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Pharm: Pre Midterm 1 > Asthma drugs > Flashcards

Asthma drugs Flashcards

1
Q

What is asthma?

A

Reversible airway obstruction as a result of bronchial hyper-reactivity, airway inflammation, mucous plugging and smooth muscle hypertrophy

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2
Q

What are the endogenous products that play important role in pathophysiology of lung?

A 
Prostaglandins 
Acetylcholine 
Beta Adrenergics 
Histamine 
Adenosine 
ACE: inactivates bradykinin, which is enhanced by ACEI that cause cough and angioedema
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3
Q

How does Bradykinin and Substance P lead to a cough?

A

Bradykinin:
–Increases release of prostaglandins, Leukotrienes and Histamine leads to type J receptors at peripheral vagal afferents ending/non myelinated or C- fibers
Substance P:
—type J receptors at peripheral vagal afferent ending/non-myelinated or C-fibers

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4
Q

What is the role of methacholine in asthma?

A 
Muscarinic Receptor (M3) agonist 
--used in bronchial challenge test to help diagnose asthma
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5
Q

Describe the role of inadequate surfactant in infants that leads to RDS.

A

Can be prevented if mothers who are about to deliver prematurely by dexamethasone administration
–test: lecithin to sphingolyelin ratio greater than 2.0m in amniotic fluid, indicated fetal lung maturity.

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6
Q

What factors precipitate an asthma attack?

A

Allergens: induce mast cell release of inflammatory mediators
Infections: viral URI or even bacterial/fungal
Pharmacological Factors: Beta Blockers, cholinergics
Exercise and Stress: Vagal and Adrenergic Influence

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7
Q

Moving on to the drugs used in asthma treatment, first are the bronchodilators (Beta receptor agonists, antimuscarinic drugs, methylxanthines). First lets start with the beta 2 receptor agonists, what are these drugs?

A 
Albuterol 
Pirbuterol
Terbutaline 
Salmeterol 
Formoterol
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8
Q

What is the MOA of beta 2 agonists?

A

Increasing intracellular concentrations of cAMP

–this leads to relaxation of bronchial smooth muscle and therefore bronchodilation

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9
Q

What are your short acting vs long acting beta 2 agonists?

A

SABA: albuterol, pirbuterol and terbutaline
LABAs: salmeterol and formoterol
–most of these drugs are inhaled, which minimizes their systemic side effects
–LABAs available in combination with ICS (inhalational corticosteriod) for long term control and prevention of symptoms in moderate to severe persistent asthma

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10
Q

What is a concern regarding long acting beta agonists?

A

Genetic Polymorphism in Beta 2 receptors

–causes slight worsening of asthma, exacerbations or even death

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11
Q

What are some clinical concerns of asthma?

A

Do not use LABAs inhaler for rescue medication!

LABAs should only be used in conjunction with an inhaled steroid

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12
Q

What drugs are used for exercise induced bronchoconstriction?

A

SABAs used just before exercise will prevent EIB for 2-4 hours after inhalation
LABAs will prevent up to 12 hours

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13
Q

What are the adverse effects of inhaled Beta 2 adrenergic agonists bronchodilators?

A

Tremors, Tachycardia, arrhythmias and hyperglycemia

–high doses of Beta 2 agonist can get into the systemic circulation and therefore into the blood stream

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14
Q

Next set of drugs for asthma are Anticholinergics as bronchodilators, Ipratropium and Tiotropium. What are their uses?

A

Ipratropium: a short acting inhaled anticholinergic can be used in asthma, QID
Tiotropium: a long acting anticholinergic used SID in COPD

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15
Q

What is the MOA of anticholinergics?

A

Parasympathetic stimulation causes bronchial constriction and mucous secretion.
–anticholinergics are used to block the muscarinic receptors in the smooth muscles and maintain bronchial dilation of the airway

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16
Q

What are the clinical uses for Ipratropium?

A

Prevent vagal mediated bronchoconstriction and drug induced bronchospasm such as beta blockers

17
Q

What are the averse effects of Ipratropium?

A

Dry mouth

Careful in patients with glaucoma and BPH

18
Q

The next drugs used in asthma are the Methylxanthines, Theophylline and Aminophylline.

A

Inhibit phosphodiesterase
–this enzyme converts cAMP to AMP
Increasing cAMP levels results in bronchodilation
also blocks adenosine receptors

19
Q

What is the role, drug interactions, and complications of theophylline?

A

Role in Asthma:
–limited because it has a very small therapeutic window
Drug Interactions:
–Cimetidine, erythromycin and Ciprofloxacin all increase plasma levels
–Phenytonin, phenobarbitone and carbamazepine all decrease plasma levels
Complications with overdose:
—tremor, insomnia, GI distress and nausea.

20
Q

Moving on to the corticosteroids used in asthma. What are they?

A 
Beclomethasone 
Dexamethasone 
Fluticasone 
Budesonide 
Flunisolide 
Prednisolone
21
Q

What is the MOA of corticosteroids?

A

Inhibit synthesis of arachidonic acid by phospholipase A2
–therefore inflammatory mediators like leuotrienes, cytokines and prostaglandins are inhibited
Steroids bind to intracellular receptors and activate glucocorticoid response elements in the nucleus, result in the synthesis of substances that inhibit expression of inflammation and allergy

22
Q

How are corticosteriods used in asthma management?

A

Both acute and maintenance:

  • –acute: systemic steroids are used primarily when the attack is severe
  • -maintenance therapy: low dose inhalational corticosteroids suppress the inflammation and reduce the risk of exacerbations
23
Q

Corticosteroids also do what?

A
  1. Increase beta 2 adrenoreceptors responsiveness in the respiratory tract
  2. Used once or twice a day: reduce the need for beta 2 agonists
  3. Prevent remodeling of resp tract
  4. Patients who remain symptomatic in spite of compliance with inhaled corticosteroid treatment addition of long acting beta 2 agonists are recommended.
24
Q

In regards to corticosteriods how are these processed in the system?

A

Ten percent deposited in the lung
Ninety percent swallowed
GI tract absorption from gut
First pass inactivation in the liver: therefore nothing gets passed to the systemic circulation
–however with long term use or high doses of drug from the liver and lungs can enter the systemic circulation and cause side effects

25
Q

What are the adverse effects of inhaled corticosteroids?

A

Cough
Oral thrush
Dysphonia
–this is from long term use

26
Q

What are the systemic corticosteroids?

A

Dexamethasone and Prenisolone: life saving steroids in status asthmaticus
Oral Glucocorticoids: short course is used for exacerbations with incomplete response to beta 2 agonists, after which tapering is needed (To avoid cushing like symptoms)

27
Q

What are adverse effects of systemic corticosteroids?

A 
Glucose Metabolism 
Increased Appetite
Weight Gain 
HTN 
Adrenal Suppression
28
Q

How are pregnant women with asthma treated?

A

Can be treated as aggressively as non-asthmatic patients

  • -risks of poorly controlled asthma include: pre eclampsia, perinatal mortality, preterm labor and low birth weight
  • -use of ICS during the 1st trimester: congenital malformation may occur but does is very high
29
Q

The next asthma drugs are the Leukotriene Inhibitors. What are these drugs?

A

Zileuton
Zafirlukast
Montelukast

30
Q

What is the MOA of leukotriene Inhibitors?

A

Block the synthesis of leukotrienes from arachidonic acid or block the leukotriene receptor
Zileuton: inhibits 5-lipoxygense, which catalyzes the formation of leukotrienes from arachiodonic acid
Zafirlukast: LTD4 receptor antagonist
Montelukast: LTD4 receptor antagonist

31
Q

What is the clinical role of leukotriene inhibitors in asthma?

A

Prevention of exercise, antigen and aspirin induced asthma
Prevent bronchoconstriction and airway inflammation
Used for chronic maintenance therapy of mild asthma they are not beneficial in acute bronchospasm

32
Q

What are adverse effects of Leukotriene inhibitors?

A

Overall very safe
Zileuton: elevated liver enzymes
Zafirlukast and Montelukast: rarely patients develop as vasculitis and systemic eosionphilia resembling churg-strauss syndrome

33
Q

The next drug is Omalizumab which is an Anti-IgE antibody. What is the MOA and use?

A

MOA:
–binds to the IgE on sensitized mast cells and prevents activation by triggers therefore prevents release of LTs and other mediators
Use:
–prophylactic management of asthmatic patients and in cases of inadequate control with inhaled ICS in patients over 12 years old
–can cause anaphylaxis because this is an IgG antibody drug

34
Q

The next two drugs, Cromolyn and Nedocromil are release inhibitors, what is their MOA, uses and toxicities?

A

MOA:
–effective prophylactic agents that stabilize the membranes of mast cells and prevent the release of inflammatory mediators
NOT USED FOR ACUTE ATTACKS
–commonly used a prophylactic agents.Pre-treatment of this drug blocks allergen and exercise induced bronchoconstriction
Other Uses:
–prevent food allergy and hay fever
Toxicity:
–cromolyn: infrequent laryngeal edema, cough or wheezing
–Nedocromil: unpleasant taste

35
Q

What are ways of asthma management failure?

A

Lack of Adherence to meds
Co-morbid conditions
Exposure to tobacco smoke, other airborne pollutants and allergens

36
Q

What are the types of asthma and their control?

A 
Intermittent (less than two episodes per week): no daily medication and for quick relief B2 agonist (Short acting) 
Mild Persistent (more than two per week): low does inhaled corticosteriods and quick relief B2 agonist (Short acting)
Moderate Persistent (daily): low to medium dose inhaled corticosteroids and long acting beta 2 agonists and quick relief short acting beta 2 agonists 
Severe Persistent (continual): increased dose inhaled corticosteroids and a long acting beta 2 agonist and quick relief short acting beta 2 agonist
37
Q

What is the asthma mnemonic??

A 
Albuterol/Pirbuterol/Terbutaline
Steroids
Theophylline
Humidifier O2
Magnesium (Severe exacerbations): when Beta 2 agonists and anti cholinergics are unsuccessful 
Anticholinergics

Pharm: Pre Midterm 1 (30 decks)

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