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Herbal M&M Kent R. Olson, MD Medical Director, SF Division California Poison Control System Clinical Professor of Medicine & Pharmacy UC San Francisco What’s Up with Herbs and Alternative Medicines? Increasing use in US $1.5 billion/year industry and growing many mistakenly assume they are safer increasing reports of adverse reactions and deaths Herbs and Patent Medicines herbs may be purchased, grown or foraged patent medicines may be domestic or imported Lack of strict FDA regulation Dietary Supplement Health & Education Act 1994 loosened FDA regulation Difficult to regulate quality inaccurate or incomplete ingredients adulterants inconsistent dosing Case 1 A 20-year-old college student on spring break took 8 tablets of a product called Ultimate Xphoria, although the package recommended 2-4. The product was promoted as delivering “increased energy, inner visions, sexual sensations, and cosmic consciousness” Developed tingling sensations and a headache Case 1, cont. Later, he was found by friends in cardiopulmonary arrest. Coroner’s report: Death from synergistic effects of ephedrine, pseudoephedrine, phenylpropanolamine, and caffeine “Herbal Ecstasy” Variety of products: “Ener-Max”, “Herbal Ecstacy”, “Ripped Fuel”, “Super Weight Loss”, etc. Ma Huang or ephedrine may also contain pseudoephedrine, PPA often combined with caffeine (guarana) Typical sympathomimetic syndrome, also may cause severe hypertension Case 2 A 5 day old infant was admitted because of jaundice, hepatomegaly, and ascites. 36 week gestation, 2740 gm. Liver palpable 5 cm below RCM, hard. AST 3725 IU/L, ALT 760 Total bilirubin 164 micromol/L (nl <21) Case 2, cont. Abdominal ultrasound showed homogeneous hepatosplenomegaly. Open liver biopsy: centrilobular fibrosis neovascularization widespread circumferential connective tissue occlusion of small and medium sized hepatic veins Child died 11 days later. Case 2, cont. Mother admitted to consumption of herbal tea throughout her pregnancy: Purchased as an expectorant from a pharmacy… manuf. stated that 9% of product consisted of leaves from Tussilago farfara (horsefoot, coltsfoot, coughwort) TLC: senecionine (a pyrrolizidine alkaloid) Mother was asymptomatic. Tussilago farfara (coltsfoot) Courtesy of Time Life Plant Encyclopedia Case 3 An elderly couple attended a health spa that recommended comfrey tea as an herbal remedy for arthritis. Later, the woman picked what she believed to be comfrey plants and made a tea, which she & her husband drank. One hour later, both developed severe nausea, vomiting, and dizziness. Case 3, cont. Within a short period of time the wife collapsed, and by the time the ambulance arrived she was dead. The husband came to the hospital with abdominal cramps and vomiting. ECG: fine atrial flutter vs. fibrillation, with ventricular rate 30/min. Serum K 5.3 mEq/L Case 3, cont. 17 hours after admission, he vomited then developed ventricular tachycardia and ventricular fibrillation, and died. Serum digitoxin was >80 ng/mL (usual therapeutic range 5-30 ng/mL) The “comfrey” was identified as foxglove (Digitalis purpurea) Comfrey vs. Digitalis Courtesy of Time Life Plant Encyclopedia Case 3, cont. Some plants and herbals containing cardiac glycosides: Digitalis purpurea (Foxglove) Nerium oleander Convallaria majalis (Lily of the Valley) Urginia maritima (Squill) Bufo toxin (Ch’ an su) Case 4 A 23 year old man and his older brother were foraging for wild ginseng in the midcoastal Maine woods. The younger brother took three bites from one of the plants collected in a swampy area. Within 30 minutes he vomited and had convulsions. On arrival of paramedics, he was unresponsive and cyanotic. Case 4, cont. Root was identified as water hemlock Water hemlock (Cicuta maculata): other names: beaver poison; children’s bane; death-of-man; poison parsnip; fool’s parsley or false parsley same family as parsley, parsnips, celery, and carrots smells like fresh turnips, tastes sweet Toxicity: seizures Water Hemlock vs. Ginseng Case 5 A 10-week old Hispanic infant was admitted for lethargy, projectile vomiting, and seizures on the 3rd day of a viral upper respiratory infection. With onset of coryza, family had reduced her formula and started herbal teas (peppermint and chamomile) Case 5, cont. CSF: clear fluid, 3 WBCs, nl glucose. Blood glucose 186 mg/dL Hematocrit 24.9% EEG: multifocal epileptiform discharges. Case 5, cont. Electrolytes: Na 112, K 4.6, Cl 82, CO2 20 mEq/L. Content of teas (mEq/L): Na K Peppermint: 0.9 1.9 Chamomile: 1.7 2.5 Estimated water intake during 3-day period: 180-200 mL/kg/day Case 6 A 35 year old woman was admitted with a 1-week history of nausea, vomiting, and bloody diarrhea. Confused, oliguric, and BP 70/50 mm. Maculopapular erythematous rash with desquamation all over the body. CXR: bilateral infiltrates. Initial Dx: Toxic Shock Syndrome Case 6, cont. She was intubated endotracheally, and hemodialyzed for acute renal failure. Vaginal swab, blood cultures negative. Fiberoptic bronchoscopy: edematous, inflamed mucosa, purulent secretions. Improved over the next 6 days, but renal function remained poor. Case 6, cont. Her husband admitted that she had been receiving treatment for vitiligo from a “native physician” prior to admission Twice each day she was confined to a room for 30 min, inhaling smoke from burning substances over an open fire. Substances included a dried lime, a few dried leaves, and a brick-red powder. Case 6, cont. The dried lime was found to be filled with liquid mercury and sealed with wax. The red powder was mercuric oxide. Serum Hg: 111.3 mcg/dL With BAL, her renal function improved after 4 weeks; cerebellar ataxia and fine tremor persisted for nearly 6 months. Case 7 A 35 yo man consumed a decoction prepared from Chinese herbs for rheumatism. After 30 min, he developed chest discomfort and dyspnea. At the hospital, he was semiconscious, tachypneic, restless, and sweating. BP 70/40, HR 150/min ECG: ventricular tachycardia. Case 7, cont. Serum K 2.6 mEq/L ECG: ventricular tachycardia, which rapidly deteriorated into v. fibrillation. Resuscitation efforts unsuccessful. The prescription contained 11 different herbs, including aconite Aconite Case 7, cont. Aconite: aconitine & related alkaloids As little as 0.2 mg aconitine toxic Activates sodium channel in cardiac, neural, muscle tissues Nausea, vomiting, parasthesias Enhanced inward Na current during action potential plateau may prolong repolarization phase, induce arrhythmias Even Chemicals Can Be “Herbals” GHB (gamma hydroxybutyrate) & GBL (gamma butyrolactone) Potent CNS depressants w/ short duration of action Popular among bodybuilders, Rave partygoers, used for sexual assault Recently, severe withdrawal syndrome described Some Herbal-Drug Interactions Warfarin + ginkgo, dong quai, garlic, etc St John’s Wort + SSRIs or MAOIs St John’s Wort: F of several drugs Ginseng + antidepressants: mania Shankapushpi (Ayurvedic) phenytoin Siberian ginseng, plantain + digoxin Many others . . . Where to Get Information? Natural Medicines Database www.naturaldatabase.com Facts & Comparisons’ Guide to Popular Natural Products (formerly Lawrence Review of Natural Products) www.drugfacts.com Poison Control Centers