Lily of the valley

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LILY OF THE VALLEY
Molly Benning
Dawn Anderson
Alisa Villarreal
INTRODUCTION
WHAT IS A TOXIN?
 A toxin is a substance produced by an organism that has an
adverse effect on other organisms.
 Any substance can be toxic depending on the dose.
 Dose determines effect.
 Plants produce secondary metabolites as a defense mechanism.
LILY OF THE VALLEY
 We chose to research Lily of the Valley after learning about it
from the television show Breaking Bad. The toxicity of Lily of the
Valley is featured in Breaking Bad and we wanted to see how
common Lily of the Valley poisoning is and if there are any
therapeutic benefits associated with this plant.
LILY OF THE VALLEY DESCRIPTION
 Convallaria majalis, commonly
known as Lily of the Valley, is
a perennial plant that forms
rhizomes.
 It forms white, bell -shaped
flowers and red berries.
 4”-8” tall
 Lily of the Valley contains
toxic cardiac glycosides. Every
part of the plant is toxic.
LILY OF THE VALLEY DISTRIBUTION
 Convallaria majalis
is native to Europe
and Asia and is an
introduced species
in North America.
 Lily of the Valley
grows in wooded
areas in rich soil.
 Lily of the Valley is
also used in
gardening as ground
cover.
Introduced
Native
HISTORY
CHRISTIAN LEGEND
 Lily of the Valley is also known
as “Our Lady ’s tears”.
 According to Christian legend,
when Mary cried at the
crucifixion of Jesus, her tears
turned into Lily of the Valley.
 Other lore states Lily of the
Valley was created when Eve
cried after she and Adam were
banished from the Garden of
Eden.
GOLDEN WATER
 In the 17 th century, Germans added Lily of the Valley to old wine
as a remedy for palpitation, vertigo, epilepsy, apoplexy as well as
a general “cure all”.
 This concoction was stored in gold and silver vessels.
 This concoction was known as aqua aurea, or “golden water ”.
MEDICINAL USES
 Lily of the Valley has been used traditionally as a diuretic and as
a treatment for heart ailment and irregular heartbeat.
 Historical medicinal use is similar to that of Foxglove, Digitalis
lanata, the plant from which digoxin is produced.
 Unlike Digitalis lanata, Convallaria majalis was never
pharmaceutically produced.
Convallaria majalis
Digitalis lanata
NARROW SAFETY MARGIN DRUGS
 C. majalis was never used as a
clinical treatment for irregular
heart function due to its
narrow margin of safety.
 A narrow safety margin drug is
a drug whose adverse effect
curve and therapeutic effects
curve are very close.
 Therapeutic index = AE 50 /TE 50
 Narrow safety margin drugs
have a therapeutic index of 2.
 Narrow safety margin drugs,
liked digoxin, are used when
there is no other effective
treatment.
TOXICITY
CARDIAC GLYCOSIDES
 Cardiac glycosides are a class
of compounds made up of a
steroid nucleus, a lactone
ring, and a series of sugars
linked to the third carbon of
the nucleus.
 Cardenolides are a class of
cardiac glycosides produced
by plants.
 Lily of the Valley contains at
least 38 known cardiac
glycosides.
CONVALLATOXIN
 Convallatoxin is one of the
main cardiac glycosides
isolated from Lily of the
Valley.
 Convallatoxin is highly
resistant to hydrolysis.
 LD50 for orally delivered
convallatoxin in mice is
>2 g /kg.
CONVALLAMARIN
 Convallamarin is another main
cardiac glycoside isolated
from Lily of the Valley.
 There is currently little
research on this compound
and no determined LD50.
LESSER CARDIAC GLYCOSIDES
 There are several lesser cardiac glycosides that have been
isolated from C. majalis that are not as well researched:








Strophanthidin-3-O-6'-deoxy-beta-D-allosido-alpha-L-rhamnoside
Strophanthidin-3-O-6'-deoxy-beta-D-allosido-alpha-L-arabinoside
Strophanthidin-3-O-alpha-L-rhamnosido-2'-beta-D-glucoside
Cannogenol-3-O-6'-deoxy-beta-D-allosido-beta-D-glucoside
Cannogenol-3-O-6'-deoxy-beta-D-allosido-alpha-L-rhamnoside
19-hydroxy-sarmentogenin-3-O-alpha-L-rhamnoside
Sarmentogenin-3-O-6'-deoxy-beta-D-allosido-alpha-L-rhamnoside
Sarmentogenin-3-O-6'-deoxy-beta-D-guloside
MECHANISM OF ACTION
 The numerous cardiac glycosides found in Lily of the Valley have similar
mechanisms.
 Cardiac glycosides inhibit the trans membrane Na + /K + -ATPase pump.
 This inhibition leads to an increase in concentration of Na + and Ca 2+ within
the cell.
 The sarcoplasmic reticulum takes up the increase in Ca 2+ resulting in an
increase in myocardial contractility, or the force with which the heart
contracts.
 In addition, there is an increase in
vagal activity which slows down the
heart.
 Excess levels of cardiac glycosides can
lead to bradycardia, or an unusually
slow heart beat.
ABSORPTION PATHWAYS
 Lily of the Valley toxicity
occurs via ingestion.
 All parts of the plant are toxic
and edible.
 Human ingestion is more
common in children than
adults.
SYMPTOMS
 Nausea
 Arrhythmias
 Vomiting
 Hyperkalemia
 Headache
 Seizures (more
common in dog/cat
toxicity)
 Sinus bradycardia
 Hypotension
 Death from cardiac
arrest (rare)
TREATMENT
 Activated charcoal can be used to induce vomiting.
 Electrocardiograms are used to monitor heart activity.
 Lidocaine and atropine can be delivered intravenously to reverse
bradycardia and hypotension.
 Digoxin Immune Fab, an antidote for the overdose of digitalis,
may be used in severe cases.
 Digoxin Immune Fab binds cardiac glycosides enabling them to be
excreted by the kidneys.
TOXICITY PREVALENCE IN HUMANS
 Although Lily of the Valley contains at least 30 cardiac glycosides
and every part of the plant is toxic, significant human toxicity is
rarely reported.
 A ten year analysis of TESS exposures to Lily of the Valley found
2,639 reported cases of toxicity with only 3 patients suffering
serious outcomes.
 93% of these cases occurred in children younger than 6.
 Human toxicity is rare due to the need to ingest the plant and the
amount required to produce severe adverse effects.
 French poison control centers consider the ingestion of 5 bays or 2 leaves
and stems severe.
 There are currently no reported cases of intentional Lily of the
Valley poisoning.
TOXICITY PREVALENCE IN PETS
 From 2002-2006, the
American Society for the
Prevention of Cruelty to
Animals Animal Poison Control
Center reported 11 cases of C.
majalis poisoning.
 Because Lily of the Valley is
commonly planted as garden
ground cover, pets may have
an increased risk of exposure
to the plant.
FUTURE RESEARCH
HOMEOPATHY
 Homeopathy is a form of alternative medicine based on the idea
that “like cures like”.
 Use of homeopathic remedies has been on the rise within the
past couple of years.
 Homeopathic remedies are not evaluated by the FDA for safety
or effectiveness.
 Homeopathic use of C. majalis could potentially lead to adverse
side effects due to lack of regulation and information regarding
the drug ’s safety.
HOMEOPATHIC USE OF LILY OF THE
VALLEY
Some homeopathic retailers make bold claims such as “no side effects”.
CARDIAC GLYCOSIDES AND CANCER
THERAPY
 Cardiac glycosides appear to be antineoplastic, meaning they have
the ability to inhibit the maturation and spread of malignant cancer
cells.
 Although the mechanism is not fully understood, cardiac glycosides
are thought to increase the immunogenicity of dying cancer cells by
inhibiting the Na + /K + -ATPase pump.
 Clinical trials are currently being conducted to evaluate the
effectiveness of cardiac glycoside use in conjunction with
conventional chemotherapeutic regimens to treat cancer.
 Although these current trials are using digoxin as their
experimental cardiac glycoside, we believe researchers should
include any of the 30+ available cardiac glycosides from Lily of the
Valley as they could also have antineoplastic effects.
POTENTIAL THERAPEUTIC USES FOR
ALL LILY OF THE VALLEY COMPOUNDS
 While the toxic and therapeutic effects have been studied for the
major compounds found in Lily of the Valley, convallatoxin and
convallamarin, there is currently very little research into the
other 30+ cardiac glycosides found in C. majalis.
 Some of these cardiac glycosides may prove to be more efficient
than current drugs like digoxin in treating heart irregularities.
 We propose further studies should be conducted using in vivo
animal testing to test the effectiveness of the many cardiac
glycosides isolated from C. majalis in treating heart irregularities
and possibly cancer.
CONCLUSION
LILY OF THE VALLEY
 Lily of the Valley can produce toxic effects if ingested due to the
numerous cardiac glycosides present.
 Cardiac glycosides inhibit the Na + /K + -ATPase pump affecting
heart rate.
 The cardiac glycosides found in Lily of the Valley may prove to be
effective treatments for cancer.
 Further studies should be conducted in order to evaluate the
adverse and therapeutic effects of all 30+ cardiac glycosides
isolated from C. majalis.
USE OF LILY OF THE VALLEY AS A
POISON
 Although the show Breaking
Bad shows Lily of the Valley
being used as a poison, there
are currently no reported
intentional real life C. majalis
poisonings.
 Potential copycat cases may
arise following the exposure
received on Breaking Bad.
 Health professionals should
be aware of the signs of C.
majalis poisoning.
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