‘Glorios’ Kidney failureKarunan Kannampoyilil(Prakashan KP)Dept of Nephrology MCH TVM

29/F/HW/Vellayam,TVM●01/04/2004. occ-vomiting.●Pregnency test +ve. ●Healthy past .●L1,P2,G2- 3MA.●1st Child one yr. ●2nd child unaffordable.●Needs termination.●Approched ‘Local Dr’- said – NO.

Indigenous Medicine●Indigenous- Dr.09/04/2005.●Menthonikizhangu&Neelamari-●<5ml of the magic decoction.●Menthonni-toxin will abort.●Neelamari-juice a diuretic.●12/04/2005.●Early morning-empty stomach.

Unconcious●Abd pain●Vomited out blood●Passed bloody stool●Called the indigenous dr●Some oil- LA- NO relief●Unconcious

Local Hospital●Conservative Mx for vomiting

●Pregnency test +ve●Asked for USG●No Rx for Toxin

Usg preg-abd●Fibroid Ut,●3Month old foetus in ut,●RK,LK,Liver,spleen-N,●No other abn in abd,●how pregn- local Dr !,●Ref-SAT,MCH

12/04/2004, Loc H to SAT

●Milk intake advised.●But Vomitig persisted.●SAT Gynec.8.30pm●Native Medicine Intake?●Ref to-MCH●Medical Casuality.9.30pm

Shuttle

●MCH casuality●Persistant vomiting ●USG-Pregnancy●Need - MTP ●Ref Back to- ●SATH-Gynecology

Again-SATH

●15/04/2005●MTP●Suction Evacuation●Cu T-Insertion.●Gen Maculopapillar Rashes●Back Home

Back home●Abd pain ●Vertigo●Vomiting●Gen edema●Petichea●bleedingPV●ANURIA

home

●Gen edema●Vomiting●UOP diminished●No fever●Normotensive●On antibiotic●Local Dr consu-●Ref to MCH casuality

MCH TVM Casuality●19/04/2004●Not able to walk. ●Gen weakness.●No Power.●No appetite.●VEPRALAM.

MCH TVM Casuality

●Gen MP Rashes●Gen. edema●Took some native decoction●Anuric●RFT Elevated.●Persistent Vomiting.●Admission to ward 19/04/2004

Nepro-Consu

●21/04/2005-7.30PM●ARF,Auric●Normotensive●Non DM●Native medicine intake●Had MTP●Vomiting.

21/04/2005

●LFT high,ARF ?cause●Total anuria●Following some native medicine intake●Not known●Normotensive ●Restless●Generalised weakness●HD to tide over.

HD 22/04/2005

●AD HD●No Improvement of RFT●Anuria persist,●Anemic

GLORIOSA SUPERBA

●Family; Colchicaceae ●Flame lily; glory lily ●All parts of the plant, especially the

tubers, are extremely poisonous. ●Colchicine, an alkaloid, is responsible

for the toxic effect.●The species also contains another

alkaloid 'gloriosine'.

Colchicine●The toxic properties of the plant are

essentially due to the highly active alkaloid - colchicine.

●Colchicine: CAS number: 64-86-8 Molecular formula: C22H25NO6 Molecular weight: 399.44 Structural name: colchicine

Other chemical contents

●3-desmethyl colchicine, ●beta-lumicolchicine, ●N-Formyldesacetyl-colchicine, ●2-desmethyl colchicine, ●Chelidonic acid and ●Salicylic acid

USES/CIRCUMSTANCES OF POISONING

●The tuber is used traditionally for the Rx of

●Bruises and sprains, ●colic, chronic ulcers,

haemorrhoids, ●cancer, impotence, ●nocturnal seminal emissions,

leprosy and also ●for inducing labour pains and

abortion.

Other uses

●Because of its similar pharmacological action, the plant is sometimes used as an adulterant of aconite ( Aconitum sp.)

●The leaf juice to kill head lice

●Ingredient in arrow poisons.

Flowers&tubers●Flowers are used in religious ceremonies. ●The tuber has commonly been used as a

suicidal agent among women in rural areas and it has also been used for homicide.

●The tuber also claims antidotal properties to snake- bite and in India it is commonly placed on window sills to deter snakes.

●Many cultures believe the species to have various magical properties.

High risk circumstances

●In parts of tropical Africa and Asia the tubers of G. Superba may be mistakenly eaten in place of Sweet Potatoes (Ipomoea batatas) since the former is a weed of farmland and the

tubers resemble those of Sweet Potatoes.

High risk geographical areas

●The highest risk areas are likely to be throughout the natural range of the species (i.e. tropical Africa and Asia, including Sri Lanka).

●Accidental exposure to the plant may also occur in cool temperate countries of the West where it is grown as an ornamental.

ROUTES OF EXPOSURE

●1 Oral Ingestion of tubers or other parts either Intentionally or accidentally.

●2 Inhalation, ●3 Dermal ●4 Eye ●5 Parenteral all NDA

KINETICS●Absorption by route of exposure

Colchicine is readily absorbed from the Gastrointestinal tract.

●Absorption may be modified by pH,

contents in the stomach and intestinal motility.

Distribution by route of exposure

●Colchicine is actively taken up intracellularly.

●Approximately 50% circulating colchicine is bound to plasma proteins.

●The apparent volume of distribution exceeds total body water (2.2 ± 0.8 1/kg)

Biological half-life●by route of exposure Colchicine has an extremely short plasma half life of about 20 minutes (Ellenhorn et al., 1996).

●Metabolism Colchicine is partially deacetylated in the liver although as much as 20% may be excreted unchanged by the kidneys.

●Large amounts of both colchicine and its metabolites are subjected to enterohepatic circulation.

Elimination and excretion

●Colchicine and its metabolites are excreted in urine and faeces

Mode of action

●Colchicine affects cell membrane structure indirectly by inhibiting the synthesis of membrane constituents

●It binds to tubulin (the structural proteins of microtubules) preventing its

polymerization into microtubules. ●This antimiotic property disrupts the spindle

apparatus that separates chromosomes during metaphase.

high metabolic rate-cells●Cells with high metabolic rates (e.g. intestinal

epithelium, hair follicles and bone marrow) are the most involved by the arrest of mitosis.

●The variable effects of colchicine may depend on its binding to the protein subunit of microtubules with subsequent disruption of microtubule functions

●Colchicine also has an inhibitory effect on various phosphatases Gloriosine also has an antimitotic effect (Gooneratne, 1966).

Toxicity●Human data ●Adults, Nickolls (1965) has suggested that

the lethal dose of colchicine for man may be about 60 mg although smaller amounts have also caused death (Angunawela &Fernando,1971).

●Gooneratne (1966) has reported a patient who survived after ingestion of 350 mg of colchicine tuber.

LD50●Children No data

available. Relevant animal data LD50 of colchicine for rats was 5 mg/kg (Dunuwille et al., 1968).

Urine analysis

●G. superba tubers are used

for abortion (Duke, 1985). ●Urine analysis could show

haematuria, proteinuria or haemoglobin casts.

The commonest clinical presentation

●Severe gastroenteritis●NVD with blood leading to dehydration,

hypovolaemic, shock &ARF. ●Muscle weakness, hypoventilation,

ascending polyneuropathy, bone marrow depression and coagulation Disorders.

are the other features of poisoning.

Death

●Death in severe poisoning occurs due to shock or respiratory failure although haemorrhagic or infective

complications may cause death after the first day.

Cardiovascular

●Heart - there is no direct effect on the heart,but fluid and electrolyte loss, often causes hypovolaemic shock manifested by hypotension and tachycardia.

Respiratory

●Respiratory failure is thought to be due to the paralysis of intercostal muscles rather than the direct depression of the respiratory centre by colchicine (Angunawela & Fernando, 1971).

●The patient may be dyspnoeic and cyanotic.

Neurological●Central nervous system (CNS)●There is progressive paralysis of the

central nervous system and peripheral nervous system (Wijesundere, 1986).

●Confusion and delirium may develop either secondary to poor cerebral perfusion or as a result of direct cerebral toxicity (Ellenhorn et al., 1996).

NS●It may also cause convulsions,

restlessness and coma. ●Peripheral nervous system ●Ascending polyneuropathy, weakness,

loss of deep tendon reflexes may be described.

●Autonomic nervous system NDA

Skeletal and smooth muscle●Colchicine could have a direct toxic

effect on skeletal muscles causing muscular weakness.

●Rhabdomyolysis may occur with significant increase in muscle enzymes and myoglobinuria as a result of direct muscular damage.

●Muscle weakness that may persist for many weeks may contribute to respiratory deficiency (Ellenhorn et al., 1996).

Gastrointestinal●Gastroenteritis including nausea,

vomiting and diarrhoea with blood accompanied by colic and tenesmus.

●Loss of fluids and electrolytes leads to hypovolaemia.

●Intestinal ileus may develop within the first several days and may persist up to a week (Ellenhorn et al., 1996).

Hepatic●Colchicine may exert direct hepatic toxicity with moderate cytolysis.

Renal ●Any direct toxic effect of the toxin on

kidney is not clear. ●Renal failure is probably secondary to

excess fluid loss or hypovolaemia and is preceded by oliguria and haematuria.

●Proteinuria could also occur (Murray et al., 1983).

Endocrine and reproductive systems

●Vaginal bleeding has been reported as a feature of intoxication. Tubers are used as an abortifacient in some countries.

●Dermatological Alopecia usually occurs one or two weeks after the ingestion of G. superba.

●A case of generalized depilation has also been reported (Gooneratne, 1966). Desquamative dermatitis has been reported as another dermatologic manifestation (Angunawela & Fernando, 1971).

●Both these conditions can be attributed to the antimitotic activity of the colchicine and gloriosine.

Eye, ear, nose, throat

●local effects Subconjunctival haemorrhages have been observed (Gooneratne, 1966). Burning and rawness of the throat may be early symptoms of toxicity.

Haematological●BM depressant- transient leucocytosis

followed by leucopenia. thrombocytopenia that may give rise to various coagulation disorders resulting in vaginal bleeding, conjunctival and gastrointestinal haemorrhages. Severe thrombocytopenia occurring within 6 hours of poisoning has been documented (Saravanapavananthan, 1985). Anaemia may occur, mostly secondary to haemorrhages

●ImmunologicalPatients are prone to infections as a result of leucopenia. Metabolic Acid-base disturbances Metabolic acidosis.Fluid and electrolyte disturbances There is an extensive fluid and electrolyte loss due to intense vomiting and diarrhoea or sometimes due to haemorrhages. Hypokalaemia, hypocalcaemia, hypophosphataemia and hyponatraemia may occur (Murray et al., 1983).

●Pregnancy: Data on effects of G. superba on the foetus are not available. However, colchicine is contraindicated in pregnancy. Down's syndrome and spontaneous abortions have been reported.

●MANAGEMENT 10.1 General principles Hospitalize the patient immediately. Constant and prolonged monitoring is essential. Ensure adequate ventilation. Before instituting symptomatic and supportive therapy remove the plant material from gastrointestinal tract by emesis or gastric lavage without delay to minimize further absorption. Give adequate intravenous fluids. Correct any electrolyte imbalance. Maintain a fluid balance chart. Specific measures should also be taken for the management of shock. Cardiac monitoring is useful. Early forced diuresis may be of value. Specific fragments a) b) have been experimented on animals. No human data are available.

●Life supportive procedures and symptomatic/specific treatment Observation and monitoring: Monitor pulse, respiration and blood pressure. Fluid and electrolytes replacement: Give adequate oral fluids. If the patient is unable to take oral fluids Ha 9 + 14. Hypotension and shock:

●Hypotension and shock: Fluid loss may lead to hypovolaemic shock with hypotension: Correct hypotension as required. Ensure a clear airway, improve ventilation and give oxygen (Ha 4 + 5 + 6).

●Decontamination If consciousness is not impaired AP4 + AP

●Enhanced elimination Forced diuresis, if instituted early should be of benefit by eliminating colchicine.

●Haemodialysis, haemoperfusion and other relevant measures are of no value because of large volume of distribution and limited renal excretion of colchicine (Ellenhorn et al., 1996).

Antidote/antitoxin treatment●Adults There is no specific antidote available, ●but immunotherapy (fragments fab) is

available for clinical trial on humans in some countries (France).

●Children There is no specific antidote available, but immunotherapy (fragments fab) is available for clinical trial on humans in some countries (France).

CLINICAL EFFECTS●Acute poisoning ●Ingestion Acute manifestations begin two to

six hours after ingestion and consist of burning pain in the mouth and throat with thirst, followed by nausea, intense vomiting, colicky abdominal pain and severe diarrhoea with blood, leading to hypotension and shock.

course●Delirium, loss of consciousness, convulsions, ●respiratory distress, ●haematuria, oliguria, ●transient leucocytosis followed by leucopenia,

thrombocytopenia with haemorrhages, ●anaemia, ●muscle weakness which may progress to

polyneuropathy are seen in the second or third day. ●Alopecia occurs 1 to 2 weeks after intoxication as a

late manifestation in survivors.

Early haemodynamic monitoring is very helpful (Murray et al., 1983).

●Respiratory: If respiratory depression is present assisted ventilation and oxygen may be necessary.

●Renal failure: Renal failure with oliguria is a common feature. Maintain an adequate urine output with plenty of intravenous fluids.

●Established renal failure may require peritoneal or haemodialysis. ●Leucopenia: Fresh blood transfusions are necessary to correct

leucopenia. ●Prophylactic antibiotic therapy is advisable if leucopenia is present. ●Coagulation disorders: If clotting time is abnormal, vitamin K and

fresh frozen plasma should be given. ●Haemorrhagic manifestations should be treated with fresh blood

transfusions. ●Hypothermia: This may be a poor prognostic sign. Adopt measures to

keep the patient warm.

The stigmas of ego

Glorious travel