Definition And Clinical Characteristics Biology Essay

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Allergic rhinitis is a condition seen worldwide, affecting more than 500 million people, most notably in developed industrialized countries. It was first described as a disease almost two centuries ago and the prevalence continues to rise without explanation in most countries. This disorder affects young and old alike, but incidence appears to peak around the late childhood to teenage years. Although many people consider AR as more of a nuisance than a disease, it does have detrimental effects on patients' social life, work productivity, academic performance and increase the risk of other health problems such as pain, fatigue, headache, and depression. The direct costs of treating AR cannot be avoided, however, indirect costs which are a burden on society, may be prevented through treatment of the disorder.

Pathophysiology (II)

Definition and Clinical Characteristics (A)

Allergic rhinitis is caused by an allergen-induced inflammation of the nasal mucosa mediated by immunoglobulin E. This disorder involves a myriad of symptoms including sneezing, rhinorrhea, postnasal drainage, nasal congestion, nasal and ocular pruritis and ocular lacrimation. A temporary loss of taste and smell may also be experienced. The ocular symptoms are helpful to distinguish allergic rhinitis from rhinitis of a different cause. The symptoms of AR are a result of the body initiating an allergic response to specific allergens. Exposure to these allergens causes the body to develop early and late phase reactions. Early phase symptoms (rhinorrhea, sneezing, pruritis and nasal congestion) generally occur within minutes of exposure to the allergen whereas late phase reactions (nasal congestion, loss in sense of smell, postnasal drainage) are delayed by a few hours. Commonly, one will see a distinction in the diagnosis of AR depending on if it occurs during a season [seasonal allergic rhinitis (SAR)] or if the patient has symptoms year-round [perennial allergic rhinitis (PAR)]. Of patients diagnosed with AR in the United States (US), it is reported that 20% suffer from SAR, 40% have PAR and 40% have some combination of both SAR and PAR. This distinction between SAR and PAR is suboptimal when discussing global impact, because of the lack of seasons in many countries of the world. Still, these terms can be found in an abundance of literature. Seasonal AR is mostly associated with outdoor allergies when various pollens are in the air. Seasonal AR in the fall is most commonly referred to as "hay fever," where symptoms seen in the spring are considered "rose fever". Conversely, PAR is generally caused by indoor allergies such as cockroaches, molds, pet dander and most commonly, dust mites. One may also be able to ascertain if the patient has SAR versus PAR as certain symptoms and comorbid disease states are more commonly seen with one more than the other. For example, nasal obstruction, smell disturbance, asthma, and chronic sinusitis are more commonly seen in PAR, where sneezing and eye symptoms are more closely associated with SAR. A link also exists with asthma and AR. Up to 40% of AR patients have asthma and up to 80% of asthma patients have AR. Therefore, if one is diagnosed, it is suggested that evaluation for the other should occur.

Etiology (B)

Allergic rhinitis is an atopic disease which appears to have a genetic component. Studies supporting the 'hygiene hypothesis' state the risk for developing allergies is directly opposite of risk of infection. Other risk factors can be found in Box 1.

Diagnosis (C)

Diagnosis of this disorder is primarily made by medical history obtained from the patient or caregiver. Patients with more severe disease may undergo further testing to determine the exact allergens causing their AR. These tests include allergy sensitivity skin testing and radioallergosorbent testing (RAST) and are generally reserved only for those who do not respond to empiric therapy. Skin testing is fairly easy, more sensitive and inexpensive compared to RAST.

Therapeutic goals/outcomes (D)

The therapeutic goal for patients with AR is to minimize or completely alleviate symptoms and allow for the patient to have a normal quality of life.

Quality Patient Care (III)

Guidelines (A)

Allergic Rhinitis and its Impact on Asthma (ARIA) (1)

The ARIA guidelines have been providing a sense of direction in the management of AR for over a decade. The World Health Organization is responsible for creating the original ARIA working group and guidelines. The most recent update published in 2008 validated many of the recommendations of the original document and gaps were filled. A revision to the 2008 guidelines occurred in 2010 (Brozek 2010) with recommendations now based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide practitioners in the management of patients with AR. The GRADE system gives a quality of evidence (high, moderate, low or very low) based on the appropriateness of methods used in clinical trials. Further, the GRADE system provides strength of the recommendation as either weak or strong. Values and preferences are also considered in these guidelines to direct practitioners in the decision making process.

US Rhinitis Practice Parameters (2)

The US Rhinitis Practice Parameters (Wallace 2008) is a joint compilation of recommendations from the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. In general, these guidelines agree with the recommendations provided by ARIA except for the recommendation to use oral antihistamines over nasal antihistamines and montelukast. This set of parameters also does not include recommendations for therapies not available in the US (eg, sublingual immunotherapy) and uses a different, more traditional system to rate the evidence. Finally, they do not include values or preferences in their recommendations.

Non-pharmacologic (B)

Avoidance of allergens (1)

The first principle that must be followed for relief of symptoms of AR is causal allergen avoidance. This is likely easier for patients affected only seasonally. For patients with SAR, some measures would include avoiding exposure to outdoor pollens, keeping doors and windows closed, and using an air conditioner with a small-particle filter. Patients with PAR should avoid dust mites, remove home carpeting, choose roller blinds over curtains, reduce home humidity to less than 40%, use hot water for washing bedding at least once per week, avoid furry toys and cushions on bedding, and minimize animal exposure. Although special allergy proof pillow and mattress covers are available, they have not been shown to be beneficial to reduce disease burden. At best, the benefits appear to be meager. However, this lack of symptom improvement may be because of a real absence in efficacy in the removal of dust mite exposure or the ineffective approach despite reductions in levels of dust mites. Other non-specific triggers to be avoided by affected patients may include smoke, fumes, changes in temperature, strong perfumes and pollution. Although total avoidance is difficult, evading allergens not only allows for fewer symptoms of AR, but also may decrease the patient's need for pharmacotherapy.

Nasal saline irrigation (2)

Intranasal saline (isotonic or hypertonic) is a non-pharmacologic option for patients either as monotherapy or in addition to their pharmacologic therapy for AR. Although this therapy is not as effective as some of the pharmacologic agents, it does afford modest benefit especially for rhinorrhea, demonstrate less adverse effects, show improvement in quality of life and is inexpensive. Although there are many proposed mechanisms of the benefit this therapy can bring, none have been confirmed in clinical trials. Daily dose, concentration of solution, and ideal method for delivery have also not been established.

Pharmacotherapy (C)

Despite the global burden of AR, the disease is often undertreated. Because the pathophysiology of AR is complex and not fully understood, there is no idyllic drug treatment currently available. No drug is completely effective, yet we have a variety of options to combat the different signs and symptoms of AR (table with ++). Certain compounds are used for the immediate relief they bring whereas others target the underlying cause of symptoms through inhibition of inflammatory mediators. Because many of the agents used to treat this disorder have few adverse effects, empiric therapy is most commonly initiated on clinical suspicion of AR. Regardless of the drug chosen, patients with SAR may benefit by starting therapy one to two weeks before the beginning of their respective allergy season. Therapy for this disorder should be approached as both step-up as well as step-down of treatment depending on symptom containment.

Intranasal corticosteroids (1)

Intranasal corticosteroids (INC) are the most effective treatment available for AR and considered first-line treatment for moderate to severe disease. No single agent within this class has shown superiority over another despite significant pharmacokinetic differences. This medication class has the greatest effect on nasal congestion, often a chief complaint from patients with AR, because of the anti-inflammatory mechanism. Furthermore, INCs show benefit with all other AR symptoms as well. The ARIA guidelines recommend these drugs for adult patients and suggest them for children with AR. A possible downfall of this medication class is that the initial effects of the INC occur within 30 minutes of administration but maximum benefits will not be seen for a few days to a couple of weeks of use. Therefore, it is recommended that patients with SAR initiate use before allergy season. They will provide the best relief for sufferers of SAR if they are taken on a continuous basis but some relief may be seen with as-needed use. Systemic adverse effects are negligible compared to oral corticosteroids because of the lower bioavailability. Despite a majority of evidence showing the INCs do not effect long term growth in children, they all carry the warning that long-term use may cause this problem and the lowest effective dose should be used. There are minor application site complications such as nasal irritation, dryness and epistaxis which tend to wane over time. If these adverse effects continue to be problem-some for the patient, switching to a different INC and/or delivery device may be beneficial. Nasal septal perforation is a very rare adverse effect seen most commonly with inappropriate administration of INCs. There are several differences between INC products that may assist with the therapeutic choice including odor and taste after administration, discomfort experienced during and directly after spray and ease and frequency of use.

Practitioners may prescribe oral corticosteroids due to treatment failure of other options. However, this should be considered last line therapy and is only suggested for a short duration in patients who have moderate or severe nasal and/or ocular symptoms where other recommended therapies have failed. Oral corticosteroid therapy should be avoided in the pediatric population, pregnant women and any patient with a contraindication to their use. Further, intramuscular corticosteroids are not recommended for any patient for the treatment of AR due to the possibility of serious adverse effects.

Antihistamines (2)

Oral (a)

Oral antihistamines may be used empirically as first line therapy for mild intermittent AR symptoms. These drugs are a good option for initial management of AR as they have mild adverse effects and are easily obtainable with many available over the counter. This class has a very rapid onset of action and therefore is helpful for patients who use them only as needed. They are very helpful in alleviating early phase symptoms but are not helpful in the late phase reactions, especially nasal obstruction. Because of this lack of real benefit on nasal obstruction, there may be benefit in the short-term use of decongestants with oral antihistamines. These agents should only be used as add on therapy in patients with persistent or moderate-to-severe AR where INC should be the drug of choice. The class is usually divided between first and second generation agents based on when they came to market, their selectivity for the histamine 1 (H1) receptor and their adverse effect profile. Because the older agents are less selective for H1 receptors, they cause more anticholinergic effects such as urinary retention and dry mouth. Due to their lipophilicity, first generation agents readily cross the blood brain barrier, cause more sedation and impair motor function. At recommended doses, cetirizine may also cause sedation despite being a newer generation agent. These adverse effects can cause significant quality of life and safety issues. However, all adverse effects seen in this class are more on a continuum with indiscriminate starting points and therefore, it is difficult to truly categorize antihistamines into groups. Current guidelines recommend using only the "new-generation" agents that do not cause sedation and do not have interactions within the cytochrome P450 system. All newer generation agents appear to have similar effectiveness in alleviating symptoms of AR.

Nasal (b)

Administration of antihistamines locally has the benefit of allowing for high concentrations of drug to the affected site and lowering possible systemic adverse effects. They have been shown to be as or more beneficial than the oral agents for most symptoms of AR including the most bothersome, nasal obstruction. However, they appear to have less benefit in the treatment of ocular symptoms. The compounds available, olopatadine and azelastine have a dual mechanism of action of not only antagonizing the H1 receptor but also stabilizing mast cells. Similarly to the oral antihistamines, they have a rapid onset of action. A bitter taste with administration has been described. One difference between guidelines can be seen in the recommended place in therapy of nasal antihistamines. Due to their similar efficacy and possible superiority to the oral antihistamines, the US Rhinitis Practice Parameters consider the intranasal antihistamines first line for mild SAR and PAR. In contrast, the ARIA guidelines only suggest their use in SAR, and suggest new-generation oral antihistamines over the intranasal antihistamines.

Ocular (c)

Ocular antihistamines may be used to ameliorate ocular symptoms of AR. Products are available by prescription and over-the-counter. Ocular symptoms may also be treated with intraocular non-steroidal anti-inflammatory drugs or intraocular cromolyn. Symptom improvement with the use of these agents is limited to those of the eye.

Intranasal cromolyn (5)

Cromolyn has fallen out of favor for AR symptom relief because of reduced efficacy compared to INC and antihistamines. The need for frequent dosing (up to 6 times daily) also limits the usefulness and adherence to this product. However, this agent is well tolerated with no serious adverse effects noted and is available over the counter. Treatment should be started before allergen exposure as cromolyn does not improve symptoms once present.

Nasal anticholinergic (6)

The one agent available in this class, ipratropium bromide is only effective for the symptom of persistent rhinorrhea. Frequent application with no effect on other associated AR symptoms limits the usefulness of this agent.

Oral/intranasal decongestants (7)

These agents produce the most benefit when combined with an antihistamine and the oral agents have little to no benefit over the antihistamine alone after a few days. Intranasal formulations appear to have better efficacy than their oral counterparts. Although they exhibit some effect on rhinorrhea and the nasal formulation is moderately effective for nasal obstruction, the class as a whole does not improve the symptoms of sneezing, itching or ocular symptoms. The intranasal decongestants may be beneficial in opening the nasal passages before the use of INC in patients with severe obstruction. These intranasal formulations are well known to cause rhinitis medicamentosa with extended use. Current guidelines suggest a course of no longer than five days of intranasal decongestants plus other pharmacotherapy for adult patients with severe nasal obstruction. They further suggest that oral decongestants should not be used regularly even in combination with an oral antihistamine. Other potential problems with excessive and sustained use of intranasal decongestants are a paradoxical rhinorrhea and ulceration of the mucosa. The choice to use these agents should not be made lightly and should be contained to short durations of time in select patients.

Leukotriene receptor antagonist (8)

Montelukast was first approved for patients with asthma and more recently has gained FDA-approved labeling for use in patients with AR and is the only agent within this class with this indication. It is effective for several symptoms of AR including rhinorrhea, itching, sneezing and congestion however, less effective than the INCs. Two studies (Di Lorenzo 2004, Pullerits 2002) and one systematic review (Rodrigo 2006) concluded the INCs were superior in efficacy compared with a combination of an antihistamine plus a leukotriene receptor antagonist where two other studies showed the efficacy to be similar (Wilson 2000, Wilson 2001). Montelukast is considered second- or third-line therapy in patients with mild AR intolerant to other agents and may be most beneficial in patients with concomitant asthma. This agent is suggested by ARIA for patients with SAR and preschool aged children with PAR. This agent was suggested in preschool aged children but not adults for PAR based on evidence demonstrating a small benefit seen in the younger children but lack of clinical benefit in the adult population. This class is generally thought to be safe, however, there have been recent reports that they may have detrimental psychiatric effects including mild irritability, hallucinations, and suicidal ideation.

Immunotherapy (9)

Immunotherapy is the only form of treatment that can cure a patient of AR. This therapy is specific to the patient based on their respective allergens as found from allergy sensitivity skin testing or RAST. One thought is that immunotherapy is most effective if the patient is found to have reactions to one or a few main allergens. If the testing shows the patient has allergies to several substances or their allergies are inadequately defined, they will have better symptom improvement with pharmacotherapy. Conversely, some physicians believe that all sensitizations are pertinent. There are no robust trials deciphering if injecting one main allergen is better than using all allergens for a patient. Increasing doses of the allergen extracts are administered until the effective maintenance dose is achieved. This treatment is usually reserved for patients with severe disease who have not responded to or are unable to tolerate pharmacotherapy. However, to see maximum benefit, it may need to be considered earlier in therapy in conjunction with other therapies. Common allergens included in the subcutaneous cocktails include: pet danders, various pollens, dust mite and cockroach. Immunotherapy is widely available as a subcutaneous injection in the US. European officials have approved two sublingual formulations. Although ARIA guidelines also discuss intranasal immunotherapy, there are no formulations currently available for administration because of the adverse local effects experienced. Guideline recommendations differ by the formulation. Because subcutaneous administration is the only form currently approved in the US, that will be the focus going forward. In ARIA, subcutaneous therapy is suggested for adults with SAR and PAR caused by dust mites and in children with SAR or PAR caused by any allergen. Unfortunately, it may take up to one year to see improvement in symptoms. If improvement is seen, subcutaneous immunotherapy should be sustained for three to five years. Subcutaneous immunotherapy should be administered only in supervised medical clinics with physicians and staff trained in resuscitation, because of the risk of fatality associated with anaphylactic reactions. Patients should be monitored for at least 30 minutes post-injection for any reactions. Immunotherapy should commonly be avoided in preschool aged and elderly patients, significant pulmonary or cardiovascular disease, patients on beta-blocker therapy, uncontrolled asthma and patients with adherence problems.

Alternative Medicine (10)

Guidelines currently do not recommend any complementary or alternative medicine for the treatment or prevention of AR. This includes homeopathy, acupuncture, probiotics, butterbur, grape seed extract or any other herbal product because of the lack of evidence of benefit to patients, insufficient safety data and at this time unjustified cost.

New therapies/formulations (11)

Beclomethasone (a)

Beclomethasone has been approved as an INC inhaler for more than 30 years. However, there have been a variety of formulations developed along the way including an aqueous and chlorofluorocarbon (CFC) containing dry aerosol. With the phase out of the CFC-containing nasal aerosols, we were left with only aqueous nasal sprays which afforded a host of patient complaints, most notably, the sensation of post-nasal drip. Recently, beclomethasone has been reformulated as the only nonaqueous "dry" powder INC spray and uses a hydrofluroalkane (HFA) propellant. A six-week study conducted in patients with PAR showed beclomethasone dipropionate HFA nasal aerosol was superior to placebo in total nasal symptom scores and measurements in quality of life (Meltzer 2012). In addition, the drug was well tolerated with similar adverse effects reported as the placebo group. A current study is in the recruiting stages to observe how this agent performs in a large population with PAR with or without SAR. This agent is approved for both SAR and PAR in patients at least 12 years of age and has a convenient dose counter starting with 120 doses. The dose of this drug is two sprays in each nostril once daily so the container will last one month for a patient using it as recommended. This agent contains 8% alcohol which could lead to complications of nasal irritation or dryness. Ratner et al. conducted a pharmacokinetic study for this drug which showed significantly lower systemic bioavailability than the orally inhaled counterpart (Ratner 2012).

Ciclesonide (b)

Ciclesonide is currently available for AR in two forms, an aqueous nasal spray and the newer aerosolized "dry" nasal inhalation. The dose is one spray in each nostril daily and like the new formulation of beclomethasone is only approved for use in patients with SAR and PAR greater than 12 years of age. The ciclesonide aerosolized product has a dose counter that decreases in increments of five to ten and uses colors of green, yellow and red indicating sufficient amount of medicine remaining, medication should be replaced soon, and canister is nearly empty, respectively. In a 26-week randomized trial in patients with PAR, focusing on tolerability this agent was found to be superior in treating symptoms of AR versus placebo and had similar incidence of adverse effects (Berger 2012).

Azelastine/fluticasone (c)

This is the first aqueous nasal spray to incorporate both a corticosteroid and antihistamine into one product. This product only has the FDA approved indication for treating SAR in patients greater than 12 years of age. A published meta-analysis which incorporated three, two- week trials in patients with SAR randomized to this compound, each drug separately, or placebo, showed the combination product was superior to all comparator groups in total nasal symptoms and each nasal symptom considered separately (Carr 2012). The most common adverse effects reported with this compound were dysguesia, headache and epistaxis. Other combination products are currently being studied.

Emerging therapies (12)

Because the full pathophysiology of allergic rhinitis is yet to be understood, there is a myriad of research currently underway for other treatment options. There is research into more selective INCs or INCs that are pro-drugs that must be metabolized by special enzymes existing at the delivery site which should therefore limit the systemic adverse effect profile even further. The oral antihistamines currently available block the H1 receptor but inhibition of other histamine receptors, such as histamine 3 (H3) and 4 (H4), may be beneficial in treating allergic rhinitis as well. Currently research is underway on dual H1/H3 receptor antagonists. The H4 receptors can be found in the hematopoietic cells and therefore, blockage of these may have anti-inflammatory actions. Prostaglandin receptor antagonists are also a target for the future of AR treatment.

Treatment plan (D)

Therapeutic choices- patient involvement (1)

There is a variety of medications currently available to treat this disease and guidelines to help practitioners determine the best course of therapy. However, patient involvement in therapeutic decision-making is imperative. Non-adherence or incorrect use of drugs may be caused by adverse effects that could be avoided by proper technique or changing medications even within a class. Although complete avoidance of allergens would be optimal, realistic goals for avoidance should be planned with the patient. Patient work schedule, insurance coverage, and medication preferences should all be considered when choosing therapy. Patients who do not achieve adequate symptom control, because of lack of involvement in their health care choices may have a reduced quality of life.

Improvement in quality of life (2)

Although generic quality of life questionnaires are helpful to determine the overall impairment to a patient, disease specific questionnaires are beneficial to appreciate the symptoms most bothersome to the patient and how the patient responds to therapy. The disease specific, rhinoconjunctivitis quality of life questionnaire (RQLQ) is used to determine the level of impairment a patient is facing from symptoms of AR. This questionnaire has been widely used around the world and is well validated in trials and found in many published articles. The validity on a small scale, single patient basis is still unknown. Patients are asked to rate their impairment on a Likert scale of zero to six (zero being no impairment to six indicating maximal impairment) on a variety of questions considering the past week as their reference. The questionnaire will offer an overall mean score as well as a mean score for seven individual areas including trouble in activities, sleep, non-allergic symptoms, practical problems, nasal symptoms, eye symptoms, and emotions. This questionnaire is meant for patients above 17 years of age and a different questionnaire, such as the Adolescent RQLQ or Pediatric RQLQ, should be used for the pediatric population.

Special populations (3)

Treatment in children (a)

The basic guidelines to direct treatment for adults can also be used to treat pediatric patients but doses may need to be altered and other special considerations must be taken. Certain therapies have less evidence for use in children and risk to benefit may also differ. Products vary by the FDA approved age of use. For instance, there are only three INC products available for ages 2 and older, where the rest are for ages 4, 6, or 12 and up (see table X). In pediatric patients with mild disease, nasal saline irrigation may be useful in clearing the nasal passages. In children with SAR, this agent may improve symptoms and reduce the need for antihistamines during their allergy season. As with adults, nasal cromolyn is devoid of many adverse effects but is less effective than antihistamines and INCs and is inconvenient for most due to the frequency of administration. Children on first generation antihistamines have had reduced performance in educational activities and therefore, newer agents are recommended. Oral antihistamines are considered a first-line treatment for mild intermittent AR because of their ease of use and therefore, likely better adherence. Topical antihistamines and montelukast may also be used. For moderate-severe AR in children, INCs remain the first choice. The concern of growth retardation has not been seen with the newer INC agents but stature should continue to be monitored in children on these products. Recommend the newer agents with the lowest bioavailability at the lowest possible effective dose. Guidelines recommend against the use of intranasal decongestants in preschool aged children due to the possible risk of serious adverse effects.

Treatment in elderly (b)

Treatment of geriatric patients does not differ significantly from the rest of the adult population. The American Geriatrics Society Beers Criteria strongly recommend the avoidance of first generation antihistamines due to the increased anticholinergic side effects and somnolence. In addition, both oral and nasal decongestants should be used with caution in the elderly due to their adverse effect profile. Conversely, mometasone has received positive recognition from the National Arthritis Foundation as being a device that is easy to use for arthritis sufferers.

Treatment in pregnancy (c)

One-third of pregnant women will have an upsurge in their AR symptoms. For moderate to severe AR, all INC agents have been given a pregnancy risk category C, except budesonide, which received a B risk due to the widespread safety data with this product. Because of the real benefit that these agents bring to patients with moderate to severe AR, it may be reasonable to continue therapy with any INC agent if the symptoms of AR are well controlled prior to conception. However, if a patient is started on therapy during pregnancy, budesonide may be the best choice. Antihistamines appear to be safe for use during pregnancy and as in all patients, second generation agents are preferred. Fexofenadine lacks epidemiologic studies and therefore is the only second generation agent with a FDA pregnancy category rating of C of the available products. Recommend pregnant women avoid oral decongestants during the first trimester due to possible risk of congenital malformations. The safe use of the intranasal decongestants has not been studied. Cromolyn and montelukast are both pregnancy category B.

Monitoring (4)

The only monitoring necessary for AR consists of that for safety and efficacy of pharmacotherapy and improvement in quality of life. Ensuring that patients are not suffering from unnecessary adverse effects will likely improve adherence.

Patient education (IV)

Directions on proper nasal spray instillation (A)

As previously mentioned, many of the adverse effects of nasal sprays, especially the INC can be diminished or alleviated with proper instillation. Pharmacists should be familiar with the different devices available and instructions on how to use these various agents. In general, the patient should shake aqueous solutions prior to each use. This is not necessary for the aerosolized drugs. Each product should be primed prior to the first use and differs by product by recommended amount priming sprays and when to prime after non-use. The patient should blow their nose prior to use to ensure clear nasal passages. Some products recommend the patient tilt their head slightly back, some slightly forward and some make no mention of head position. Each product's package insert should be reviewed for instructions on appropriate use. The INC should be aimed out away from the septum when administered to avoid the adverse effect of septal perforation. A general recommendation is to spray the left nostril using the right hand and vice versa as the angle allows for spray away from the septum. The opposite nostril should be closed so to not allow drug to escape. The patient should be asked to lightly sniff during instillation but not hard enough to send drug down the throat. Ask the patient to hold their breath for a few seconds for the aerosolized products. The individual should then breathe through their mouth. Finally, the patient should avoid blowing their nose for 15 minutes.

Comparison of drug cost (B)

In addition to weighing efficacy, safety, and patient preference, cost of drug always needs to be a consideration of therapy. Luckily for mild disease, there are many inexpensive options available with intranasal cromolyn being over the counter as well as three of the second generation oral antihistamines. In addition, even the prescription second generation antihistamines are all generic. The intranasal antihistamines are more expensive and no generic is available at this time. For patients with more severe disease, the price associated with treatment increases, not only due to more expensive first line therapy, but also the possible need for multiple therapies. There are three generic options in the INC class but are not inexpensive. Montelukast and ipratropium are generically available. For short term use, the oral and intranasal decongestants are all available over-the-counter. Over a usual treatment course, immunotherapy costs no more than managing symptoms with pharmacologic options.

Drug-drug and drug-food interactions (C)

In reviewing the medications used for AR, there are very few significant drug interactions that exist. For the antihistamines, the main drug-drug interactions have to do with any agent that may further central nervous system (CNS) depression. Alcohol can also cause CNS depression so caution should be advised. Apple, grapefruit and orange juice have decreased the bioavailability of fexofenadine by approximately 36% and therefore, this medication should only be taken with water. Montelukast is a major substrate of CYP 2C9 and 3A4 and therefore, should be monitored with inducers and inhibitors of these enzymes. Fluticasone should not be administered with ritonavir as serum concentrations of the steroid may increase. Telaprevir similarly, can increase serum concentrations of fluticasone and budesonide. Finally, tocilizumab may decrease the concentrations of CYP 3A4 substrates so many of the products discussed here should be monitored if tocilizumab is initiated.

Conclusion (V)

Allergic rhinitis is a disorder affecting millions of patient worldwide with a number remaining undiagnosed and undertreated. Avoiding environmental triggers and adherence to therapy is essential for best meager patient outcomes. Treatment should be initiated and chosen according to disease severity and frequency of symptoms. A variety of therapeutic options exist for mild disease with antihistamines being favored. For patients with more severe disease, INCs are the drug of choice as they alleviate all symptoms of AR and have been shown to be superior to all other options currently available.