Pain Management/ Sedation
Would you know what advice to give someone who’s using or considering using an herbal supplement? If not, it’s time you learned more about herbs. Millions of Americans use herbal remedies and other dietary supplements. Walk down the aisle of a retail pharmacy and you’ll see a mind-boggling array of herbs, vitamins, minerals, and similar products touting a wide range of health benefits.
This wasn’t always so. Until 1994, the only supplements permitted on store shelves were vitamins and minerals. Then Congress passed the Dietary Supplement Health and Education Act (DSHEA). Ever since, consumers have been able to purchase many types of herbs and other supplements—some helpful, some harmful, some useless.
Defining dietary supplements
The DSHEA defines a dietary supplement as a product taken by mouth that “bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet by increasing the total daily intake, or a concentrate, metabolite, constituent, extract, or combinations of these ingredients.” (See How herbs are regulated.)
Simply put, herbal and other botanical preparations are considered dietary adjuncts, not medications—even though the most commonly used herbal products have well-known pharmacologic effects.
Anyone can purchase a dietary supplement over the counter in a retail store or pharmacy or on the Internet. And typically, consumers assume that if a product is easily available, that means it’s safe and effective. Many would be surprised to learn that dietary supplements are regulated more like foods than like drugs. Before a prescription drug reaches the market, its manufacturer or distributor must conduct research to establish its safety and efficacy. Not so with herbs and other dietary supplements.
Some dietary supplements unlawfully contain products not listed on the label—in some cases, small to significant doses of prescription drugs, heavy metals, or other contaminants. For example:
• an herbal product used for erectile dysfunction was found to contain a drug similar to tadalafil and had to be pulled from the market
• a traditional Middle Eastern remedy was found to be contaminated with lead.
For the latest FDA warnings on dietary supplements, visit www.cfsan.fda.gov/~dms/ds-warn.html.)
Your sister-in-law gets four to six migraines a month, each lasting a day or two. She has been taking several prescription drugs to prevent them, including tricyclic antidepressants, beta blockers, and anticonvulsants. Although these medications have helped, they’ve caused significant adverse effects. She tells you she’s considering switching to an herbal remedy.
The feverfew plant, a member of the Asteraceae family, originally was native to Europe’s Balkan mountains but now grows throughout North and South America as well. Supplements are made from the dried leaves, flowers, or stems. Feverfew comes in capsules, tablets, and liquid extracts.
Feverfew is used for migraine and other types of headaches, as well as dizziness, rheumatoid arthritis, fever, and stomachache, to name a few. It may help prevent migraine by inhibiting platelet aggregation and stabilizing serotonin release from platelets and leukocytes—effects that produce vasodilation and reduce the inflammation that contributes to migraine symptoms. However, studies of its efficacy in preventing migraine have produced mixed results—probably at least in part due to variations in product strength. Some studies also support a mild antiplatelet effect. Generally, feverfew is well tolerated, causing few adverse reactions.
• Be aware that feverfew occasionally causes an allergic reaction similar to hay fever. This reaction is more common in people with ragweed allergies.
• In patients taking diazepam, warfarin, or losartan, feverfew may increase drug blood levels by inhibiting drug-metabolizing liver enzymes.
• Because of feverfew’s potential to increase bleeding tendencies, caution patients not to use it if they’re taking anticoagulants or using other herbs or drugs with antiplatelet properties.
• Caution patients not to use feverfew in combination with prescription drugs for headache prevention (such as propranolol or amitriptyline). Feverfew is likely to inhibit that drug’s metabolism, leading to such potentially dangerous effects as bradycardia (with propranolol) or increased somnolence and arrhythmias (with amitriptyline).
• If your patient has been using feverfew but wishes to discontinue it, advise her to taper the dosage slowly. Abrupt withdrawal may increase migraine severity and frequency.
Your 49-year-old patient is scheduled for surgery in 10 days. On her list of medications and supplements is a “memory-boosting” preparation she bought online. On investigation, you learn the product contains ginkgo biloba.
Ginkgo biloba (also sold under such names as Bai Guo Ye, Baiguo, and Fossil Tree) has been used in Asia for centuries and is among the most commonly used herbs in North America. The preparation may be extracted from leaves of the ginkgo biloba tree, or its seeds may be cooked and eaten.
Proponents claim ginkgo biloba may preserve brain function through multiple mechanisms, including antioxidant and free-radical scavenging effects and by inhibiting beta-amyloid deposition. Some also believe it enhances endothelial function to promote vasodilation, improves mental function in milder dementia forms, decreases intermittent claudication, and improves sexual functioning. Its use in preventing dementia hasn’t been well studied. In a 1998 open-label study of patients with sexual dysfunction who were taking the antidepressant fluoxetine, ginkgo biloba improved sexual function significantly.
• Instruct a preoperative patient to stop taking ginkgo biloba at least 36 hours before surgery because it inhibits platelet-activating factor. (Some authorities recommend stopping it 14 days before surgery.)
• When taken with warfarin, ginkgo biloba commonly increases the International Normalized Ratio (INR). Also, subdural hematoma and subarachnoid hemorrhage have been reported in patients taking the herb alone or in combination with ergotamine or aspirin. Caution patients taking anticoagulants or platelet aggregation inhibitors to avoid ginkgo.
• Be aware that ginkgo may interact with numerous prescription drugs. For instance, it may decrease blood levels of alprazolam and citalopram, reducing their efficacy. When taken with ibuprofen, it increases bleeding risk (probably through a cumulative effect on platelets).
Patients with type 2 diabetes mellitus who start taking ginkgo biloba are likely to notice increased blood glucose levels, because it can reduce insulin secretion and alter insulin metabolism. This effect can be corrected quickly by discontinuing ginkgo or adjusting the glucose-lowering drug. If a formerly well-controlled diabetic patient suddenly has poor glycemic control, find out if he recently started taking ginkgo.
Red rice yeast
Your friend, age 56, has been taking atorvastatin to treat his dyslipidemia. His lipid profile is now at goal and he’s tolerating the medication well. He asks you, “Do you think I should switch to red yeast rice? I’ve heard that’s a natural way to lower cholesterol.”
Red yeast rice is produced by fermenting rice with a yeast called Monascus purpureus. This process must be done carefully to produce the desired effect—an increase in mevinic acid concentration. Mevinic acid inhibits the action of an enzyme needed for cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.
Red yeast rice is used to decrease levels of low-density lipoproteins. It also contains plant sterols, monounsaturated fats, and isoflavones that may help lower the cholesterol level further and protect the heart.
• Incorrectly fermented red yeast rice may contain citrinin, a potential nephrotoxin.
• Red yeast rice may cause muscle aches and myositis. Caution a patient already taking a statin drug not to use red yeast rice, as this may increase the risk of myositis or liver problems.
• The U.S. Food and Drug Administration (FDA) recently warned that certain red yeast rice products unlawfully contain lovastatin, a prescription cholesterol-reducing drug. Caution patients taking these products (listed at www.fda.gov/bbs/topics/NEWS/2007/NEW01678.html) that potential interactions with lovastatin may increase the risk of adverse effects.
• Because red yeast rice is less potent than prescription statins in lowering cholesterol, patients and healthcare providers must consider treatment goals.
• Advise patients not to consume grapefruit juice while using red yeast rice. Substances in grapefruit juice inhibit CYP450 3A4, the enzyme that metabolizes red yeast rice and lovastatin. Concurrent use may increase the myositis risk.
Your 78-year-old uncle mentions he’s taking a “natural remedy” to treat an enlarged prostate.
The ripe fruit of saw palmetto (also called American dwarf palm tree, cabbage palm, or ju-zhong) contains the plant’s therapeutically active portion. Saw palmetto supplements come in liquid extracts, tablets, capsules, infusions, and teas.
Saw palmetto is used mainly to relieve urinary symptoms of benign prostatic hyperplasia (BPH). Proponents claim it has an antiandrogen effect that prevents normal activity of male hormones, such as testosterone and other androgens, by inhibiting the enzyme 5-alpha-reductase. Presumably, this activity doesn’t reduce prostate size but allows the inner prostatic epithelium to shrink and may slow prostate cell proliferation. Some people believe saw palmetto also enhances the normal process of prostate cell death.
The herb’s mechanism of action may resemble that of finasteride, a prescription drug used to treat BPH symptoms. Short-term-use studies comparing it to finasteride found similar outcomes with use of a high-quality saw palmetto formulation in patients with mild to moderate BPH symptoms. However, a large 2006 study funded by the National Institutes of Health found no improvement in men with moderate to severe BPH who used 320 mg of saw palmetto daily for 1 year.
Some proponents also believe saw palmetto has anti-inflammatory and antiplatelet effects (through its actions on arachidonic acid and serotonin) and may be useful in chronic pelvic pain, bladder disorders, decreased sex drive, hair loss, and hormone imbalance. Generally, the herb is well tolerated.
• Because of saw palmetto’s antiplatelet effect, caution patients using aspirin or nonsteroidal anti-inflammatory drugs that this herb may increase the bleeding risk.
• Advise patients to discontinue saw palmetto about 2 weeks before surgery to reduce the risk of bleeding.
• Know that saw palmetto may increase INR in patients receiving warfarin.
• If your patient has acute urinary retention from BPH, tell him that starting saw palmetto won’t help. It must be taken for at least 1 to 2 months before clinical improvement (if any) occurs. In this case, a fast-acting prescription drug, such as an alpha blocker (terazosin or tamsulosin), is indicated.
Although saw palmetto sometimes is added to oral products marketed to increase breast size, little evidence shows it’s effective for this purpose.
St. John’s wort
Your neighbor confides that she has been depressed lately and has started using St. John’s wort.
St. John’s wort has been used for centuries for various ailments. The plant’s therapeutically active parts include the flowers and, to a lesser extent, leaves; these parts are used to prepare teas and tablets containing concentrated extracts.
St. John’s wort is used for depression, anxiety, sleep disorders, and nerve pain. Proponents claim its clinical effects include activity against the monoamine oxidase enzymes that break down serotonin and other major mood-regulating neurotransmitters. In several short-term clinical trials that studied treatments for mild to moderate depression, St. John’s wort proved superior to placebos. In other trials comparing it to prescription antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), clinical outcomes in patients with mild to moderate depression treated with St. John’s wort were similar to those in patients using SSRIs; however, patients with more severe depression had relatively little improvement.
• Inform patients that while it may be tempting to treat a mood disorder with an over-the-counter product, depression and anxiety typically are chronic and recurring—and may be life-threatening. A skilled healthcare professional should be involved in the patient’s therapeutic plan.
• Know that St. John’s wort may alter the activity of CYP450 enzymes extensively involved in drug metabolism, and thus may interact significantly with many drugs. This interaction may make those drugs less effective or increase the dosage requirements.
• St. John’s wort may significantly reduce blood levels of antiretrovirals used to treat human immunodeficiency syndrome (HIV) infection, causing reduced antiviral efficacy, development of viral resistance, and treatment failure. Advise HIV patients taking antiretrovirals to consult a healthcare provider before taking this herb.
• Using St. John’s wort with cyclosporine, an antirejection drug prescribed after organ transplantation, can cause a 30% to 70% drop in cyclosporine blood levels—resulting in organ rejection. Warn patients receiving cyclosporine not to use this herb. In patients who develop transplant rejection, consider the possibility that they’re using St. John’s wort.
• Inform patients who use St. John’s wort concurrently with SSRI antidepressants (such as fluoxetine, paroxetine, or sertraline) that this combination may cause serotonin syndrome—a potentially serious condition marked by muscle rigidity, fever, confusion, increased blood pressure and heart rate, and GI upset. However, caution them not to stop taking the SSRI suddenly and to consult their healthcare provider.
A nurse who works the night shift at your hospital tells you he’s using valerian to help him get to sleep.
Valerian is among the most commonly used herbal products in North America. Supplements include tablets, capsules, liquid extracts, teas, and bath oils.
Valerian probably has multiple mechanisms of action, including action at the brain’s gamma-aminobutyric acid receptors. It’s most often used as a sleep aid and anxiolytic; some people take it for headache, irregular heartbeat, depression, and trembling. For insomnia, it’s taken as a single daily dose near bedtime; for anxiety, it’s used in multiple daily doses. Generally, valerian is well tolerated and causes few adverse effects.
• Inform a patient using valerian that benzodiazepine-like withdrawal symptoms may occur when the herb is discontinued, especially if the patient has been taking multiple daily doses.
• Be aware that valerian may cause GI upset, nervousness, disturbed sleep, and liver toxicity (rare).
• Advise patients to avoid using valerian concurrently with a benzodiazepine, alcohol, or other sedating substance, because increased drowsiness is likely to occur.
Finally, inform patients with known plant allergies that they may be more susceptible to allergic reactions to herbs.
If you suspect your patient has experienced an adverse effect of an herb or an herb-medication interaction, report this to the FDA by calling MedWatch at 800-FDA-1088 or by visiting www.fda.gov/medwatch/report/hcp.htm. You don’t need to establish proof of a connection between an adverse effect and a product or wait until the evidence seems compelling before making the report.