Herbal M&M

1. Herbal M&M Kent R. Olson, MD Medical Director, SF Division California Poison Control System Clinical Professor of Medicine & Pharmacy UC San Francisco

2. 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

3. 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

4. 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

5. 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

6. “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

7. 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)

8. 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.

9. 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.

10. Tussilago farfara (coltsfoot) Courtesy of Time Life Plant Encyclopedia

11. 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.

12. 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

13. 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)

14. Comfrey vs. Digitalis Courtesy of Time Life Plant Encyclopedia

15. 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)

16. 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.

17. 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

18. Water Hemlock vs. Ginseng

19. 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)

20. Case 5, cont. • CSF: clear fluid, 3 WBCs, nl glucose. • Blood glucose 186 mg/dL • Hematocrit 24.9% • EEG: multifocal epileptiform discharges.

21. 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

22. 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

23. 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.

24. 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.

25. 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.

26. 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.

27. 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

28. Aconite

29. 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

30. 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

31. 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 . . .

32. 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