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Rauvolfia serpentina
Rheum officinale
Rhamnus frangula
Rhamnus purshiana
Rehmannia glutinosa


 

 

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Rhamnus purshiana D.C. (Rhamnaceae)

Synonims
Frangula purshiana (D.C.) A. Gray ex J.C. Cooper., Rhamnus purshianus D.C.

Local names
Amerikanischen Faulbaum, bear wood, bitter bark, cascara bark, cascararinde, chittem bark, cortex cascara sagradae, écorce de cascara, purshiana bark, quishron moquaddas, Rhamnus, sacred bark

Description
A tree, 4–10m high, with reddish-brown bark and hairy twigs. Leaves petiolate, elliptical, acuminate, serrulate, or sometimes entire, with 10–15 pairs of veins, dull green upper surface and pubescent underside. Inflorescence an axillary umbellate cyme of small greenish flowers. Fruit a turbinate, purplish-black drupe, about 8mm long, composed of 3 indehiscent cocci

Plant material used
dried bark

Chemical assays
Contains not less than 8.0% hydroxyanthracene glycosides of which not less than 60% consists of cascarosides, both calculated as cascaroside A. Quantitative analysis is performed by spectrophotometry at 515nm. A highperformance liquid chromatography method for the quantitative analysis of cascarosides has been reported

Major chemical constituents
The active constituents are hydroxyanthracene glycosides (6–9%). Of these, 70–90% are C-10 glycosides, with the 8-O-glycosides, aloins A and B, and 11-desoxyaloins A and B (chrysaloins A and B) accounting for 10–30%. The diastereoisomeric pairs, cascarosides A and B and cascarosides C and D and cascarosides E and F constitute 60–70% of the total O-glycosides. Other major hydroxyanthracene glycosides (10–20%) include the hydroxyanthraquinones, chrysophanol-8-O-glucoside and aloe-emodin-8-O-glucoside. In the fresh bark, anthraquinones are present in the reduced form, and are converted by oxidation from their corresponding parent anthraquinone glycosides during drying and storage

Medicinal uses
Uses supported by clinical data
Short-term treatment of occasional constipation.

Uses described in pharmacopoeias and well established documents
As a cathartic

Uses described in traditional medicine
Internally for treatment of diabetes and externally for skin irritations

Proven pharmacological activity
Animal studies
Laxative

Toxicity and overdose
As with other anthraquinone laxatives, the major symptoms of overdose are intestinal pain and severe diarrhoea with consequent loss of fluid and electrolytes. Treatment of overdoses should be supportive with generous amounts of fluid. Electrolyte levels should be monitored, particularly those of potassium. This is especially important in children and the elderly

Toxicity and overdose
As with other anthraquinone laxatives, the major symptoms of overdose are intestinal pain and severe diarrhoea with consequent loss of fluid and electrolytes. Treatment of overdoses should be supportive with generous amounts of fluid. Electrolyte levels should be monitored, particularly those of potassium. This is especially important in children and the elderly

Contraindications
Cortex Rhamni Purshianae should not be administered to patients with intestinal obstruction and stenosis, atony, inflammatory diseases of the colon (such as ulcerative colitis, irritable bowel syndrome, Crohn disease), appendicitis,severe dehydration with water and electrolyte depletion, or chronic constipation. As with other stimulant laxatives, Cortex Rhamni Purshianae is contraindicated in patients with cramps, colic, haemorrhoids, nephritis or any symptoms of undiagnosed abdominal disorders such as pain, nausea or vomiting. Owing to the pronounced action on the large intestine and insufficient toxicological investigations, Cortex Rhamni Purshianae and other anthranoid laxatives should not be administered to pregnant women. As anthranoid metabolites may appear in breast milk, Cortex Rhamni Purshianae should not be used during lactation, since there are insufficient data to assess potential pharmacological effects in the breastfed infant. Use of Cortex Rhamni Purshianae in children under 10 years is contraindicated

Warnings
Products containing Cortex Rhamni Purshianae should only be used if no effect can be obtained through a change of diet or by the use of bulk-forming laxatives. Patients should also be warned that certain constituents of the bark are excreted by the kidney and may colour the urine orange, which is harmless. Cortex Rhamni Purshianae and other stimulant laxatives should not be used in patients with abdominal pain, nausea or vomiting. The use of stimulant laxatives for longer than 2 weeks requires medical supervision. Rectal bleeding or failure to have a bowel movement after taking a laxative may indicate a serious condition. Chronic use may result in aggravation of constipation with laxative dependence, a need for increased dosages and disturbances of water and electrolyte balance (e.g. hypokalaemia). Chronic use may also lead to colonic dysfunction (atonicity) and melanotic pigmentation of the colonic mucosa (pseudomelanosis coli), which is harmless. Laxative abuse resulting in diarrhoea and consequent fluid and electrolyte losses (mainly of potassium) may cause albuminuria, haematuria, and cardiac and neuromuscular dysfunction. Neuromuscular dysfunction may arise particularly in the case of concomitant use of cardiotonic glycosides (e.g. digoxin, digitalis or strophanthin), diuretics, corticosteroids or liquorice root.

Precautions
General
Cortex Rhamni Purshianae and other laxatives containing anthraquinone glycosides should not be used continuously for longer than 1–2 weeks, because of the risk of electrolyte imbalance.

Drug interactions
Increased intestinal transit time may result in reduced absorption of orally administered drugs. Electrolyte imbalances, such as hypokalaemia, may potentiate the effects of cardiotonic glycosides (e.g. digoxin, digitalis orstrophanthin). Hypokalaemia resulting from long-term laxative abuse can also potentiate the effects of antiarrhythmic drugs (e.g. quinidine) that change sinus rhythm by affecting potassium channels. Hypokalaemia caused by drugs such as thiazide diuretics, adrenocorticosteroids or liquorice root may be enhanced, and electrolyte imbalance may be aggravated.

Drug and laboratory test interactions
Anthranoid metabolites may not be detectable in faeces or urine by standard methods. Thus faecal excretion measurements may not be reliable. Urinary excretion of certain anthranoid metabolites may cause discoloration of the urine which is not clinically relevant, but may cause false-positives in urinary urobilinogen tests and in estrogen measurements using the Kober procedure.

Carcinogenesis, mutagenesis, impairment of fertility
Although chronic use of anthranoid-containing laxatives has been hypothesized to play a role in colorectal cancer, no causal relationship has been demonstrated. No specific data on carcinogenicity or mutagenicity are available for Cortex Rhamni Purshianae or the cascarosides. Data for aloin derived from aloe indicate no genotoxic risk. Emodin derived from aloe showed both positive and negative results in vitro, but was negative in vivo. Emodin was mutagenic in the Salmonella/microsome assay, but gave inconsistent results in gene mutation assays (V 79). It showed positive results in the test for unscheduled DNA synthesis with primary rat hepatocytes, but negative results in the sister chromatid exchange assay.

Pregnancy: teratogenic effects
See Contraindications. Administration of aloin A to rats at doses up to 200mg/kg body weight had no embryotoxic, teratogenic or fetotoxic effects.

Pregnancy: non-teratogenic effects
See Contraindications.

Nursing mothers
See Contraindications.

Paediatric use
See Contraindications.

Adverse reactions
Single doses of Cortex Rhamni Purshianae may result in cramp-like discomfort of the gastrointestinal tract, which may require a reduction of dosage. Overdose can lead to colicky abdominal spasms and pain, as well as the formation of thin, watery stools. Long-term laxative abuse may lead to electrolyte imbalance (hypokalaemia and hypocalcaemia), metabolic acidosis, malabsorption of nutrients, weight loss, albuminuria and haematuria. Weakness and orthostatic hypotension may be exacerbated in elderly patients when stimulant laxatives are repeatedly used. Secondary aldosteronism may occur after prolonged use due to renal tubular damage. Steatorrhoea and protein-losing gastroenteropathy with hypoalbuminaemia have also been reported after long-term laxative abuse. Pseudomelanosis coli has been observed in individuals taking anthraquinone laxatives for extended time periods. The pigmentation is harmless and usually reversible within 4–12 months after the drug is discontinued. Conflicting
data exist on other toxic effects after long-term use such as intestinalneuronal damage. In incontinent patients using anthranoid laxatives, prolonged exposure of the skin to faeces may cause skin damage. Use of the fresh bark of Rhamnus purshiana may cause severe vomiting, with possible abdominal spasms. One case of occupational asthma and rhinitis has been reported.

Dosage forms
Finely cut crude drug, powder, dried extracts, extract, fluidextract, other liquid and solid preparations. Store in a tightly sealed, light-resistant container.

Posology
The correct dosage for the treatment of occasional constipation is the smallest dosage necessary to maintain a soft stool. Daily dosage: 0.3–1.0g crude drug in a single dose; all preparations standardized to contain 20–30mg of hydroxyanthracene derivatives calculated as cascaroside A; taken at bedtime, or in two divided doses, one in the morning and one at bedtime

 

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