Pharmacotherapeutics for Advanced Nursing Practice 433
Allergic rhinitis and asthma will be the prototypical disease states used to introduce these agents.
· Sympathetic stimulation causes vasoconstriction, resulting in reduction of tissue size and airway widening.
· Parasympathetic stimulation causes vasodilation and airway narrowing.
· The nasal mucosa contains mast cells.
o Mast cells release histamine which increases epithelial permeability.
o This allows allergens to reach the submucosa where there is a high density of mast cells.
o Once a patient is susceptible, allergens react with IgE on these mast cells.
o The release to cytokines from these cells produce local inflammation.
· Signs/symptoms commonly seen include: rhinorrhea, sneezing, itching in the nose and throat, watery eyes
· Exacerbations of asthma
· Acute and chronic sinusitis
· Antihistamines and decongestants work to alleviate symptoms.
· Nasal steroids and nasal cromolyn are also very helpful in reducing symptoms in chronic patients.
· Leukotriene inhibitor used for asthma has also been found to be of benefit for allergy symptoms
Note: There are two types of histamine blockers (“antihistamines”): histamine1 (H1) blockers are used for treatment of seasonal allergic rhinitis, anaphylaxis, insect reactions, whereas histamine2 (H2) blockers are used in the treatment of gastric acid disorders such as ulcers. The following discussion relates to histamine1 blockers.
· Mechanism of action: antagonize the histamine receptor, preventing the action of histamine.
o All antihistamines work best when given before allergen exposure.
· Oral antihistamines are systemic; use especially if person is experiencing eye symptoms of allergy along with the nasal symptoms.
· The use of antihistamines in allergic rhinitis is effective, but side effects and cost can limit their use.
o All are equally effective.
o Side effects determine the choice of agent.
|
Generic Name |
Brand Name |
Anticholinergic Effects* |
Sedative Effects |
Comments |
|
Brompheniramine |
Dimetane, Codimal-A |
Moderate |
Low |
Cause
less drowsiness and more CNS stimulation; suitable for daytime use |
|
Chlorpheniramine |
Chlor-Trimeton |
Moderate
|
Low |
|
|
Clemastine |
Tavist |
High |
Moderate |
Substantial
anticholinergic effects; commonly cause sedation; with usual doses drowsiness
occurs in » 50% of patients; diphenhydramine and dimenhydrinate
also used as antiemetics |
|
Diphenhydramine |
Benadryl |
High |
Low
to Moderate |
|
|
Dimenhydrinate |
Dramamine |
High |
Low
to Moderate |
|
|
Promethazine |
Phenergan |
High |
High |
Also
used as antiemetics, antivertigo |
|
Hydroxyzine |
Atarax, Vistaril |
Moderate |
Moderate |
Also
used as a tranquiller, sedative, antipruritic, and antiemetic |
|
Loratadine |
Claritin
(OTC) |
Low
to none |
Low
to none |
Very
few adverse effects from anticholinergic or sedative effects; almost exclusively
antihistaminic effects; can take during day because no sedative effects. In general they are longer acting and have
fewer side effects. |
|
Desloratadine |
Clarinex |
Low
to none |
Low
to none |
|
|
Cetirizine |
Zyrtec |
Low
to none |
Low
to none |
|
|
Fexofenadine |
Allegra |
Low
to none |
Low
to none |
* If anticholinergic effects are “high”, high risk of urinary retention, paradoxical excitation.
· The sedating agents are less expensive and generally safe, thus it may be worth beginning therapy with these agents. Caution with elderly, others at risk for falls.
· With sedating agents such as chlorpheniramine (ChlorTrimeton), begin with 1 mg. BID (short acting) and work up over 2-6 weeks to full dose (8-12 mg/day) to prevent dose limiting side effects such as sedation in patients with significant allergy.
· Cardiovascular system (small blood vessels)
o Histamine effect: Dilation of blood vessels, increased blood vessel permeability (allows substances to leak into tissues)
o Antihistamine effect: Prevent dilation of blood vessels and increased permeability
· Smooth muscle (on exocrine glands)
o Histamine effect: Stimulates salivary, gastric, lacrimal, and bronchial secretions
o Antihistamine effect: Prevents salivary, gastric, lacrimal, and bronchial secretions
· Immune system (release of various substances commonly associated with allergic reactions)
o Histamine effect: Mast cells release histamine and several other substances, resulting in allergic reactions
o Antihistamine effect: Do not stabilize mast cells nor do they prevent the release of the substances such as histamine, but they bind to histamine receptors and prevent the actions of histamine.
Problem with the early non-sedating antihistamines (terfenadine [Seldane] and astemizole [Hismanal]):
· Metabolized by the liver
· Erythromycin, ketoconazole (Nizoral), itraconazole (Sporanox) could inhibit their metabolism.
· In some patients, this could result in toxic concentrations of terfenadine and astemizole, resulting in arrhythmias from prolongation of the QT interval.
· These medications were removed from the market.
Monoamine oxidase inhibitors such as Nardil (phenelzine) may prolong or intensify the anticholinergic effects of antihistamines. Avoid the combination of these drugs.
Decongestants are useful for immediate relief of symptoms while waiting for onset of action of antihistamines and anti-inflammatories.
· Examples: oxymetazoline (Afrin, Dristan Q12-24 h) and phenylephrine (Neosynephrine q6-24 h)
· Drug administration: have patient lay on bed with head tilted back. Have patient stay reclined for 3-5 minutes to allow for absorption.
· Duration of therapy: use only when needed for no longer than 3-5 days.
o With prolonged therapy, “rhinitis medicamentosa” occurs in virtually all patients.
o More of the drug is required to produce the same effect.
o Once the drug is stopped, there is rebound congestion (rebound vasodilation) following the extreme vasoconstriction. Patients will want to use the drug again to treat this.
o Treatment involves a 2-3 week wean of the topical agent while combining a nasal anti-inflammatory agent such as cromolyn.
Phenylpropanolamine [PPA] (as in Allerest, Contac, Rhinedecon, and Dexatrim): pulled from market in 2000 due to risk of hemorrhagic stroke, particularly in women
Pseudoephedrine (as in Pediacare, Sudafed): still available
Phenylephrine (also a decongestant): avoid in HTN patients
Examples:
· Good if patient’s only allergy symptoms are nasal
· All of these agents may be more effective than antihistamines for long term control of allergic rhinitis.
· They need to be used once the patient is decongested and with clear nasal passages.
· The steroids work by stabilizing the epithelial mediator cells and decreasing epithelial permeability.
· Cromolyn works by stabilizing the mast cells.
· They have little additive effect when used in combination with antihistamines.
· Their onset is within a few days to 2 weeks.
o During this time it is useful to use an antihistamine and decongestant if needed.
· Note: These can be very drying (® nasal bleeding) and will have only a local effect. Warn patients of drying effect. Avoid use in nasal trauma.
Intranasal Antihistamine: azelastine nasal (Astelin)
If patient’s symptoms also include watery eyes, will need a systemic medication:
Asthma
· Allergic
o May be seasonal or non-seasonal
o Most likely cause: allergens (antigens) such as animal dander, dust, and molds
· Idiopathic
o Most likely cause: poorly defined etiologic factors; may be induced by stress, respiratory infections, or strenuous exercise
· Mixed
o Most likely cause: combination of allergens and some of the idiopathic factors
· Beta-Agonists (= sympathomimetics)
o Cause relaxation of the smooth muscle that surrounds the airways
o May stimulate alpha and beta receptors, beta1 and beta2 receptors, or just beta1 receptors
o Beta2 stimulants are the most specific for the lungs and have the fewest side effects
o Examples:
· Beta2-agonist: albuterol (Proventil HFA inhaler, Ventolin)
· Beta1-beta2 agonist: metaproterenol (Alupent)
· Alpha-beta agonist: epinephrine (Adrenalin, Primatene, Bronkaid)
· Long-acting: salmeterol (Serevent) – 2 puffs every 12 hours
· Long-acting: formoterol (Foradil Aerolizer) – 12 mcg inhalation every 12 hours (12 mcg/powder cap) $80/month
CAUTION: A 2002 study (Salmeterol Multi-center Asthma Research Trial [SMART] showed a statistically significant greater number of primary events and asthma-related events, including deaths, in patients taking salmeterol compared to those taking placebo. This was seen in African Americans enrolled in the study, but not in Caucasian patients in the study.
Recommendations: National
Asthma Education and Prevention Program (NAEPP) guidelines recommend patients
requiring more than as-needed short-acting beta2-agonists should be prescribed
regular and adequate doses of an inhaled anti-inflammatory asthma medication,
such as inhaled corticosteroids, for optimal benefit in the management of their
asthma. Consistent with these guidelines and reinforced by trends seen in the
interim analysis of the SMART data, GlaxoSmithKline recommends that patients
receiving salmaterol for asthma should normally also
be receiving regular and adequate doses of an effective asthma controller medication,
such as inhaled corticosteroids.
(Source: Safety information released by GSK in 2003)
New as of 2010: The FDA required label changes and other initiatives to promote safe use of long-acting beta agonist (LABA) agents, noting that these agents should never be used alone in children or adults with asthma. This affected the two single-agent LABAs approved for asthma: salmeterol (Serevent) and formoterol (Foradil). The labels were changed to require that the drugs always be used in combination with an asthma controller medication such as an inhaled corticosteroid.
o Contraindications to use: history of cardiac disease, dysrhythmias, angina, CAD, HTN, seizure disorders
o Side effects: tremor, insomnia, restlessness, vascular headache
o Interaction: Beta-agonist bronchodilator + nonselective beta-blocker = antagonizes the bronchodilation
· Diabetics: epinephrine increases blood glucose levels
· Inhaled Corticosteroids
o Work by stabilizing the membranes of cells that release harmful bronchoconstricting substances
o Not first-line agents; commonly used when conventional bronchodilators fail
o Examples: beclomethasone (Vanceril), budesonide (Pulmicort Turbuhaler), dexamethasone (Decadron), flunisolide (AeroBid), fluticasone (Flovent), triamcinolone acetonide (Azmacort)
o Inhaled steroids do not suppress HPA axis except at high doses (exception: Decadron)
· Combination Product: Advair Diskus
o Combination of fluticasone (steroid) + salmeterol (Serevent, long-acting beta agonist)
o 1 inhalation bid
o If not currently on a steroid, can start with 100/50 dose ($189.99/$103)*
o If currently on a steroid, start with either 250/50 ($219.99/$129) or 500/50 ($289.99/$178)*
o Taper to lowest effective dose
* Prices shown $/$: First price listed is current as of 2012/Second price is from 2006.
· Anticholinergics
o Work by blocking the bronchoconstrictive effects of acetylcholine
o Used for maintenance and not relief of acute bronchospasms
o Examples of agents used for treatment of asthma:
- Ipratropium bromide (Atrovent) - 2 puffs qid
- tiotropium inhaled (Spiriva HandiHaler) - 1 capsule inhalation daily ($261.99 as of 2012/$159.98 in 2010 for box of 30)
o Contraindicated in patients with BPH or glaucoma
· Indirect-Acting Agents
o Work by stabilizing the mast cell wall, thereby preventing potentially harmful vasoconstrictive substances from being released
o Only used prophylactically; used for management of chronic pulmonary disease; must be used year-round
o Examples: cromolyn, nedocromil (Tilade)
· Xanthines
o Work by inhibiting phosphodiesterase, which breaks down cAMP, which is needed to relax smooth muscles
o Examples: caffeine, theophylline
o Theophylline is the most common xanthine used; aminophylline is the parenteral form of theophylline.
o Contraindications to use: history of GI tract disorders or peptic ulcer disease
o Factors affecting theophylline clearance
· Decrease clearance: cimetidine, erythromycin, allopurinol, propranolol, OCPs, ciprofloxacin, norfloxacin, ofloxacin, febrile viral illness
· Increase clearance: rifampin, carbamazepine, phenobarbital, phenytoin, smoking, high-protein diet, charcoal broiled meat
o Theophylline half-life
· Neonates: 20-30 hours
· Child 1-12 years old: 3-4 hours
· Nonsmoking adult: 7-8 hours
· Smoking adult: 4-5 hours
· Elderly: 9-10 hours
·
Leukotriene
Receptor Antagonists
o
These
relatively new products are used only for long-term control of asthma
o
They
affect the late phase of the asthmatic response
o
They
are a useful alternative if patients are unable to tolerate the side effects of
the other medications
o
They
may be effective as first-line therapy for patients with mild-to-moderate
asthma when used alone or in combination with beta-agonists used PRN.
o
They
may be especially effective in patients with exercise- or aspirin-induced
asthma
o
The
oral administration is useful for patients who have difficulty using inhalers
o
They
have a very low incidence of side effects
o
There
are four classes of leukotriene receptor antagonists
in development, and three are currently on the market.
·
Montelukast (Singulair) 10 mg qd at hs ($161 for 30 tabs
of brand--generic not available)
· Zafirlukast (Accolate) 20 bid 1 h ac or 2 h pc ($90 for 60 tabs of generic)
·
Zileuton (Zyflo) CR 1200 mg bid ($610 for 120 tabs [600 mg])
o
Leukotriene antagonists prevent the binding of leukotrienes to their receptors in the airways, thereby
blocking bronchospasm
· Only 10-15% of the dose actually gets to the lungs; only 30-45% of patients use proper technique
o Use of spacer
· How to check if full/empty—floating in water not adequate; need to count doses, keep a spare!
· Demonstrate/return demonstration
· Use bronchodilator (Beta-agonist), wait 2-5 minutes, use inhaled steroid
· Rinse mouth after using steroid