Download Herbal Medication Pitfalls Question “Natural Product” or Drug

Question
“Natural Product” or Drug?
What do you get when you combine:
Acetyl chloride
Spiraea ulminia extract
with
acetyl chloride?
Spiraea ulminia
Herbal Supplements
Herbal Supplements
Introduction
Introduction
Why Might Herbal Products Be
Dangerous?
Herbal Medication Pitfalls
Supplements,
Natural Remedies, &
Human Guinea Pigs
Cyrus Rangan MD
Assistant Medical Director
California Poison Control System
Los Angeles, California
• Earliest use documented in 1500 B.C. in
India and Egypt
• First century A.D. publications
– Divine Husbandman’s Classic (China)
– De Materia Medica (Greece)
• Shamans and folk healers began to promote
herbals for spiritual and medicinal purposes
• Scientific Revolution: first controlled
purification of morphine extracts
• Edward Stone (mid 18th c.) wrote to Royal
Society of Medicine regarding the curative
powers of willow tree bark in cases of
“agues” (fever). Active ingredient was
purified and synthesized widely in 1899.
Vitamin-Mineral Amendments of 1976
• Prohibited FDA from establishing maximal
safe doses of vitamins and minerals to be
contained in dietary supplements
• Prohibited FDA from classifying a product
as a drug just because a certain level was
exceeded
Why Might Herbal Products Be
Dangerous?
Anti-science Attitude of
“Herbalist Experts"
1994 Dietary Supplement and Health Education Act
(DSHEA)
• Herbal products could be marketed with no
efficacy or safety testing.
• FDA powerless to regulate dietary supplements in
most instances
• Shifted the burden of proof:
"When properly used, herbs are the safest and surest
medicines available. However, one must be aware
of the power of herbs to heal and, if misused, to
cause imbalance. Herbs produce no side effects
when used in the amounts required to effect a
cure. Negative effects occur only when one fails
to observe the cautions that herbalists have
recognized after many years of experience.“
– Manufacturers no longer had to demonstrate safety
– FDA now had to demonstrate a lack of safety, to take
an action
Herbal Supplements
Acceptable Marketing
“..this product is not designed or sold to
diagnose, cure, treat, or prevent any
disease…”
• Claims regarding how a supplement affects
“body structure or function” are acceptable
• No FDA input is solicited regarding
packaging or advertisement
The Way of Herbs, Michael Tierra, Pocketbooks, 1998:
Sidenote
• The herbal industry in the US was a $1.5 billion annual
industry by 1994. By 1998 the alternative medicines
industry in the United States accounted for $8.1 billion.
US political donations by "nutrition companies" in the
1999-2000 political were $5.6 million, and included:*
R Sen. Orrin Hatch:
D Rep. Robert Wexler:
R Rep. Dan Burton:
D Sen. Tom Harkin:
R Gov. George Bush:
$107,100
$82,512
$79,249
$58,250
$52,750
*US News and World Report, February 12, 2001.
Herbal Supplements
Toxicity factors
•
•
•
•
•
Squill
Oleander
Seasons
Plant parts
Geographic regions
Conditions/length of storage
Misrepresentation, contamination,
misidentification, unlisted ingredients,
unknown interactions
Foxglove
Lily of the Valley
Herbal Supplements
Other Cardiac Glycosides
Aconite
“Oleander, Squill, Foxglove, Lily of the Valley”
Herbal Supplements
Aconite
“Caowu, chuanwu, monkshood, wolfbane”
• Source: dried plant root/tubers
• Desired effects: topical analgesic
• Toxic Effects:
• Source: ubiquitous plants
• Desired effects: treatment of asthma,
cancer, epilepsy
• Toxic Effects:
– GI: nausea, vomiting, diarrhea
– Neuromuscular: weakness
– CVS: delayed repolarization (holds fast cardiac sodium
channels open), resulting in ventricular dysrhythmias
– Death may occur from dysrhthmias
– CVS: digitalis effects, from multiple
compounds
– Death may occur from dysrhythmias
• Treatment: ?sodium bicarbonate, ?lidocaine,
?procainamide, ?atropine, ?overdrive pacing
• Treatment: serum digoxin level, Digibind®
(Digoxin-specific Fab fragments)
Bufo spp. Toads
Bufotenin
Herbal Supplements
Bufo spp. toads
“Ch’an su, Stone, Love Stone, Rock Hard”
• Source: parotid and sebaceous secretions
• Desired effects: topical anesthetic, “heart
medicine”, aphrodisiac
• Toxic Effects:
– CNS: LSD-like effects (bufotenin)
– CVS: digitalis effects (bufadienolides)
Absinthe
Vermouth
Herbal Supplements
Absinthe
“Vermouth, Oil of Wormwood”
• Source: volatile oil extracts (thujones),
likely used by Van Gogh
• Desired effects: hallucinations, euphoria
• Toxic Effects:
– CNS: psychosis, seizures, visual distortions
(acute), intellectual deterioration (chronic)
– Death may occur from seizures
“Starry Night”
Vincent van Gogh
Belladonna
Henbane
Jimson Weed
Herbal Supplements
Belladonna alkaloids
“Jimson Weed, henbane, mandrake”
• Source: numerous plants containing
atropine/scopolamine analogs
• Desired effects: asthma/GI upset remedies,
aphrodisiacs
• Toxic Effects:
– CNS: hallucinations, seizures, anticholinergic effects
– Deaths may occur from ALOC-associated trauma
• Treatment: supportive care, benzodiazepines,
physostigmine (for diagnostic purposes)
Jimson Weed
Jimson Weed
Ephedra
Ephedra
Metabolife®, Xenadrine®
Herbal Supplements
Nutmeg
Ephedra
“Ma-huang, Mormon tea, herbal ecstacy, Metabolife®”
• Source: evergreen plants resembling small shrubs,
contain ephedrine analogs
• Desired effects: bronchial remedies, CNS
stimulant effects
Toxic Effects:
– CNS: adrenergic hyperstimulation, hyperthermia
– CVS: dysrhythmias, MI, hemorrhagic strokes
– Causes of death may be multifactorial
• Treatment: supportive care
Herbal Supplements
Myristica fragrans
“Nutmeg, mace”
• Source: evergreen tree (Spice Islands)
• Desired effects: euphoria, Tx dyspepsia, arthritis,
depression; abortifacient
• Toxic Effects:
– CNS/CVS: amphetamine-like reactions (myristicin is
converted to several amphetamine-like compounds)
– Hypothermia after large amounts (unknown
mechanism)
– Death occurs from amphetamine-like effects
• Treatment: supportive
Herbal Supplements
Pennyroyal
Pennyroyal
• Source: volatile oil
• Desired effects: antispasmodic, insect repellant,
antiseptic, fragrance, abortifacient
• Toxic Effects:
–
–
–
–
Liver: fulminant hepatic failure (centrilobular necrosis)
CNS: seizures
Renal: ATN
Pulm: bronchial epithelium toxicity
• Treatment: N-acetylcysteine
Herbal Supplements
Comfrey
Pyrrolizidine alkaloids
Ginseng
“Comfrey, Bush Tea, coltsfoot, gordolobo, T’u-san-chi’i”
• Source: multiple plant families in Afghanistan,
India, Jamaica
• Desired effects: Tx respiratory ailments, tumors,
topical treatment of bruises
• Toxic Effects:
– Liver: hepatic veno-occlusive disease, cirrhosis
– Pulm: pulmonary hypertension
– Death unlikely in the absence of other liver disease
• Treatment: supportive
Herbal Supplements
Ginseng
Ginseng
• Source: deciduous, perennial Panax plants
• Desired effects: Tx respiratory, GI illnesses, “whatever ails
you…”
• Toxic Effects:
–
–
–
–
–
–
Metabolic: hypoglycemia
Heme: increased erythropoiesis
CVS: hypertension
CNS: sympathetic stimulation
G.A.S (HTN, sleeplessness, morning diarrhea)
Death is unlikely
• Treatment: supportive
Echinacea
Herbal Supplements
Herbal Supplements
Herbal Supplements
Echinacea
Chinese Patent Medications
Chinese Patent Medications
• Source: plant native to Nebraska, Kansas,
Missouri; (Compositae family)
• Desired effects: wound healing, immune system
stimulation
• Toxic Effects:
– Immune: immune system suppression after chronic use
– Death unlikely
• Treatment: supportive
• Leng Pui Kee Cough Pills
• Jin Bu Huan
– morphine analogs, pyrrolizidines
• Nan Lien Chiu Fong Toukuwan
– aminopyrine, phenacetin, phenylbutazone,
indomethacin, mefenamic acid, diazepam,
hydrochlorothiazide, dexamethasone, mercuric sulfide,
lead, cadmium
• Dr. Tong Shap Yee’s Asthma Pills
Chinese Patent Medications
• Kwei Ling Chi, Tse Koo Choy & Qing Fen
– Mercuric sulfide and mercuric chloride
• White Flower Medicine Oil, Red Flower Oil,
Kwan Loong Medicated Oil
– Wintergreen (methylsalicylate)
– Camphor
– Turpentine
– diazepam, mefenamic acid
• Gan Mao Ton Pian
– phenylbutazone
• Chui Feng Su Ho Wan
– licorice
– theophylline
Herbal Supplements
– bromhexine
• Tung Shieh
Licorice
Herbal Supplements
Licorice
• Source: Glycyrrhiza glabra
• Desired effects: Tx gastric irritation
• Toxic Effects:
– Neuro: weakness, hyporeflexia, lethargy
– Renal: myoglobinuria, ATN, hypernatremia,
hypokalemia (aldosterone-like effects), HTN
– Death may occur from dysrhythmias or renal failure in
severe cases
• Treatment: supportive
Herbal Supplements
Kava Kava
Herbal Supplements
Kava kava
“Awa, kew, tonga”
• Source: Piper methysticum plant
• Desired effects: relaxation, tx headaches,
PMS, aphrodisiac
• Toxic Effects:
– CNS: euphoria, muscle weakness (lactoneinduced)
– Death unlikely to occur
• Treatment: supportive
Herbal Supplements
Garlic
Garlic
“Stinking rose, nectar of the gods, da suan”
• Source: perennial bulb
• Desired effects: Tx DM, cholesterol, bacterial
infections
• Toxic Effects:
–
–
–
–
Heme: antiplatelet effects from ajoene
Derm: contact dermatitis
GI: nausea/vomiting
Death may occur from bleeding secondary to drug
interaction
• Treatment: supportive
Ginkgo biloba
“Maidenhair tree, tebonin, rokan, kaveri”
• Source: trees that live up to 1000 years
• Desired effects: Tx Raynaud’s, asthma, improve
memory
• Toxic Effects:
–
–
–
–
–
CNS: headache, dizziness
CVS: palpitations
GI: Nausea/vomiting
Immune: allergic reactions similar to poison ivy
Death unlikely to occur
• Treatment: supportive
Elder
Herbal Supplements
Cyanogenic agents
Morning Glory
Morning Glory
“apricot pits, apple seeds, elder”
• Source: multiple fruit pits/seeds
• Desired effects: diuretic, laxative, cancer
remedies
• Toxic Effects: cyanide toxicity
• Treatment: amyl/sodium nitrite, sodium
thiosulfate
Morning Glory
Herbal Supplements
Morning Glory
“Heavenly blue, blue star, flying saucers”
• Source: ubiquitous flower, often found “choking”
other flora
• Desired effects: hallucinogenic
• Toxic Effects:
– LSD/LSA and other analogs produce hallucinations,
adrenergic stimulation, and flashbacks
– Death may occur from ALOC-associated trauma
• Treatment: supportive
Autumn crocus
Herbal Supplements
Autumn crocus
Herbal Supplements
Periwinkle
“Fall crocus, meadow saffron, mysteria, vellorita”
• Source: seasonal plant
• Desired effects: Tx gout, rheumatism, prostate
hypertrophy, hepatic disease, cancer, gonorrhea
• Toxic Effects:
• Source: ornamental plant native to Madagascar
(also called Vinca)
• Desired effects: Tx DM, hemorrhage, insect bites,
cancer
• Toxic Effects: same as vincristine, vinblastine
• Death may occur from drug interaction, sepsis
• Treatment: supportive
– colchicine toxicity (GI upset, renal failure,
agranulocytosis)
– Death may occur from renal failure, sepsis
• Treatment: supportive, ?GCSF
St. John’s Wort
Periwinkle
“Old Maid, church-flower, ram-goat rose, myrtle,
magdalena”
Herbal Supplements
St. John’s Wort
“Klamath weed, goatweed, sho-ren-gyo”
• Source: perennial flower in US, Canada, and
Europe
• Desired effects: Tx anxiety, depression, gastritis,
AIDS
• Toxic Effects:
– Derm: photosensitization
– Neuro: MAOI reactions, serotonin syndrome, NMS
– Death may occur from hyperthermic syndromes from
drug interactions
• Treatment: supportive
Tonka Bean
Herbal Supplements
Tonka Bean
Extra Credit
“Tonquin bean, cumaru”
• Source: large trees in Venezuela, Guyana, and
Brazil
• Desired effects: flavoring agent, fragrance
• Toxic Effects:
Herbal Supplements
Summary
• Hundreds of agents, little regulation
• Uses are increasing dramatically
– anticoagulant effects from coumadin-like compounds
– Death may occur from bleeding secondary to drug
interaction
• Herbal or natural medications are:
– neither inherently efficacious nor inherently
inefficacious
– neither inherently safe nor inherently unsafe
• Treatment: vitamin K, plasma, supportive care
Herbal Supplements
Herbal Supplements
Herbal Supplements
Summary
Summary
Summary
• Use of herbal medicines is generally safe, so long
as one is well informed with respect to the dangers
associated with lack of regulation
• Because herbal medicines can come on the
market as “food supplements” not regulated
by the FDA, there is bound to be poor
science in some herbal use
• Occasional poor science on the part of “experts”
leads to product misuse: misidentification;
contamination; lack of dose standardization;
variability of plant constituents; misrepresentation;
product adulteration; and herb-drug and herb-herb
interactions… all contribute to safety concerns
• Good scientific information is gradually
growing – describes the content, potential
efficacy, and toxicity of herbal medicines
• Paucity of data on effects in children
• Public perception of “natural” products
warps reality
• What can we do…?