Anorectal Disorders

Anorectal disorders are the diseases that affect the lower part of the rectum (the last segment of the large intestine) and the anal canal. These are the most commonly encountered disorders in the practice of emergency medicine. Most of these anorectal disorders can be diagnosed and treated in the emergency department setting (1). Once they are diagnosed and treated in the emergency department, they need appropriate follow-up to ensure adequacy of treatment, and further possible diagnostic procedures (e.g., endoscopy, and biopsy).

Hemorrhoids
Hemorrhoids are the most prevalent anorectal disorder and are the most common cause of bloody stool. Treatment is dependent on the degree of hemorrhoid prolapse and symptoms. Most cases can be treated by conservative medical treatment (e.g., dietary changes, sitz baths), phlebotonics, soothing cream and nonsurgical procedures (e.g., rubber band ligation and infrared coagulation). 
The thrombosed hemorrhoid is the only hemorrhoidal condition that is actually painful. It arises suddenly when a clot forms inside one of the hemorrhoid areas. It causes a painful, grape-like protrusion. The pain level can vary from mild to extreme. Thrombosed hemorrhoids can be so extensive that they involve the anorectal region all the way around. 

A thrombosed hemorrhoid is usually caused by straining, by a bout of constipation or diarrhea, or, occasionally, from severe physical exertion. Thrombosed hemorrhoid gives rise to pain for a limited amount of time. They are not the cause of long-standing pain. An episode of thrombosed hemorrhoids will not persist longer than a few weeks. 
Surgical excision of symptomatic thrombosed external hemorrhoids is indicated if within 48 to 72 hours after the onset of pain that is not responding to conservative treatment. Surgical intervention is contraindicated when the patient has a bleeding abnormality, is taking blood thinner, or has increased portal venous pressure.
The study of the comorbid occurrences of hemorrhoids with other diagnoses in identical patients may point to a common underlying patho-physiology. A study has been undertaken to determine which diagnoses are associated with the occurrence of hemorrhoids. A chart review of a random sample of 100 cases diagnosed as having hemorrhoids has been studied. 

The variety of diagnoses associated with hemorrhoids has been broken down into five large categories 
 

1.		Diseases associated with diarrhea.
2.		Spinal cord injuries.
3.		Constipation and related diseases.
4.		Various types of anorectal diseases.
5.		Conditions that could be considered manifestations or sequelae of the hemorrhoidal disease itself.

The types and spectrum of comorbid diagnoses associated with hemorrhoids suggested that an increased tone of the anal sphincter constitutes a common patho-physiologic mechanism for the development of hemorrhoids.

Types:
Hemorrhoids are differentiated by their anatomical origin in the anal canal. 
 

1.		Internal hemorrhoids develop above the dentate line (embryonic endoderm), are covered by anal mucosa (simple columnar epithelium) and lack sensory innervation.  Classification: They are classified by the degree of tissue, which prolapse into the anal canal:  Grade I hemorrhoids:  project into the anal canal but do not prolapse. They have minimal bleeding or may be asymptomatic. Grade II hemorrhoids: protrude beyond the anal verge with straining or defecating and reduce spontaneously when straining ceases.  Grade III hemorrhoids: protrude spontaneously or with straining and require manual reduction.  Grade IV hemorrhoids: chronically prolapse and if manually reduced, they fall out again. Others prolapse out of the anus and are irreducible (strangulated), creating a surgical emergency.
2.		External hemorrhoids arise below the dentate line (embryonic ectoderm) and are covered by stratified squamous epithelium with innervation by the inferior rectal nerve.
3.		Mixed hemorrhoids are confluent internal and external hemorrhoids.

Prolapsed hemorrhoids

The venous drainage of hemorrhoids is as follows: 

Internal hemorrhoids drain into the superior rectal vein, which drains into the portal system. 
External hemorrhoids drain into the inferior rectal vein, which drains into the inferior vena cava vein IVC. Anastamosis exists between all the three veins superior rectal, inferior rectal and inferior vena cava. 
Hemorrhoids are dilated arterio-venous complexes.

The Patho-physiology of hemorrhoids:
 

•		High sphincter pressures.
•		Venous stasis.
•		Local ischemia.
•		Activation of the endothelial cells.
•		Increased circulating endothelial autoantibodies.
•		increased anal tone

Anatomically, there are anal cushions within the submucosa of the anal canal which contain blood vessels (i.e., arterioles, venules, arteriolar-venous shunts), muscle and connective tissue. These vascular cushions, found at the anorectal junction, above the dentate line, are normal anatomy and present in adults, in children and even in the embryo. It is believed that the displacement of these cushions distally by loss of their supportive structure leads to hemorrhoids, which can prolapse, bleed or thrombose. 

In vitro data suggested that endothelium alteration is the key event in the development of the pathology found in varicose veins. In order to confirm this hypothesis, the number of circulating endothelial cells in the plasma of patients with chronic venous insufficiency was compared to control normal population. A twofold increase in the circulating endothelial cells has been found in chronic venous insufficiency. (3) The authors concluded that the main mechanism which account for the alterations observed in varicose veins is the activation of endothelial cells by ischemia occurring in the veins during blood stasis, and the cascade of reactions that follows. 

Many authors have studied the influence of the venous stasis, which favors the appearance of varicose veins. It has been found that activation of the endothelial cells was due to lowering of adenosine-triphosphate concentration as well as increase of intracell calcium concentration. The ensued numerous reactions lead to adherence and activation of blood neutrophils (a subtype of white blood cells) as well as to the proliferation of smooth muscular cells. All these elements allow the understanding of the appearance of a typical tissue of the varicose vein (4). 
Altered immune response leads to the formation of autoantibodies against the circulating endothelial cells. The interaction of immune component with the endothelium could constitute a mechanism determining hypertonia. The presence or absence of circulating anti-endothelial cells autoantibodies (AECAs) was determined in the serum of patients with anorectal diseases. The assay result was positive for AECAs in 12 patients, all with anorectal disease when compared to the control group (P = .001). The basal anal tone was higher in the AECA-positive patients than in the AECA-negative patients (P = .001). It has been concluded that only the patients with anal fissure or hemorrhoids were AECA positive. All healthy controls tested negative for AECA. Although the number of subjects studied is small, the presence of auto-antibodies directed against the endothelial cells in the serum of these patients supports the hypothesis that the endothelium is involved in the anal disease (5)

Frequency:
Race: The frequency of hemorrhoidal disease is increased among whites, higher socio-economic status and rural dwellers. 

Sex: The prevalence is equal between the sexes. 
Age: External hemorrhoids are more commonly seen in young and middle aged adults. The prevalence of hemorrhoidal disease increases with age until the seventh decade and then diminishes slightly. It also increases in pregnancy due to direct pressure on the hemorrhoidal veins. 

Risk factors:
Risk factors associated with dilated veins of the hemorrhoidal plexus and tight internal anal sphincter:
 

•		Pregnancy
•		Lack of erect posture
•		Familial tendency
•		Constipation
•		Diarrhea, especially in alcoholics
•		Colon malignancy
•		Hepatic disease
•		Portal hypertension
•		Occupations that require prolonged sitting
•		Obesity
•		Loss of muscle tone
•		Rectal surgery
•		Episiotomy
•		Anal intercourse

Complications:
 

•		Thrombosis
•		Secondary infection
•		Ulceration
•		Abscess
•		Anemia (rare)
•		Incontinence

Prognosis:
The recurrence rate is 10-50% over a five-year period. Usually, spontaneous resolution.
Investigations

Lab Studies:
Lab studies should include a CBC to check for infection and anemia. 

Imaging Studies:
Proctogram may be indicated if rectal prolapse exists. 

Procedures:
Proctoscope may be done if pathology is not seen with the anoscope. 
Sigmoidoscopy is indicated if cancer is the differential. 
Colonscopy is indicated if there is any abdominal symptom, weight loss or change in bowel habits or if the patient is over 50 years of age.

CONVENTIONAL TREATMENT OF HEMORRHOIDS

Treatment of external hemorrhoids:
Medical conservative therapy consisting of sitz baths, stool softeners, topical and systemic analgesics, proper anal hygiene and, in some cases, a short course of topical steroids cream, a high fiber diet and adequate fluid intake. Surgical removal of the hemorrhoid is indicated if bleeding or chronic symptoms persist.

Treatment of internal hemorrhoids (6)
Internal hemorrhoids are treated according to their classification. If the patient has minor symptoms (Grade 1) and has a reducible mass, the conservative treatment (as in external hemorrhoids), avoiding NSAIDs and spicy or fatty foods, is recommended.

Non-Surgical Techniques:
 

•		Rubber Banding:  It is used for Grade II and III hemorrhoids. It is the standard by which other methods are compared. A band ligature is passed through an anoscope and placed on the rectal mucosa above the dentate line. The tissue eventually sloughs off in about a week and leaves an ulcer that will become fibrotic.
•		Infrared Coagulation:  Best for Grade I, II and some III. The light energy coagulates the hemorrhoid tissue. It is as effective as banding and complications are less severe and fewer.
•		Bipolar Electrocoagulation:  This is best for higher-grade hemorrhoids and it is quick with coagulation leaving a white scar.
•		Sclerotherapy:  It is used if banding is not possible or if bleeding is a problem. The drawbacks are greater incidence of a poor outcome, the possibility of anaphylaxis, sepsis and ulceration.
•		Laser Therapy:  It is expensive and has no advantage over other methods. The operator must control the laser to avoid bleeding.

There are contraindications to the above mentioned treatments, including: 
 

1.		AIDS
2.		Immunodeficiency disorders
3.		Blood clotting disorders
4.		Irritable bowel disease
5.		Pregnancy
6.		Immediate post-partum period
7.		Rectal wall prolapse
8.		Large anorectal fissure or infection
9.		Tumor

Surgical removal of hemorrhoids: It is now reserved for only the most bothersome hemorrhoids that continue to recur after repeated in-office treatments. The operation, which involves the surgical excision of the hemorrhoid and an adjacent portion of the skin, must be performed in the hospital under anesthesia. The operation used to involve a several day hospital stay, but now it is outpatient surgery. It is usually the treatment for severe Grade III, IV or strangulated hemorrhoids. The complication is anal stenosis (anal narrowing). 

Conventional Medications
 

•		Stool Softeners: To avoid straining and constipation
•		Nitroglycerin Ointment: To decrease sphincter spasm and, possibly, relieve pain
•		Topical Anesthetic: 5% lidocaine ointment
•		Systemic Analgesia: Extra-strength Tylenol for relief of pain

Anal Fissure
Anal fissure is a common anorectal disorder. It is a small tear in the anal skin just at or inside the anal verge typically causes symptoms of severe pain after defecation and bright red rectal bleeding. Anal fissures are easy to diagnose by taking a history and performing an appropriate physical examination, visualizing a sentinel skin tag and everting the anal canal by opposing traction of the patient's buttocks. Instrumentation generally produces sever discomfort and should be deferred until the fissure has healed.

Anal fissures are highly likely to occur in the midline, particularly posteriorly. Fissures off the midline raise the question of an underlying disorder, such as Crohn's disease, anal carcinoma, human Immunodeficiency virus infection, or syphilis (7). 

Patho-physiology of anal fissure:
Although typical fissures are commonly described as idiopathic, current evidence suggests that they are caused by:
 

1.		High sphincter pressures.
2.		Secondary local ischemia.
3.		Activation of the endothelial cells.
4.		Increase of the circulating endothelial autoantibodies.
5.		Increased anal tone.

There is a relative deficiency of blood vessels in the posterior commissure of the anal canal of most people (8). 
Anodermal perfusion is particularly low at the base of fissure (9). This explains the common occurrence of anal fissure in the midline, particularly posteriorly.

The anal-sphincter mechanism comprises:
 

•		The internal anal sphincter.
•		The smooth-muscle termination of the rectal circular muscle layer that provides most of the anal canal's resting tone.
•		The external anal sphincter, a striated muscle under voluntary control.

Patients with anal fissure typically have high resting anal pressures and infrequent spontaneous relaxation of the internal anal sphincter (10). Because the anodermal blood supply passes through the internal anal sphincter, these high pressures can impede blood flow with secondary ischemia. 

Circulating anti-endothelial cell auto-antibodies (AECAs):
It has been hypothesized that at the perianal level the interaction of immune component with endothelium could constitute a mechanism determining ischemia and hypertonia. The presence or absence of circulating anti-endothelial cells autoantibodies (AECAs) was determined in the serum of patients with anal fissure. The assay result was positive for AECAs in 12 patients, all with anorectal disease when compared to the control group (P = .001). The basal anal tone was higher in the AECA-positive patients than in the AECA-negative patients (P = .001). It has been concluded that only the patients with anal fissure or hemorrhoids were AECA positive. All healthy controls tested negative for AECA. Although the number of subjects studied is small, the presence of auto-antibodies directed against the endothelial cells in the serum of these patients supports the hypothesis that the endothelium is involved in the anal disease (11). 

Conventional Treatment of anal fissures
For many years treatment of anal fissure has focused on alleviating sphincter hypertonia. 
Most patients with a newly diagnosed anal fissure should have an initial trial of conservative therapy, and the majority of patients with acute fissures heal with such treatment alone. For patients for whom medical treatment fails or for those who simply hurt too much to wait for its success, lateral internal sphincterotomy (wedge excision of the internal sphincter to relieve the increased anal tone) is usually the next step. 

Conservative therapy:
Consisting of sitz baths, topical anesthetics, and the use of bulking supplements, aims to alleviate pain and dilate the sphincter with large, soft stools. 

Operative therapy decreases sphincter pressures either by forceful dilation (increasingly of historical interest only) or, now far more commonly, by lateral internal sphincterotomy. Although this technique is a simple and effective outpatient surgical procedure performed under local anesthesia, its fundamental drawback is its potential to cause minor but sometimes permanent alterations in the control of gas, mucus, and occasionally stool (12,13). 

Pharmacological treatment: is used to create a temporary or reversible "sphincterotomy," one that would lower sphincter pressures only until the fissure had healed. Some investigators hypothesized that relaxation of the internal anal sphincter is mediated by the neurotransmitter nitric oxide (14). 

Various topical organic nitrate preparations have been used to induce internal-anal-sphincter relaxation in-patients with chronic fissures. (15). The maximal resting anal pressure decreased and anodermal blood flow increased in the treatment group but not in the placebo group. Fissures recurred in 8 percent of the successfully treated patients, but all the fissures healed with a second course of treatment. Other investigators reported similar results in an uncontrolled series of 34 patients with chronic fissure treated with topical nitrate. 

One clinical problem with topical nitrate therapy is a substantial incidence of headache, particularly at higher drug concentration (16). A second potential difficulty is the development of drug tolerance, a problem well documented with nitrate therapy for cardiovascular disease and now also reported during treatment for anal fissure (17). 

Botulinum toxin:
The other pharmacological approach to anal fissure involves the use of Botulinum toxin. Once again, the aim is to decrease the resting anal pressure, in this case by preventing the release of acetylcholine from presynaptic nerve terminals. More famous as a lethal poison, Botulinum toxin has found its way into the therapy of a number of skeletal-muscle disorders, including strabismus, blepharospasm, and spasmodic torticollis. A report of the results of a double blind, placebo-controlled study of Botulinum toxin in 30 patients with chronic anal fissure showed a convincing therapeutic effect. After two months, 87 percent of the treated patients had symptomatic relief and 73 percent were healed, as compared with 27 percent and 13 percent, respectively, of the controls. Resting anal pressure decreased significantly in the treated patients but not in the controls. (18). However, this needs more studies to estimate the proper dosing essential for relieving the resting anal pressure and any possible side effects.

Other less common anorectal diseases
Anorectal abscesses are categorized into four types: perianal, ischiorectal, intersphincteric, and supralevator. Most are idiopathic and contain mixed aerobic-anaerobic pathogens. 

Fistula formation varies from 25% to 50% and is much more common with gut-derived organisms (e.g., E. coli). Definitive treatment for an anorectal abscess is timely surgical incision and drainage to prevent more serious complications (e.g., serious infection, and extension of the abscess). 

Anal carcinomas are infrequent, the majority of them being squamous cell or epidermoid carcinomas. The emergency physician must maintain a high index of suspicion and obtain a biopsy of suspicious lesions in order not to miss the diagnosis of a cancer. The most common presenting complaint of anal tumors is rectal bleeding. Combination chemotherapy and radiotherapy have shown promising results in the treatment of anal canal tumors.

Bacterial, viral and protozoal infections can be transmitted to the anorectum via anoreceptive intercourse. Such infections must be considered when a patient presents with rectal pain or discharge, tenesmus, or rectal or perineal ulcers. Proctosigmoidoscopy and rectal cultures may be necessary to determine the cause. 

Rectal complications of HIV infection include infectious diarrhea, acyclovir-resistant strains of HSV2, Kaposi's sarcoma, lymphoma, and squamous cell carcinoma. 

Rectal injuries may result from penetrating or blunt trauma, or foreign bodies. Rectal injury should be suspected when a patient presents with low abdominal, pelvic, or perineal pain or blood per rectum after sustaining trauma or undergoing an endoscopic or surgical procedure.

PhytoMe Hemorrhoid Cream
A New Herbal Remedy for Treating the Most Common Anorectal Disorders (hemorrhoids and anal fissures)

The Goal of the herbal remedy is:
 

•		Exhibits Fast analgesic effect.
•		Modulates the altered hemorrhoidal venous plexus through phelebotonic action that leads to vasoconstriction mainly of the venous tributaries of the varicose veins of the hemorrhoids, not the large veins.
•		Reduces the anxiety and the mild depression that is usually associated with pain with secondary decrease of the internal anal sphincter tone.
•		Improves the blood supply of the anorectal part of the digestive canal, relieves the ischemia.
•		Modulates the immune system and thus decreases the circulating anti-endothelial autoantibodies which leads to vicious circle of increased anal tone and ischemia.
•		Reduces the inflammation and edema of the hemorrhoidal tissue and adjacent anorectal tissue.
•		Helps fast healing of anal fissure, and any other wound that might be caused by a foreign body.

HERBAL INGREDIENTS FOR TREATING HEMORRHOIDS
Europe has a very long tradition in phytomedicines. Today, almost 40% of all drugs listed in the German Physicians Desk Reference are derived from plant material. Fifty percent of the world sales of herbal remedies occur in Europe with a retail sales volume of over $6 billion. In several countries such as Germany and France health insurance companies cover the reimbursement of several herbal drugs. Within Europe, Germany is the leading country for herbal drugs and establishment of monograph of all medicinal herbal ingredients. The annual sales is about $2.5 billion and per capita spending of $37 on phytomedicines, followed by France, Italy, the United Kingdom, Spain, the Netherlands, and Belgium. The phytomedicines industry is in the process of concentration allover the world (19).

Ruscus aculeatus
Function:
Venotropic property (greater on varicose tributaries than on the main veins):

A literature review of 24 pharmacological studies has revealed the fundamental properties of venotonic remedies containing Ruscus extract as venoconstrictor agent (20). Experimental studies showed that Ruscus aculeatus extract caused concentration dependent vasoconstriction which were greater in varicose tributaries than in main veins. Its main contraction effect on the varicose vein tributaries explains its rational use in the treatment of varicose veins and hemorrhoids. In -vitro studies showed that contractions were similar in rings of detached veins with and without endothelium. It has been postulated that the contraction response to Ruscus extract is independent of the endothelium and mediated by activation of adrenergic receptors and not endothelin-A (a vasoconstrictive substance secreted by the endothelium) on the smooth muscle. This endothelium independent action explains its beneficial effect on varicose veins in which there is endothelial ischemia with secondary endothelin-A deficiency (21). 

Protective action on the endothelium against hypoxia:

Also it has been found to offer good protection of the endothelial cells against hypoxia, one of the first stages of vascular disease associated with venous stasis and this explains further its beneficial effect in the treatment of hemorrhoids. Ruscus aculeatus extract has been tested for its toxic effect and has been found to be the least toxic of many tested phelebotonic drugs (22). 

The protective action on the endothelium against hypoxia is due to the stimulation of mitochondrial enzymes and inhibition of endothelial leukocyte adhesions. The results obtained support the benefits to be expected in the control of chronic venous insufficiency, a multi-faceted pathology involving various vascular compartments of the return flow circulatory system. Experiments studies showed Ruscus aculeatus dose dependent protection against hypoxia of the endothelial cells (23). 

Clinical trial on the efficacy of Ruscus aculeatus extract in the treatment of acute haemorrhoidal crisis was tested on 124 patients. The investigated symptoms were painful symptoms (discomfort, heaviness, burning, pruritis, tenesmus), accompanying symptoms (rectal bleeding, altered intestinal, abdominal pains), local signs (prolapse, congestive state, inflammation). The results have proved that Ruscus aculeatus extract has therapeutic benefits in the treatment of acute hemorrhoids as it decreases the overall severity score of the symptoms including the painful and accompanying symptoms. Ruscus aculeatus extract has been found to be well tolerated by all the tested patients (24). 

Prophylactic effect against secondary infection :

The ethanolic extract of Ruscus aculeatus together with other plant species used in folk medicine were investigated for its antimicrobial activity against five bacterial species including staphylococcus aureus and escherichia coli (25). These two types of bacteria could cause secondary infection of anal fissure and lead to the common complication of anal fissure: anorectal abscess and fistula. This antimicrobial effect explains the beneficial effect of Ruscus aculeatus extract as prophylactic agent against secondary infection of the anal fissure, which could lead to anorectal abscess. 

Aesculus hippocastanum (horse chestnut tree)
Function
Correct phlebopathological conditions:

Seeds and bark Aesculus hippocastanum seeds (horse chestnut tree) have been widely used in European traditional medicine since 16 th century. Acylated triterpene oligoglycosides, escins IIIb, IV, V, and VI and isoescins Ia, Ib, IIa, and IIb and V, are isolated from the seeds of horse chestnut tree (26,27). 
Nowadays the Aesculus hippocastanum seed extract is widely employed in clinical practice mainly for the treatment of chronic venous insufficiency. 

Studies showed that topical drug preparations containing the extract of Aesculus hippocastanum are beneficial in the topical treatment of phlebopathological conditions. The main active component of that extract, escin, is a mixture of triterpene saponin (28). 

A systemic review with computerized literature search was performed to assess the evidence for or against Aesculus hippocastanum seeds as a symptomatic treatment of varicose veins. Double blind randomized controlled trials for patients with varicose veins were included. The obtained data imply that its seed extract is superior to placebo and as effective as reference medications in alleviating the objective signs and subjective symptoms of chronic venous insufficiency. It has been postulated that Aesculus hippocastanum extract could represent a treatment option for chronic venous insufficiency (29).

Reduces the inflammation and edema

Due to the effect on capillary permeability, Horse Chestnut extract reduces the cellulitis that usually accompanies the inflammatory process (30). Experimental studies showed that active ingredients in Aesculus hippocastanum, inhibited the acute inflammation and edema induced in animals. With regard to the relationship between their chemical structures and activities, the acyl groups in escins were essential (31).

Calendula Officinalis
Function
Hemostatic, Anti-inflammatory and anti-oedematous properties:

For many years Calendula extract has been included in many aerosol formulations, to act as medicated aerosol dressing due to its hemostatic property (32). 

The healing properties of Calendula Officinalis are well known for long time. In order to establish a pharmacological rationale for the traditional use of these plants as anti-inflammatory remedy, ethanol extract of Calendula was tested on patients with varicose ulcers and different skin lesions. The data obtained in those studies suggested that the treatment with Calendula is effective in the process that brings wounds to close and thus it has provided the basis to an alternative treatment of varicose ulcer (33). Experimental studies showed that the best wound healing effect was kept by the Calendula extract when compared to other types of medicinal herbs used for wound healing. Wound healing period was shorter than that of the eyewitness. It has been well received by the tissues, without irritation, its action being primarily local rather than general, as was noticed from the paraclinic exams (34). 

Other animal experimental studies have been made to confirm the healing effect of Calendula extract containing ointment. Multiple open wounds were created experimentally on each side of the vertebral column of 12 buffalo calves. The wounds on one side were treated with Calendula Officinalis ointment while those on the other side were kept as control and treated with normal saline. The wound healing was evaluated clinically and by microscopic examination of biopsy specimens. On the basis of these observations it was revealed these dressing materials containing Calendula extract enhanced the tissue repair effectively (35). 

Controlled study of the degree of tolerability of ointments containing Calendula extract has lead to the conclusion that Calendula extract is significantly better tolerated than other types of ointment used for wound healing (36). 

The triterpenoids were shown to be the most important anti-inflammatory principles of the extract of Calendula flowers. Among them, the Faradiol monoester appears to be the most relevant principle for the activity of the drug, due to its quantitative prevalence. The anti-inflammatory activity of different extracts is proportional to their content of Faradiol monoester, which is a suitable parameter for the quality control of Calendula preparations (37). Faradiol esters also showed dose dependent anti-oedematous activity as it reduced the edema induced in experimental animals (38). 

Analgesic effects:

Calendula extract has been also tested for its analgesic effects. It has been found to have significant analgesia, pain threshold increased by 58.9 and 62.1% of that of control rats, which was comparable to analgin-induced analgesia (39). 

Hamamelis virginiana
Function
Anti-inflammatory and antiphlogistic property:

Studies provided evidence for an anti-inflammatory action of lotions containing Hamamelis which was significantly higher than most of the other anti-inflammatory lotions (40). The Oligomeric to polymeric proanthocyanidins fractions of Hamamelis virginiana bark extract, were found to exhibit significant antiphlogistic effect and reduces the edema induced in animals (41,42). 

Ginkgo biloba
Phytomedicines based on extracts from the leaves of Ginkgo biloba are used in Germany and in France a rather long time for the treatment of peripheral vascular insufficiency (43). 
Function
Protective effect on the endothelium against hypoxia secondary to venous stasis (best protection with least concentration:

A study was performed to evaluate the effects of Ginkgo biloba extract, as a phelebotonic drug, on neutrophil adherence to the endothelium under hypoxic conditions. It has been found that Ginkgo biloba extract prevented the activation of the endothelium which is the first step of the activation cascade, and it blocks subsequent increase in neutrophil adherence as well as neutrophil activation which explains its beneficial effect as a phelebotonic agent (44). 

Experimental studies have been performed to compare the effectiveness of different phlebotonics in protecting endothelial cells against hypoxia, one of the first stages of vascular disease associated with venous stasis. It has been found that Ginkgo biloba offered the best protection at lowest concentration (45). 

The protective effect of the phelebotonic drug, Ginkgo biloba extract was tested by a randomized double blind, placebo-controlled clinical trial. In the active-treatment group, the mean values of the circulating endothelial cells count decreased by 14.5% after a 4-week treatment, whereas in the placebo group, the decrease was less 8.45. These results confirm the important role of the endothelium alterations in the development of varicose veins and suggested the beneficial action of the phlebotonic drug on the venous wall (46). 

Reduces proliferative tissue activity of the haemorrhoidal plexus(reduces the size of the hemorrhoids:

Studies have been performed to know how venous stasis favors the appearance of varicose veins. It has been found that activation of the endothelial cells was due to lowering of adenosine-triphosphate concentration as well as increase of intracell calcium concentration. The ensued numerous reactions lead to adherence and activation of blood neutrophils (a subtype of white blood cells) as well as to the proliferation of smooth muscular cells. All these elements allow the understanding of the appearance of a typical tissue of the varicose vein. Studies showed that Ginkgo biloba-based drugs showed a protective effect of this drug on the whole process (47). 

Hawthorn -crataegus
Hawthorn is among the leading plants prescribed as mono-preparations in Europe, which has the most developed market in the world in the area of phytomedicines (48). 
Function
Antioxidants activity; Protects the tissues against cell damage and cancer cell formation:

Studies showed that extracts of ginkgo biloba and hawthorn leaves have very high inhibitory action on oxygen free radicals. This antioxidant property of the extract protects the tissues against cell damage and cancer cell formation (49) Experimental studies showed that Hawthorn extract exhibit in vitro antioxidant activity, the most efficient being fresh young leaves, fresh floral buds and pharmaceutical dried flowers. The activities seem to be especially bound to the total phenolic proanthocyanidin and flavonoid contents (50) which has phelebotonic activity:
Hawthorn has been used since long time for medicinal purposes. It is effective and safe therapeutic agent with no adverse effect. Recent researches showed that it has the ability to reduce the venous congestion and stasis due to its phelebotonic effect (51). 

Mild sedative and tranquilizer

Crataegus has mild sedative effect and helps to relieve the anxiety usually associated with pain (52). 
The technology of manufacturing thorn preparations is improved by optimizing the concentration of an extractant, by reducing the size of raw material particles and by elevating the temperature of extraction (53). 

LINDEN (Tilia)
Function
Mild sedative and tranquilizer

Tilia species are traditional medicinal plants widely used in Latin America as sedatives and tranquilizers. It has clear anxiolytic effect. Validated pharmacological tests, to measure its anxiolytic and sedative effect has been used in experimental animals and the results obtained confirmed its ethnopharmacological use as an anxiolytic agent (54). 

Roman Chamomile
Function
Antibacterial activity:

Experimental studies showed that the ethanol extract of blossoms of Roman Chamomile has medium antibacterial activity (55). 

Wound healing

Double-blind trial, on the therapeutic efficacy of Chamomile extract was tested on 14 wounded patients. The period of the healing and drying of wound were judged by the doctors. The decrease of the weeping wound area as well as the drying tendency was statistically significant. (56) 

Antiphlogistic activity

It has antiphlogistic activity. Chamomile extracts has been tested for its in vivo skin penetration. It was concluded that it is not only adsorbed at the skin surface, but penetrate into deeper skin layers, this is important for its topical use as antiphlogistic agent (57). 

Evening Primrose oil
Function
Anti-inflammatory effect:

Experimental and clinical studies showed that Evening primrose oil exhibited a significant increase in plasma dihomo-gamma-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E2 and leukotriene B4). Thus the GLA- rich Evening primrose oil help shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n-6 essential fatty acids (58). 

Soothing and moisturizing effect:

Evening primrose oil has a soothing, strong moisturizing effect by stabilizing tissue hydration as it stops water loss (59). The moisturizing effect of Evening primrose oil soothes the inflamed skin and mucous membrane in the area close to the anorectal diseases. It helps prophylaxis against anal fissures.

Hypericum perforatum L
Wound healing:

Hypericum perforatum extract is known since ancient times as medical plant. It has many activities including wound healing. Increasing application continuously makes cultivation under controlled conditions of Hypericum perforatum L. more important. Most active extract is a methanolic extract derived from non-fertilized, broadleaved plant (60) 

Modulate the immune system and inhibit the formation of endothelial autoantibodies:

Hypericum perforatum L modulate the immune system (61). This function helps decreasing the formation of autoantibodies against the circulating endothelial cells, which is one of the important pathogenic factors in hemorrhoids.

Mild sedative:

The Hypericum perforatum extract containing preparations helps relieving the slight depression usually associated with bothersome long -standing pain of flared up hemorrhoids and in the same time it has an encouraging safety profile (62). 

Antibacterial activity:

Hypericum perforatum was the most active of 15 tested plant extract, known of antistphylococcal activities against many virulent strains of staph. Aureus. (63,64)

Reference 
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