluticasone
3. Triamcinolone

Front 44

List 2 types of systemic corticosteroids used for asthma treatment.

Back 44

1. Prednisone
2. Methylprednisolone

Front 45

What type of drug is Beclomethasone?

Back 45

Inhaled corticosteroid

Front 46

What type of drug is Fluticasone?

Back 46

Inhaled corticosteroid

Front 47

What type of drug is Triamcinolone?

Back 47

Inhaled corticosteroid

Front 48

Chronic use of inhaled corticosteroids has what sort of benefits for treating asthma?

Back 48

1. Reduces inflammatory response
2. Reduces airway reactivity to irritants

Front 49

Why is patient compliance an issue with inhaled corticosteroids?

Back 49

Patients have heard about the adverse effects of SYSTEMIC corticosteroids and stop taking the drugs.

Front 50

What are some adverse effects of inhaled corticosteroids?

Back 50

1. Cough upon inhalation
2. *Oral thrush (oropharyngeal candidiasis
3. Osteoporosis
4. Cataracts

Front 51

Oral thrush can develop from the use of which asthma treatment?

How can this be alleviated?

Back 51

Inhaled corticosteroids

*Rinse out mouth after each dose

Front 52

List 2 chloride channel inhibitors

Back 52

1. Cromolyn
2. Nedocromil

Front 53

What type of drug is Cromolyn?

Back 53

Cl- channel blocker

Front 54

What type of drug is Nedocromil?

Back 54

Cl- channel blocker

Front 55

How are the chloride channel blockers administered?

Back 55

Inhalation

Front 56

Which group of drugs can be used acutely before a bout of exercise or before exposure to a known allergen to reduce the likelihood and intensity of an asthmatic attack?

Back 56

Cl- channel blockers

Front 57

Why are Cl- channel blockers not used as much currently?

Back 57

Because they are not as predictively effective as inhaled corticosteroids

Front 58

Due to their safety, which anti-asthmatics are used for maintenance therapy in children?

Back 58

1. Cl- channel blockers (not used as much anymore)
2. Leukotriene pathway inhibitors (especially Montelukast)

Front 59

Which anti-asthmatics can be used to reduce the frequency of episodes of asthma that occur during the night?

Back 59

1. Cl- channel blockers (not used as much anymore)
2. Leukotriene pathway inhibitors

Front 60

What are the adverse effects of Cl- channel inhibitors?

Back 60

No significant adverse effects!

*This is a major reason why they were used in children. Although today, inhaled corticosteroids are more commonly used

Front 61

What is the MOA of Zileuton?

Back 61

(leukotriene pathway inhibitor)

*Blocks 5-lipoxygenase, preventing the SYNTHESIS of leukotrienes

Front 62

What is the MOA of Zafirlukast and Montelukast?

Back 62

Block LTD4 RECEPTORS that mediate bronchoconstriction, increased airway reactivity, mucosal edema, and increased secretion of mucus.

Front 63

List 3 anti-asthamtics that are leukotriene pathway inhibitors.

Back 63

1. Zileuton
2. Zafirlukast
3. Montelukast

Front 64

What type of drug is Zileuton?

Back 64

Leukotriene pathway inhibitor

Front 65

What type of drug is Zafirlukast

Back 65

Leukotriene pathway inhibitor

Front 66

What type of drug is Montelukast?

Back 66

Leukotriene pathway inhibitor

Front 67

How are the leukotriene pathway inhibitors administered?

Back 67

Orally

Front 68

What is a MAJOR advantage of the leukotriene pathway inhibitors?

Back 68

They can be administered orally
(some people have difficulty operating inhalers)

Front 69

Are leukotriene pathway inhibitors equally effective as inhaled corticosteroids in reducing the frequency of occurrences of asthmatic attacks?

Back 69

Yes, they are equally effective in this regard

*However, their effects on the symptoms of asthma are not as pronounced as the inhaled corticosteroids

Front 70

What is the mechanism of action of the Anti-IgE monoclonal antibody?

Back 70

1. Inhibits the binding of IgE to mast cells
2. May inhibit the synthesis of IgE by B-lymphocytes

*Reduces the immune response to allergens

Front 71

Which drug is an anti-IgE monoclonal antibody?

Back 71

Omalizumab
(used for long-term treatment of asthma)

Front 72

Why is the use of Omalizumab so limited?

Back 72

It is VERY expensive
($10,000 - $30,000 per year!)

Front 73

For which patients is Omalizumab used?

Back 73

Only used in people with:
1. severe asthma
2. frequent exacerbations
3. asthma that cannot be controlled adequately by high dose corticosteroids

Front 74

What are the adverse effects of Omalizumab?

Back 74

1. Anaphylaxis
2. May slightly increase the risk of cancer

Front 75

List 2 combination therapies for treating asthma.

Back 75

1. Fluticasone and salmeterol
2. Budesonide and formoterol

*inhaled corticosteroids + B2-agonists

Front 76

While taking combination drugs to treat severe asthma, patients should be advised to continue to take which drug for acute asthmatic attacks?

Back 76

Albuterol

Front 77

What is the adverse effects of combination anti-asthmatics?

Back 77

Small risk of fatal asthma attacks (FDA black box warning)

Front 78

How are acute exacerbations of COPD treated?

Back 78

Ipratropium
(drug of choice for producing bronchodilation because it seems to work better than a B2-agonist in most patients)

*If the exacerbations are due to bacterial infections, then broad-spectrum antibiotics are used

Front 79

Which drugs are used for long-term relief of COPD?

Back 79

1. Long-acting B2-agonists (Salmeterol, formoterol)
2. Long-acting anticholinergics (Tiotropium)

*Reduce exertional dyspnea

Front 80

How does the effectiveness of inhaled corticosteroids used for COPD compare to when they are used for asthma?

Back 80

They are less effective when used to treat COPD

Front 81

If a COPD patient has frequent bouts of dyspnea, which group of drugs can be used for relief?

Back 81

Inhaled corticosteroids

Front 82

The CDC recommends which vaccine for all people with COPD?

Back 82

Pneumococcal vaccine

Front 83

Eventually, most people with COPD will require _____ to relieve breathlessness.

Back 83

Oxygen

Front 84

What is the key to the reduction of COPD?

Back 84

Help patients stop smoking

Front 85

Discuss the length of counseling sessions that can have a positive impact on the cessation of smoking

Back 85

Sessions > 10 minutes are effective
Sessions lasting only 3 minutes are better than no discussion

Front 86

What is the most effective therapy for smoking cessation?

Back 86

Counseling combined with pharmacotherapy

Front 87

How are all of the nicotine replacement products designed for smoking cessation?

Back 87

Designed to prevent the:
1. Craving for tobacco
2. Signs of withrdrawl

Front 88

How should Nicorette gum be used?

Back 88

Chewed slowly until taste occurs, and then the gum should be "parked between the cheek and gums to facilitate absorption of nicotine.

*Chew on a consistent schedule of at least one piece every 1-2 hours for at least 1-3 months.

Front 89

List 2 types of nicotene patches

Back 89

1. Nicotrol
2. Nicoderm

Front 90

How are the nicotene patches used?

Back 90

They are applied when the patient wakes up in the morning

There are two versions-- a 16 hour and a 24 hour patch
*The 24 hour patch should be used first, but if the patient's sleep is being disrupted, the 16-hour patch should be used instead

Front 91

Which type of nicotene replacement therapy is a nasal spray formulation?

What is the minimum recommended treatment?

What is the maximum treatment?

Back 91

Nicotrol
(also formulated as a patch)

*Minimum treatment is 8 doses per day

*Maximum treatment is 40 doses per day; 5 doses per hour

Front 92

Which type of nicotene replacement therapy can be used as a lozenge?

Back 92

Nicorette
(also used in nicotine gum)

Front 93

How often should nicotene lozenges be used?

Back 93

Use at least 9 lozenges per day for the first 6 weeks, and then the patient can taper off for the remaining 6 weeks of therapy

Front 94

What is the primary side effect of nicotene lozenges?

Back 94

Nausea

Front 95

Is nicotene release more controlled with a gum or lozenge?

Back 95

Lozenge

Front 96

How long is the typical duration of nicotine replacement therapy?

Back 96

Usually 3 months
(longer duration may be necessary in some patients)

Front 97

What is the most common side effect with the nicotine patch?

Back 97

Skin irritation

Front 98

What are the adverse side effects of all nicotine replacement products?

Back 98

(mild side-effects)

1. Nausea
2. Lightheadedness
3. Sleep disturbances

Front 99

List 2 drugs that are FDA approved for smoking cessation that do not replace nicotine?

Back 99

1. Buproprion
2. Varenicline

Front 100

What is the MOA of Buproprion?

Back 100

1. Blockade of NE and dopamine uptake
2. Blockade of nicotinic receptors

Front 101

Which drug was originally developed as an antidepressent but was found to help smoking cessation?

Back 101

Bupropion

Front 102

How long is Bupropion used for smoking cessation?

Back 102

7 - 12 weeks, with maintenance therapy for up to 6 months

Front 103

What are the adverse effects of Bupropion?

Back 103

1. Seizures
2. Depression
3. Agitation
4. Anxiety
5. Suicidal ideation/ attempted suicide

Front 104

What is the MOA of Varenicline?

Back 104

Partial agonist at nicotinic receptors
*Bind to the receptors with a greater affinity than nicotine, but produced less of an effect as nicotine.

Front 105

How long is Varenicline used for?

Back 105

12 weeks initially
(and then a second 12 week treatment if necessary)

Front 106

What are the adverse side effects of Varenicline?1

Back 106

1. Suicidal thoughts
2. Erratic behavior
3. Aggressive behavior
4. Impairment of the ability to drive
5. Strange or vivid dreams