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Zedoary-Induced Cardiovascular Disorders

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In this case report, two young adult female patients with cardiovascular disorders (hypotension and bradyarrhythmias), caused by ingestion of an extract of Zedoary (overdose) were described. The most patient clinical issues were discussed. – PowerPoint PPT presentation

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Title: Zedoary-Induced Cardiovascular Disorders


1
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Zedoary-Induced Cardiovascular Disorders case
report
  • Usama M. El-Barrany
  • Magdy A. Ismail
  •  
  • Forensic Medicine and Toxicology Department,
    Faculty of Medicine, Cairo and Al-Azhar
  • Boys Universities

3
  • intoduction

4
intoduction
  • Many people use traditional remedies as a first
    line medication.
  • Some herbal toxicity is predictable, based on
    known botanical content.
  • Many other adverse effects are idiosyncratic or
    not commonly appreciated.
  • Zedoary (Curcuma Zedoaria) is one of these
    commonly used herbs.

5
Zedoary (Curcuma Zedoaria)
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Zedoary (Curcuma Zedoaria)
  • Species Curcuma zedoaria.
  • Family Zingiberaceae (ginger family).
  • Origin The plant is native to India and
    Indonesia. but today is widely cultivated in
    India, South-East Asia and China.
  • It was introduced to Europe by Arabs around the
    sixth century.
  • Etymology The European names for zedoary
    originate from Arabic jadwar and Farsi zedwaar.

7
Zedoary (Curcuma Zedoaria)
  • Characteristics
  • A rhizomatous herb with a 6-foot tall leafy stem.
  • The leaves are 1 foot long and 3 inches across.
  • The flowers are white or yellowish with a lip
    that is pale yellow-shaded, with a deeper yellow
    color near the base.
  • The fruits have 3-valved capsules.
  • The rhizome is short, firm, and of externally
    wrinkled gray, ash-colored appearance, but with a
    brownish red color from the inside.

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Zedoary (Curcuma Zedoaria)
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Zedoary (Curcuma Zedoaria)
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Zedoary (Curcuma Zedoaria)
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Zedoary (Curcuma Zedoaria)
  • Active ingredients
  • Curcumin, berberine, hydrastine, canadline,
    zingiberine, dihydrocurdione, ar-turmerone,
    beta-turmerone, some volatile oils, and resins.
  • The highest concentrations of these constituents
    are in the root (rhizomes), the lowest, in the
    leaves and stem.

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Zedoary (Curcuma Zedoaria)
  • Uses The used part is the rhizomes.
  • Food
  • It has a fragrant smell (more similar to ginger,
    except with a very bitter taste).
  • Due to its bitter taste, its use as a spice today
    is rare, having been replaced by ginger.
  • Although it is seldom used today as an individual
    spice, it may be employed in spice mixtures.

13
Zedoary (Curcuma Zedoaria)
  • Food
  • In Indonesia Thailand, the young rhizomes are
    often eaten as an aromatic vegetable, zedoary can
    also be ground to a powder and added to curry
    pastes.
  • In India, it tends to be used fresh or in
    pickling.

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Zedoary (Curcuma Zedoaria)
  • Medicinal uses
  • Zedoary is used in the form of powdered root,
    tincture, fluid and solid extract the medicinal
    substance obtained has a fragrant smell, and a
    warm bitter aromatic taste.
  • It is much used as a medicine in China and Japan.
    It has been used as an antivenom for the Indian
    cobra.
  • It has been also used in traditional eastern
    medicines to help digestion, relieve colic, as a
    laxative, antifungal, analgesic and
    anti-inflammatory agent.

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Zedoary (Curcuma Zedoaria)
  • Medicinal uses
  • Dihydrocurdione, the major component of Zedoary
    has anti-inflammatory potency related to its
    antioxidant effect.
  • The anti-inflammatory and cancer chemopreventive
    effect of some components of Zedoary might be due
    to decreased prostaglandin and nitric oxide
    production through respective inhibition of
    cyclooygenase 2 (COX-2) and nitric oxide
    synthase, which have been implicated as important
    mediators in the processes of inflammation and
    carcinogenesis.

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Zedoary (Curcuma Zedoaria)
  • Medicinal uses
  • Zedoarin, kurdiona and kurkumol are substances
    that can be also found in Zedoary.
  • These substances have anti-neoplastic functions
    through breaking ribosome formation in cancer
    cells and wild tissue.
  • They enhance the formation of fibroblast tissue
    around the cancer and form a layer of lymphocytes
    in the cells of cancer wrap it.
  • So, the tissue cells of cancer can not grow,
    eventually the cancer cells will die.

17
Zedoary (Curcuma Zedoaria)
  • Medicinal uses
  • Zedoary has been used to treat some liver and
    coronary heart disease.
  • It has been used to treat anemia, prevent
    leukopenia due to cancer therapies and as an
    agent for purifying the blood.
  • It has been also applied locally as poultice for
    skin lesions and eyes.

18
Zedoary (Curcuma Zedoaria)
  • Others
  • The essential oil produced from the dried roots
    of Zedoary is used in perfumery as well as an
    ingredient in bitter tonics.

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Zedoary (Curcuma Zedoaria)
  • On the other hand, a protein flour, prepared from
    rhizomes of Zedoary , proved to be highly toxic
    to 5-week-old rats and caused 100 mortality
    within 6 days when given at 320 g/kg diet.
  • When a meal formed of fresh minced and dried
    rhizomes of Zedoary was given to weanling rats at
    400 g/kg diet, all the animals lost weight
    rapidly, and two of the five rats died within 4
    days.

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  • Case Report

21
Case Report
  • This study describes 2 cases of Zedoary-induced
    bradyarrhythmias and severe prolonged hypotension
    (during our work in Center of Poison Control and
    Clinical Forensic Chemistry, in Holy Makkah
    region, Saudi Arabia).

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  • CASE I

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CASE I
  • A 20-year-old woman was admitted to Al-noor
    special hospital in Holy Makkah region, Saudi
    Arabia at 3/11/2003 after ingestion of an unknown
    quantity of Zedoary extract to reduce pain (the
    history was taken from her father).
  • On admission, she was unresponsive except for
    painful stimuli, with diaphoresis, cyanosis, and
    respiratory depression.
  • Pupils were slightly dilated systolic blood
    pressure was 50 mmHg, with a third degree heart
    block and a ventricular rate 40 beats/minute.

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CASE I
  • Following intubation, gastric lavage was done,
    and activated charcoal was given 3 times (every 4
    hours).
  • Routine toxicological screening using,
    immunoassay techniques (AxSYM), was negative for
    alcohol, opiates, barbiturates, benzodiazepines,
    amphetamines, cocaine, cannabis, tricyclic
    antidepressants (TCAs), digoxin, theophylline,
    salicylates, acetaminophen, phenytoin,
    carbamazepine as well as valproic acid.

25
CASE I
  • Color tests, TLC Toxi-Lab System showed ve
    results for other common substances such as
    phenothiazines, antihistamines, beta blockers,
    calcium channel antagonists, NSAIDs, SSRIs,
    organophosphates as well as carbamates.
  • Bradycardia and hypotension were unresponsive to
    atropine, infusion of dopamine, saline, or even
    pacemaker insertion.
  • She died within 24 hours after admission from
    cardiovascular collapse.

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  • CASE Ii

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CASE Ii
  • An 18-years old woman was admitted to Al-noor
    special hospital in Holy Makkah region, Saudi
    Arabia at 4/11/2003 after ingestion of a large
    quantity of Zedoary extract as a tonic. (the
    history was taken from the patient).
  • On admission, she was alert, but had nausea,
    vomiting, abdominal pain, dizziness and lethargy.
  • Systolic blood pressure was 60 mmHg, with
    junctional bradycardia (as slow as 27
    beats/minute) but without evidence of myocardial
    infarction.

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CASE Ii
  • Following spontaneous emesis, gastric lavage was
    done, and activated charcoal was given 3 times
    (every 4 hours).
  • Routine toxicological screening, using
    immunoassay techniques (AxSYM), was also negative
    for alcohol, opiates, barbiturates,
    benzodiazepines, amphetamines, cocaine, cannabis,
    TCAs, digoxin, theophylline, salicylates,
    acetaminophen, phenytoin, carbamazepine as well
    as valproic acid.

29
CASE Ii
  • Color tests, TLC Toxi-Lab System showed also
    ve results for other common substances such as
    phenothiazines, antihistamines, beta blockers,
    calcium channel antagonists, NSAIDs, SSRIs,
    organophosphates as well as carbamates.
  • Dopamine, intravenous saline, and 20 ml of 10
    calcium gluconate intravenously were
    administered, and a pacemaker was placed.
  • Calcium gluconate was repeated and pressor agents
    were infused for additional 18 hours.
  • Blood pressure became normal after 24 hours, and
    sinus rhythm returned after 35 hours from
    admission. The patient was discharged free 5 days
    post-admission.

30
  • Discussion

31
Discussion
  • The rapid course of the two cases pushed the team
    of center to work in two ways
  • One way was the analysis of biological fluids
    from the two patient as well as the possible
    analysis of Zedoary.
  • The other one was getting all possible data about
    the mentioned herb.

32
Discussion
  • In the two cases, routine toxicological screening
    for the previously mentioned substances was done
    to exclude any of them as a cause of toxicity.
  • Many substances such as beta blockers,
    antihistamines, CCAs, NSAIDs or SSRIs are not
    analyzed routinely as one group but as individual
    drugs in the group, meaning that getting ve
    results for some drugs in the group does not
    exclude the presence of other ve unknown drugs
    or substances belonging to the same group.

33
Discussion
  • Although HPLC-MS needed for analysis of zedoary
    into their different components was available in
    the center, we did not have the special method
    for detection of this herb.
  • In addition to that, the rapid course of the two
    cases especially the first one enforced all the
    team of the center to depend on the available
    data received from our search about Zedoary.

34
Discussion
  • Some of these data included that Curcuma herbs
    have showed hypotensive and protective effect on
    the endothelium in spontaneously hypertensive
    rats.
  • Especially, C. Zedoaria was more effective than
    C. Longa, and its mechanism was thought to be
    related to a radical scavenging effect and
    improvement of hemorheology.
  • Hemorheology is the study of flow properties of
    blood and its elements (plasma and formed
    elements, including red blood cells, white blood
    cells and platelets).

35
Discussion
  • Dihydrocurdione, the major component of Zedoary
    has calcium channel antagonist-like effects.
  • Zedoary contains both hydrastine and berberine,
    which cause a decrease in blood pressure.

36
Discussion
  • Berberine is thought to be seven times as potent
    as hydrastine in producing hypotension.
  • A dose of 1mg/kg of Zedoary extract will produce
    a slight increase then decrease in blood
    pressure, while 2mg/kg will produce significant
    prolonged hypotension.

37
Discussion
  • On the other hand, hallmarks of CCAs overdose
    include bradyarrhythmias, myocardial depression,
    peripheral vasodilatation, hypotension, and
    syncope.
  • These symptoms and signs of toxicity coincided
    with the two cases of Zedoary toxicity, presently
    reported, whereas their main manifestations were
    cardiovascular disorders in the form of severe
    prolonged hypotension and bradyarrhythmias.

38
Discussion
  • Although plasma concentrations of CCAs correlate
    well with cardiovascular depression in the
    experimental setting, plasma concentrations in
    humans show no significant correlation with the
    amount of drug reportedly ingested by patients.
  • Moreover, fatal verapamil overdose has occurred
    with a peak plasma concentration slightly higher
    than the high-therapeutic range (687 ng/mL).

39
Discussion
  • Thus, managing patients with suspected herbs
    having signs and symptoms similar to CCA overdose
    should be based on clinical features rather than
    analysis.
  • Based on these data, calcium gluconate 10 was
    given to the second patient to treat the
    refractory hypotension and to avoid death as in
    the first case.

40
  • Conclusion AND RECOMMENDATIONS

41
Conclusion AND RECOMMENDATIONS
  • There is no logic supporting the popular
    conception that herbal products are safer or more
    natural than pharmaceutical medications.
  • The use of herbs by most individuals should be
    put under strict medical regulations.

42
Conclusion AND RECOMMENDATIONS
  • More studies are needed regarding the clinical
    manifestations as well as the chemical analysis
    of most commonly-used herbs.
  • Toxicology centers should be equipped with modern
    analytical facilities as well as information
    centers to help clinicians in managing different
    toxic cases.

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