REGULATORY CONTROLS ON HERBAL MEDICINES IN EUROPE

THE USE OF HERBAL MEDICINE IN EUROPE


Herbal products are available in all Member States of the European Union (EU), although the relative size of their markets varies between countries. Since the late 1980s, the regulation of herbal products has been a major issue within the EU because of the differences between Member States in the way herbal products are classified and the difficulties this might present in the completion of the single market for pharmaceuticals.

According to Council Directive 2001/83/EEC, as amended, a medicinal product is defined as 'any substance or combination of substances presented as having properties for treating or preventing disease in human beings or any substance or combination of substances which may be administered to human beings with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a diagnosis.'(31)

Herbal products are considered as medicinal products if they fall within the definition of the Directive. However, the legal classification is complicated by the fact that in most Member States herbal products are available both as medicinal products with therapeutic claims and also as food/dietary supplements without medicinal claims.

The situation is further complicated in that some Member States, including the UK (see Current regulatory position of herbal products in the UK), have national provisions which permit certain herbal medicinal products to be exempt from the licensing provisions under specific conditions. In general, in all Member States, herbal products are classified as medicinal products if they claim therapeutic or prophylactic indications.

The advent of the new pan-European marketing authorisation system in 1993 raised questions with regard to herbal products and, in particular, concerns that major differences in their classification/assessment would hinder free circulation within the EU. The new systems for marketing authorisations involve three procedures: centralised, decentralised (mutual recognition) and national.

The centralised procedure is mandatory for biotechnology products and since November 2005 was mandatory for orphan medicinal products and any medicinal product for human use containing new active substances (i.e. one not previously authorised in the Community) for the treatment of AIDS, cancer, neuro-degenerative disease and diabetes.

The decentralised procedure or mutual recognition system involves agreement of assessment between the Member States involved; this procedure became compulsory from January 1998, for products requesting authorisation in more than one Member State. Since then, simultaneous national applications have been
possible, but the mutual recognition system automatically becomes involved once an authorisation has been granted in the first Member State.

The original intention was to retain existing national procedures for medicinal products requesting authorisation in a single Member State only. However, the European Commission agreed that national procedures could continue for bibliographic applications, including those for herbal products until the harmonisation issues could be resolved.

In 1997, upon the initiative of the European Parliament, the European Commission and the (then) European Medicines Evaluation Agency (EMEA), now European Medicines Agency, an ad hoc Working Group on Herbal Medicinal Products (HMPWG) was established at the EMEA. The main thrust of the HMPWG was the protection of public health by preparing guidance to help facilitate mutual recognition of marketing authorisations in the field of herbal medicines, and to minimise CHMP (Committee on Human Medicinal Products) formerly the Committee on Proprietary Medicinal Products (CPMP) arbitrations.

A major study undertaken by the AESGP (Association of the European Self-medication Industry) in 1998 at the request of the European Commission confirmed the different approaches taken by Member States in the regulation of herbal medicinal products. Different traditions in the therapeutic use of herbal preparations, coupled with different national approaches to their assessment, have resulted in differences in the availability of some herbal medicines.

For example, ginkgo (Ginkgo biloba) is available as a prescription-only medicine in some EU countries, but as a food supplement in others. Similarly, St John's wort (Hypericum perforatum) is accepted as a treatment for depression in some Member States, but not in others.

The AESGP study revealed that, in general, herbal medicinal products were either fully licensed with efficacy proven by clinical trials or by bibliography (in accordance with Article 10.1 a (i) of Council Directive 2001/83/EC), or that herbal products had a more or less simplified proof of efficacy, according to their national use. Furthermore, the study found major discrepancies between Member States in the classification of individual herbal preparations and products into one of these categories, as well as in the requirements for obtaining a marketing authorisation (product licence).

The report highlighted the need for clarification of the regulatory framework and harmonisation of the regulatory requirements to ensure that herbal medicinal products could have access to the single market for pharmaceuticals.

An important initiative in the harmonisation process has been the formation of the European Scientific Cooperative on Phytotherapy (ESCOP), an organisation representing national associations for phytotherapy. ESCOP was founded in 1989 by six EU national scientific associations with the objective of establishing
a scientific umbrella organisation to provide harmonised criteria for the assessment of herbal medicinal products, to support scientific research and contribute to the acceptance of phytotherapy in Europe.

ESCOP now comprises 13 national associations across Europe, and the American Botanical Council. The ESCOP Scientific Committee has published 80 monographs for individual herbal drugs; the monographs follow the European Summary of Product Characteristics (SPC) format.

The EMEA Herbal Medicinal Products Working Party (HMPWP) formerly used the ESCOP monographs as a basis for its work in developing core SPCs from ESCOP monographs. The HMPWP has now been superseded by the Herbal Medicinal Products Committee (HMPC) as discussed below and the collaboration with ESCOP continues in accordance with the new EU regulations.


If symptoms persists consult you doctors!

HERBAL MEDICINES AND PHYTOTHERAPY BASICS AND TUTORIALS

PHYTOTHERAPY AND HERBAL MEDICINES BASIC INFORMATION


Herbal medicines are also referred to as herbal remedies, herbal products, herbal medicinal products, phytomedicines, phytotherapeutic agents and phytopharmaceuticals. The use of herbal medicines in an evidence- or science-based approach for the treatment and prevention of disease is known as (rational) phytotherapy.

This approach to the use of herbal medicines contrasts with traditional medical herbalism which uses herbal
medicines in a holistic manner and mainly on the basis of their empirical and traditional uses. Although these two approaches – traditional/holistic and rational/evidence-based – are entirely different, in some instances they use the same terminology.

For example, traditional herbalism is also described as 'phytotherapy' and refers to preparations of plant material as 'herbal medicines'. Today, a continuum between these approaches exists and many
herbalists also use scientific evidence to support their traditional use of herbal medicines.

Plants have been used medicinally for thousands of years by cultures all over the world. According to the World Health Organization, 80% of the world's population uses plant-based remedies as their primary form of healthcare;(30) in some countries, herbal medicines are still a central part of the medical system, such as Ayurvedic medicine in India and traditional Chinese medicine in China.

Herbal medicine has a long history and tradition in Europe. Herbal medicines and homeopathic remedies are often mistaken by the layperson to be similar. However, homeopathy is based on the principle of 'like should be treated by like', and involves the administration of minute doses of remedies that, in larger doses, produce symptoms in a healthy person mimicking those expressed by people who are ill.

Many, but not all, homeopathic remedies originate from plants. By contrast, herbal medicine (phytotherapy) involves the use of dried plant material or extracts of plant parts in therapeutic doses to treat the symptoms exhibited. In this latter respect, it is similar to conventional medicine.


If symptoms persists consult you doctors!

HERBAL MEDICINES BASICS AND TUTORIALS

HERBAL MEDICINE BASIC INFORMATION
What Are Herbal Medicines?

Herbal medicines are increasingly popular among the general public, particularly women of childbearing age. These medicines are not only viewed as having clinical benefits but are also generally believed to be safe. In some cases, a systematic review of the evidence-based medicine literature shows that this is not the case.

In pregnancy, soon-to-be mothers are concerned about all medications that may affect their health, the health of their fetus, and the pregnancy outcome. When it comes to the types of evidence for herbal medicines during pregnancy and lactation, not all evidence is created equally.

The type of evidence for the safety of herbal medicines during pregnancy and lactation ranges from theoretical to animal studies, to case reports, to cohort studies and finally to randomized controlled trials.

Herbs that are frequently used during pregnancy, e.g. black and blue cohosh, red raspberry, evening primrose oil

Herbs that are used to treat pregnancy-related complaints, e.g. ginger

Herbs that are known abortifacients, e.g. pennyroyal, parsley

Herbs that have narrow therapeutic indices and are toxic, e.g. digitalis, deadly nightshade, ephedra

Herbs that are used more often by women than men, e.g. red clover, don quai

Herbs that are known to have hormonal effects, e.g. chastetree

The most frequently used herbs, e.g. St. John’s wort (depression), garlic (hyperlipidemia), ginkgo (memory), Echinacea (immune system)

If symptoms persists consult you doctors!

PHARMACOGNOSY – THE SCIENCE OF NATURAL SOURCE MEDICINES

WHAT IS PHARMACOGNOSY?
PHARMACOGNOSY Info

The study of medicinal plants and their properties is called pharmacognosy. This science has led to the development of many drugs in use today including aspirin (the basic salicylate structure was discovered from the white willow while aspirin was synthesized from meadowsweet), opioids (originally from opium poppies), the birth control pill (synthesized from steroid structures found in a wild Mexican yam), and chemotherapeutic agents like vincristine and vinblastine (from Madagascar periwinkle) or taxol (from the Pacific yew tree).

Today, herbal medicine is big business. However, there is much confusion about what herbal medicine is and is not. While pharmacognosy is a science that deals with the discovery of medicines from natural substances, it is certainly not the same as herbalism.

According to the American Society of Pharmacognosy, its scope includes ‘the study of the physical, chemical, biochemical and biological properties of drugs, drug substances, or potential drugs or drug

substances of natural origin as well as the search for new drugs from natural sources. Research problems in pharmacognosy include studies in the areas of phytochemistry, microbial chemistry, biosynthesis, biotransformation, chemotaxonomy, and other biological and chemical sciences’.

The term herbalism refers to a folk and traditional medicinal practice based on the use of plants and plant extracts. In essence, herbalism is the practice of herb-based care and pharmacognosy is the scientific study of herbs with medicinal purposes. Within the practice of herbalism there are a variety of different traditions including, for example, traditional Chinese medicine or the Indian ayurvedic medicine.

Each of these has a unique paradigm on health, illness, and disease. Unlike pharmacognosists, herbalists are not particularly interested in specific active constituents found within a plant. Instead, they focus on the healing properties of the plant or part of plant (seed, root, leaf, etc.) and how it will benefit the body to heal itself.

Although non-herbalists may also use herbal medicines in their clinical practice, they likely do so under a different health paradigm. Homeopaths also have a holistic approach to health, but their material medica uses a ‘like cures like’ philosophy of treating patients with ultra-dilute formulations unlikely to contain significant (if any) ‘active’ ingredient.

Homeopathy, then, is unlike herbal medicine, herbalism, or pharmacognosy.  The current trend in natural product use follows many different health paradigms – some are popular because of their use in traditional Chinese medicine or Ayurveda, some from the widespread use of herbal medicine in Europe, and some due to increasing published studies on natural medicines, somewhat representative of the renewed interest in pharmacognosy.

So, irrespective of the particular health paradigm from which the natural health products summarized in this text are derived, we will adopt the pharmacology perspective (or perhaps in this case, pharmacognosy would be the more accurate term). As such, individual constituents (chemical entities) of each natural product are discussed with regard to their pharmacologic or toxicologic properties.

If symptoms persists consult you doctors!

BERIBERI DISEASE: SYMPTONS, DIAGNOSIS, TREATMENT

What is a Beriberi Disease?

Thiamine deficiency, or beriberi, refers to the lack of thiamine pyrophosphate, the active form of the vitamin known as thiamine (also spelled thiamin), or vitamin B-1. Thiamine pyrophosphate, the biologically active form of thiamine, acts as a coenzyme in carbohydrate metabolism through the decarboxylation of alpha ketoacids; it also takes part in the formation of glucose by acting as a coenzyme for the transketolase in the pentose monophosphate pathway. Persons may become deficient in thiamine either by not ingesting enough vitamin B-1 through the diet or by excess use, which may occur in hyperthyroidism, pregnancy, lactation, or fever. Prolonged diarrhea may impair the body's ability to absorb vitamin B-1, and severe liver disease impairs its use.


Thiamine is a water-soluble vitamin that is absorbed in the jejunum by 2 processes. When the thiamine level in the small intestines is low, an active transport portal is responsible for absorption. When the thiamine concentration is high, a passive mucosal process takes place. Up to 5 mg of thiamine is absorbed through the small intestines. The small intestine is where phosphorylation of thiamine takes place.



The body cannot produce thiamine and can only store up to 30 mg of thiamine in its tissues. Thiamine is mostly concentrated in the skeletal muscles. Other organs that it is found in are the brain, heart, liver, and kidneys. The half-life of thiamine is 9-18 days. It is excreted by the kidney.



Causes
There are two major types of beriberi:


Wet beriberi affects the cardiovascular system.


Dry beriberi and Wernicke-Korsakoff syndrome affect the nervous system.


Beriberi is rare in the United States because most foods are now vitamin-enriched. If you eat a normal, healthy diet you should get enough thiamine. Today, beriberi occurs mostly in patients who abuse alcohol. 


Drinking heavily can lead to poor nutrition, and excess alcohol makes it harder for the body to absorb and store thiamine.


A rare condition known as genetic beriberi is inherited (passed down through families). People with genetic beriberi lose the ability to absorb thiamine from foods. This can happen slowly over time and symptoms occur when the person is an adult. However, because doctors may not consider beriberi in non-alcoholics, this diagnosis is often missed.


Beriberi can occur in breast-fed infants when the mother's body is lacking in thiamine. The condition can also affect infants who are fed unusual formulas that don't have enough thiamine.
Getting dialysis and taking high doses of diuretics raise your risk of beriberi.

Symptoms

Symptoms of dry beriberi include:

• Difficulty walking
• Loss of feeling (sensation) in hands and feet
• Loss of muscle function or paralysis of the lower legs
• Mental confusion/speech difficulties
• Pain
• Strange eye movements (nystagmus)
• Tingling
• Vomiting

Symptoms of wet beriberi include:

• Awakening at night short of breath
• Increased heart rate
• Shortness of breath with activity
• Swelling of the lower legs

Exams and Tests

A physical examination may show signs of congestive heart failure, including:

• Difficulty breathing with neck veins that stick out
• Enlarged heart
• Fluid in the lungs
• Rapid heartbeat
• Swelling in both lower legs

A person with late-stage beriberi may be confused or have memory loss and delusions. The person may be less able to sense vibrations.

A neurological exam may show signs of:

• Changes in the walk
• Coordination problems
• Decreased reflexes
• Drooping of the eyelids

The following tests may be done:

• Blood tests to measure the amount of thiamine in the blood
• Urine tests to see if thiamine is passing through the urine

Treatment

The goal of treatment is to replace the thiamine your body is lacking. This is done with thiamine supplements. Thiamine supplements are given through a shot (injection) or taken by mouth.

Other types of vitamins may also be recommended.

Blood tests may be done after you are given thiamine supplements to see how well you are responding to the medicine.

Outlook (Prognosis)

Untreated, beriberi is often deadly. With treatment, symptoms usually improve quickly.

Heart damage is usually reversible, and a full recovery is expected. However, if acute heart failure has already occurred, the outlook is poor.

Nervous system damage is also reversible, if caught early. If it is not caught early, some symptoms (such as memory loss) may remain even with treatment.

If a patient with Wernicke's encephalopathy receives thiamine replacement, language problems, unusual eye movements, and walking difficulties may go away. However, Korsakoff syndrome (or Korsakoff psychosis) tends to develop as Wernicke's symptoms go away.

Possible Complications

• Coma
• Congestive heart failure
• Death
• Psychosis

When to Contact a Medical Professional

Beriberi is extremely rare in the United States. However, if you feel your family's diet is inadequate or poorly balanced, and you or your children have any symptoms of beriberi, call your health care provider.

Prevention

Eating a proper diet that is rich in thiamine and other vitamins will prevent beriberi. Nursing mothers should make sure that their diet contains all vitamins and be sure that infant formulas contain thiamine.

People who drink heavily should try to cut down or quit, and take B vitamins to make sure their body is properly absorbing and storing thiamine.

STEVENS JOHNSON SYNDROME SYMPTOMS AND TREATMENT

What is Stevens Johnson Syndrome?

Stevens-Johnson Syndrome is a potentially deadly skin disease that usually results from a drug reaction. Another form of the disease is called Toxic Epidermal Necrolysis, and again this usually results from a drug-related reaction. Both forms of the disease can be deadly as well as very painful and distressing. In most cases, these disorders are caused by a reaction to a drug, and one drug that has come under fire lately is the cox-2 inhibitor Bextra, which is already linked to these disorders.

There are other drugs that have been linked to Stevens-Johnson Syndrome, and these include some other NSAIDS (non-steroid anti-inflammatory drugs), Allopurinol, Phenytoin, Carbamazepine, barbiturates, anticonvulsants, and sulfa antibiotics. The condition can sometimes – although not very often – be attributed to a bacterial infection, and in some cases there is no known cause for the onset of Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. However, the most common cause is through drug related reaction.

Stevens-Johnson Syndrome can affect any age group. However, it occurs most commonly in older people, and this could be because older people tend to use more of the drugs associated with the disease and are therefore collectively more at risk from the disease. People that have AIDS are also at an increased risk of contracting Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. Those in the higher risk groups are urged to remain vigilant for any signs of these skin diseases, and are also advised to remain well informed about the symptoms that could indicate the presence or onset of Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis.

The symptoms :

Both Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis can start with non-specific symptoms such as cough, aching, headaches, and feverishness. This may be followed by a red rash across the face and the trunk of the body, which can continue to spread to other parts of the body. The rash can form into blisters, and these blisters can form in areas such as the eyes, mouth and vaginal area. The mucous membranes can become inflamed, and with Toxic Epidermal Necrolysis layers of the skin can also come away with ease and often the skin peels away in sheets. The hair and nails can also come away in some cases, and sufferers can become cold and feverish.

With Toxic Epidermal Necrolysis the most common cause of death is infection, which can enter through the exposed areas. This disease can leave the skin looking as though it has been burned, and areas where skin has flayed away can seep copiously and quickly become infected.

Treating these diseases:

Those suffering from SJS or TEN are treated in hospital, and if the cause of the problem is drug related then the drugs are stopped with immediate effect. Surviving patients are treated intravenously to replace any lost fluids, and the skin is left to re-grow on its own. However, the chances of survival can be hit and miss depending on the level of damage and the degree of infection incurred by the patient.

It is vital that those taking drugs that could result in these skin diseases are vigilant and can identify the danger signs associated with these problems. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis can be deadly, and the earlier the symptoms are recognised the faster treatment can be initiated.

Of course, those affected by drugs in this way – or the families of those that have passed away from these skin problems – have every right to file for compensation against the manufacturer of the drug in question. Lawyers now specialize in this type of litigation, and those that feel as though they have grounds for compensation are advised to go through an experienced drugs litigation lawyer.

Stevens-Johnson syndrome is an immune-complex–mediated hypersensitivity disorder that may be caused by many drugs, viral infections, and malignancies. Cocaine recently has been added to the list of drugs capable of producing the syndrome. Additionally, the antidepressant mirtazapine and tumor necrosis factor (TNF) – alpha antagonists infliximab, etanercept, and adalimumab have been reported as causes. In up to half of cases, no specific etiology has been identified.

Although not currently relevant to the practice of emergency medicine, research into the pathophysiology of SJS/TEN may soon allow for the development of tests to aid in the diagnosis as well as to identify those at risk.

Pathologically, cell death results causing separation of the epidermis from the dermis. The death receptor, Fas, and its ligand, FasL, have been linked to the process, as has TNF-alpha. Researchers have found increased soluble FasL levels in the sera of patients with SJS/TEN before skin detachment or inset of mucosal lesions.

Others have also linked inflammatory cytokines to the pathogenesis.

A "killer effector molecule" has been identified that may play a role in the activation of cytotoxic lymphocytes.

There is also strong evidence for a genetic predisposition to severe cutaneous adverse drug reactions such as SJS. The US FDA and Health Canada advise screening for a human leukocyte antigen, HLA-B*1502, in patients of southeastern Asian ethnicity before starting treatment with carbamazepine. (The risk is much lower in other ethnic populations, making screening impractical in them). Another HLA antigen, HLA-B*5801, confers a risk of allopurinol-related reactions. Pretreatment screening is not readily available.