Transcript Cardiac Glycosides

Toxic Plants
Plants containing Cardiac glycosides •
Cardiac Glycosides
• Cardiac glycosides are divided into two
main types:
* Bufadienolides are C24 steroids,
• The primary cardiac glycoside present in
Helleborus is the bufadienole, hellebrin.
• Hellebrigenin, the aglycone of hellebrin is
more potent than the glycoside itself.
• Cardenolides have a hormonal nature as
substances. Their effects are on the heart and
kidney.
• Strong, bitter and disagreeable taste.
• Cardiotonic = affect contractions of the heart
muscle.
• Break down in fermentation by enzymatic action.
• Treatment: atropine and activated charcoal,
lidocaine for H. viridis
• Assumed mechanism of action: inhibition of the
Na+, K+-ATPase resulting in increased
intracellular sodium and subsequent intracellular
calcium leading to enhanced muscle contraction in
cardiac tissue.
• Cardenolides are classified according
to the chemical composition of their
aglycones as lanataglucosides A, B,
C, D and E. OnlyDigitalis lanata, the
woolly foxglove contains all five
forms.e. The entire foxglove plant is
toxic. Symptoms of poisoning include
dizziness, vomiting, irregular heart
beat, and delerium or halucinations.
Digitalis
• Digitoxin, a glycoside
which stimulates the
heart. A carefully
prescribed dose often
has miraculous effects
on people with heart
conditions, but an
overdoes may be
FATAL
Digitalis lanata
• POISON LOCATION:
• Sap, flowers, seeds, and leaves of
Foxgloves, but the greatest
concentration of the toxin occurs in
the leaves, even dried ones.
• TYPICAL POISONING SCENARIO:
• Accidental consumption of leaves or flowers
by livestock, or children who are attracted by
the showy flowers, or the nectar, both of
which contain the glycoside poison. The sugar
in the glycoside breaks down during digestion,
releasing the active chemical. Adults are
occasionally poisoned by the misuse of herbal
preparations- tea from dried Foxglove leaves
is traditionally a diuretic- or by overdoses of
prescribed digitalis . Like any other medicine,
digitalis must be kept out of the hands of
children.
• Another possible cause of poisoning is
misidentification. The leaves of Foxgloves are
easily mistaken for those of Comfrey, which
are traditionally brewed for tea; both share
the same general form and a coasely hairy
surface. Additional confusion occurs because,
in its first year, Foxgloves produce only
leaves, no flowers. Foxglove leaves, however,
have finely toothed edges, whereas Comfrey
leaves are smooth. Digitoxin is dangerous, so
Foxgloves must be treated with caution .
Nerium oleander
• Common name: ‫دفلة‬
• Scientific name:
Nerium oleander L.
• Family:
Apocynaceae
• Toxic ingredient:
• It contains cardiac glycosides
(oleandrin, neriin, folinerin,
digitoxigenin, rosagenin, nerigoside),
oleandrin is one of the major
glycosides present in the plant.
Toxic parts:
• All parts of the plant, including the leaves, flowers,
sweet nectar and twigs are poisonous
• The highest percentages of cardiac glycosides are
found in the seeds, stems and roots followed by the
fruit and leaves which contain the greatest oleandrin
concentrations.
• The nectar makes a toxic honey.
• The bark contains rosagenin which has strychninelike
actions.
• Four CNS depressant cardenolides including a new
cardenolide, neridiginoside and three known
constituents, nerizoside, neritaloside and odorosideH, have been isolated from the leaves which
exhibited CNS depressant activity in mice at a dose
of 25 mg/kg.
Toxic dosage:
• Fatal oleander poisonings have been reported in
humans 4,8, but the human mortality associated
with oleander ingestion is generally very low, even
in cases of intentional consumption (suicide
attempts) 9.
• A child who ingested three leaves developed a
partial right bundle branch block but was able to
leave the hospital after 24 hours.
• Seeds: the absorption of 10 has led to serious
symptoms 2.
Exposure:
• Modes of exposure to the plant include
accidental ingestions by children, as well as
intentional administration in foods, drinks
or medicinal preparations from its leaves
which have been used as treatments for
malaria, leprosy, venereal diseases, and to
induce abortions Oleander has also been
used in suicide attempts 4,9, in criminal
poisonings and in rat poison.
• Children have been poisoned by chewing
leaves and sucking the nectar from
flowers.
• Adults have been poisoned after eating
meat roasted on oleander stems used as
skewers 5, consumption of stagnant
water contaminated by leaves or
flowers, or inhalation of smoke from
burning wood and leaves 2.
Manifestations:
• Symptoms of oleander intoxication are very similar to those
of digoxin, in that nausea and vomiting are followed by
potentially lethal cardiotoxicity 4.
• Nausea and vomiting usually occur within several hours .
• Serious toxicity results from cardiotoxicity and specifically
from cardiovascular collapse and ventricular ectopy.
• Conduction delays may persist 3-6 days, displaying classical
digitalis toxicity as characterized by increased ectopy and
conduction delay (e.g. supraventricular tachycardia with
atrioventricular block) 9
• Bradycardia may be as down as 30-40 beats/min, the pulse
is weak and irregular.
• Other toxic effects of the oleander
include burning of the mucous membranes
of the eyes, mouth and gastrointestinal
tract 4, bloody diarrhea 4,5, xanthopsia
(yellow vision) 2,4, convulsions, respiratory
paralysis and loss of consciousness 4,5 .
• Clinical tests reveal a more or less
pronounced hyperkalemia.
Treatment:
• Supportive, gastric lavage (but should be avoided
after the onset of cardiac symptoms).
• Fluid administration, atropine (which in young
victims, or when small quantities ingested) is
sufficient to prevent bradycardia and allows the
cardiac rhythm to return to normal within a few
hours.
• Isoproterenol, antiarrhythmics and early
administration of activated charcoal may be
useful, sometimes in combination with sorbitol.
Mechanism of action
• • Inhibition of Na,K-ATPase activity by the cardiac
glycosides.
• Cardiac glycosides interfere with transport of
Na+ and Ca+2 out of the cell. They bind with high
affinity to an inhibitory site on the portion of Na,
K-ATPase structure that faces the outside of the
cell. Consequently, sodium and potassium
transport is blocked.
Squill:
• Common name: ‫ عيصالن‬, ‫بوصالن‬, ‫بصول‬,
‫عود الري‬
• Scientific name: Urginea maritima
(L.) Baker Syn. Drimia maritima (L.)
Stearn Syn. Scilla maritima (L.)
• Family: Liliaceae 1
Squill Bulb
• Toxic ingredients:
• The principal compounds are glycosides of
scillarenin (scillaren A, glucoscillaren A and
proscillaridin A) and of scilliphaeosidin
(glucoscilliphaeoside), scilliphaeoside and
12-epi-scilliphaeoside together with
scillicyanoside 2 .
• Toxic parts:
• The bulb, but possibly the whole plant
contains several cardioactive glycosides 3.
• Manifestations:
• Squills are rarely implicated in poisoning, yet,
fatal cases were reported due to the
consumption of the bulbs of the plant
• The toxic effects of squill are similar to
those of digitalis glycosides.
• Vital signs
- Bradycardia or tachycardia may be seen;
either could lead to secondary hypotension.
- In absence of concomitant ingestion,
environmental exposure, thyroid disorder, or
underlying infection, patient generally is
normothermic.
- Lungs: Examination findings typically are
normal in the absence of preexisting disease,
but rales have been reported.
• - Heart
• Bradydysrhythmias or tachydysrhythmias can
occur, typically with increased automaticity and
depressed conduction.
• Hypotension and shock may ensue.
• Pulses may be weak, thready, and irregular.
• Abdomen
• Abdomen is generally soft.
• Vomiting and diarrhea may be noted.
• Emesis may contain plant material.
• Neurologic
• Findings may include an altered level of
consciousness, hypotonia, hyporeflexia,
dysarthria, ataxia, horizontal nystagmus,
and generalized seizures.
• The patient typically is nonfocal with
pupillary reflexes intact.
• Skin: Skin may be pale, diaphoretic, and
cool.
Other Plants
1. Strophanthus
2. Veratrum virid
3. Lilly of the Valley