Statins and Grapefruit

grapefriut

If you’re taking a statin medication for your cholesterol, you have undoubtedly heard the warning against consuming grapefruits or grapefruit juice. This restriction also applies to a number of other medications including certain cardiovascular medications, anti-cancer agents, antibiotics, antidepressants and others. For a more detailed list and approximations about the extent of the interaction with particular medications click on to the following site: http://www.cmaj.ca/content/suppl/2012/11/26/cmaj.120951.DC1/grape-bailey-1-at.pdf.

The discovery of the interaction was serendipitous. Researchers noticed a higher drug concentration in certain test subjects than others when a medication was initially being tested. Those with an elevated drug level were eventually found to have also consumed grapefruit. Pomelo, lime and marmalade can also produce the same effects.

The compounds in grapefruit responsible for the effect are called furanocoumarins and act by blocking the enzymes in the intestines responsible for the degradation of certain medications. It only takes one glass of grapefruit juice to produce the maximum effect, an effect that persists for longer than 24 hours. Therefore, taking grapefruit juice at a time well-separated from the medication dose is ineffective in solving the problem.

How big an issue does this represent? That depends on a number of factors, particularly on how dependent the medication is on the enzyme that is blocked by the juice. Some medications have a wide “therapeutic range.” In other words, increased blood levels don’t represent much of a concern. On the other hand, some medications have a narrow therapeutic range, with increased concentrations causing serious problems.

Although most statins should not be taken in combination with grapefruit products Crestor (rosuvastatin) and Pravachol (pravastatin) are exceptions since they are not significantly metabolized by the enzyme blocked by grapefruit.

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Aspirin and Disease Prevention

AspirinRecently the New York Times ran an op-ed entitled “The 2,000-Year-Old Wonder Drug” extolling the benefits of aspirin for a number of illnesses including cardiovascular disease and cancer. Although quite enthused about aspirin as a disease preventive, the author does advise medical consultation about the risks versus the benefits.

Is aspirin usually a good idea for middle-aged American? For those with known cardiovascular disease it usually is. However, one year ago a large study in the Archives of Internal Medicine did not show a reduction in cardiovascular or cancer deaths in patients without prior cardiovascular disease taking low-dose aspirin. A reduction in non-fatal heart attacks was noted. This benefit, however, was associated with a 30% increased risk of significant bleeding. The authors conclude against the routine use of aspirin for patients at low risk for cardiovascular disease.

More concerning, than the well-known risk of bleeding from the stomach or intestines, is the possibility of bleeding in the brain. Although the absolute risk of intracranial vessel bleeding is small (two hemorrhagic strokes per 10,000 patients taking aspirin) the consequences can be devastating.

Also, does aspirin prevent cancer? The evidence suggests that it is effective in preventing colon cancer and might be effective in preventing other cancers, although the evidence for the latter is less clear. The dose necessary to produce a statistically significant reduction in colon cancer is not certain, but some suggest that a full aspirin (325 mg) rather than low-dose aspirin (81 mg) might be needed.

The increased risk of bleeding associated with any dose of aspirin, and the possibility of greater risk with a higher dose, along with the very useful colon cancer prevention strategy of colonoscopy now in place caused the American Cancer Society not to recommend the routine use of daily aspirin to prevent colon cancer.

Patients at low risk for cardiovascular disease should consult their doctor before committing to a lifetime of daily low-dose aspirin. Low risk is defined as a patient whose 10-year absolute risk of a first coronary disease event is less than 10%. The doctor can calculate the risk by using a formula derived from the Framingham study of cardiovascular disease.

Aspirin is the wonder drug touted in the New York Times but, as usual in medical matters, every situation is different.

Chronic Lyme Disease

Lyme disease is usually divided into three stages: early localized disease, early disseminated disease and late Lyme disease. The first stage is characterized by the characteristic rash with or without systemic symptoms such as fever, body aches and joint pains. Early disseminated disease is characterized by rashes and/or neurologic symptoms and/or heart problems. Late Lyme disease is associated with arthritis, usually involving one or a few large joints, particularly the knee, and/or neurological problems. The neurological problems can involve the brain, the covering of the brain or a specific nerve possibly creating headaches, paralysis, or nerve pain. Arthritis symptoms, particularly if only the knee is involved, can appear to be a solitary problem, with no clue that the problem is caused by Lyme disease.

Early disseminated disease occurs weeks to several months after the initial infection from the tick bite. These symptoms can be the first manifestation of Lyme disease since 20% of people with the disease do not recall any rash and approximately 25% of people with the disease do not recall a tick bite.

Late Lyme disease occurs months to years after the tick bite and, as in the case with early disseminated Lyme disease, the history of a rash or tick bite might not be present or a history of having had the earlier stages of Lyme disease. The symptoms include arthritis, predominantly of the large joints, especially the knees. Neurological symptoms can also occur.

Symptoms usually resolve gradually, as they do in most infectious diseases, after a full course of antibiotics. Post-Lyme disease syndrome refers to symptoms such as headache, muscle pain, joint pain and fatigue that persist, but generally resolve after six months to one year.

A confusing issue develops when a person who has, by all accounts, been successfully treated for Lyme disease suffers continuing health problems that do not resolve with time. This situation has been termed chronic Lyme disease by some and is the subject of much dispute.

Briefly, certain doctors and advocacy groups maintain that, in these situations, the symptoms are caused by Lyme disease that failed to be eradicated by the standard treatments. Medical authorities counter that the persisting symptoms are due to another illness that, perhaps, was triggered by Lyme disease.

The “other illness” suggested is often either fibromyalgia or chronic fatigue syndrome. Both usually respond poorly to any one of a number of medications or treatments traditionally employed. Many, if not most, physicians suspect that fibromyalgia and chronic fatigue syndrome are, at the root, psychological problems.

You can imagine how frustrated a person feels who had been totally healthy, was bitten by a tick, became ill with Lyme disease, failed to improve after treatment, and is now told he has a psychological illness! Personally, I think that the development of symptoms compatible with fibromyalgia or chronic fatigue syndrome after Lyme disease is further proof that these illnesses are not psychological.

I suspect that chronic Lyme disease is not due to the persistence of the Lyme organism, but that the Lyme organism has triggered some other illness. Therefore, additional antibiotics directed at Lyme would be pointless, and possibly harmful.

What to do? It is necessary to search for other illness triggered by Lyme. I have seen cases where Lyme triggers an arthritic illness. What initially was arthritis caused by the Lyme organism is now arthritis caused by another arthritic disease, itself triggered by Lyme. Look closely at the blood for autoimmune markers. If the symptoms suggest arthritis get treatment for arthritis even in the absence of confirmatory blood tests.

Persisting fatigue with or without bodily pain is usually the most troubling symptom for patients with “chronic Lyme disease.” Long courses of antibiotics are ,almost always, fruitless. A more productive approach is to start fresh, evaluating each symptom as a new issue using standard, individualized treatments as needed. For instance, despite the patient’s firm belief that persisting Lyme infection is causing severe fatigue treating fatigue with medications known to improve it can be very worthwhile. A creative and unprejudiced approach, as usual in medicine, offers the best chance for success.

Zithromax and Sudden Death

A recent study in the New England Journal of Medicine described an increased risk of death from cardiovascular causes in patients taking azithromycin. Azithromycin (Z-pack, Zithromax) is a very commonly used antibiotic and this warning merits concern.

The increased risk of cardiac death relates to the tendency of azithromycin to increase the risk of an irregular heartbeat. In this study a similar risk of increased cardiac death was noted in patients who took levofloxacin but not in patients who took amoxicillin.

The increased risk was small (47 additional deaths per 1,000,000 courses of treatment) and largely limited to patients with very significant heart problems. This increased risk is probably significantly less than that which had been noted with erythromycin in the past.

Since vulnerability is limited mostly to patients with significant heart problems (the top 10% severity of heart disease in this study) and, presumably, patients taking a number of cardiac medications some caution is needed when prescribing to these patients. Since the blood concentration of azithromycin causes the problem, particular caution is needed in patients with very severe heart disease who are also taking cardiac medications that will raise the blood concentration of azithromycin such as diltiazem and verapamil.

Chronic Sinusitis

Chronic sinusitis is the most common chronic illness in the United States.  Both the diagnosis and treatment are, unfortunately, controversial.  Some feel that signs of obstruction and inflammation are required to accept chronic sinusitis as an appropriate diagnosis.  Others feel confident that it is defined by its symptoms regardless of X-ray or other findings.  Similarly, one physician may feel that evidence of infection is necessary before prescribing antibiotics.  Another may consider worsening of symptoms alone as justification for their use.

Some Cautions

Natural treatments for sinusitis are quite appropriate after considering several caveats.  See your doctor if you develop a fever, severe facial pain, or symptoms not typical of your experience with chronic sinusitis in the past.  Remember that a fever may indicate an acute sinus infection or a worsening of chronic sinusitis.  Antibiotics are usually needed in the presence of fever and may be required for persisting colored nasal discharge, poor response to other treatments, unrelenting fatigue, continuing facial pain, or simply failure to improve.

Medication Side Effects

Certain medications can cause or exacerbate sinusitis.  In vulnerable individuals, these include particular medicines for high blood pressure, depression, and heart conditions.  Oral contraceptives also occasionally cause problems.

Diet

Remember the basics:  What are you putting into your body each day?

Foods That May Cause Problems

One the most common dietary causes of nasal congestion is milk.  Eliminating milk and milk products from your diet will tell the tale; no need for a medical allergy evaluation.  Give it two weeks.  Often the results can be dramatic.  Eliminating milk and milk products cures sinusitis and fatigue in approximately 10% of our patients.

Although less often than milk, wheat can cause sinus symptoms.  A wheat elimination diet is difficult, but can be fruitful.

Likewise, other foods and food additives, such as artificial sweeteners, can cause problems.  Try eliminating different groups of foods either by yourself or with the help of a dietitian.  As you might guess, the foods we often like best are sometimes to blame.

Foods That May Help

On the other hand, some foods clear the sinuses.  Garlic, horseradish root, and cayenne (red pepper) may produce a desirable effect.  Drinking substantial amounts of water or other fluids frequently help to loosen nasal mucous.

Few people with sinus trouble are able to drink wine or beer without causing problems.  Spirits are generally better tolerated.

Climate

Outdoor Climate

A crisp cool day with a slight breeze and no dust, molds, pollens, or pollutants is just what you need.  But where?  If you could find the place, you probably couldn’t make a living there!

Heavy, humid, still days with atmospheric inversions are terrible, particularly if you add in smog and pollutants.  Dry, dusty days are also a problem.

Barometric shifts often swell the nose, blocking sinus drainage ducts, since spongy areas inside the nose expand to equalize pressure with the outside lower pressure.

Indoor Climate

Evaluate your house for allergens, irritants, humidity and dust.  Clean scrupulously while watching for dust collectors such as books, carpets and bedding.  Bedding can be a difficult problem.  Try covering your mattress and box spring with a special fabric encasing (a product is available through National Allergy Supply, Inc. (www.nationalallergysupply.com), and equipping the heating, ventilation and air conditioning duct system (HVAC) with good filters.  For single rooms, a high-efficiency particulate air filter (HEPA) is best.  A good one is available through Bionaire, Inc. at www.bionaire.com.  One caveat:  Air supplied  continuously to a room (home or office) from a central fan through a duct system washes out the filtered room air.  Consider a HEPA filter for the entire central air system.  Alternatively, you may also apply disposable filters monthly over the incoming air ducts to the room.  These are also available from National Allergy Supply, Inc.

Sick Building Syndrome

Many “sealed buildings” built in the last 30 years, particularly office buildings with no functioning windows, do not permit the introduction of adequate fresh air, causing sinus symptoms (sick building syndrome).  Smoke, substances in cleaners, copiers, rug adhesives, etc. can also be irritating to vulnerable individuals.  Try talking to the building engineer.  Are the fresh air intake valves open far enough or, for reasons of economy, is the same air being continuously recycled?   Where is the fresh air intake duct located: on the top of the building to minimize pollution, or is it near street level where exhaust fumes are highest?  Similar problems exist in airplanes.  The “virus” many people feel they caught while flying is actually a sinus infection caused by dry, stale, polluted airplane air.  Air pressure changes as the plan changes altitude also exacerbate sinus problems.

Personal Habits

Smoking irritates the sinuses and should be avoided.  Some people become exquisitely sensitive to perfumes, soaps, newsprint, etc.  Individuals should avoid these and other substances that prove problematic.

Adequate sleep is good, but excessive amounts of sleep can be trouble.  Lying down reduces the size of the sinus ducts by 20%.  Raising the head with a few pillows can help restore flow.  Curiously, sleeping on one side of the body improves airflow in the opposite nostril.  Stick with the amount of sleep that you usually require when healthy when your sinuses act up.

Exercise can be a highly effective and healthy way to deal with sinus trouble.  It can open the nose and improve sinus drainage.  Sinus clearing is the benefit that many people feel after exercise.

Vitamins & Supplements

Many people feel that vitamins and dietary supplements are helpful.  This is difficult to prove.  Vitamins, herbs and food supplements can produce beneficial changes in the nose and, occasionally, a marked improvement.  Large doses of certain vitamins, supplements and herbs can cause medical problems.  Additional concerns include the lack of standardization and government testing of herbal products.  Those with medical problems or those who take regular medications should consult with their doctor before taking such preparations.  Of course, when pregnant or nursing, no product should be taken without careful consultation.

Some individuals may benefit from a multivitamin, vitamin C in large doses, zinc (25mg), evening primrose oil (linoleic acid and gamma linolenic acid in a gel cap – twice daily), Echinacea pallida herbs and ginseng.

Local Treatments

Nasal Saline Spray

Nasal saline spray often soothes dry, inflamed nasal membranes and reduces mucous viscosity.  In some individuals, it has a separate decongestant effect.  All commercial preparations are not the same.  Some contain a preservative that may be irritating.  AyrTM is a well-tolerated product (available from B.F. Ascher & Co.:  www.bfascher.com).

Saline Nasal Rinses

Warm, hypertonic saline nasals rinses (see below) may be quite helpful, but occasionally are counterproductive and cause irritation.  A saline rinse is prepared easily:  Mix two to three heaping teaspoons of pickling or canning salt (not table salt) and one teaspoon of baking soda with one quart of clean tap water.  Instill into the nostrils by using a bulb syringe or a pulsating jet (Water Pic with nasal adapter, Teledyne Water PicTM at www.waterpic.com).  Store at room temperature and discard after one week.  If the solution seems too strong, decrease the salt content to one or one-and-a-half teaspoons.  A similar spray in prepackaged form is available at ENTsol (available from Kenwood Therapeutics at http://www.entsolwash.com).

Wetting Agents

Wetting Agents (propylene and polyethylene glycol) may be beneficial between or instead of nasal rinses (PretzTM, available at Parnell Pharmaceuticals, Inc. at www.parnell.com).

Because the nose tends to dry and crust, paving the way for sinus infection, nasal emollients are often helpful.  Spraying with sesame oil is quite effective. Alternatively, an antibacterial ointment moisturizes and kills germs in the nose that lead to infection.   BactrobanTM (available in pharmacies) is particularly effective against nasal staph bacteria.  Nasal barriers also protect against continual irritation during vulnerable times.  Ayr gelTM (www.bfascher.com) protects delicate membranes.  Viscous lidocaine, a topical anesthetic, may be applied inside the nose with the tip of the small finger.

Nasal Steam Inhalation

Nasal steam inhalation, with or without astringents (eucalyptus, pine oil, menthol), decongests and soothes the nose.  Warm, dry air alone is also often productive.  Likewise, infrared heat directed at the face may help.  Nasal steamers offer convenience (available at the Steam Inhaler, Bernhard Industries, Inc., at www.steaminhaler.com, and as VirothermTM from Sunbeam-Oster Household Products, Inc., www.sunbeam.com).  You may also simply inhale from a cup of hot water.  Try a damp face cloth heated by the microwave for approximately 20 seconds.  A warmed or chilled mask filled with jell and placed on the face is another alternative.

In the colder months, or in drier climates, indoor humidification helps prevent drying, irritation, swelling and secondary infection. Steam humidification is superior to cold mist or ultrasonic.  Warm mist may be added to filtered air in a single unit (available as the BionaireTM series of warm humidifiers, www.bionaire.com).  The BionaireTM CM-I is small and particularly convenient for simple humidification.  Larger, evaporator type humidifiers for the house include the BionaireTM W-65 (www.bionaire.com), and the Emerson HD850 (emersonelectric.com.

Nostril Expanders

Occasionally, abnormalities of the nasal openings may predispose to chronic sinusitis symptoms.  These small passageways control the flow of air across the nasal membranes.  Minor changes because of accidents or inflammation can cause increased nasal obstruction.   Even in the absence of abnormalities, spreading this area using a small stainless steel dilator spring occasionally offers dramatic help with nasal symptoms (available as the Mechanical Therapeutic Nasal Dilator from Breathe With Eze, Inc., Brooklyn, N.Y. 11207, 718.498.1686)

An adhesive spreader externally applied to the lower nose can give similar benefit with greater comfort although it is visible on the nose, unlike the dilator spring which is placed  inside the nose (available as Breathe RightTM external nasal dilator, manufactured by CNS Inc., Chanhassen, MN. 55317; 612.474.7600).

Local Nasal Treatments

Nasal Decongestant Sprays

Nasal decongestant sprays may be of help when used sparingly three times daily for three days or less.  Xylometazoline (OtrivinTM) or oxymetazole (AfrinTM) is effective but not particularly harsh.  Chronic use (more than three consecutive days) may induce “rhinitis medicamentosa,” a problematic condition of rebound swelling often requiring oral corticosteroids as therapy.  The risk of rebound is less with more dilute nasal sprays.  Adding water to the spray bottle to accomplish I:2 to I:8 dilution is helpful.

Local Corticosteroids

Local Corticosteroids (BeconaseTM, NasacortTM, RhinocortTM, VancenaseTM, FlonaseTM, NasalideTM, and NasonexTM are the sprays least associated with absorption into the body and the potential problems that could cause.

Cromolyn (Nasal CromTM) blocks the nasal response to allergic challenge but is usually less effective than steroids sprays.  Both local corticosteroids and cromolyn can cause nasal irritation and drying.  Often it is prudent to discontinue these mediations during a worsening of sinus symptoms.

AtroventTM is a nasal spray used primarily to stop watery nasal discharge.  AstelinTM antihistamine nasal spray blocks allergens as they come in contact with the nose.

Oral Medications

Oral Decongestants

Oral decongestants often help the symptoms of chronic sinusitis.  Pseudoephedrine reduces nasal blood flow and, thereby, nasal engorgement.  It is occasionally associated with blood pressure elevation.  Some people find the drying agents used in “cold preparations” to be helpful and other do not.  Ipratropium (AtroventTM) is recommended by some physicians as a nasal inhaler under certain conditions, but it may cause excessive drying and increased nasal mucous viscosity.

Antihistamines

Antihistamines are sometimes helpful with the symptoms of chronic sinusitis.  Allergic inflammation, often seasonal, predisposes some individuals to chronic sinusitis.  A selective HI-antihistamine (ClaritinTM, AllegraTM, ZyrtecTM) may be a desirable option.  Iodinate glycerol is a mucolytic agent that stimulates ciliary action and offers some help.  Guaifenesin (HumibidTM, or with an oral decongestant, EntexTM) reduces mucous adhesiveness.

Oral Corticosteroids

Oral corticosteroids may provide relief for sinus disorders not responsive to local steroid sprays.  Their effect can be dramatic, although they must be used with caution.  Aspirin and nonsteroidal anti-inflammatories (AdvilTM, MotrinTM, etc.) can trigger asthma, nasal problems, and sinusitis in susceptible individuals. Occasionally these medications are helpful as anti-inflammatories, decreasing the symptoms of chronic sinusitis.

Oral Medications continued

Antibiotic Therapy

Antibiotic therapy usually offers the most help for those with sinusitis.  When the sinus cavity contains pus, antibiotics may be required for a number of weeks.  If this is not the case, antibiotics may still help.  Often the nasal membranes are covered with infected mucus and the individual experiences sinus pain, aching and fatigue.  Antibiotics can resolve the problem in days, although the medicine should be taken for an entire week or more.  In the absence of infected nasal discharge or evidence of superimposed acute sinusitis, the use of antibiotics for chronic sinusitis has been questioned.   Some feel that most cases do not represent an infectious process and do not require antibiotics.  Most authorities, however, consider evidence for the importance of antibiotics to be strong.  A one-week course is often beneficial.

Other Options

Surgery

Surgery is an excellent option if medical treatment isn’t working.  The newest method (endoscopic surgery) is much less traumatic than earlier techniques.  Most people, armed with determination and the help of a physician, can beat this illness or substantially reduce symptoms.