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DRUGS FOR ASTHMA

Asthma is a common, chronic disorder that occurs in children and adults.
- symptoms are a sense of breathlessness, tightness in the chest, wheezing, dyspnea, cough
- immune-mediated airway inflammation is the underlying cause (chronic inflammatory disorder of the airway)
- inflammation makes airways smaller - - more difficult to move air in and out of lungs

Acute bronchospasm causes severe respiratory distress and a wheezing sound from expiration of air
- symptoms are forceful expiration, dyspnea
- medical emergency - - REPORT IT IMMEDIATELY

I. ADMINISTRATION OF DRUGS BY INHALATION

Advantages: therapeutic effects are enhanced (by delivering drugs directly to their site of action)
systemic effects are minimized
relief of acute attacks is rapid

Inhalation Devices: metered dose inhalers

dry-powder inhalers
nebulizers

A. METERED DOSE INHALERS (MDIS)

- small, hand-held, pressurized devices
- dosing accomplished with 1 or 2 puffs
- when 2 puffs are needed, an interval of at least 1 minute should separate the 1 st puff from the
2nd
- hand-lung coordination is required (patient must begin to inhale prior to activating the device)
- demonstrations, as well as written and verbal instructions are needed for the patients
- spacers may be needed
- devices that attach directly to the MDI to increase delivery of drug to the lungs and decrease
deposition of drug

B. DRY POWDER INHALERS (DPIS)

- deliver drugs in the form of a dry, micronized powder directly to the lungs
- breath activated, requiring no hand-lung coordination
- much easier to use
- deliver more drug to the lungs than MDIs
- example = Advair

C. NEBULIZERS
- droplets in the mist are much finer than those produced by inhalers
- can be done through a face mask or through a mouthpiece
- for certain patients, nebulizers may be superior to inhalers
- patients who have become unresponsive to a beta 2 agonist delivered with an inhaler may
respond when the same drug is administered with a nebulizer because the dose is administered
slowly (over several minutes) allowing bronchi to gradually dilate and the drug gains deeper and
deeper access to the lungs
- often used for children and “ill” adults
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II. BETA2-ADRENERGIC AGONISTS (BRONCHODILATORS)

- trade name: Albuterol, Proventil
- “rescue” drug
- most effective drugs available for relieving acute bronchospasm and preventing exercise-induced
bronchospasm
- by activating beta2 receptors in smooth muscle of the lung, these drugs promote bronchodilation,
relieving bronchospasms
- administered orally or by inhalation
- oral agents are long-acting
- inhaled agents are short acting, except salmeterol and formoterol whose effects are delayed
and persist for up to 12 hours
- long acting agents are well suited for prophylaxis but should not used to abort an ongoing
attack
- all asthma patients inhale short-acting beta 2 agonists on a PRN basis to relieve break-through
symptoms
- for patient undergoing and acute severe attack, a nebulized beta 2 agonist is the traditional
treatment of choice

Adverse Effects:
- unpleasant taste in the mouth can be managed with frequent sips of water, sucking on
sugarless candy, or chewing gum
- caution with dizziness - - patient may need help walking
- nausea can be managed with frequent small meals

Inhaled Agents = generally minimal

= systemic effects – tachycardia, angina, tremor

Oral Agents = excessive doses will cause stimulation of cardiac beta 1 receptors to cause angina
pectoris and tachydysrhythmias
- patients should be instructed to report chest pain or changes in heart rate or rhythm
- tremor is caused by stimulation of beta 2 receptors in skeletal muscle
- with continued drug use, condition declines spontaneously

High Risk Patients: diabetics, hypertensive, heart disease, angina, hyperthyroidism

III. GLUCOCORTICOIDS (ANTI-INFLAMMATORY AGENT)

- trade name: Prednisone
- most effect antiasthma drugs available
- administration is usually by inhalation but may also be oral or IV
- must be done on a fixed schedule – not PRN because beneficial effects develop slowly,
therefore these drugs cannot be used to abort an ongoing attack
- bronchospasm may occur - - immediate wheezing after administration
- IMMEDIATELY administer short acting inhaler bronchodilator, stop inhaled
glucocorticoid, and start alternate treatment!
- all patients with moderate to severe asthma should use these drugs daily
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- reduce symptoms by suppressing inflammation

- decreased synthesis and release of inflammatory mediators (histamine, prostagladins)
- decreased infiltration and activity of inflammatory cells (leukocytes)
- decreased edema of the airway mucosa
- decrease airway mucus production and increase the number of bronchial beta 2 receptors as well as
their responsiveness to beta2 agonists
- used for prophylaxis of chronic asthma

Adverse Effects:
Inhaled Agents = largely devoid of serious toxicity, even in high doses
= orophyaryngeal candidiasis and dysphonia (hoarseness, speaking difficulty)
- to minimize: gargle after each administration
employ a spacer during administration
= adrenal suppression may occur with long-term, high-dose therapy
- patients who have been switched from oral glucocorticoids to inhaled
glucocorticoids must be given supplemental oral or IV doses at times of stress
= bone loss – at least in premenopausal women
- to minimize: use the lowest dose possible
ensure adequate intake of calcium and vitamin D
participate in weight-bearing exercise
= slow growth in children / adolescents, but not decrease adult height (slows growth but
only temporarily)
- not sure if these agents suppress growth and development of the brain, lungs
and other organs
- prudent to reserve these drugs for older children and young children with
relatively severe asthma
= may increase risk of cataracts and glaucoma

Adverse Effects:
Oral Agents = prolonged therapy even in moderate doses can be hazardous
= adrenal suppression, osteoporosis, hyperglycemia, peptic ulcer disease, and
suppression of growth
= patients must be given increased doses of oral or IV glucocorticoids at times of stress
- failure to do so can prove fatal!

IV. MAST CELL STABILIZERS-CROMOLYN SODIUM(ANTI-INFLAMMATORY )

- trade name: Intal
- safe and effective for prophylaxis of asthma
- suppresses inflammation but is not a bronchodilator
- acts in part by stabilizing the cytoplasmic membrane of mast cells, preventing release of
histamine and other mediators
- can be administered with a power driven nebulizer or an MDI
- when administered on a fixed schedule, reduces both the frequency and intensity of attacks
- must be administered prior to the onset of an attack
- first drug of choice for childhood asthma
- can prevent bronchospasm in patients predisposed to exercise induced asthma
- should be administered 15 minutes prior to anticipated exertion
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Adverse Effects: safest of all antiasthma medications

occasionally causes cough or bronchospasm

V. METHYLXANTHINES
- most prominent actions are: central nervous system (CNS) excitation, bronchodilation
cardiac stimulation, vasodilation, diuresis

A. THEOPHYLLINE
- benefits derive primarily from bronchodilation
- narrow therapeutic range
- usually administered by mouth
- not by inhalation because it is not active by this route
- although less effective than beta2 agonists, has a longer duration of action (when administered in a
sustained release formulation)
- because effects are prolonged, may be most appropriate for patients who experience
nocturnal attacks
- safe and effective therapy requires periodic measurement of blood levels
- do not change brands without the physician’s OK

1. Toxicity:
- uncommon at plasma levels below 20 mg/ml
- relatively mild reactions include nausea, vomiting, diarrhea, insomnia, restlessness
- serious adverse effects are most likely at levels above 20 mg/ml
- include severe dysrhythmias (v-fib) and convulsions that can be highly resistant to
treatment
- at first signs of toxicity, administration should cease
- if large amount of the drug has been ingested , ipecac can be given to induce vomiting,
followed by activated charcoal with a cathartic
- v-fib responds to lidocaine
- IV diazepam may help control seizures
2. Drug Interactions:
a. Caffeine – can intensify adverse effects on the CNS and heart
- can compete with theophylline for drug-metabolizing enzymes, causing levels to rise
- should avoid caffeine-containing beverages, chocolates, and grilled foods
b. Drugs that Reduce Theophylline Levels – phenobarbital, phenytoin, rifampin
- lower theophylline levels by inducing hepatic drug-metabolizing enzymes
- concurrent use with these agents may require an increase in theophylline dosage

c. Drugs that Increase Theophylline Levels – cimetidine, fluoroquinolone antibiotics (cipro)

- elevate theophylline levels primarily by inhibiting hepatic metabolism
- concurrent use with these agents may require a decrease in theophylline dosage

3. Oral Formulations – available in standard and sustained release formulations

- sustained release formulations are more convenient and can produce drug levels that are
relatively stable
- available in 8-, 12-, and 24-hour forms
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- can be affected markedly by food

- Theo-24 is accelerated in presence of fatty foods
- Theo-Dur Sprinkle’s (recently removed from market) absorption is reduced by food
- accelerated absorption can produce dangerous elevations in blood levels, therefore,
some physicians avoid the once-a-day 24-hour form

4. Dosage and Administration

a. Oral – maintenance plasma levels should be between 10 and 20 mg/ml
- some patients learn their symptoms and skip doses
- if a dose is missed, the following dose should NOT be doubled because doing so
could produce toxicity
- patients should be instructed not to chew sustained release formulations

b. IV – reserved for emergencies

- administration must be done slowly, since rapid injection can cause fatal
cardiovascular reactions
- incompatible with many other drugs
VI. LEUKOTRIENE MODIFIERS
- newest class of drugs for asthma
- first new drugs for asthma in over 20 years
- suppress the effects of leukotrienes, compounds that promote bronchoconstriction

A. ZILEUTON (TRADE NAME: ZYFLO)

- approved for prophylactic and maintenance therapy of asthma in adults and children 12 yrs and older
- symptomatic improvement can be seen within 1 – 2 hours of dosing
- given orally
- undergoes rapid absorption, regardless of food
- can injure the liver
- patients have developed symptomatic hepatitis, which reversed following drug withdrawal
- to reduce risk of serious liver injury, ALT (alanine aminotransferase) activity should be
monitored

B. ZAFIRLUKAST (TRADE NAME: ACCOLATE)

- approved for maintenance therapy of chronic asthma in adults and children 5 yrs and older
- administered orally
- undergoes rapid absorption, reduced by presence of food
- should be administered at least 1 hr before meals or 2 hrs after

C. MONTELUKAST (TRADE NAME: SINGULAIR)

- indicated for maintenance therapy of asthma – but not for quick relief
- approved for all patients over the age of 1 yr
- maximal effects develop within 24 hrs of 1 st dose, and are maintained with once-daily dosing in the
evening
- administered orally
- undergoes rapid absorption, regardless of food

MANAGEMENT OF ASTHMA

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A. MEASURING LUNG FUNCTION

1. Forced Expiratory Volume (FEV) – single most useful test of lung function
- instrument required (spirometer) is both expensive and cumbersome - - not suited for home
- patient inhales completely, then exhales as completely and forcefully as possible into the
spirometer
- spirometer measures how much air was expelled
- results are then compared to “predicted normal value for a healthy person of similar
age, sex, height, and weight

2. Peak Expiratory Flow Rate (PEFR) – maximal rate of airflow during expiration
- patient exhales as forcefully as possible into a peak flow meter (relatively inexpensive,
handheld device)
- patients should measure their peak flow every morning
- if peak flow is less than 80% of their personal best, more frequent monitoring should
be done

B. DRUG THERAPY
- some agents are taken to establish long-term control
- administered daily to achieve and maintain control of persistent asthma
- anti-inflammatory drugs – especially inhaled glucocorticoids – provide the foundation for long-
term control
- long-acting inhaled beta 2 agonists are also important

- some agents are taken for quick relief

- quick relief medications are taken to promptly reverse bronchoconstriction, providing rapid
relief from cough, chest tightness, and wheezing
- short-acting beta2 agonists are the most important

C. CLASSIFICATION OF CHRONIC ASTHMA

1. Mild Intermittent – treated on a PRN basis
- long-term control medication is not needed

2. Mild Persistent – requires a combination of long-term control medication plus quick-relief medication
- foundation of treatment is daily inhalation of an anti-inflammatory drug

3. Moderate Persistent – requires intensive long-term control achieved by either inhaling a glucocorticoid
in a medium dose (compared to low dose in #1) OR inhaling a glucocorticoid in a low dose and
adding a long-acting inhaled beta 2 agonist (generally preferred method)

4. Severe Persistent – severe chronic asthma managed with daily inhalation of a high dose glucocorticoid
plus a long-acting beta2 agonist
- if symptoms are especially severe, an oral glucocorticoid should be added to regimen
- administration may be once daily or once every other day
- breakthrough attacks are managed with a short-acting, inhaled beta 2 agonist

D. REDUCING EXPOSURE IN ALLERGENS AND TRIGGERS

- important sources of asthma-associated allergens include house dust mite, warm-blooded pets,
cockroaches, and molds
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- triggers include tobacco smoke, wood smoke, strong odors, weather changes, viral or sinus infections,
exercise, reflux disease, medications or food, emotional anxiety and household sprays

Risk Reducers: weekly washing of family pets that must stay in the home
encasing the patient’s pillow, mattress and box spring with covers that are impermeable
to allergens
washing all bedding and stuffed animals weekly on the hot cycle
removing carpeting or rugs form the bedroom
don’t smoke or be around smoke

E. ACUTE SEVERE EXACERBATIONS

- require immediate attention
- foundation of treatment is repetitive inhalation of beta 2 agonist, administered by nebulizer or MDI
- if patient is unconscious or unable to generate PEFR, subcutaneous epinephrine should be
given)
- if there is no response to the 1st dose of beta2 agonist, a glucocorticoid (IV
methylprednisolone or oral prednisone) should be given
- oxygen is administered to maintain oxygen saturation above 95%
- full recovery of lung function may take weeks

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