4
Antihistamines
Allergies had been part of Amit’s life since childhood—beginning with seasonal symptoms: watery and itchy eyes, runny nose, nasal congestion, and uncontrollable sneezing fits. Antihistamines managed these symptoms, but by the time Amit turned thirty-five, his allergies were present year-round, and the drugs had become less effective. Worse were the unacceptable side effects. Not only did he feel like he was “operating in a cloud” while on them, but his wife noticed a change in his mood: he was more volatile and argumentative. Amit’s doctor tried him on several “non-sedating” antihistamines, but they failed to control his symptoms. He twice tried desensitization (allergy shots) but got no benefit and once nearly died from a severe reaction (anaphylaxis). Although nasal corticosteroid sprays helped marginally, his nose continued to run. Doses of prednisone and other oral steroids worked for Amit but kept him up all night and made him so moody that co-workers avoided him.
By the time he was fifty-five years old, he had tried just about every prescription therapy available, each with drawbacks. His dependable older antihistamines now caused a new symptom that was shocking—pain and difficulty emptying his bladder, prompting one panicky visit to an emergency room.
It was at this point that Amit became fearful of drugs and sought a more integrative approach. He saw a practitioner who recommended fundamental changes in Amit’s lifestyle: an anti-inflammatory diet* along with meditation and breath control to relax. Amit learned about the effectiveness of freeze-dried stinging nettle leaves for hay fever, and found that two capsules totally eliminated his itching and sneezing, although he had to repeat the dose as often as every four hours during the day. He experienced no side effects at all from this herbal remedy.
Through all the years of relying on suppressive medication, his symptoms had persisted and gotten worse. After two seasons of this alternative regimen, his hay fever subsided and eventually disappeared.
ALLERGIC REACTIONS
Allergies have plagued us throughout history; records from ancient Egypt describe them. The development of an immune system was a major milestone in evolution that helped ensure our survival, but with it came complications.
It has been proposed that allergies represent the immune system “going awry”; however, this may not be the case. Many believe that allergic reactions originally served to eradicate parasites, which were much more of a problem before we lived in clean environments, seriously threatening human health. The allergies that cause us trouble today may be evolutionary remnants of this parasitic defense system, now inappropriately redirected against harmless substances in the environment, such as pollen. An alternative theory is that allergic reactions evolved to help rid the body of, or protect it from, toxins. Some evidence for this is the fact that most allergy symptoms serve to expel irritants from the body—whether through sneezing, a runny nose, watery eyes, or, in the case of food allergies, diarrhea.
Hay fever, or allergic rhinitis, affects about 8 percent of adults in the United States and is responsible for more than 11 million visits to physician offices annually. We try to deal with allergens as we deal with many conflicts in life: by avoidance. Unfortunately, pollens from grasses and trees are wind-borne and hard to avoid.
HOW ANTIHISTAMINES WORK
The allergic reaction releases chemicals that are stored inside a specialized immune cell called the mast cell. The mast cell is like a time bomb, waiting for an allergen to set it off. After activation, it breaks open, rapidly releasing its store of potent chemical messengers, histamine among them. Once histamine gets into the bloodstream, it binds to special receptors in blood vessels, smooth muscle, and elsewhere, causing such allergic symptoms as itching, flushing, headache, runny nose, and occasionally shortness of breath and wheezing.
Antihistamine drugs bind to the same receptors and block these symptoms—but only if they get there first. To do the most good, they have to be used prior to the start of the reaction. Once the reaction has started, taking an antihistamine will still be useful but not as effective as a prophylactic dose.
COMMON USES FOR ANTIHISTAMINES
Most commonly, antihistamines are used for relief of seasonal or perennial nasal and ocular allergies—the stuffiness, runny nose, and itchy and watery eye symptoms that are the hallmark of an allergy attack. Some people use these drugs in an attempt to treat similar symptoms that occur with a common cold or the flu (see chapter 5), but their benefit here is minimal.
There are, however, other common indications for antihistamines. Arguably, their most important use is in the treatment of anaphylaxis, the most dangerous allergic reaction. People with severe allergies to certain foods, insects, or drugs can develop this life-threatening reaction, marked by a sudden drop in blood pressure, airway closure, and consequent breathing difficulties. Prompt treatment is necessary to prevent death—with potent drugs such as epinephrine (adrenalin) and corticosteroids, along with aggressive intravenous hydration. Antihistamines, given in large doses intravenously, can also help arrest the reaction and save a life.
Urticaria—hives—can be caused by contact with a provocative trigger (such as poison ivy), ingestion of a specific food, or stress, or it can occur for no apparent reason. Hives can erupt all over the body, usually accompanied by severe itching (pruritus). Antihistamines offer some level of relief from the incessant itch, while at the same time facilitating needed sleep.
One reason to use antihistamines is supported more by advertising than by research. Many people with insomnia, and without access to the more expensive (and harmful) prescription sleep drugs, have been persuaded to use over-the-counter (OTC) products like Simply Sleep, Unisom, Tylenol PM, and others that contain the antihistamine diphenhydramine (Benadryl) in various doses. True, this compound causes drowsiness, but is the sleep quality the same as that of natural sleep? Most experts say no; overall sleep quality after taking Benadryl is usually not very good. In addition, most users suffer side effects of dry mouth, urinary retention, and a high frequency of next-day sluggishness and mental clouding.
THE PROBLEMS WITH ANTIHISTAMINES
Antihistamines are among the oldest drugs still in use, discovered in 1937 by Daniel Bovet, who later won a Nobel Prize for his work. Among the most commonly sold OTC medications in the United States are cough-cold and allergy remedies, many of which are, or include, antihistamines. The fact that they are available without a prescription leads many people to believe that they are perfectly safe, which is simply not true. Many of their adverse effects become apparent only after many years of use.
The first antihistamines have a long track record, and most of their adverse effects are known. They include diphenhydramine (Benadryl), chlorpheniramine (Chlor-Trimeton), clemastine (Tavist), and others. By nature of their chemical structure, these drugs readily cross the blood-brain barrier, affecting the central nervous system. First-generation antihistamines cause significant sedation. In fact, they can impair driving ability as much as or more than alcohol. The impairment can be subtle: prior to falling asleep on antihistamines, there is a drowsy period with mental fogginess and a decline in thought processes that may not be apparent to the patient.
The search for less sedating (incorrectly termed “non-sedating”) antihistamines led to the discovery of a second generation of drugs. The first of these, terfenadine (Seldane), was released in 1985 to great fanfare and an advertising blitz. Within a few years, serious heart arrhythmias were reported, especially when the drug was taken with certain antibiotics. By the time Seldane was removed from the market, it was blamed for eight deaths—in people who were just trying to stop sneezing. Other drugs in this class include fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec). While a smaller amount of these medications crosses the blood-brain barrier, they still cause drowsiness, prompting the warning to “be careful when driving a motor vehicle or operating machinery.” Unfortunately, many users continue to drive under their influence—a potential public health hazard. In elderly patients, the risks are elevated, with potential adverse effects of next-day sedation, dizziness, and falls.
Both first-and second-generation antihistamines can affect mood and cognitive function, causing or worsening depression and interfering with thinking and concentration. Anyone struggling with depression should avoid them.
And more ominous adverse effects have been attributed to these popular drugs. A recent study of more than three thousand men and women over the age of sixty-five revealed a link between long-term use of anticholinergic medications, including Benadryl and other first-generation antihistamines, and the risk of dementia. (Anticholinergic drugs block the action of acetylcholine, a neurotransmitter in the brain, and include the tricyclic antidepressants, discussed in chapter 9, as well as the older antihistamines.) Taking such medications for the equivalent of three years or more increased the risk of developing dementia by 54 percent. Other notable anticholinergic effects that have been seen with first-generation antihistamines are low blood pressure, delirium, and behavioral changes. In men, particularly those with an enlarged prostate gland, these drugs can cause urinary retention—both acute and chronic. Rarely, this can lead to severe bladder and kidney dysfunction.
Other adverse effects attributed to antihistamines have been proposed but are still under investigation. They are, however, concerning. There is a body of evidence linking antihistamine use with the development of brain tumors, especially gliomas. Gliomas are the most common primary malignant brain tumors, and few risk factors for them have been identified. However, several studies show that people who report regular long-term use of antihistamines are nearly three times as likely as non-users to develop these tumors, regardless of asthma/allergy history. These data are more interesting in view of the fact that an inverse relationship between allergies and glioma is one of the most consistent associations in the brain tumor literature. I wonder if allergies have a protective effect of some sort that is negated by antihistamines.
Drug therapy for allergies, taken as a whole and including OTC medications, costs more than $6 billion per year. An individual taking a second-generation antihistamine could spend anywhere from $8 to more than $200 per month.
INTEGRATIVE MEDICINE APPROACHES TO MANAGING ALLERGIC CONDITIONS
There are many effective methods for managing allergies that do not rely on antihistamines. One of the more obvious is avoidance—reducing contact with allergens by using common-sense strategies. High-efficiency particulate air (HEPA) filters, which remove particles from the air by forcing it through screens with microscopic pores, work well for lighter-weight allergens like pet dander and not so well for heavier ones like most pollen particles.
Frequent nasal irrigation with a warm saline solution (¼ teaspoon salt to 1 cup distilled water) will flush allergenic particles from the lining tissue of the nose. A neti pot is often employed for this purpose. This device resembles an Aladdin’s lamp made of ceramic, glass, or plastic and is easy to use, although the practice may take some getting used to. Pour sterile saline into the neti pot. Then, standing over a sink with your head tilted about 45 degrees to one side, place the spout into the higher nostril and slowly pour the solution into your nose. Spit out any liquid that enters your mouth. Once the neti pot is empty, gently blow your nose, tilt your head the opposite way, and repeat the process with the other nostril.
Many supplements and botanicals have proven value in controlling allergic rhinitis. Stinging nettle (Urtica dioica) is one of the best natural remedies. It is best taken in freeze-dried form in capsules. In a randomized, double-blind study of nearly one hundred patients, 57 percent rated nettle effective in relieving allergic rhinitis symptoms, and 48 percent said it equaled or surpassed the effectiveness of previously used allergy medications. It is a symptomatic treatment, not a preventive one; the usual dose is one or two capsules every two to four hours as needed.
Butterbur (Petasites hybridus) has been used for decades to treat allergies as well as asthma and migraine headaches and is one of the few botanicals to go head-to-head with a drug in a clinical trial. A study of 132 people with hay fever found that an extract of this herb was as effective as cetirizine (Zyrtec) with fewer side effects; butterbur was also much less sedating than the pharmaceutical product. The study lasted only two weeks and required four to five doses of the herb daily, but results were promising.
Bioflavonoids are compounds that give many vegetables and fruits their bright colors. They also have remarkable activity in allergic diseases—they actually prevent mast cells from “exploding” and releasing histamine. Like antihistamines, these compounds work best when taken in advance of an allergen exposure; as stated above, preventing histamine release is always preferable to trying to mitigate its effects once it gets into the bloodstream. Unlike antihistamines, bioflavonoids have few side effects. Some, like quercetin and fisetin, are available in supplement form. (Due to poor bioavailability, quercetin is often combined with bromelain—an enzyme found in pineapple—or vitamin C to improve oral absorption.) Because effects of bioflavonoids are not long lasting, they must be taken every four to six hours, but they work very well for many patients. Cromolyn, a bioflavonoid-related mast-cell stabilizer, is available in nasal sprays (like NasalCrom) and in nebulizers (for allergic asthma). I consider it safe and effective.
Mind-body interventions have been shown to modify allergic responses. In a controlled setting, allergic individuals received skin tests to assess their reactivity to allergens after viewing either a documentary dealing with the weather or a humorous movie. In those who watched the humorous film, skin test reactivity decreased significantly, demonstrating that emotions can powerfully mitigate the effects of allergen exposure. This supports the connection between the immune system and emotions, the subject of a field of study known as psychoneuroimmunology. You can take advantage of this connection with such interventions as clinical hypnotherapy, which can reduce allergic responsiveness in many people.
Most discussions of the impact of diet on allergies are limited to food allergies, but what you eat can also affect your body’s reactions to airborne allergens. The body activates similar inflammatory pathways for many diverse triggers, including infection and trauma. Allergic reactions are simply inflammatory reactions with a specific allergen as the inciting catalyst. Specialized cells of the immune system produce compounds—inflammatory mediators—to contain the infection or extent of injury. Other immune cells migrate to the site of the problem to act as reinforcements. Following an anti-inflammatory diet reduces allergic reactivity by inhibiting synthesis of the inflammatory mediators. Simply adding omega-3 fats to the diet, in the form of fatty fish or fish oil supplements, can accomplish this in many people.
BOTTOM LINE
Antihistamines can save lives in the case of anaphylaxis and other severe allergic reactions. That is their greatest value. People with allergic rhinitis and others who suffer from common allergy symptoms would be wise not to rely on antihistamines but instead to try natural remedies and lifestyle changes, including dietary changes and stress management, to control symptoms. Those approaches can result in reduced allergic responsiveness and even complete disappearance of allergies. I do not see this happen in people who rely on antihistamines to suppress allergic symptoms. Like other long-term suppressive medications, they tend to perpetuate the problem they are meant to treat.