Respiratory: Corticosteroids Flashcards
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Basic Understanding:
What does The Expert Panel Report 3 state in regard to Corticosteroids?
PARAGRAPH ONE
The Expert Panel Report 3 states that corticosteroids are the “most potent and effective anti-inflammatory medication
currently available” (NAEPP, 2007, p 213). Their antiinflammatory effects lead to reduction in the severity of asthma symptoms, increased peak flow readings, and decreased airway hyperresponsiveness. In general, inhaled
steroids are safe and well tolerated at recommended dosages and can be used by both children and adults. Cortico -
steroids are also used intranasally for the treatment of allergic rhinitis
PARAGRAPH TWO
The commonly prescribed inhaled corticosteroids for asthma are beclomethasone dipropionate (QVAR), triamcin - olone acetonide (Azmacort), budesonide (Pulmicort), flunisolide (AeroBid), mometasone furoate (Asmanex Twisthaler), fluticasone (Flovent), and ciclesonide (Alvesco). There are significant differences among the different formulations in the amount of steroid delivered per inhalation, and they are not
interchangeable without adjusting the inhalations per day.
PARAGRAPH THREE
The corticosteroids that are available for intranasal use are beclomethasone (Beconase), triamcinolone (Nasacort AQ),
budesonide (Rhinocort Aqua), flunisolide (Nasalide, Nasarel), mometasone (Nasonex), fluticasone (Flonase), and ciclesonide (Omnaris).
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Examples:
beclomethasone [QVAR], budesonide {Pulmicort
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacodynamics:
In the treatment of asthma and allergic rhinitis, the primary actions of orally inhaled corticosteroids are anti-inflammatory. The inhaled adrenocorticosteroids inhibit the immunoglobulin E (IgE) and mast cell–mediated migration of inflammatory
cells into the bronchial tissue (late-phase allergic reaction). The exact mechanism of action by which the inhaled cortico -
steroids inhibit bronchoconstrictor mechanisms and produce smooth muscle relaxation is unknown. The exact mechanism of action of corticosteroids on the nasal mucosa is unknown. Intranasal corticosteroids applied topically to the nasal tissues exert local anti-inflammatory effects without any systemic glucocorticoid effects.
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacokinetics: Absorption and Distribution:
PARAGRAPH ONE
Absorption of inhaled corticosteroids occurs from the lungs and from the GI tract. Approximately 10% to 30% of the dose from an MDI is delivered to the lungs. If a spacer device is not used, approximately 80% of the dose from an MDI is swallowed, with the oral bioavailability differing from drug to drug
PARAGRAPH TWO
Beclomethasone is rapidly absorbed from the nasal and pulmonary tissues and GI tract. Upon inhalation, 10% to 25% of the drug is deposited in the tissues of the mouth, trachea, and lungs, where it is completely absorbed. The remainder of the dose is swallowed. The oral bioavailability of inhaled beclomethasone is 20%. Beclomethasone is highly protein bound. It and its metabolites do not appear to distribute into the tissues, but beclomethasone does cross the placenta. With systemic administration, steroids are excreted in breast milk; it is unknown whether inhaled beclomethasone is found in
breast milk.
PARAGRAPH THREE
Triamcinolone (Azmacort) MDI is packaged with a builtin spacer to enhance the delivery of the medication to the
lungs. Triamcinolone (Nasacort) for intranasal use is delivered via intranasal metered-dose pump. Triamcinolone is
rapidly and completely absorbed from lung tissues and nasal mucosa. It is distributed throughout the hilar areas of the lungs. The oral bioavailability of the swallowed portion of the dose is 10.6%. Triamcinolone is weakly protein bound and crosses the placenta. It is unknown whether inhaled triam - cinolone is excreted in breast milk.
PARAGRAPH FOUR
Approximately 20% of the inhaled dose of budesonide reaches the systemic circulation. Once absorbed from the nasal tissues or lungs, the distribution of budesonide is extensive. Budesonide is 88% protein bound. It is unknown if budesonide is excreted in breast milk, but it passes through the placenta
PARAGRAPH FIVE
Flunisolide is rapidly absorbed from the bronchial tree, with 10% to 20% of the inhaled dose distributing into the 384 • Pharmacotherapeutics With Single Drugs 3827_Ch17_361-414 02/07/15 12:11 PM Page 384 lungs. Fifty percent of an intranasal dose of flunisolide is absorbed into the systemic circulation. The oral bioavailability of the dose is 20% to 40%. Flunisolide crosses the placental
barrier. Breast milk excretion is unknown
PARAGRAPH SIX
Less than 1% of mometasone oral powder for inhalation is absorbed. With nasal administration, the medication that is swallowed is absorbed, although plasma concentrations are near or below the level of quantification. Breast milk excretion
is unknown.
PARAGRAPH SEVEN
Fluticasone is primarily absorbed in the lungs, resulting in systemic bioavailability of 30% of the dose. Intranasal fluticasone has a systemic bioavailability of less than 2%. It is highly lipid-soluble, is rapidly distributed into the tissues, and is 91% protein bound. Fluticasone crosses the placenta. Breast milk excretion is unknown.
PARAGRAPH EIGHT
Ciclesonide is minimally absorbed and what is absorbed is 99% protein bound in distribution
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacokinetics: Metabolism and Excretion:
PARAGRAPH ONE
Some portion of the dose of all inhaled corticosteroids is swallowed. After GI absorption, they all undergo high first-pass liver metabolism
PARAGRAPH TWO
In the lung, beclomethasone is rapidly metabolized to beclomethasone 17-monopropionate and more slowly to free
beclomethasone. Metabolites of beclomethasone are excreted mainly in the feces, with a small portion excreted in
the urine.
PARAGRAPH THREE
Triamcinolone is metabolized into three less-active ingredients: 6-β-hydroxy triamcinolone acetonide, 21- carboxytriamcinolone, and 21-carboxy-6-β-hydroxytriamcinolone acetonide. All of the metabolites of triamcinolone are eliminated in the feces
PARAGRAPH FOUR
Budesonide undergoes extensive first-pass metabolism into two main metabolites: 16-α-hydroxyprednisolone (24%) and 6-β-hydroxybudesonide (5%). The metabolites are excreted in the urine (66%) and the feces
PARAGRAPH FIVE
The part of the flunisolide dose that is swallowed is absorbed and metabolized by the liver into several metabolites.
One of the metabolites has minor glucocorticoid activity. The drug is further metabolized into inactive metabolites. Excretion of inhaled flunisolide is not described, but oral doses are excreted equally in the feces and the urine.
PARAGRAPH SIX
Mometasone is extensively metabolized in the liver via CYP3A4 isoenzyme. It is excreted primarily via the bile; 74% of metabolites is excreted in feces
PARAGRAPH SEVEN
Fluticasone is metabolized in the liver primarily by CYP3A4. The only detectable metabolite is a 1-β-carboxylic acid derivative. Excretion is primarily in the feces; less than 5% is excreted in the urine
PARAGRAPH EIGHT
Ciclesonide is metabolized by CYP3A4 into an active metabolite, des-ciclesonide. Sixty-six percent of ciclesonide is excreted in the feces and approximately 20% in the urine.
PARAGRAPH NINE
Pharmacokinetics is presented in Table 17-7.
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacotherapeutics: Precautions and Contraindications:
PARAGRAPH ONE
All of the inhaled corticosteroid preparations are contraindicated in acute status asthmaticus or when intensive, acute therapy is warranted. They should not be used for relief of acute bronchospasm.
PARAGRAPH TWO
Care should be used when substituting any of the inhaled corticosteroids for oral corticosteroid therapy. There have been deaths due to adrenal insufficiency in asthmatic patients who were switched from oral to inhaled corticosteroids.
PARAGRAPH THREE
The risk for hypothalamic-pituitary-adrenal (HPA) suppression is low with inhaled corticosteroids, but the risk
increases when inhaled corticosteroids are administered while the patient is taking oral steroids.
PARAGRAPH FOUR
Inhaled corticosteroids should be avoided in patients with Cushing’s syndrome. They should be used with caution in patients with ocular herpes simplex infections, tuberculosis, oral or nasal surgery or trauma, healing nasal septal ulcers, and untreated respiratory infection (viral, fungal, or bacterial).
PARAGRAPH FIVE
All of the inhaled corticosteroids are Pregnancy Category C. There have been no well-controlled studies of the effects of inhaled corticosteroids during pregnancy.
PARAGRAPH SIX
The use of high-dose inhaled steroids in children may inhibit growth, but so can poorly controlled asthma. A large (N = 943) long-term study of the effects of inhaled corticosteroids on children followed for more than 12 years, to an average age of 25 years, observed a 0.47 inch difference in average height for the subjects in the budesonide
group (NHLBI, 2012). Doses higher than 400 mcg/day in younger children warrant close monitoring of growth. Triamcinolone inhalant therapy should not be prescribed to children under age 6 years because the safety and efficacy have not been established. Budesonide safety has been determined for children as young as 6 months. Inhibition of
growth has been noted in children on high-dose inhaled fluticasone. Fluticasone must be prescribed with caution to children under age 4 years. Mometasone nasal spray may be prescribed for children as young as age 2 years, but the safety of mometasone oral inhalation powder for asthma management has not been established for children younger than age 12. The safety of inhaled flunisolide in children under age 6 has not been established. Studies were conducted in children aged 6 to 11 years regarding the safety of nasal ciclesonide; nasal ciclesonide (Omnaris) is considered safe and effective in children aged 6 or older. During clinical trials the safety and efficacy of inhaled ciclesonide (Alvesco) was studied in children aged 4 to 11 years with asthma. To control asthma symptoms, ciclesonide (Alvesco) was determined to be safe, but not effective, in children younger than 12.
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacotherapeutics: Adverse Drug Reactions:
PARAGRAPH 1
All of the inhaled corticosteroids have associated xerostomia, hoarseness (5% to 50% of patients), tongue and mouth
irritation, flushing, and dysgeusia (altered taste sensation). Rash and urticaria have been reported with the use of flunisolide, beclomethasone, and fluticasone. Dysmenorrhea has been reported in 1% to 3% of patients using inhaled fluticasone and 4% to 9% using mometasone oral inhalation
powder.
PARAGRAPH 2
Local immunosuppression can lead to oral candidiasis with any of the inhaled corticosteroids. Cataracts can be induced with corticosteroid use, even with inhaled cortico - steroids. Bronchospasm may occur with any of the inhaled corticosteroids. With high-dose inhaled corticosteroid use, HPA suppression is theoretically possible. Concurrent use of systemic corticosteroids with inhaled corticosteroids increases the likelihood of HPA suppression, compared with the use of either one alone.
PARAGRAPH 3
Pulmonary infiltrates with eosinophilia may occur with inhaled flunisolide, usually when inhalation corticosteroid therapy replaces systemic corticosteroid therapy. The cause is unknown
PARAGRAPH 4
Intranasal corticosteroid use may cause nasal irritation, itching, sneezing, and nasal dryness. The patient may experience bloody nasal mucus or epistaxis.
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacotherapeutics: Drug Interactions:
PARAGRAPH 1
There are no known drug interactions with inhaled triamcinolone, flunisolide, mometasone, beclomethasone, or
ciclesonide.
PARAGRAPH 2
Ritonavir significantly increases fluticasone serum concentrations and may lead to increased corticosteroid effects of fluticasone. Ketoconazole increases plasma concentration
of fluticasone and budesonide when coadministered. The interaction is due to inhibition of CYP3A4 isoenzyme, the
enzyme that metabolizes fluticasone and budesonide. There are no other known drug interactions, but close monitoring
for corticosteroid-related side effects is advisable if coadministered with other drugs that are known to inhibit CYP3A4.
Those drugs include anastrozole (Arimidex) in high doses, delavirdine (Rescriptor), erythromycin, fluconazole (Diflucan), fluoxetine (Prozac), itraconazole (Sporanox), mibefradil
(Posicor), nefazodone (Serzone), nelfinavir (Viracept), ritonavir (Norvir), and zileuton (Zyflo). Drug interactions are presented in Table 17-8.
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacotherapeutics: Rational Drug Selection:
PARAGRAPH 1
The Expert Panel Report 3 and update (NAEPP, 2007) do not recommend one inhaled corticosteroid over another; therefore, the choice is mostly based on ease of dosing and the adverse drug interactions and indications previously addressed. There are no generic equivalent formulas for the inhaled cortico - steroids but there is generic fluticasone nasal spray, which may
make cost a factor as more generic formulas are available
PARAGRAPH 2
Dosing
If a patient requires a high dose of inhaled steroid, the bec - lomethasone 42 mcg/puff dose would be more than 20 puffs per day, whereas the dose of budesonide would be 8 or more
puffs per day. High-dose triamcinolone would also be 20 puffs per day. Fluticasone and flunisolide have the highest steroid anti-inflammatory effect per puff, which makes dosing highdose inhaled steroids more convenient (see Table 17-9 for dosing). If the patient requires a low dose or if trying to wean
the dose, beclomethasone or triamcinolone would be the first
choice.
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacotherapeutics: Monitoring
PARAGRAPH 1
The patient who is using inhaled corticosteroids needs to be
monitored for adverse effects of the medication, effectiveness of the medication, and the asthma disease process. If highdose inhaled corticosteroids are used for a long time, blood glucose and potassium should be monitored, as well as
growth in young children.
Types of Respiratory Drugs:
Respiratory Inhalants: Corticosteroids
Pharmacotherapeutics:
Patient Education:
PARAGRAPH 1
Administration
Patients who are concurrently using an inhaled bronchodilator should administer the bronchodilator first and wait several
minutes before using the inhaled corticosteroid. This procedure enhances the absorption of the steroid in the bronchial tree.
PARAGRAPH 2
The administration of inhaled corticosteroids via an MDI can be difficult for most adults and all children. Learning to
coordinate the release of the medication from the inhaler with a deep breath is difficult. Written and pictorial instructions
are available with the inhaler, but the provider must not assume that the patient understands the proper method of administering inhaled medications. Use verbal instructions as well as actual demonstration with a placebo inhaler to reinforce the written instructions. These instructions and demonstrations should be repeated at follow-up visits.
PARAGRAPH 3
To use an inhaler properly, the patient should first exhale and then tilt the head slightly back and place the inhaler
mouthpiece either about 2 inches from the open mouth or between the open lips. While inhaling, the patient should
press down on the canister, breathe in slowly and deeply, and hold his or her breath for 10 seconds (count of 10) or as long as comfortable. If multiple puffs are prescribed, then the patient should wait at least 1 full minute between inhalations.
PARAGRAPH 4
To assist with the delivery of inhaled medications, spacers can be prescribed to ensure the medication is deposited in the
lungs, not the mouth. The Aerochamber is a tube-like device that has pictures drawn on the outside to remind the patient of the proper techniques. For younger children and older adults, the InspirEase spacer gives a visual cue of the spacer bag
deflating to help in taking a deep-enough breath. Both of these devices cue the patient to breathe slowly by emitting a whistling sound if the patient is taking too rapid a breath. The Global Initiative for Asthma Web site has extensive information and diagrams on the use of the different types of spacers and inhalation delivery devices (www.ginasthma.org/documents/11).
PARAGRAPH 5
Dry powder, breath-actuated inhalers require adequate inspiratory effort to deliver the medication into the bronchial
tree. Patient self-administration should be observed to determine whether the medication is being used appropriately.
PARAGRAPH 6
Patients should rinse their mouth with water after each use to help reduce dry mouth, hoarseness, and candidiasis infection.
PARAGRAPH 7
The patient should clear the nasal passages of mucus prior to using intranasal corticosteroids. If the nasal passages are
swollen and blocked, the patient should administer a topical decongestant prior to using intranasal corticosteroids. The
medication is sprayed into the nasal passages. The patient does not need to inhale the medication. The patient should
understand that the effects are not immediate and that clinical improvement may take 3 to 7 days. Rinsing the mouth
with water after use will reduce the rare chance of candidiasis infection associated with intranasal corticosteroid use
PARAGRAPH 8
Inhaled steroids are not to be used as abortive asthma medications; they are for preventive therapy only. The provider should have patients bring in all their inhalers and review which are to be used for abortive therapy (short-acting
beta agonists) and which are for preventive therapy. The patient should be advised to continue to use the inhaled corticosteroid even when not having asthma symptoms.
PARAGRAPH 9
Adverse Reactions
The patient should be advised to notify the provider if sore mouth or throat occurs. Oral Candida infections are possible, and the patient should get prompt treatment. The patient should be aware of the possibility of dysphonia developing. Rinsing the mouth with water and using a spacer device will
decrease its incidence. Other adverse effects occur less often, but the patient should be aware of them and be instructed to Drugs Affecting the Respiratory System • 391 3827_Ch17_361-414 02/07/15 12:11 PM Page 391 notify the provider if adverse effects begin to develop from
the inhaled medication.
PARAGRAPH 10
Relatively few medications interact with the inhaled corticosteroids. Ketoconazole should be avoided for patients who are prescribed fluticasone, ciclesonide, and budesonide. Patients should be instructed to notify all providers that they are on inhaled corticosteroids to avoid possible
interactions
PARAGRAPH 11
Lifestyle Management
Lifestyle management issues related to the disease process should be discussed. They often include the following:
- Patients need to self-monitor their respiratory status with a peak flowmeter to determine the effectiveness of the medication prescribed.
- The patient should avoid or quit smoking.
- The patient should avoid environmental triggers for asthma at home, work, and school.
Available dosage forms are presented in Table 17-9
