Posts Tagged ‘mast cells’

Generic Name
Cromolyn (KROE-inuh-lin) [9
Brand Names
Crolom    Intal
Gastrocrom    Opticrom
The information in this profile also applies to the following drugs:
Nedocromil
Alocril    Tilade
Type of Drug
Allergy preventive and antiastk)m-aft_.
Prescribed For
Prevention of severe allergic reactions, including asthma, runny nose, and mastocytosis; also prescribed for food allergies, eczema, dermatitis, chronic itching, and hay fever. It may be used to treat and prevent chronic inflammatory bowel disease. The eyedrops are used to treat conjunctivitis (pinkeye) and other eye irritations.
General Information
Unlike antihistamines, which work against histamine that has been released into the system, cromolyn sodium prevents allergy, asthma, and other conditions by stabilizing mast cells, a key component in any allergic reaction because they release histamine. Cromolyn prevents the release of histamine and other chemicals from mast cells. The drug works only in the areas to which it is applied; only 7-8% of an inhaled dose and 1 % of a swallowed capsule is absorbed into the blood. Even the oral capsules, which one would normally expect to be absorbed into the blood, treat only gastrointestinal -tract allergies. Cromolyn products must be used on a regular basis to be effective in reducing the frequency and intensity of allergic reactions.
Cautions and Warnings
Do not take cromolyn if you are allergic or sensitive to any of its ingredients. Rarely, people have experienced severe allergic attacks after taking cromolyn.
cromolyn should never be used to treat an acute allergy attack. It is intended only to prevent or reduce the number of allergic attacks and their intensity. Once the proper dosage level has been established for you, reducing that level may result in a recurrence of attacks.
People with kidney or liver disease require reduced dosage.
Cough or bronchial spasm may occasionally occur after the inhalation of a cromolyn dose. Severe bronchospasm is rare.
cromolyn aerosol should be used with caution in people with abnormal heart rhythm or diseased coronary blood vessels because of a possible reaction to the propellants used in the product.
Possible Side Effects
V Most common: rash and itching. Headache and diarrhea (for capsules). Watery, itchy, dry, or puffy eyes; and iztjes (for eyedrops). Most capsule and eyedrop side effects are mkw and may be attributable to the underlying condition; a variety have been reported but cannot be tied conclusively to the drug.
V Less common: local irritation, including nasal stinging, sneezing, tearing, cough, and stuffy nose; urinary difficulty or frequency; dizziness; headache; joint swelling; muscle Possible Side Effects (continued)
pain-, a bad taste in the mouth; sore throat-, nosebleeds’, abdominal pain-, and nausea.
♦ Rare: severe drug reactions, consisting of coughing, difficulty in swallowing, hives, itching, breathing difficulties, or swelling of the eyelids, lips, or face. Contact your doctor if you experience any side effect not listed above.
Drug Interactions None known.
Food Interactions
Inhaled or swallowed cromolyn products should not be mixed with any food, juice, or milk. The nasal and eye products may be taken without regard to food or meals.
Usual Dose
Inhaled Capsules or Solution
Adult and Child (age 2 and over): starting close-20 mg 4 times a day. Children under age 5 may inhale cromolyn powder if their allergies are severe. The solution must be given with a power-operated nebulizer and face mask. Handheld nebulizers are not adequate. To prevent exercise asthma, 20 mg may be inhaled up to 1 hour before exercise.
Aerosol
Adult and Child (age 5 and over): up to 2 sprays 4 times a day, spaced equally throughout the day. To prevent exercise asthma, 2 puffs may be inhaled up to 1 hour before exercise.
Nasal Solution
Adult and Child (age 6 and over): 1 spray in each nostril 3-6 times a day at regular intervals. First blow your nose, and then inhale the spray.
Oral Capsules
MAI and Child (age 12 and over): 2 dissolved capsules 4 times a day taken a half hour before meals and at bedtime.
Child (age 2-12): 1 dissolved capsule (100 mg) 4 times a day a half hour before meals and at bedtime. Dosage may be increased to about 13-18 mg per lb. of body weight in 4 equal doses.
Child (under age 2): about 10 mg per lb, of body weight a day divided into 4 equal doses. This product is recommended in infants
and young children only if absolutely necessary.
Eyedrops
Adult and Child (age 4 and over): 1-2 drops in each eye 4-6 times
a day at regular intervals. Overdosage
No action is necessary other than medical observation. Call your local poison control center or a hospital emergency room for more information. ALWAYS bring the prescription bottle or container.
Special Information
Cromolyn is taken to prevent or minimize severe allergic reactions. It is imperative that you take cromolyn products on a regular basis to provide equal protection throughout the day.
If you are taking cromolyn to prevent seasonal allergies, it is essential that you start taking the medication before you come into contact with the cause of the allergy and that you continue treatment while you are exposed to it.
Cromolyn oral capsules should be opened and their contents mixed with about 4 oz. of hot water. Stir until the powder completely dissolves and the solution is completely clear, then fill the rest of the glass with cold water. Drink the entire contents of the glass. Do not mix the solution with food, juice, or milk.
Do not wear soft contact lenses while using cromolyn eyedrops. The lenses may be replaced a few hours after you stop taking the drug. To prevent contamination, do not touch the applicator tip to any surface including the eyes or fingers.
Call your doctor if you develop wheezing, coughing, a severe drug reaction (see “Possible Side Effects”), rash, or any bothersome or persistent side effect.
Call your doctor if your symptoms do not improve or if they worsen.
If you forget to administer a dose, do so as soon as you remember and sqa(ZRMBmn-maining daily dosage evenly throughout ‘i!M day. Do not take a double dose.
Special Populations
PregnancylBreast-feeding. In animal studies, very large dosages of cromolyn administered by vein have affected the fetus, though no birth defects were reported. When this drug is considered crucial by your doctor, its potential benefits must be carefully weighed
against its risks.
It is not known if cromolyn passes into breast milk. Nursing
mothers who must use cromolyn should use infant formula. Seniors: Older adults with reduced kidney or liver function may require lower dosages.

Generic Name
Cyclobenzaprine (sye-cloe-BEN-zuh-prene) M
Brand Names Amrix
Type of Drug
Skeletal muscle relaxant.
Flexeril
Prescribed For
Serious muscle spasm and acute muscle pain; also used to treat fibrositis (muscular rheumatism).
General Information
Cyclobenzoprine hydrochloride is used to treat severe muscle spasms; it is prescribed as part of a coordinated program of rest, physical therapy, and other measures.
Cautions and Warnings
Do not take cyclobenzaprine if you are allergic or sensitive to any of its ingredients.
This drug should not be taken for several weeks following a heart attack or by people with abnormal heart rhythms, heart failure, heart block (disruption of the electrical impulses that control heart rate), or hyperthyroidism (overactive thyroid gland).
Cyclobenzaprine should be avoided by people with urinary retention, glaucoma, UC 1ntlreased eye pressure.
W)t arug may increase the chances of cavities or gum disease. Cyclobenzaprine is intended only for short-term use of 2-3 weeks.
Cyclobenzaprine is chemically similar to tricyclic antidepressants and may produce some of the more serious side effects associated with those drugs. Abruptly stopping cyclobenzaprine may cause nausea, headache, and feelings of ill health; this is not a sign of addiction.
Drug Interactions
•    The effects of alcohol, sedatives, or other nervous system depressants may be increased by cyclobenzaprine.
•    Cyclobenzaprine may increase some side effects of atropine, ipratropium, and other anticholinergic drugs.
•    The combination of cyclobenzaprine and a monoamine oxidase inhibitor antidepressant may produce very high fever, convulsions, and possibly death. Do not take these drugs within 14 days of each other.
•    Cyclobenzaprine may increase the effects of haloperidol, loxapine, molindone, pimozide, anticoagulant (blood-thinning) drugs, anticonvulsants, thyroid hormones, antithyroid drugs, phenothiazines, thioxanthenes, and nasal decongestants such as naphazoline, oxymetazoline, phenylephrine, and xylometazoline.
•    Barbiturates and carbamazepine may counteract the effects of cyclobenzaprine.
•    Fluoxetine, ranitidine, cimetidine, methylphenidate, estramustine, estrogens, and contraceptive drugs may increase the effects and side effects of cyclobenzaprine.
•    Cyclobenzaprine may counteract the effects of cto(\idine, guanadrel, and guanethidine.
Food Interactions  None known.
Usual Dose
Adult and Child (age 15 and over): 5-10 mg 3 times a day. Child (under age 15): not recommended.
above.    drowsiness, and dizziness.
le weakness. fatigue, nausea, consti-
ch, unpleasant taste, blurred vision,
ess, and confusion.
cts can occur in almost any part of the doctor if you experience any side ef- e.
Possible Side Effects
♦    Most common: dry
♦    Less common: muscl
upset stomach
nervousness, • Rare: Rare side effects
body. Contact your
fect not listed Overdosage
Cyclobenzaprine overdose may cause confusion, loss of con- centration, hallucinations, agitation, overactive reflexes, fever or vomiting, rigid muscles, and other side effects of the drug. It may also cause drowsiness, low body temperature, rapid or irregular heartbeat and other kinds of abnormal heart rhythms, heart failure, dilated pupils, convulsions, very low blood pressure, stupor, coma, and sweating. Overdose victims must be taken to a hospital emergency room. ALWAYS bring the prescription bottle or container.
Special Information
Cyclobenzaprine causes drowsiness, dizziness, or blurred vision in more than 40% of people who take it, which may interfere with the ability to perform complex tasks like driving or operating equipment. Avoid alcohol, sedatives, and other nervous system depressants because they can enhance sedative effects of cyclobenzaprine.
Call your doctor if you develop rash; hives; itching; urinary difficulties; clumsiness; confusion; depression; convulsions; difficulty breathing; irregular heart rate; chest pain; fever; yellowing of the skin or whites of the eyes; swelling of the face, lips, or tongue; or any other persistent or bothersome side effect.
If you forget a dose of cyclobenzaprine, take it as soon as you remember. If you take cyclobenzaprine once a day and it is almost time for your next dose, skip the one you forgot and continue with your regular schedule. If you take cyclobenzaprine twice a day and it is almost time for your next dose, take 1 dose as soon as you remember, another in 5 or 6 hours, and then go back to your regular schedule. If you take cyclobenzaprine 3 times a day and it is almost time for your next dose, take 1 dose as soon as you remember, another in 3 or 4 hours, and then go back to your regular schedule. Never take a double dose.
Special Populations
Pregnancy/Breast-feeding: -The safety of cyclobenzaprine in ‘jftg)T)1 women has not been established. Cyclobenzaprine should only be used if the potential benefits outweigh the risks.
It is not known if cyclobenzaprine passes into breast milk, but antidepressants with a similar chemical structure do pass into breast milk. Nursing mothers who must take this drug should consider using infant formula.
Seniors: Seniors are more likely to be sensitive to the effects of cyclobenzaprine. Use of Amrix in particular is not recommended
in the elderly.

Generic Name
Cyclosporine (sye-kim-SPQR-in)
Brand Names
Gengraf Neoral
Type of Drug  Immunosuppressant.
Restasis Ophthalmic Emulsion Sandimmune
Prescribed For
Kidney, heart, or liver transplantation; also used for bone-marrow, heart-lung, and pancreas transplants; also prescribed for patchy hair loss, rheumatoid arthritis, aplastic anemia, atopic dermatitis, Beh~et’s disease, cirrhosis of the liver, ulcerative colitis, dermatomyositis, eye symptoms of Graves’ disease, insulin-dependent diabetes, kidney inflammation, multiple sclerosis (MS), severe psoriasis and psoriasis-related arthritis, myasthenia gravis, pemphigus, sarcoidosis of the lung, and pyoderma gangrenosum. Cyclosporine eye emulsion is prescribed for dry eyes.
General Information
Cyclosporine is used to prevent rejection of transplanted organs. It works by blocking the activity of T-cells, which protect the body against invading microorganisms or foreign substances. Cyclosporine also prevents the production of a substance known as interieukin-11 that activates T-cells. In 1995, a new form of Cyclosporine called Neoral, a microemulsion, was introduced by its manufacturer. This form is as safe and effective as the original product but is better absorbed into the bloodstream and requires less medication to achieve the same effect. Cyclosporine eye emulsion treats dry eye caUV ,d by inflammation of the cornea and tissue kWA1 Covers the white part of the eye. It reduces inflammation and allows tears to form and flow.
Cautions and Warnings
Cyclosporine should be prescribed only by doctors experienced in immunosuppressive therapy and the care of organ-transplant patients. Sandimmune is always used with corticosteroid drugs like prednisone. Neoral and Gengraf have been used with a corticosteroid and azathioprine, an immune suppressant. When combined with other immune suppressants, cyclosporine must be used with great care because oversuppression of the immune system may lead to lymphoma or extreme susceptibility to infection.
Sandimmune, the original oral form of cyclosporine, is poorly absorbed into the bloodstream; it must be taken in a dosage that is 3 times greater than the injectable dosage. People taking this drug by mouth for a long period of time should have their blood checked for cyclosporine levels so that the dosage may be adjusted if necessary. Since more of both Gengraf and Neoral is absorbed into the blood you will probably need less of it. Do not substitute Neoral or Gengraf for Sandimmune; they are not equivalent to each other.
cyclosporine causes kidney toxicosis (kidney poisoning)—different from transplant rejection—in 25-35% of people taking it to prevent organ rejection. Mild symptoms usually start after about 2 or 3 months of treatment. Reducing drug dosage may control this effect. In one study, clonidine skin patches used before and after surgery decreased toxic risks to the kidney.
Liver toxicosis is seen in about 5% of transplant patients taking cyclosporine. It usually appears in the first month and may be controlled by reducing dosage.
Convulsions may develop, especially in people also taking high dosages of corticosteroids. Other nervous system side effects are listed below (see “Possible Side Effects”).
In one study, cyclosporine increased cholesterol and other blood-fat levels. It is not known how this affects people who take the drug on a long-term basis.
There is conflicting information on how cyclosporine affects blood sugar. Kidney-transplant patients taking the drug have developed insulin-dependent diabetes, which is related to the dosage of cyclosporine and reverses itself when you stop taking the drug. On the other hand, cyclosporine preserves the function of insuli(Nproducing cells in the pancreas and has allowed many insulin-dependent diabetics t0 11ve Without taking insulin.
UVb vaccines should not be given to people taking cyclosporine.
Do not use cyclosporine eye drops if you have an eye infection.
Small amounts of cyclosporine eye emulsion may be absorbed
into the bloodstream, but the risk of body-wide side effects is small.
Possible Side Effects
V Most common: Cyclosporine is known to be toxic to the kidneys. Your doctor will carefully monitor your kidney function while you are taking it. Other side effects are high blood pressure, increased hair growth, infection, and enlargement of the gums. Lymphoma may develop in people whose immune systems are excessively suppressed.
V Less common: tremors, cramps, acne, brittle hair or fingernails, convulsions, headache, confusion, diarrhea, nausea or vomiting, tingling in the hands or feet, facial flushing, reduced white-blood-cell and platelet counts, sinus inflammation, swollen and painful male breasts, drug allergy (symptoms include rash, itching, hives, and breathing difficulties), conjunctivitis (pinkeye), fluid retention and swelling, ringing or buzzing in the ears, hearing loss, high blood sugar, and muscle pain.
♦    Rare: blood in the urine, heart attack, itching, anxiety. depression, lethargy, weakness, mouth sores, difficulty swallowing, intestinal bleeding, constipation, pancreas inflammation, night sweats, chest pain, joint pain, visual disturbances, and weight loss. Contact your doctor if you experience any side effect not listed above.
Cyclosporine Eye Drops
♦    Most common: burning sensation.
✓    Less common: red-eye, discharge from the eye, overflow of tears, eye pain, a feeling of something in the eye, itching, stinging, and visual disturbances, usually blurring.
Drug Interactions
•    Cyclosporine should be used carefully with other kidney-toxic drugs including nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, ac\d s0indac; ciprofloxacin; gentamicinjQtswnydin; vancomycin; trimethoprimsUM,M1~0oxazole; melphalan; amphotericin B; ketoconazole; azapropazon; colchicine; diclofenac; cimetidine; ranitidine; and tacrolimus.
•    Drugs that may increase blood levels of cyclosporine include contraceptive drugs; amiodarone; diltiazem; nicardipine; verapamil; fluconazole; itraconazole; ketoconazole; azithromycin; clarithromycin; erythromycin; quinapristin and dalfopristin; methylprednisolone—this combination also causes convulsions; allopurinol; bromocriptine; colchicine; imatinb-, danazol; and metoclopramide. With ketoconazole, your doctor may use this drug interaction to reduce your cyclosporine
dosage.
•    Drugs that decrease cyclosporine levels and may lead to organ rejection include octreotide, orlistat, sulfinpyrazone, ticlopidine, terbinafine, nafcillin, rifampin, carbamazepine, phenobarbital, phenytoin, and St. John’s wort. Rifabutin may also decrease concentrations of cyclosporine and should be used with caution.
•    Cyclosporine interferes with the body’s ability to clear digoxin, prednisolone, and statin drugs. People taking any of these drugs who start on cyclosporine must have their drug dosage reduced.
•    Combining cyclosporine and nifedipine may lead to gum overgrowth.
•    Cyclosporine increases blood potassium. Excessive blood-potassium levels may be reached if cyclosporine is taken with enalapril, lisinopril, a potassium-sparing diuretic such as spironolactone, salt substitutes, potassium supplements, or high potassium—low sodium—food.
•    Psoriasis patients using other immunosuppressant drugs or receiving radiation therapy should not take cyclosporine due to the danger of infection.
•    Cyclosporine prevents the normal body response to live vaccines. People taking cyclosporine should be vaccinated only after specific discussions with their doctors. You must wait for a period of several months to several years after stopping the medication before vaccination may be considered again.
Food Interactions
Cyclosporine may be taken with fMd 1111 upsets your stomach. For optimal QftlaWr~T)ess, avoid eating a fatty meal within half an hour of taking Neoral.
You may mix Neoral in a glass—not a paper or plastic cup—with room-temperature orange or apple juice or chocolate milk to make it taste better. Do not drink grapefruit juice because it speeds the breakdown of cyclosporine. Drink immediately after mixing, then put more juice or chocolate milk in the glass and drink it to be sure that the entire dose has been taken. Neoral should not be taken with unflavored milk because it may be unpalatable.
Usual Dose
In general, the usual dosage of Neoral is lower than Sandimmune, but dosage must be individualized for you by your doctor. Do not substitute one brand for the other.
Sandimmune
Adult: The usual oral dosage of cyclosporine is 6-8 mg per lb, of body weight a day. The first dose, typically 15 mg per lb., is given 4-12 hours before the transplant operation or immediately after surgery. This dosage is slowly reduced to 11-22 mg per lb. of body weight.
Child: Similar dosages are usually prescribed, but because children tend to release the drug from their bodies faster than adults, larger and more frequent doses may be needed.
Neoral and Gengraf
Adult: In newly transplanted patients, the usual oral dosage of Neoral is 3-4 mg per lb. of body weight a day divided into 2 doses. The initial oral dose of Gengraf is the same as for Sandimmune. The first dose is given 4-12 hours before the transplant operation or immediately after surgery. This dosage is continued after the operation for 1-2 weeks and then slowly reduced to maintain a target amount of cyclosporine in the body. Dosage may vary according to the organ transplanted.
In people being treated for rheumatoid arthritis or psoriasis, the initial dose of Neoral and Gengraf is 1.13 mg per lb. of body weight increased gradually to a maximum of 1.8 mg per lb. of body weight.
Child: Similar dosages are usually prescribed but, because children tend to release the drug from their bodies faster than adults, larger and more frequent doses may be needed.
cyclosporine Eye Emulsion
One drop in the affected eye(s) every Q hours. Before using, rotate and turn the vial Over a few times until you have a uniform, lft8, opaque fluid inside. If you use artificial tears, allow 15 minutes between products. Discard the open vial immediately after use.
Overdosage
Overdose victims may be expected to develop side effects and symptoms of extreme immunosuppression. Induce vomiting with ipecac syrup—available at any pharmacy—which is recommended up to 2 hours after the overdose was taken. Call your doctor or local poison control center before inducing vomiting. If you must go to a hospital emergency room, ALWAYS bring the prescription
bottle or container.
Special Information
Call your doctor at the first sign of fever; sore throat; tiredness’, weakness’, nervousness; unusual bleeding or bruising; tender or swollen gums; convulsions; irregular heartbeat; confusion; numbness or tingling of your hands, feet, or lips; breathing difficulties; severe stomach pain with nausea; or blood in the urine. Other side effects such as shaking or trembling of the hands, increased hair growth, acne, headache, leg cramps, nausea, or vomiting are less serious but should be brought to your doctor’s attention, particularly if they are bothersome or persistent.
Maintain good dental hygiene while taking cyclosporine and use extra care when brushing and flossing because the drug increases your risk of oral infection. cyclosporine may also cause swollen gums. See your dentist regularly.
Continue taking your medication as long as your doctor prescribes it. Do not stop taking it without your doctor’s knowledge. If you cannot take one of the oral forms, cyclosporine can be given by injection.
Do not keep either brand of the oral liquid in the refrigerator. After the bottle is opened, use the medication within 2 months. At temperatures below 68°F, Neoral can form a gel and a light sediment can form in Sandimmune. These do not affect the potency of either product. They can still be used and are effective.
If you forget a dose, take it as soon as you remember if it is within 12 hours of your regular dose. If not, skip the dose you forgot and continue with your regular schedule. Do not take a double dose.
For cyclosporine eye emulsion, each small plastic container is meant to be used once and then thrown away along with any remaining medication. Do not allow the tip of the disposable vial to touch 0Z QyE or any surface, as this may contaminate the emulsion.
Patients with decreased tear production typically should not wear contact lenses. But those that do must remove them before using cyclosporine eye emulsion. Lenses may be reinserted 15 minutes after using the medicine.
Special Populations
Pregnancy/Breast-feeding: In animal studies cyclosporine damages the fetus. Though a small number of pregnant women have taken cyclosporine without major problems, it is recommended that pregnant women avoid cyclosporine. When this drug is considered crucial by your doctor, its potential benefits must be carefully weighed against its risks.
cyclosporine passes into breast milk. Nursing mothers who must take cyclosporine should use infant formula.
Seniors: Due to decreased kidney function, seniors are more susceptible to kidney toxicosis.

Generic Name
Darunavir (dah-ROON-uh-vere)
Brand Name Prezista
Type of Drug  Protease inhibitor.
Prescribed For
Advanced human immunodeficiency virus (HIV) infection that has not responded to other protease inhibitors.
General Information
Part of the multidrug “cocktail” responsible for important gains in the fight against acquired immunodefiency syndrome (AIDS), darunavir is a member of a group of anti-HIV drugs called protease inhibitors. These drugs work at the end of the HIV reproduction process, whet) proteins are “cut” into strands of exactly tht VbYrect size to duplicate HIV. An enzyme known as protease cuts the protein. Protease inhibitors prevent the mature HIV virus from being formed by inhibiting this cutting process. Proteins that are cut to the wrong length or that remain uncut are inactive.
Darunavir must be taken with a low dose of ritonavir, another protease inhibitor, to extend the action of darunavir in the body.
Without ritonavii, darunavir would be eliminated too rapidly to be effective. Darunavir must also be accompanied by at least 2 other AIDS antivirals. Protease inhibitors revolutionized HIV treatment because, when taken in combination, they reduce the amount of HIV virus in the bloodstream to levels that are often undetectable by current methods—CD4 (immune system) cell counts and viral load (amount of virus in the blood) measurements. Multiple-drug therapy has transformed HIV from a fatal disease to a manageable chronic illness.
Cautions and Warnings
Do not take darunavir if you are allergic or sensitive to any of its ingredients, to sulfa drugs, or to ritonavir.
Darunavir can cause a severe or life-threatening rash.
If a serious toxic reaction occurs while taking darunavir, you should stop the drug until your doctor can determine the cause or until the reaction resolves itself. Then treatment can be resumed.
This drug is primarly broken down in the liver. Use caution if you have moderate to severe liver disease.
Darunavir may raise your blood sugar, worsen your diabetes, or bring out latent diabetes. People with diabetes who take darunavir may need the dosage of their antidiabetes medication adjusted.
People with hemophilia may be more likely to bleed while taking a protease inhibitor.
The HIV virus may become resistant to darunavir or other protease inhibitors. For this reason it is essential that you take darunavir exactly according to your doctor’s directions.
Protease inhibitors can cause body fat redistribution, including increased fat deposits in the upper back and neck, breast and around the back, chest, and stomach. Fat may be lost from the legs, arms, and face. Some people with HIV and a history of an opportunistic infection may develop signs and symptoms of the infection soon after anti-HIV treatment is started. This is called immune reconstitution syndrome.
Darunavir is involved in many drug interactions. Check with your doctor before adding angt ng new to your treatment program.
Possible Side Effects
V Most common: diarrhea, nausea, headache, and common cold symptoms.
of constipation.
Drug Interactions
•    Do not take any of the following medicines with darunavir + ritonavir: astemizole, terfenidine, ergot-based drugs for migraine headache, cisapride, pimozide, midazolam, or triazolam. Mixing these drugs with darunavir + ritonavir can result in very high blood levels and serious side effects.
•    Carbamazepine, phenobarbital, phenytoin, rifampin, and St. John’s wort can substantially reduce blood levels of darunavir. Do not mix these medicines.
•    Lopinavir + ritonavir and saquinavir can significantly reduce blood levels of darunavir. Darunavir significantly increases blood levels of lopinavir + ritonavir. Do not mix these drugs.
•    Mixing darunavir with indinavir can increase blood levels of both drugs.
•    Darunavir + ritonavir does not appear to affect blood levels of atazanavir, nor does atazanavir appear to affect blood levels of darunavir + ritonavir. It may be possible to combine these two protease inhibitors.
•    Taking darunavir with tenofovir can increase blood levels of both drugs. These drugs can be combined with no dose adjustments, though it is necessary to watch carefully for kidney damage related to tenofovir.
•    Darunavir can increase blood levels of efavirenz and efavirenz reduces darunavir levels. These medicines should be mixed with caution.
•    Darunavir increases nevirapine blood levels but the raMUNnation can be taken with no dose a-Syoslment.
•    If didanosine (SWpat 01 a darunavir + ritonavir treatment pro~ram, it must be taken on an empty stomach, 1 hour before or 2 hours after darunavir + ritonavir, which should be taken with food.
•    Darunavir increases blood levels of clarithromycin, itraconazole, and ketoconazole. Daily dosage of itraconazole and ketoconazole should not exceed 200 mg. No clarithromycin
Possible Side Effects (continued)
♦    Less common:    abdominalinal pain, and
♦    Rare: Rare side effects can occur in almost any part
body. Contact your doctor if you
ou experience any side ef
fect not listed above.
adjustment is necessary in people with normal kidney function.    the Darunavir + ritonavir may reduce vonconazole levels in t e
blood. Do not mix these medicines.
•    Darunavir + ritonavir can increase rifabutin levels in the blood-
stream. Rifabutin can also reduce darunavir levels in the
bloodstream. If rifabutin is mixed with darunavir + ritonavir,
the rifabutin dose should be 150 mg every other day.
•    Caution should be exercised when combining darunavir + ritonavir with calcium channel blockers such as felodipine, nifedipine, and nicardipine.
•    Darunavir increases blood levels of the heart antiarrhythmic drugs bepridil, lidocaine, and quinidine. These drugs should be used together with caution and only in situations where blood levels of the heart drugs can be monitored regularly.
•    Darunavir + ritonavir can reduce blood levels of warfarin. It is necessary to monitor warfarin levels while taking this combination.
•    Darunavir + ritonavir can raise blood levels of the tricyclic antidepressant desipramine and the tetracyclic antidepressant trazodone. Dosage reduction is recommended.
•    Darunavir + ritonavir may reduce blood levels of the SSRI antidepressants sertraline and paroxetine. SSRI doses may have to be increased to account for this effect.
•    Darunavir + ritonavir can drastically increase the blood levels of some statin-type cholesterol-lowering drugs, substantially increasing the risk of statin side effects. Simvastatin, pravastatin, and lovastatin should not be mixed with darunavir + ritonavir. It is also possible to take darunavir + ritonavir with atorvastatin, although it can increase the level of atorvastatin in the bloodstream. If atorvastatin is prescribed, it is best to begin with 10 mg a day and slowly increase the dose as necessary. Little is known about how darunavir + ritonavir affects rosuvastatin. The safest statin to take with darunavir + ritonavir is fluvastak”.
•    Darunavir + ritonaxk Can increase blood levels of inhaled MT lCosteroids dexamethasone and fluticasone, the anti-rejection drugs cyclosporine, tacrolimus, and sirolimus. The corticosteroids reduce darunavir blood levels, interfering with its effectiveness.
•    Darunavir + ritonavir can reduce methadone levels in the bloodstream. Methadone dose adjustment may be needed.
•    Darunavir + ritonavir reduces the effectiveness of some contraceptive drugs by decreasing the amount of the hormones ethinyl estradiol and norethindrone in the bloodstream. Women mixing these medicines should use additional contraceptive measures (e.g., condoms).
•    Protease inhibitors may drastically increase blood levels of erectile dysfunction drugs sildenafil, vardenafil, and tadalafil, increasing the risk of side effects including low blood pressure, visual changes, and persistent, painful erection.
•    Dexamethasone may reduce blood levels of darunavir.
Food Interactions
Take darunavir with food. The amount of darunavir absorbed into the blood is vastly reduced when it is taken on an empty stomach, thus negating its antiviral effects.
Usual Dose
Adult: 600 mg (2 300-mg tablets) with 1 00 mg ritonavir twice a day. Do not chew these tablets.
Child: not recommended.
Overdosage
Little is known about the effects of darunavir overdose, but 3200 mg of darunavir has been given to study volunteers with no adverse effects. Call your local poison center or hospital emergency room for more information. If you take the victim to a hospital emergency room, ALWAYS bring the prescription bottle or container.
Special Information
Darunavir is not a cure for HIV. It will not prevent you from transmitting the HIV virus to another person; you must still practice safe sex. You may still develop opportunistic infections or other complications associated with advanced HIV disease.
The long-term effects of this drug are not known.
It is imperative for you to take this medication exactly according to your doctor’s instructions. Do not skip any doses. Skipping doses of darunavir increases the risk that you will become resistant k,3 ft drug. If you forget a dose of darunavir or ritonavir and remember within 6 hours, take it as soon as you remember and then continue with your regular schedule. If 6 hours have passed since the time when you should have taken your medicine, skip the forgotten dose and take your next dose at the regular time. Do not take a double dose.
Special populations
Pregnancy/Breast-feeding: Animal studies with darunavir reveal no damage to the fetus, but there are no data on how this drug affects pregnant women. Darunavir should only be used during pregnancy after carefully weighing its potential benefits against its risks.
It is not known if darunavir passes into breast milk. Nursing mothers with HIV should use infant formula, regardless of whether they take this drug, to avoid transmitting the virus.
Seniors: Seniors can take this drug without special precaution.

Breathing Exercises
Breathing is a delicate art, and it is possible to get it wrong, in a variety of ways and for a variety of reasons. A poor breathing pattern can gradually become habitual,

without the person concerned being aware that his or her breathing is at all abnormal.
Allergy and sensitivity reactions sometimes play a part in causing abnormal breathing, and the symptoms produced by a poor breathing pattern may then augment the symptoms of

sensitivity, creating a vicious circle. Correcting an abnormal breathing pattern, by means of breathing exercises and re-training, can produce remarkable improvements in health

for some people.
Breathing too much
Taking in too much air, often called over-breathing or hyperventilation, is the most common breathing disorder. It can produce a variety of rather strange symptoms (see p. 227)

that are sometimes diagnosed correctly, and treated appropriately, but often get overlooked or misdiagnosed.
The primary purpose of breathing is to obtain oxygen from the air and absorb it into the blood. The lungs are a crucial interface here, a trading post for gases that are

exchanged between the bloodstream and the external air. The delicate, moist membranes that cover the inner surface of the lungs are accessed by millions of tiny thread-like

blood vessels known as capillaries. Oxygen from the air seeps into the blood through the thin walls of these capillaries. At the same time, the lungs clean the blood of carbon

dioxide, a waste gas produced by the body’s metabolism. As oxygen seeps into the blood, carbon dioxide seeps out.
That is the school-textbook view of breathing, and it is correct up to a point. But it is over-simplified and misleading if it simply portrays oxygen as totally
good and carbon dioxide as totally bad. In fact, there is a correct level in the blood for both gases, and too little or too much of either can cause problems.
Carbon dioxide plays an important role in the equilibrium of the blood because, when dissolved in any liquid, carbon dioxide makes a weak acid. So the amount of carbon dioxide

present is crucial in deciding the acidity of the blood. Given that the blood reaches every part of the body, it is not surprising that any changes from its normal composition

have far-reaching effects.
Normally, blood is very slightly acidic, and that is what the body is accustomed to. While some body parts can cope with small changes in the acidity of the blood, other parts

respond very badly. The nerve cells are particularly vulnerable to changes in acidity.
Hyperventilation, or over-breathing, has relatively little effect on the level of oxygen in the blood, which is carefully controlled, but it can lower the level of carbon

dioxide in the blood, thus making it less acid. More commonly, hyperventilation just makes the level of carbon dioxide vary a great deal.

When the carbon dioxide levels in the blood yo-yo about all the time, this has some unpleasant effects. In particular, it disrupts the smooth running of the nerve cells, which

is why many of the symptoms of hyperventilation involve the senses, feelings or behaviour.
The symptoms of hyperventilation can include:
•    numbness or pins-and-needles in the hands and feet, occasionally affecting the lips and tongue as well
•    difficulty in swallowing
•    aching muscles, cramps, tremors and twitches
•    sudden loss of strength in the muscles
•    dizziness, confusion, unreal or spaced-outfeelings
•    blurred vision, ringing in the ears
•    headache, migraine
•    breathlessness
•    aching in the chest
•    abnormal heart rhythm
•    sensitivity to bright lights and loud noises.
There may also be some severe psychological symptoms:
•    panic – a brief but intense state of anxiety
•    prolonged anxiety or depression
•    hallucinations, although this is rare
•    mood swings and phobias, most frequently a fear of dying. The irrational conviction that death is imminent can be overwhelming, even in someone who is young and

apparently in good health.
Each of these symptoms can, of course, be caused in several other ways, but when this whole cluster of symptoms – or a large number of them –occurs together in an individual,

that person is very likely to be a hyperventilator.
When there are short self-contained bursts of hyperventilation, the effects are often described as a panic attack. Doctors usually have no trouble recognising this problem, but

– not surprisingly – are often misled by the sustained psychological symptoms of chronic (long-term) hyperventilation. Many people with chronic hyperventilation are diagnosed as

having some kind of mental illness, and they may go for years without getting the right diagnosis.
Hyperventilation and sensitivity reactions The link between sensitivity reactions and hyperventilation seems to be a complex one. Unfortunately, very little research has been

done in this area, so what follows is based on the case-histories of patients, and the collective experience of doctors, not on hard scientific data.
In some cases, a sensitivity reaction may
directly provoke a change in breathing pattern. This
is what appears to happen for some people with
caffeine sensitivity. Cutting out all caffeine-con-
taining drinks (coffee, tea and colas) seems to put a
stop to the hyperventilation symptoms, because the
multiple symptoms promptly disappear (see p. 235).
In other cases, a severe sensitivity problem such
as multiple chemical intolerance results in an anxious
state of mind, and the anxiety leads to hyperventi-
lation. Hyperventilation, pure and simple, may also
masquerade as chemical intolerance (see p. 236).
Wheezy as a mountain breeze
Ionisers — devices that supposedly turn indoor urban air into a fresh mountain breeze — are often promoted as alternative devices that can clear allergens from the air. They do

remove some allergens, but in the case of asthma, research shows that some ionisers can actually make symptoms worse, by generating ozone which irritates the airways. It is

usually the cheaper ionisers that do this. More expensive models are less likely to produce ozone, but they are unlikely to help either. Several scientific trials show that

ionisers have no significant benefits when used by asthmatics.
Hyperventilation and asthma
While hyperventilation can develop in anyone, asthmatics are particularly vulnerable. During an asthma attack, especially a severe one, developing an abnormal breathing pattern

is an entirely understandable reaction. In an attempt to get more air, you may start breathing more rapidly and taking air into the upper chest, using the accessory muscles of

breathing (see p. 230). These muscles should not normally be used when you are at rest — they exist to give you extra breathing capacity when running fast.
As long as the asthma attack lasts, this forced breathing does no harm, because its effects are cancelled out by the narrowing of the airways. But if this over-breathing

persists after the attack has ended, then too much air is going in and out of the lungs, so carbon dioxide levels in the blood begin to fall.
Simply feeling anxious can also trigger off rapid upper-chest breathing. If you get very worried when an asthma attack starts, you may begin hyperventilating just out of

anxiety.
For asthmatics, in addition to the usual symptoms of hyperventilation (see p. 227) there are some subtle effects of hyperventilation that can make asthma worse:
•    The airway muscles (and all other muscles that are not under voluntary control) contract slightly when carbon dioxide levels in the blood fall.
•    Mast cells are quicker to degranulate (see box on p.12) when
there is less carbon dioxide, and this triggers allergic symptoms. Just to complicate matters, one of the symptoms of hyperventilation is breathlessness. Sometimes this is the

most prominent symptom in non-asthmatic hyperventilators, and the doctor overlooks the other symptoms and gives a diagnosis of asthma. In such cases, people are told they have

asthma when they are actually suffering from hyperventilation alone.
Testing for hyperventilation
You can do two simple tests for hyperventilation at home, if you think that it could be playing a part in your symptoms. (If you are asthmatic, only do these tests when you have

no asthma symptoms and your peak-flow reading is good. Make sure your reliever inhaler is nearby, in case of a bad reaction to the test.)
The first test should be done when you have some symptoms that might indicate hyperventilation (see p. 227).
Find a clean paper bag and hold it over your nose and mouth while breathing normally. Any symptoms that are due to hyperventilation should clear up, because, by re-Inhaling the

air that you have just breathed out, you will increase the level of carbon dioxide in your blood.
The second test is done when you don’t have any of the symptoms listed for hyperventilation.
Speed up your breathing, and inflate your upper chest with each breath. Do this for a few minutes. Do any of your usual symptoms appear? If they do, this suggests that they may

be caused by hyperventilation.
If either of these tests indicates hyperventilation, make an appointment to see your doctor. It is important that you should have a proper medical diagnosis, so that you get the

right professional treatment.
Treating hyperventilation
If you hyperventilate, you could be taught a more healthy breathing pattern by a physiotherapist — ask your doctor for a referral. Certain complementary therapists, such as

osteopaths and Feldenkrais practitioners, can also teach good breathing patterns, and so can experienced yoga teachers (see p. 224). A teacher or therapist who works at a

relaxed pace, is not too dogmatic, and helps you to find your own way to healthy breathing, is preferable to one who tries to impose a regimented breathing pattern on you.
On the assumption that most hyperventilators don’t just over-breathe, but also breathe with their upper chest and under-use the diaphragm (see pp. 229-230), all these different

practitioners will take a combined approach — tackling both sides of the problem at once. This represents an important difference from the Buteykc, method (see below).
The Buteyko method
The stated aim of the Buteyko method (also called the Buteyko treatment) is to stop people from hyperventilating. However, Buteykc, practitioners do not work with people who

have the symptoms of hyperventilation, as recognised by conventional medicine (see p. 227). Instead they work with asthmatics — any asthmatics, not just those whose symptoms

suggest that they might be hyperventilators.
The rationale for this is the claim, by the originator of the exercises, Professor Konstantin Buteyko, that asthma is actually caused by hyperventilation. (What is more,

Professor Buteyko cites hyperventilation as the cause of no fewer than 150 different diseases, including allergies, eczema, migraines, insomnia, bronchitis, high blood pressure

and haemorrhoids. However, his treatment is only marketed for asthma.)
The claims made for the success of the Buteyko method in treating asthma are startling. According to one training centre, it can get 97% of asthmatics off most of their drugs

and able to control attacks within a week of starting.
Not surprisingly, this is a bit of an exaggeration. But the real achievements of the Buteykc, method are still quite impressive: an Australian research study showed that during

the course of Buteyko lessons, the overall use of reliever inhalers (e. g. Ventolin) fell substantially and remained relatively low three months later. However, the patients’

average peak flow stayed the same, and 15% of those studied were admitted to hospital with a severe asthma attack during the trial. In the eight months that followed, 30% needed

a course of steroid tablets – indicating a substantial worsening in their condition. In other words, the Buteyko method can give some help to many asthmatics, but the claim that

it can get almost everyone off asthma drugs and free of asthma is just hype.
Professor Buteyko’s claim to have discovered the fundamental cause of asthma is clearly untrue. What he seems to have discovered is that there are many more hyperventilators

among asthmatics than was widely realised, and that they generally show no obvious symptoms of hyperventilation. His other important contribution is to suggest that

mouth-breathing may create a lot more problems for asthmatics than previously recognised.
The Buteyko method has three aspects:
•    unblocking the nose
•    training to breathe through the nose, not the mouth
•    training to take fewer breaths and pause between breaths. Unlike other treatments for hyperventilation (both conventional and alternative), the original Buteyko method

pays no attention to teaching asthmatics to breathe with the diaphragm. However, a few Buteyko practitioners are now beginning to incorporate this aspect of treatment.
If you decide you would like to try the Buteyko method, there are several different options. Classes are the most expensive route, with very high fees being charged. There are

video cassettes you can buy, which are less expensive. Alternatively, there are various books, which are much less costly, and which explain how to do the exercises (see p.

255).
Whichever option you choose, it is vital that you get your doctor’s permission before starting. Ensure that your reliever inhaler is in your pocket while doing the exercises,

because they could provoke an asthma attack. Keep taking your preventer drugs regularly throughout the treatment. If you start to feel much better and want to reduce your dose

of preventer, you must talk to your doctor first.
Don’t follow the Buteyko method blindly, because some of the advice given is dangerous. For example, some Buteyko publications advise you to refuse oxygen if you are taken to

hospital with a severe asthma attack. They claim that oxygen levels in the blood are not reduced during a severe asthma attack, but this is just not true. Measurements clearly

show that the level of oxygen
gets very low, and this is frequently the cause of death.
Another very peculiar Buteyko idea is that you should not try to shift mucus from your airways because mucus ‘protects you’ against losing too much carbon dioxide. This too is

dangerous advice. Accumulated mucus narrows the airways, adding to your asthma symptoms, and it can even block a small airway completely. The part of the lung served by that

airway then collapses – a serious complication that no asthmatic would want.
Using the right muscles
Hyperventilation is often linked with an abnormal way of breathing, in which the wrong muscles are used. This is one common pattern that conventional doctors recognise for

hyperventilators:
•    The main muscle of breathing – the diaphragm (see below) is not used fully
•    The muscles of the upper chest become involved in breathing, even at rest, when they should not be needed
•    There are lots of rapid, shallow breaths
•    The breathing is quite irregular, with deep, sighing breaths from time to time, or frequent yawning.
Even in those who do not hyperventilate, breathing with the upper chest, and/or neglecting the diaphragm, can become a problem. This pattern of breathing is sometimes linked to

anxiety and emotional problems (see p. 230).
To understand what goes wrong, you need first to know about the healthy way to breathe.
The rib-cage and the diaphragm are the work-horses of breathing. You can feel your rib-cage through your skin, and feel its movements, but the diaphragm is far more

inaccessible. It lies below the lungs, but above the stomach and intestines.
In its contracted state, the diaphragm becomes a thick slab of muscle, with a slight curve, like an inverted saucer. When it relaxes, it becomes far more curvaceous, changing to

a shape like an inverted bell. In this shape, there is less space for the lungs above the diaphragm.
If you are breathing correctly, the diaphragm contracts when you breathe in and relaxes when you breathe out. The contraction lowers the dome of the diaphragm, pulling the base

of the lungs downwards and so making them expand.
Breathing out requires no muscular force whatever, as long
as you are just sitting or walking about (and therefore not breath-
ing hard). The lungs are naturally elastic, like balloons, so they
automatically contract and force out the air, once the diaphragm
relaxes into its bell-like shape and stops pulling them downwards.
While you cannot feel the diaphragm itself, you can feel the
effect of its in-breath contraction. As it contracts, the diaphragm
pushes down on the stomach and intestines, so that your abdomen bulges out a little with each breath. Western women, conditioned to admire an unnatural flat-bellied body shape

(unnatural for a woman, that is), often breathe badly because they are trying to ‘hold the tummy in’. This steely tightening of the muscles across the front of the abdomen

opposes the contraction of the diaphragm, and prevents a natural and relaxed in-breath.
The diaphragm should do virtually all the work of breathing in, when you are not exerting yourself much. The upper part of the rib-cage should hardly expand at all and the

muscles that run between the ribs, the intercostal muscles, should not be working.
When you become more active, and therefore need more oxygen, the upper chest automatically starts to expand with each in-breath. At this point the intercostal muscles become

involved, along with a whole team of other muscles in the chest region —these are known as the accessory muscles of breathing.
The effects of an asthma attack
In the grip of a severe asthma attack, you may well start using the accessory muscles of breathing to try to take in more air. If you have frequent attacks, or if this way of

breathing gets to be a habit and goes on between attacks, then the chest may be distorted by the constant use of the accessory muscles, plus the over-inflation of the lungs.

Severe asthmatics often have high shoulders and a `barrel-chested’ look as a result of this. Hyperventilation may also start in this way.
Observing how you breathe
To discover whether you are breathing with your diaphragm or your upper chest, lie on your back with your left hand on your belly, and your right hand on your upper chest. Just

lie still for a few minutes, let your arms relax, then start to pay attention to your hands. When you breathe in, which hand rises? It should be the left hand, with little or no

movement in the right.
Alternatively, bend over and hold the back of a chair with your hands. Your back, head and arms should form a straight horizontal line, at right angles to your legs. Just stay

quietly in this position for a while. It is very difficult to breathe with the upper chest in this pose, whereas breathing with the diaphragm is easy. If you feel fine in this

position, then you are probably breathing well normally.
Correcting upper-chest breathing
Learning to breathe with the diaphragm is often an important part of correcting hyperventilation (see p. 228). It should also be taught to anyone who has the kind of chest

deformities that develop in severe asthma (see above).
Diaphragmatic breathing, or abdominal breathing as it is sometimes called, should help make you feel more relaxed
because the in-breath can disperse tensions in your abdomen. This is where many people ‘hold on to’ their fears, with chronically tense abdominal muscles. When you start

breathing into this area of tension, it is important to take things gently and not force the breath downwards. Be aware of any resistance to the in-breath in the abdomen, and of

any emotional reactions that occur when you challenge this resistance.
Sometimes breathing in this way for the first time can bring up emotional difficulties that may need careful handling. That is why it may be better to learn abdominal breathing

from someone who has time to deal with such issues, and with whom you feel very comfortable and relaxed — for example, a yoga teacher or an alternative therapist who you like

and trust. Physiotherapists tend to take a very brisk and practical approach to breathing, which may not be entirely appropriate or helpful when habitual ways of breathing are

tied up with emotional problems.
When learning to breathe with the diaphragm, be careful not to get carried away and become a ‘belly breather’, whose every in-breath sends the abdomen bulging out like a

mainsail. The abdominal muscles should oppose the downward movement of the diaphragm to some extent, without being too tense.
Clearing the nose
Breathing through the nose, rather than the mouth, is beneficial for asthmatics, because it cleans and warms the air. It can also help those with chronic sinusitis because it

oxygenates the air in the sinuses, which discourages some of the more troublesome microbes responsible for sinus infections.
This technique for clearing a blocked nose, part of a set of breathing exercises for opera singers, is based on a time-honoured yoga exercise called alternate nostril breathing:
•    Sit with your mouth closed.
•    Press your right nostril against your nose to close it, using the thumb of your right hand.
•    Breathe out through your left nostril.
•    Press your left nostril against your nose with the index finger of your right hand, to close it. (The hand makes only a very small movement from side to side.)
•    Breathe in through your right nostril.
•    Repeat the sequence.
Once you have got the hang of this, do ten fairly rapid breaths, with no pause between out-breath and in-breath. Pause and rest.
Repeat using your left hand, and reversing the flow of the breath: out through the right nostril and in through the left. Again, do ten breaths and then rest.
Alternatively, try the following exercise, which is recommend by Buteyko practitioners for unblocking the nose. This technique has not been tested scientifically, but the

reports of asthmatics who have used it suggest that it often works wonders, even with children who could never breathe through their noses previously:
•    Have your reliever inhaler to hand, just in case the exercise brings on an asthma attack.
•    Breathe as you do normally, and at the end of a normal out-breath, close your mouth and hold your nose
•    Stay like this, without inhaling, for as long as you can without discomfort. Walk around the room while you are doing this or, if you are young and fit, do something

more strenuous – either walk upstairs or squat-then-stand several times.
•    When you need to breathe in, keep your mouth shut but release your nose
•    Breathe in slowly through the nose
•    Repeat the exercise if your nose becomes blocked again.
Special exercises for asthma
In addition to tackling the problem of hyperventilation, if one exists, asthmatics can use other breathing exercises to tackle specific aspects of their asthma.
Clearing mucus from the lungs A physiotherapist can teach methods of clearing mucus from the airways which are suitable for asthmatics. Ask your doctor for a referral. You could

also try the following exercises:
Huffing Take an in-breath, then tighten your abdominal muscles very sharply, to push the air out. Imagine there is a candle in front of you, and you are trying to extinguish it,

but using your belly muscles only. Your out-breath should make a short soft ‘huff’ sound – if it is more of a loud ‘w000sh’, you are contracting the muscles in your chest as

well as those in the belly. Try again, and focus your attention on your belly as you make the out-breath.
The in-breath should be effortless with this exercise – it just bounces back in. Do as many huffs as you can without feeling breathless. Rest and repeat. The aim is to build up

stamina until you can do 30 or more huffs in succession.
Pursed-lips breathing Take a fairly deep in-breath, then purse your lips together. As with huffing, your belly muscles have to do all the work of the out-breath, but in this

exercise they are working against the muscles of the lips. The aim is to divide the out-breath into as many fragments as possible – to push the air out through the lips in a

succession of tiny, forceful blasts.
One objective of these exercises is to encourage mucus to start moving up to the top of the airways. From there, it can be cleared with a little throat-clearing cough. Note that

the mucus will probably take a while to reach the throat – this may happen some time after you do the exercise. For maximum effect, repeat these exercises several times each

day.
Coping with asthma attacks
The crucial thing during an asthma attack is to focus on your out-breath, not your in-breath. Of course this goes against the grain, because you feel so desperate for air, but

remember that the central problem is stale air from your last in-breath, now trapped in your lungs by the narrow airways. If you can focus on exhaling this used air, you will

have more space for fresh air to come in with the next in-breath.
At times when you are not suffering from an asthma attack, it is worth doing some exercises that improve the strength of your out-breath. The key problem during an asthma attack

is that the natural elasticity of the lungs, which should power the out-breath, is not equal to the challenge of pushing out all that air through narrowed airways in a short

space of time. In this situation, contracting your abdominal muscles so that they push upwards and assist in emptying the lungs is helpful.
The two exercises described above for clearing mucus –huffing and pursed-lips breathing – also strengthen those abdominal muscles which can assist you with your out-breath

during asthma attacks.
Strengthening exercises
Several different exercises or pursuits that strengthen the breathing muscles seem to produce an improvement in asthma. The reasons for this are not understood.
Asthmatics who take up a wind instrument, such as the flute, often report that their asthma improves considerably. The same effect has regularly occurred with asthmatics who

undertake classical training in singing. One set of exercises, taught to aspiring opera singers and designed specifically to strengthen the diaphragm, has been scientifically

tested and shown to improve asthma and reduce the need for drugs. These exercises can be learned at home (see p. 255). There are also some mechanical devices which can

strengthen the breathing muscles (see p. 255).

Various anti-allergy drugs
An allergic reaction is a lengthy, complex process, and the various anti-allergy drugs all work on different stages of that process. That is why it often makes sense to use several different drugs for the same allergic condition: they each tackle the problem in their own way.
Steroids (see p. 140) intervene at a very late stage, quelling the inflammation that follows on from an allergic reaction. Using a steroid is rather like calling the fire brigade to put out a fire, whereas using an antihistamine (see p. 138) is like having fire-proof doors, to prevent the fire spreading at an early stage. Cromoglycate-type drugs (see below) intervene at an even earlier stage. They are like basic fire prevention - teaching children not to play with matches, or fitting smoke detectors.
Anti - leukotnene drugs (see p. 149) work at roughly the same stage of the process as anti-histamines but tackle an entirely different aspect of the allergic reaction.
Cromoglycate-type drugs
These drugs are also referred to as mast-cell stabilisers or mast-cell Mockers.
There are three drugs in this group, sodium cromoglycate (also spelled cromoglicate), nedocromil sodium, and lodoxamide. All operate at an early stage of the allergic reaction, stopping it before it actually starts. They stabilise the outer membrane of the mast cells (see box on p. 12), which prevents the allergic response from occurring.
Some common brand names
Common brand names of cromoglycate-type drugs include:
inhalers - Cromogen Easi-Breathe, Intal, Tilade
eye drops - Hay-Crom, Opticrom, Rapitil, Vividrin, Viz-on nose sprays - Rynacrom, Vividrin
capsules - Nalcrom
This is a far more satisfactory way of dealing with an allergic reaction than trying to tackle it after the reaction has occurred. But from a purely practical point of view, it has a drawback. I order to work at all, these drugs must reach the mast cells in advance of the allergen. They are of very little use if taken after the allergic reaction has begun.
For those who are taking cromoglycate-type drugs on a regular schedule, several times a day, it is very important to be conscientious about taking them on time. This maintains the protective effect of the drug, without any gaps.
If you are using these drugs on an ‘as-needed’ basis, you should take them 30 minutes before an allergen is encountered. or 30 minutes before a bout of exercise, if they are being prescribed for exercise-induced asthma. (Note that children sometimes respond differently, getting protection from these drugs immediately.)
The effect of these drugs takes time to build up. You should take them regularly for at least four weeks before deciding whether they are helping you or not.
One point in favour of cromoglycate-type drugs is that they are extremely safe, with few or no side effects in most people. Sadly, they do not work for everyone. A fairly high percentage of children respond well to them, but the response rate is much lower for adults. Nevertheless, adult allergy sufferers, especially those who need steroids to control their symptoms, should always be given the opportunity to try out these drugs. When cromoglycate-type drugs do work, they are very effective and almost always trouble-free, so they are a good alternative to steroids.
Both sodium cromoglycate and nedocromil sodium are available in inhaler form for asthma (see p. 157). Sodium cromoglycate is also available as nose drops for hayfever and other nasal allergies.
All three drugs are available as eye drops. Recent evidence suggests that sodium cromoglycate drops are less effective than the other two, particularly for the treatment of severe allergic conjunctivitis (inflammation of the eye).
Sodium cromoglycate is available in capsule form for food allergy. Note that these capsules are of very limited value in food allergy, and are certainly not a substitute for food avoidance. They do reduce sensitivity a little and can sometimes be helpful for those with multiple food allergies (see p. 67).
Side effects
There are no serious side effects at all for nedocromil sodium. cromoglycate can, very rarely, cause joint pain and swelling. An allergic reaction to the drug itself is even more uncommon. Stop taking the drug and see your doctor promptly if either of these occurs.
The only other side effects that have occasionally been reported are headache, nausea and vomiting. None of these indicates any damaging effect by the drugs – they are all minor side effects.
Eye drops containing these drugs may cause stinging and burning when inserted, but this is a minor side effect and usually wears off. Flushing and dizziness have sometimes been reported with lodoxamide eye drops.
Nose drops may also cause local irritation. This could be due to the drug itself, in which case it is a minor side effect. Alternatively, the irritation may be due to the preservative used or some other non-drug ingredient (see box on p. 33).
Occasionally cromoglycate nose drops cause bronchospasm – contraction of the airway muscles – but this tends to wear off quite quickly. Bronchospasm can also occur when cromoglycate-type drugs are inhaled (see p. 157).
Anti - leu kotriene drugs
These drugs, which have a set of very specific effects (see p. 159), were originally designed to treat asthma. Their potential for treating other allergic diseases is currently being explored:
•    Several studies show that they work well for perennial allergic rhinitis brought on by allergens such as house-dust mite. They also have some effect on hayfever, but standard treatment (such as antihistamines plus a steroid spray for the nose) is more effective.
•    They are especially useful for both rhinitis and asthma in patients suffering from triad (see box on p. 28). Research shows that they also reduce asthmatic reactions to very small test doses of aspirin, but they don’t give protection against anaphylaxis brought on by normal doses.
•    They have also been used successfully in cases of chronic urticaria and for some patients with delayed pressure urticaria. It seems plausible that they would also be helpful for chronic urticarla linked to aspirin sensitivity.
•    Preliminary trials suggest that these drugs might be useful in atopic eczema. Some studies show a very good response that allows a reduction in steroid creams.
•    Montelukast works very well for eosinophilic gastroenteritis and eosinophilic oesophagitis (see p. 72), according to some new studies.
For side effects of these drugs see pp. 159-60.
Anti-IgE drugs
Since the antibody IgE (see box on p. 12) is such a crucial player in allergic reactions, developing drugs that disable this antibody should help allergy sufferers. The first such drug is omalizumab (brand name Xolair) which was licensed for use in the United States in 2003. It is expected to become available in Britain some time in the next few years.
Omalizumab binds to IgE antibodies and stops them from interacting with mast cells, so blocking any allergic reaction. The drug is given as a ‘depot injection’, just under the skin, every 2-4 weeks. It is gradually released from the injection site and moves around the body in the blood, mopping up IgE molecules.
At present, omalizumab is used for severe hayfever and for people with asthma who are not responding well to the usual treatments. It is only worth using if there is clear evidence that allergies play a part in the asthma. Patients who use omalizumab are often able to reduce their dose of inhaled steroids – and they suffer fewer serious asthma attacks and have better lung function. Some patients can even stop using steroids completely.
Other anti-IgE drugs are in the pipeline. Pilot studies show that one works very well for peanut allergy: after just four injections, sensitivity to the allergen falls sharply, reducing the risk of anaphylaxis from traces of peanut eaten accidentally.
More powerful anti-allergy drugs
Occasionally people with severe allergies, who are on constant high doses of steroid tablets, or who fail to respond to steroids, need treatment with powerful anti-inflammatory drugs, such as methotrexate or cyclosporin. These suppress the immune system, and extremely careful monitoring for side effects is needed.
Adrenaline (epinephrine)
Anyone who has suffered anaphylactic shock (see p. 58) should be carrying a special syringe, called an auto-injector, loaded with adrenaline. The injector is very simple to operate and is designed for emergencies. Most allergy sufferers, even children, can give themselves the injection – or a parent or other adult can give it.
Some asthmatics, and those with food allergy who suffer swelling of the throat, may be given adrenaline in inhaler form as well (see pp. 155-6). This can be useful as an additional treatment but it’s definitely not a substitute for an injector.
See pp. 98-9 for instructions on using adrenaline in a crisis.
Wherever you go, take your injector with you. Always keep it close at hand: you need to be able to use it within minutes of the allergic reaction starting. You may be unable to speak (and therefore unable to ask someone else to fetch it) quite soon after the attack begins. The injector must never be refrigerated. It can also be damaged by sunlight and excess heat.
If you live in the countryside or in an area with a poor ambulance sevice, or if you are going camping or hiking somewhere remote, ask your doctor for a second injector, or one that can deliver multiple injections. Also ask about the maximum number of injections that can be given, and never exceed this total. Some doctors believe everyone should have two injectors, just in case the first dose doesn’t do the trick and help is slow in coming.
It is vital that you are shown exactly how to use the auto-injector. Canadian researchers discovered that only one in four
Some common brand names
Common brand names of adrenaline preparations include: auto-injectors – Anapen, EpiPen
inhalers – AsthmaHaler Mist, Bronkaid, Epiphrine
health professionals got the technique correct when demonstrating how to use an auto-injector In this study, pharmacists were much the best as regards accurate instructions. Dummy injectors are useful for training purposes and most pharmacies have them.
When the adrenaline auto-injectors expire, they can be very useful for practising with, or for showing a new baby-sitter or teacher – practise on an orange or grapefruit.
If you are taking beta-blockers (e.g. for a heart condition or anxiety), adrenaline may not have much effect.
Heavy daily use of beta-2 relievers for asthma (see p. 152) will also make adrenaline less effective when you need it.
Side effects
The important side effects of adrenaline involve the heart. Anyone with a heart condition should be given special advice in advance by their doctor about using adrenaline. The same goes for people with diabetes, hyperthyroidism or high blood pressure, and anyone taking tricyclic anti-depressants. There are quite a few minor side effects from adrenaline, such as anxiety, trembling, nausea. sweating, dizziness and cold extremities. These soon wear off.
Drugs that can make you worse
Aspirin and its relatives have a very bad effect on some people with rhinitis and/or asthma (see box on p. 151). Unfortunately, recent research shows that paracetamol is not safe either. It makes asthma more likely to develop in those who do not yet have the disease, and increases the severity of asthma symptoms for those who do. Unlike aspirin, paracetamol affects everyone, because it lowers the levels of a natural antioxidant, called glutathione, which the body makes to protect the lungs from oxidants. The greatest effects are seen in people who take paracetamol regularly (once a week or more), but even an occasional dose makes some difference.
All the other drugs that can make you worse are prescription drugs, and your doctor should be alert to the dangers. But doctors are overworked and sometimes forget, so it is sensible to know about the risks for yourself. If you have any doubt about the drugs you are taking, ask a pharmacist.
Beta-blockers are a major hazard for people with allergies. They can make the airways contract, and can bring on a serious asthma attack. They also make anaphylaxis more likely in someone who already has allergic reactions (see p. 59) and they increase the risk of a severe reaction to
immunotherapy (see p. 166) or skin-prick tests (see p. 91). Beta-blockers are prescribed for high blood pressure, angina and other heart problems, migraine and thyroid disease. There are alternative drugs in all cases. Sometimes asthma develops in people who have been taking beta-blockers for years. The beta-blockers are not responsible for this, but once asthma has begun, they will make symptoms worse. Eye drops for the treatment of glaucoma may also contain beta-blockers and can have a bad effect on asthmatics.
ACE inhibitors, used for heart conditions, may cause a cough and airway narrowing. They may also increase the risk of a severe reaction to immunotherapy.
Female hormones affect asthmatics, so taking the contraceptive pill or hormone replacement therapy (HRT) may make asthma worse. Progesterone-only contraceptive pills tend to cause fewer problems.
The drug isoniazid (INH), prescribed for tuberculosis, makes the body far more susceptible to histamine in foods (see p. 200).
An allergic reaction to a specific drug (e.g. penicillin) can also occur in some people, resulting in urticaria, or even anaphylactic shock.
Aspirin sensitivity
Aspirin sensitivity is not an allergic reaction, because neither IgE nor mast cells are involved. What causes this problem is a metabolic abnormality — a malfunction in one aspect of the body’s chemistry. The details of this are very complicated: you may want to skip the next three paragraphs and
simply read about how to cope with the problem.
The exact nature of aspirin sensitivity is still far from clear, but it seems to involve a relatively poor production of prostaglandins, combined with a plentiful production of leukotrienes. Both these substances are messenger chemicals which, broadly speaking, promote inflammation. But the details of their pro-inflammatory activities differ. It seems that, ideally, the body should have a harmonious balance between the two, and an imbalance produces problems.
Both prostaglandins and leukotrienes are manufactured from certain fats that are found in the diet. These fats, the raw materials, are worked on initially by two different enzymes — one that leads to the production of prostaglandins and another that leads to the production of leukotrienes.
If one of these enzymes is defective, it may mean that the other is oversupplied with raw materials, resulting in a serious imbalance between prostaglandins and leukotrienes. In those with aspirin sensitivity, or at risk of developing aspirin sensitivity, the enzyme that produces prostaglandins seems to be defective.
Even in the absence of aspirin, this imbalance in the production of prostaglandins and leukotrienes causes problems. It leads to symptoms such as chronic urticaria (see p. 51) or rhinitis, nasal polyps and asthma (a cluster of symptoms that is commonly called triad — see box on p. 28).
Taking aspirin can make the imbalance between prostaglandins and leukotrienes even worse in a person with this underlying abnormality. Aspirin exerts its painkilling effects by disabling the main prostaglandin-making enzyme — the enzyme that is already defective.
When someone with aspirin sensitivity takes aspirin, they may suffer worsening asthma, a severe asthma attack or — the worst-case scenario —collapse. This is a potentially fatal reaction, similar to anaphylaxis, requiring emergency medical treatment (see p. 101).
The greatest puzzle about aspirin sensitivity is why it often takes so long to develop in someone who already has the symptoms of triad —indicating the basic metabolic abnormality. It may be as much as 20 years from when someone has their first triad symptoms to when they begin reacting badly to aspirin.
If you have triad symptoms already, but no aspirin sensitivity yet, what should you do? Unfortunately, there are no safe tests for aspirin sensitivity at present — taking a small dose of aspirin and seeing what happens is very hazardous. It is probably best to assume that you are going to become sensitive to aspirin at some stage, and avoid all aspirin and aspirin-like drugs. Caution is the best plan here because aspirin sensitivity can come on very suddenly, and be life-threatening the very first time it occurs. Note
that some triad sufferers have polyps and rhinitis but no asthma until they actually develop aspirin sensitivity — a dose of aspirin suddenly brings on their first asthma attack plus other symptoms of aspirin sensitivity.
Avoiding aspirin itself is not difficult, but aspirin-like drugs pose more of a problem. Every year there are a number of deaths from these drugs. Some cases occur because a busy doctor momentarily forgets that a patient should not take these drugs. The drugs that need to be avoided are all known as non-steroidal anti-inflammatory drugs (NSAIDs), COX-1 inhibitors or COX-2 inhibitors. However you will not see any of these names on the packet. These drugs are very widely used for pain relief (e.g. in headache and backache remedies such as Nurofen), for the treatment of arthritis, and for several other inflammatory diseases.
There are dozens of non-steroidal anti-inflammatory drugs available, and many are sold under several different brand names. The list grows every year, as new drugs or new brands are launched. The only way to avoid these drugs is to be very cautious:
•    When buying any cold- or flu-remedies, painkillers, medicines for sprains or sports injuries (including those you apply directly to the skin), headache tablets or migraine tablets, always buy them at a chemist’s shop rather than a supermarket, and check with the pharmacist that they do not contain aspirin or aspirin-like drugs.
•    Be cautious also about remedies for an upset stomach. A few (e.g. Alka-Seltzer) contain aspirin.
•    Don’t take any drugs unless you are 100% sure of what they contain. Remember that the ingredients of a familiar brand name can sometimes change — read the label every time.
•    When a doctor prescribes any new drug, always mention that you are sensitive to aspirin, or that you have triad symptoms. Alternatively, check with the pharmacist when the prescription is filled.
•    Aspirin-free painkillers almost always contain paracetamol, a drug which can cause a severe reaction (similar to the collapse induced by aspirin itself) in about 5% of those with aspirin sensitivity. If you are taking paracetamol for the first time, start with half a tablet. Be sure that, for the next 2-3 hours, you have a way of getting to hospital quickly should you start to feel ill. (Note that paracetamol has another entirely separate effect, increasing the severity of asthma, and it is best not to take it too often — see box on p. 150.)
Avoiding all aspirin-like drugs will prevent you having anaphylaxis or severe attacks of asthma. Unfortunately, triad symptoms will not go away however careful you are about avoiding aspirin.
It is well worth trying the new anti-leukotriene drugs (see p. 149), especially if you have aspirin-induced asthma. They seem to help with triad symptoms by curtailing the activities of leukotrienes and so redressing the balance between leukotrienes and prostaglandins.