Lower Respiratory

Medications

Physiology
The lower respiratory tract is virtually sterile
because of the various defense mechanisms in the
upper respiratory system.
Protective mechanisms
All the tubes in the lower airway contain goblet cells,
which secrete mucus to entrap any particles.
Microorganisms and other foreign bodies are removed
from the air by tiny hair-like structures called cilia.

Gas exchange, perfusion, and respiration

Lung tissue receives its blood supply from the bronchial
artery, which branches directly off the thoracic aorta.

Ventilation
The act of breathing is controlled by the central nervous
system (CNS).

Lower Respiratory Tract

Pathophysiology
Acute bronchitis most frequent cause: viruses.
Asthma recurrent episodes of bronchospasm, bronchial
muscle spasm that leads to narrowed or obstructed
airways.
Chronic airway limitation (CAL, COPD) an umbrella
term that describes gradually progressive, degenerative
diseases, such as chronic bronchitis, emphysema, or
repeated, severe asthma attacks.
Chronic bronchitis long-standing, largely irreversible
inflammation of the bronchial tree.
Emphysema an abnormal distention of the lungs with air
characterized by loss or degeneration of elastic tissue,
disappearance of capillary walls, and breakdown of the
alveolar walls.
Pneumonia an inflammation of the lungs, can be caused
by bacterial or viral invasion, or aspiration of foreign
substances into the lower respiratory tract.

Drugs for asthma

Lower Resp. Drug Overview

Two main types: Anti-inflammatory
agents and bronchodilators (also
mucolytics).
The principal anti-inflammatory
agents are glucocorticoids.
The principal bronchodilators are
beta 2 agonists.
Both types frequently delivered by
inhalation.

Administering Meds by
Inhalation
Three advantages of inhalation:
Therapeutic effects are enhanced, delivered
directly to site of action
Systemic effects minimized
Rapid relief of acute attacks

Three types of inhalation devices:

Metered-dose inhalers
Dry-power inhalers
Nebulizers

Administering Meds by
Metered-Dose Inhalation
Inhalers (MDI)
Small, hand-held, pressurized devices that deliver a
measured dose of drug with each actuation
Dosing usually 1-2 puffs
When 2 puffs are ordered, an interval of at least
1 minute should separate the puffs
Pts must begin to inhale before activating
**Can be difficult to use correctly: give written,
demonstration, and verbal instructions
Spacers attach directly to the MDI can increase drug
delivery
If used for exercise-induced asthma, must use
BEFORE exercise
Children should use inhaler, or 2 inch space
between mouth & inhaler

Administering Meds by
Inhalation

Dry Powder Inhalers (DPI)

Deliver dry micronized powder directly to lungs

Breath activated (no hand-lung coordination)
Easier to use, deliver more drug
Do NOT use spacers

Nebulizers
Machine used to convert drug solution into
mist
Much finer than droplets in an MDI inhaler.
Delivered through a mouthpiece or mask
Take several minutes to deliver the same
amount of drug found in 1 puff of inhaler

**Administering
Instruct client to sitMDI**KNOW
Insert MDI canister into the holder
Remove mouthpiece cover from inhaler
Shake inhaler vigorously five or six times (attach spacer if indicated,
particularly with children)
Have client take a deep breath and exhale
Instruct client to position inhaler:
Either: close mouth around MDI with opening toward back of throat
Or: position the device 1-2 inches in front of the mouth (more
common approach with children)

Have client hold inhaler with thumb at the mouthpiece and the index
finger and middle finger at the top.
Client tilt head back slightly, inhale slowly and deeply through
mouth for 3-5 seconds while depressing canister fully.
Hold breath for approximately 10 seconds.
Remove MDI from mouth and exhale through pursed lips, repeat after
one minute if 2 puffs ordered
Assess respiratory status before and after each dose.

Administering DPI
Remove cover from mouthpiece, do NOT shake.
Prepare medication as directed by manufacturer
(turn dial to load and crush pellet, etc.)
Exhale away from the inhaler before inhalation.
Position mouthpiece between the lips.
Inhale deeply and forcefully through the mouth.
Hold breath 5-10 seconds, most are one puff, if
two are ordered wait a full min between puffs
Assess respiratory status before and after each
dose.

**MDI Administration, other

Important information:
Wait 1 minute before a second dose of the same
medication
Wait 2-5 minutes before inhalation of a different
medication
Always take the bronchodilator BEFORE other
inhalers, that way the airways are open and
more of the other medication will be
absorbed
Must Rinse mouth after using ANY inhaler
with a glucocorticoid (even Combo inhalers).
Do NOT exceed prescribed dose or frequency
Assessing for respiratory status: lung sounds, ease
of respirations, and pulse oximetry

Anti-inflammatory
Respiratory Drugs

Inflammatory Response
Inflammation- pain, swelling, redness, warmth caused by
chemical mediators (prostagladins, histamine,
leukotrienes) amplified by actions of lymphocytes &
phagocytic cells (neutrophils and macrophages).
Neutrophils and macrophages:
Heighten inflammation by releasing lysosomal enzymes, cause
tissues injury.

Lymphocytes intensify inflammation by:

Causing direct cell injury & promote formation of antibodies
which help perpetuate inflammatory response

Prostaglandins and histamine (chemical mediators):

Promote swelling, redness, warmth by causing vasodilation and
increasing capillary permeability.
Contribute to pain, histamine stimulates pain receptors,
prostaglandins sensitize pain receptors to stimulation by
histamine and other mediators

Anti-inflammatory Drugs: Glucocorticoids

Glucocorticoids: Most effective anti-asthma
drugs
Can be delivered by inhaler, oral or
intravenous
Suppress Inflammation:
Decrease the synthesis & release of
inflammatory mediators (leukotrines,
histamine, prostaglandins)
Decreased infiltration & activity of
inflammatory cells (eosinophils, leukocytes)
Decreased edema of the airway mucosa
(Secondary to a decrease in vascular
permeability)

Anti-inflammatory:
Glucocorticoids

Glucocorticoid Inhalers: (Local, not/or minimal

systemic absorption)
*Used for prophylaxis of chronic asthma
Beneficial effects develop slowly
Should be used daily
Can give extra IV or oral doses if symptoms
uncontrolled
Adverse effects are few with inhalers

Oropharyngeal candidiasis*
Dysphonia (hoarseness, speaking difficulty)
*Bone loss in premenopausal women
*Rinse mouth/Gargle after each use, use a spacer
Take lowest dose possible
*Take calcium and vitamin D
*Perform weight bearing exercises

Anti-inflammatory:
Glucocorticoids

**Inhaled Glucocorticoids:
Beclomethasone propionate
(QVAR)
Budesonide (Pulmicort,
Asthmacort)
Fluticasone propionate (Flovent)
Ciclesonide (Alvesco)
Flunisolide (Aerospan)
Mometasone furoate (Asmanex)

Anti-inflammatory, Glucocorticoids: Oral,

Parenteral (IM,IV) Systemic Corticosteroids
Oral/IV Use: See chapter 11, p 1010-1027
Only severe asthma/bronchospasm
Potential for toxicity increases over time (only
used when symptoms are not controlled with
safer medications); the longer the duration of
oral use, the higher the risk of toxicity.
Increased Adverse Effects than for inhaled
corticosteroids WHY??
adrenal suppression, osteoporosis, delayed
growth in children and adolescents,
hyperglycemia, peptic ulcer disease (PUD).

Systemic Glucocorticoids/Corticosteroids
Very similar to endogenous steroids produced by
adrenal gland.
Physiologic effects are achieved with low doses
Pharmacologic effects are achieved with high
doses
Low doses: used to treat adrenocortical
insufficiency, (Addisons Disease)*
High doses: used to treat inflammatory disorders
(asthma, rheumatoid arthritis, certain cancers)
Toxicity is severe, determined by pattern of drug
use:
Almost devoid of toxicity when used in low doses
Pharmacologic doses (especially in long-term use) can
cause an array of serious adverse effects

Glucocorticoids/Corticosteroi
ds

Physiologic Effects: Metabolic

Carbohydrates - Hyperglycemia
Promotes the synthesis of glucose from amino acids
Reduce peripheral uptake/utilization of glucose by
muscle and adipose tissue.
Promote storage of glucose as glycogen.

Proteins- Reduces muscle mass, decreases

protein matrix of bone, and causes thinning
of skin.
Suppress synthesis of proteins from amino acids,
diverts amino acids to production of glucose

Fats- Fat redistribution- Pot belly, moon face

and buffalo hump (Like Cushings)
Stimulates lipolysis

Glucocorticoids/Corticosteroi
ds

Physiologic Effects: Cardiovascular

If endogenous glucocorticoids are LOW,
capillaries become more permeable (third
spacing), vasoconstriction is suppressed,
& BP drops (hypotension)

Glucocorticoids increase circulating RBCs

and polymorphonuclear leukocytes
Glucocorticoids decrease lymphocytes,
eosinophils, basophils and monocytes

Glucocorticoids/Corticosteroi
ds

Physiologic Effects: During Stress

Adrenal glands secrete large quantities of

glucocorticoids and epinephrine during stress
(surgery, trauma, infection, hypovolemia, etc.)
If release is insufficient, hypotension &
hypoglycemia occur, can cause circulatory
collapse & death

Effects on Water & Electrolytes:

Glucocorticoids promote water and sodium
retention, while increasing urinary excretion of
potassium
This can cause: Hyponatremia, hypokalemia,
& edema.

Glucocorticoids/Corticosteroids
Pharmacodynamics (PD): mechanisms
of action
Glucocorticoid receptors are located inside
the cell, rather than on the cell surface
Glucocorticoids modulate the production of
regulatory proteins, rather than the activity
of signaling pathways

Glucocorticoids/Corticosteroids
Pharmacotherapeutics (PT): Antiinflammatory & Immunosuppressant
Effects:
Inhibit synthesis of chemical mediators
(prostaglandins, leukotrienes, histamine), to
reduce swelling, warmth, redness, & pain

Suppress infiltration of phagocytes

Suppress proliferation of lymphocytes to
reduce the immune component of
inflammation

Glucocorticoids/Corticosteroids
Adverse Effects:
Typically ONLY occur when doses are high and
duration is longer than a few days
Adrenal Insufficiency- glucocorticoids can
suppress production of glucocorticoids by the
adrenal glands
Osteoporosis- & resulting fractures, frequent
& serious complication of prolonged therapy
Give topical or inhaled steroids when possible as
side effects are greatly reduced.
Take calcium and vitamin D
Biphosphonate drugs can prevent glucocorticoidinduced bone loss

Glucocorticoids/Corticosteroi
ds

Adverse Effects:

Infection- Suppression of the immune

system increases risk of infection
Pts should avoid close contact with
people who have communicable diseases
If infection occurs, glucocorticoids should
be continued only if absolutely necessary
Pneumocystic pneumonia is occurring
more often in pt with high dose
glucocorticoids, May need antibiotic
prophylaxis

Glucocorticoids/Corticosteroi
ds
Adverse Effects:

Glucose Intolerance- Pts with diabetes may

need to reduce caloric intake or increase the
dosage of hypoglycemic medication

Glucocorticoids can unmask latent diabetes, so even

nondiabetics should undergo periodic evaluation of
blood glucose levels

Myopathy- Can cause myopathy (muscle

injury), manifests as weakness, proximal
muscles of the arms & legs affected most often
Growth Retardation- suppresses growth in
children.
Can be minimized with alternate-day therapy

Glucocorticoids/Corticosteroi
ds
Adverse Effects:
Fluid and Electrolytes: Hypernatremia, Edema &
*Hypokalemia
Can be reduced by using glucocorticoids that have low
mineralcorticoid activity, restricting sodium intake & taking
potassium supplements/potassium-rich food
s/s of hypokalemia- muscle weakness or fatigue, irregular pulse)

Psychological Disturbances: 60% have mild reaction:

insomnia, anxiety, agitation or irritability; 6% severe
reaction: delirium, hallucinations, depression, euphoria, or
mania, 1/3 can become suicidal. Previous psychiatric illness
does not predispose pt to psychological response
Long-term low-dose therapy: more likely to cause depression
Short-term high-dose therapy: more likely to cause mania & other
psychoses
Cognitive impairment (distraction, memory loss) can occur with
either dosing pattern.

Glucocorticoids/Corticosteroi
ds
Adverse Effects:
Cataracts & Glaucoma: complication of longterm Tx
eye exam Q 6 months, pt report cloudy or blurred
vision

Peptic Ulcer Disease:

Glucocorticoids can augment the secretion of
gastric acid & pepsin, inhibit production of cytoprotective mucus and reduce gastric mucosal blood
flow
Can also reduce gastric pain, masking ulcer
development,(perforation & hemorrhage w/o
warning)
Risk increases with use of NSAIDS

Glucocorticoids/Corticosteroids
Adverse Effects:
Iatrogenic Cushings Syndrome: Can cause cushingcoid
syndrome. (Hyperglycemia, glycosuria, fluid and
electrolyte disturbances, osteoporosis, muscle weakness,
cutaneous striations, lowered resistance to infection, and
redistribution of fate (potbelly, moon face, and buffalo
hump)
Pregnancy- Can cross the placenta
carefully weigh risk/benefit ratio
Increased incidence of cleft palate, spontaneous abortion, & low
birth weight
Prolonged therapy can cause fetal adrenal hypoplasia

Lactation- Can enter breast milk

Growth retardation & other adverse effects
Concentration: Low dose typically not enough to cause
problems, high doses can cause above symptoms

Glucocorticoids/Corticosteroids
Drug Interactions:
Interactions related to potassium loss*Used with caution when combined with
digoxin, thiazide or loop diuretics.
NSAIDS- increases risk of PUD.
Insulin/oral hypoglycemics- May need to
increase doses to combat hyperglycemia
Vaccines- Can decrease antibody
response of vaccines & if live virus
vaccine is used, increased risk of
developing the viral disease

Glucocorticoids/Corticosteroids
Contraindications
Pts with systemic fungal infections or receiving
live virus vaccines

Precautions, Use with caution in pts:

pediatric, pregnant or breast feeding
Hypertension, heart failure, renal impairment,
esophagitis, gastritis, peptic ulcer disease,
myasthenia gravis, diabetes mellitus,
osteoporosis, & infections resistant to
treatment
concurrent therapy with potassium-depleting
diuretics, digoxin, insulin, oral hypoglycemics &
NSAIDS.

Glucocorticoids/Corticosteroi
ds
Taper to Withdraw- To allow time for
recovery of adrenal function, withdraw
slowly.
Need to taper from parenteral & high oral
dose
Taper schedule depends on current dose:
Taper dose to physiologic range over 7 days.
Taper from multiple daily doses to single doses
administered am daily
Taper the dose 50% of physiologic values over the next
month
Monitor for production of endogenous cortisol, when
basal levels return to normal, cease routine
glucocorticoid dosing (be prepared to give
supplemental doses at times of stress)

Glucocorticoids/Corticosteroi
ds

Routes of administration:
Local therapy- minimizes systemic
toxicity
Topical- for dermatologic disorders
Inhalation- used for asthma
Intranasal- allergic rhinitis

Systemic therapy Oral- (Preferred over IV)

Parenteral- IM, IV Reserved for serious or
life threatening disorders or those with
potential to cause permanent disability

Glucocorticoids
Inhaled (Listed above & nasal, see upper resp. ppt)
Oral
methylprednisolone (Medrol)
Prednisone (Deltasone)
Betamethasone (Celestone)
Hydrocortisone (Cortef)
Dextamethasone (Decadron)
Topical/ocular forms: Bethemethasone, Triamcinolone,
Hydrocortisone, methylprednisolone, & othersp 1024
IM & IV preps: methylprednisolone (IV:solumedrol,
IM: Depo-medrol), prednisolone acetate (IV & IM),
Hydrocortisone succinate (IV, IM) Dextamethasone (IV
& IM) betamethasone (IM, IL, IA) charts: 1015-16, 1024

Glucocorticoid Summary
See Table 35.1 and Know. End in SONE or
SOLONE
Often Category C for Pregnancy
Common Adverse Effects: See Box 35.3
Infection
Hyperglycemia
Fluid Retention
Bone loss (Osteoporosis)
CNS Stimulation (irritability, mood swings, insomnia,
anxiety).
GI- nausea, vomiting, INCREASED appetite, wt gain,
and dyspepsia, PUD
HYPOKALEMIA

Glucocorticoids
Nursing Considerations:
Risk for infection: Monitor_______________
Monitor and regulate insulin/antidiabetic
drugs
Monitor and regulate diet (wt. gain common)
Loose muscle strength, Risk for injury/falls
Anxiety common
Fluid Volume Excess-monitor for edema
Monitor potassium levels
Monitor BP
**Multiple Drug Interactions
Wear an ID bracelet

Leukotriene Modifiers
PD:
Suppress effects of leukotrienes (chemical mediators that
promote vasoconstriction, eosinophil infiltration, mucus
production, & airway edema.)
Decrease inflammation, bronchoconstriction, edema, mucus
secretion, & recruitment of eosinophils &other inflammatory
cells
Three leukotriene modifiers are available: zileuton
(Zyflo), zafirlukast (Accolate), and montelukast
(Singulair).
All three dosed orally
PT: Recommended as second-line therapy for
asthma/bronchospasm; add-on therapy when an inhaled
glucocorticoid alone is inadequate
Adverse E:All can cause adverse neuropsychiatric effects,
including depression, suicidal thinking, & suicidal behavior

Leukotriene Receptor
Antagonists

Leukotrienes: inflammatory mediators

that are powerful broncho-constrictors
and vasodilators
Leukotrienes identified as important
mediators in the pathology and
symptomatology of asthma
Result in airway hyper-reactivity,
bronchoconstriction, and hypersecretion
Prototype drug: zafirlukast
(Accolate)

Leukotriene Modifiers
Zafirlukast (Accolate)-PK: Food
reduces absorption (give 1hr before
or 2 hrs after meals)
Adverse E: Neuropsychiatric effects,
possible liver injury, and Churg-Strauss
syndrome (potentially fatal disorder
characterized by wt loss, flu-like syndrome,
and pulmonary vasculitis).
Can cause theophylline (Theo-dur)and
warfarin (Coumadin) drug concentration
levels in blood to rise to toxic levels

Leukotriene Modifiers
zileuton (Zyflo)- Improvement in
symptoms can be seen in 1-2 hrs.
liver, few patients have developed
symptomatic hepatitis (reversed when drug
was stopped)
Neuropsychiatric effects- depression, anxiety,
agitation, abnormal dreams, hallucinations,
insomnia, irritability, restlessness, and
suicidal thinking/behavior (if these develop
switch to another medication)
Can increase theophylline levels, coumadin
levels and propanolol levels.

Leukotriene Modifiers
Montelukast (Singulair) Does NOT cause liver injury.
Can cause Churg-Strauss syndrome
(when glucocorticoid dose was
reduced) See prior slide for details
about Churg-Strauss.
Does NOT cause drug interactions.

Mast Cell Stabilizer drugs

Cromolyn Sodium: 2 types
Nasal: trade Nasal crom
Inhalation: trade: Intal
A preventative drug that decreases episodes
of asthma/bronchospasm (nasal:
rhinitis)induced by different antigens
(exercise, pollutants, allergans)
PD: An anti-inflammatory agent, shields
mast cells and prevents them from
rupture & degradation after contact with
antigen, prevents release of histamine,
possibly leukotriene's, & other chemical
mediators by an unclear mechanism, possibly

Cromolyn (Intal)
Inhalation drug, suppresses bronchial
inflammation (MDI, nebulizer solution, nasal
inhaler)
*Does NOT cause bronchodilation
Indication:*Used for prophylaxis, not quick relief,
mild to moderate chronic asthma, exerciseinduced bronchospasm, & allergic rhinitis
Anti-inflammatory effects less than glucocorticoids
Adverse effects: Safest of all anti-asthma meds,
occasionally cough or *bronchospasm
Available in power-driven nebulizer and MDI
If used for exercise-induced bronchospasm
should use PRIOR to exercise

IgE Antagonist
Omalizumab (Xolair)
Monoclonal antibody that causes antagonism of IgE
antibody
Only used for allergy-related asthma, when all other
options fail
Small risk of anaphylaxis & cancer
Must be given subcutaneously
Costs over $10,000 a year
Long-term safety unknown
Adverse Effects: injection-site reactions, viral infection,
upper respiratory infection, sinusitis, headache, and
pharyngitis. Risk of cardiovascular events (ischemic heart
disease, dysrhythmias, heart failure, pulmonary
hypertension, CVA, and thromboembolic events).
Lifethreatening anaphylaxis is rare, when occurs it is
with first dose

Bronchodilators

Bronchodilators
PD: Bronchodilator drugs: used to facilitate
respiration by dilating the airways
Bronchodilator administration: oral, parenteral,
or inhalation
Inhalation is the most frequent method using
metered-dose inhalers (MDIs) or dry-powder
inhalers (DPIs), or nebulizer
Beta agonists (sympathomimetics)
One of the actions of beta stimulation in the
sympathetic nervous system is dilation of the
bronchi and increased rate & depth of respiration

Prototype drug: albuterol (Proventil,

Ventolin)

Bronchodilators
PT: (Asthma, CAL) Symptomatic relief of
bronchospasm & bronchoconstriction,
does not alter underlying disease
process (inflammation)
In most all cases, pts taking a
bronchodilators are prescribed inhaled
glucocorticoid for long-term suppression
of inflammation

Bronchodilators: Beta 2Adrenergic Agonists

Given by inhalation, most effective
drugs available for relieving acute
bronchospasm and preventing
exercise-induced bronchospasm (EIB)
Long-acting formulations (oral or inhaled)
can protect against bronchospasm over
an extended time
Long-acting inhaled beta2 agonist can
increase the risk of asthma-related deathonly when used alone

Bronchodilators: Beta 2-Adrenergic

Agonists
PD:
Selective activation of beta 2-adrenergic
receptors in smooth muscle of the lung, promotes
bronchodilation
Suppress histamine release in the lung & increases
ciliary motility

Route and Time Course:

All oral preparations are long acting
Short-acting inhaled preparations, effects begin
almost immediately, peaks in 30-60 min. Used to
end an attack, NOT for prophylaxis
Long-acting inhaled preparations, onset depends on
the drug, used on a fixed-schedule

Bronchodilators: Beta 2-Adrenergic

Agonists
PT: Asthma, Bronchospasm:
Short-Acting Inhaled Beta2 Agonists (SABA) Taken prn to relieve ongoing attack
Take before exercise to prevent an attack
For a severe acute attack, a nebulized SABA is the
treatment of choice, but MDI may be equally
effective

Long-Acting Inhaled Beta2 Agonists Frequent attacks can inhale a LABA for long-term control
Fixed schedule, not PRN
Should be combined with a glucocorticoid,
contraindicated for use alone. Many times both drugs
are delivered in the same inhaler (Combo inhaler)

Bronchodilators: Beta 2-Adrenergic

Agonists
PT: Asthma, CAL, COPD:
Oral Beta 2 Agonists:
Only used for long-term control
Onset is too slow to stop an ongoing attack
Should not be used alone

Bronchodilators: Beta 2-Adrenergic

Agonists
Adverse Effects:
SABA inhaled- well tolerated, systemic effects
include tachycardia, palpitations, angina and
tremor
LABA inhaled- Increased risk of severe asthma &
asthma related death but only when used as a
monotherapy (used alone)
Oral- Relative selectivity (can produce beta 1
receptor activation in the heart which results in
angina pectoris, palpitations, and tachydysrythmias)
Can also cause tremor by activating beta 2 receptors
in skeletal muscle. (tremor is reduced by lowering
the dosage)

Bronchodilators: Beta-2
Adrenergic Agonists
WARNING: ContraI./Precautions:
Use caution in patients with cardiac
disorders, diabetes mellitus, digitalis
intoxication, hypertension,
hyperthyroidism or history of seizures
Can potentiate these symptoms (worsen)

Bronchodilators: Beta 2-Adrenergic

Agonists
Preparations:
Inhaled preparations for quick relief can
be given by MDI, DPIs & nebulizers
Typically 1-2 puffs, 3-4 times a day. When 2
puffs are needed, wait at least 1 minute
between puffs (to improve bronchodilation &
penetration of second puff)

Inhalers for Long-term control: Typically

taken Q12 hrs or Twice a day.
Oral Long-term control: Typically taken 34 times daily.

LABA/Glucocorticoid Combinations
Fluticasone/salmeterol (Advair)
Budesonide/formoterol (Symbicort)
Mometasone/formoterol (Dulera)
Provide anti-inflammatory benefits
(glucocorticoids) and bronchodialtion (beta 2
agonists)
For pts whose asthma is not controlled by
glucocorticoids alone
All carry black box warnings: possible increased
risk of asthma severity or asthma-related death
(Due to LABA, but risk should be minimal as
they are combined with glucocorticoid)

Beta2-Adrenergic Agonists

Inhaled: Short Acting

Albuterol (AccuNeb, ProAir, Proventil, Ventolin)
Levalbuterol (Xopenex)
Pirbuterol (Maxair)
Inhaled: Long Acting
Arformoterol (Brovana)
Formoterol (Foradil, Perforomist)
Indacaterol (Arcapta Neohaler)
Salmeterol (Serevent)
Oral (Long Acting)
Albuterol (VoSpire ER)
Terbutaline (Brethine)

Methylxanthines or Xanthine
Derivatives
PD: prominent CNS excitation, &
bronchodilation
May also cause cardiac stimulation,
vasodilation & diuresis.
Theophylline (Theo-24, Theochron,
Elixophyllin) is the principle
methylxanthine used in asthma
Caffeine is also a methylxanthine

Xanthine Derivatives
Xanthine derivatives, including
theophylline, aminophylline, diphylline,
and caffeine, come from a variety of
naturally occurring sources
They are excellent bronchodilators but
do not work as rapidly as betaadrenergic agonist drugs
Prototype drug: theophylline (Slophyllin)

Methylxanthines: Theophylline
Very narrow therapeutic window or
range
Must monitor blood concentration of
drug

Use has declined sharply, because safer

and more effective drugs are available
(inhaled glucocorticoids & inhaled beta 2
agonists)
Not effective when inhaled (oral only)
PD: Produces bronchodilation by relaxing
smooth muscle of the bronchi.

Methylxanthines: Theophylline
PT: Asthma, CAL, COPD)
Oral: used for maintenance therapy for
chronic stable asthma.

Less effective than beta 2 agonist, but

longer duration of action (sustained
release formulations)
Intravenous- has been used in
emergencies, NOT more effective than
beta 2 agonists & glucocorticoids, more
serious adverse effects

Methylxanthines: Theophylline
THERAPEUTIC DRUG LEVELS: 10-20 mcg/mL.
Some achieve benefits at 5 mcg/mL, no
additional benefit seen @ level 15 vs. 10 mcg/mL
20-25 = mild adverse symptoms (diarrhea,
nausea, vomiting, insomnia, & restlessness)
30 or higher = severe ventricular dysrhythmias,
convulsions, cardiorespiratory collapse and
death.
STOP treatment immediately if signs of toxicity
develop, give activated charcoal together & a
cathartic, lidocaine for arrhythmias, diazepam for
convulsions

Methylxanthines: Theophylline
Drug Interactions:
Caffeine- Intensifies the effects of
theophylline (adverse effects on CNS &
heart).
NO CAFFEINE IF TAKING THEOPHYLLINE

Drugs That Reduce Theophylline Levels:

Phenobarbital, phenytoin, and rifampin

Drugs that Increase Theophylline Levels:

Cimetidine and fluoroquinolone antibiotics
(ciprofloxacin)

Methylxanthines: Others
Aminophylline- Basically the same as
theophylline, more fluid soluble
Preferred for IV use (MUST GIVE SLOWLY)
because rapid injection can cause severe
hypotension and death.

ANTICHOLINERGIC DRUGS
PD: Improve lung function by blocking
muscarinic receptors in bronchi, causes
bronchial dilation
Two agents available: ipratropium
(Atrovent) & tiotropium (Spiriva).
PT: Approved only for chronic obstructive
pulmonary disease (COPD), but often
used for asthma.
Spiriva has a longer duration of action

Respiratory Anticholinergic
Agents

Inhaled anticholinergic drugs are

considered first-line treatment for
patients with CAL.
Anticholinergic agents diminish the
effect of acetylcholine
In the respiratory system, use of inhaled
anticholinergic drugs stops
bronchoconstriction
Prototype drug: ipratropium
bromide (Atrovent)

Anticholinergic: Ipratropium (Atrovent)

Atropine derivative, adm. By inhalation, relieves
bronchospasm, Promotes bronchodilation
Therapeutic effects begin 30 seconds, reach
50% max. 3 minutes, lasts approx.6 hrs
Effective against allergen-induced asthma
and EIB, but less effective than beta 2
agonists
Often combined with beta 2 agonists as
beneficial effects are additive (work
through different mechanisms of action)Combivent and Duoneb (ipratropium and
albuterol)

Anticholinergic: Ipratropium (Atrovent)

Adverse Effects:
Systemic effects minimal, Quaternary ammonium
compound, carries a positive charge, therefore not
readily absorbed from lungs or GI tract (local action)
Most common- dry mouth and irritation of
pharynx
If systemic absorption occurs can raise intraocular
pressure in pts with glaucoma
Associated with adverse cardiovascular events (MI,
CVA, and death).
Combivent (ipratropium/albuterol) contains soya
lecithin and individuals with peanut allergy can
react

Anticholinergic: Tiotropium (Spiriva)

Tiotropium: a long-acting inhaled
anticholinergic
PD: Relieves bronchospasm same as Atrovent.
Therapeutic effects begin about 30 minutes
after inhalation, peaks in 3 hrs, and
persists for 24 hrs (see difference, long acting)
Bronchodilation improves with each dose,
reaches plateau (max effect) after eight
consecutive doses
Will not help with acute attack
Do NOT swallow capsules,(Inhalation only,
DPI)

Anticholinergic: Tiotropium (Spiriva)

Adverse Effects:
Most common: dry mouth, (sugarless
candy can help)diminishes over time
Systemic anticholinergic effects
(constipation, urinary retention,
tachycardia, blurred vision) are minimal
due to poor systemic absorption

Anticholinergics
Ipratropium, inhaled (Atrovent)
Tiotropium, inhaled (Spiriva)