Presented by Shu Mabel Lum

University of Buea

Abstract

Herbal medicine, sometimes referred to as herbalism or Botanical Medicine is the use of herbs for their therapeutic or medicinal value .A herb is a plant or plant part valued for its medicinal, aromatic or savory qualities. Herbs produce and contain a variety of chemical substances that act upon the body and treat many diseases.

The use of plants in the treatment of diseases is more commonly used because medicinal plants are more efficient and less toxic. Plants also are of a natural source, hence are less costly when prepared. Medicinal plants also have an advantage over drugs because they can be consumed in their natural form, whereas drugs must first of all be prepared before consumption. Major pharmaceutical companies are presently conducting research on plant materials due to their potential medicinal value.

Introduction

The brain is made up of interrelated neural systems that regulate their own and each others activity. These divisions make it easier for the brain to function efficiently since it is responsible for carrying out many other activities. The sympathetic nervous system is vitally involved in the homeostatic regulation of a wide variety of functions such as heart rate, force of cardiac contraction, blood pressure and fatty acid metabolism. Stimulation of the sympathetic nervous system normally occurs in response to physical activity, physiological stress and other situations in which the organ is provoked. Because the functions that are mediated by the sympathetic nervous system are diverse, agents that mimic or alter its activity are useful in the treatment of several clinical disorders like shock, cardiac failure, hypertension and many others.

Drugs that affect the Central Nervous System may selectively relieve pain or fever, suppress disorder or movements or prevent seizures. They may as well induce sleep or arousal, reduce the desire to eat or reduce the tendency of vomiting and hence may be used to treat anxiety, mania, depression or schizophrenia without altering consciousness.

The major scientific challenge is an attempt to understand the way the brain functions and the major goals include:

1) To use drugs to dissect the mechanisms that operate in the normal Central Nervous System

2) To develop appropriate drugs to correct events in the abnormal Central Nervous System.

CHAPTER ONE

LITERATURE SURVEY

History of medicinal plants

Herbal medicine has a long and respected history. Many familiar medications of the twentieth century were developed from ancient healing traditions that treated health problems with specific plants. Today, science has isolated the medicinal properties of a large number of plants, and their healing components have been extracted and analyzed. Many plant components are now synthesized in large laboratories for use in pharmaceutical preparations. For example , vincristine (an antitumor drug), digitalis (a heart regulator) and ephedrine (a bronchodilator used to decrease respiratory congestion) were all originally discovered through research on plants.

Chemistry of medicinal plants

The use of plants in the treatment of diseases is attributed to their secondary compounds. They are called “secondary” compounds because they have no known functions in primary physiological processes like photosynthesis and respiration. Many classes of secondary compounds such as alkaloids and steroidal glycosides are found in medicinal plants.

i) Alkaloids are a chemically diverse group. They contain nitrogen which is usually found in rings although there are exceptions where the nitrogen atoms are not included in the rings e.g. epinephrine and ephedrine.

ii) Steroidal glycosides contain sugar molecules. The steroidal molecules are the same as those found in animal hormones produced by the pituitary glands and sex organs.

Advantages of medicinal plants over synthesized drugs

Herbs are medicinal plants (also called phytomedicals) that can be administered either as a whole plant or plant part while synthetic drugs are synthesized chemically in the laboratory to produce drugs not found in nature. Most of these drugs are derived from plants by extracting the active ingredients from the plant, replicating its structure in the lab and mass producing it.

Herbal medicines have three main advantages over synthetic drugs.

1) Their long term use already indicates that they provide a high degree of safety and efficacy for human consumption.

2) Plant materials are less costly to prepare.

3) With medicinal plants, there is a reduced incidence of adverse drug interaction which is common to most therapies using synthetic drugs.

Herbal drugs are considered less potent than prescribed medicines. Drugs contain one highly active ingredient while herbs may have several active ingredients that are chemically similar. Herbal ingredients work synergistically to contribute to the therapeutic effect of each individual ingredient.

Herbalism

Herbalism which is healing with plants is sometimes considered as a collection of home-made remedies to be applied to one symptom or another provided the ailment is not too serious. However, we often forget that herbal medicine provides a good system of healing and prevention of disease. It is the oldest and most natural form of medicine. When skillfully applied, herbal medicine offers very real and permanent solutions to very real problems. Herbalism should not be confused with Traditional medicine. Nowhere is the efficacy of herbalism more evident than in problems related to the nervous system. Stress, anxiety, tension, and depression are intimately connected with most illnesses. Because they are organic substances and not man-made synthetic molecules, they possess a natural affinity for the human organism. They are extremely efficient in balancing the nervous system, restoring a sense of well-being and relaxation is necessary for optimum health and for the process of self-healing.

Rather than using a whole plant, pharmacologists identify, isolate, extract and synthesize individual components, thus capturing the active properties. However, in addition to active ingredients, plants contain minerals, vitamins, volatile oils, glycosides, alkaloids, bioflavonoids and other substances that are important in supporting a particular herbs’ medicinal properties. These elements also provide an important natural safeguard. Isolated or synthesized active compounds can become toxic in relatively small doses; it usually takes a much greater amount of a whole herb, with all of its components to reach a toxic level.

What is a mental disorder?

According to the diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, a mental disorder is any clinically significant behavioural or psychological syndrome characterised by the presence of distressing symptoms, impairments of functioning, a significantly increased risk of suffering death, pain, disability or loss of freedom.

Mental disorders are assumed to be the manifestation of behavioural or psychological dysfunction in the individual.

Types of mental disorders.

There are many different conditions that are recognized as mental illnesses. The more common types include;

Anxiety disorders: Responding to certain objects or situations with fear and dread, as well as with physical signs of anxiety and nervousness. They include panic disorder, social anxiety disorder and specific phobias

Mood disorders: Involve persistent feelings of sadness or periods of feeling too happy or fluctuation from extreme happiness to extreme sadness. Examples are mania and bipolar disorder.

Psychotic disorders: Involve distorted awareness and thinking. Symptoms include hallucinations and delusions e.g. schizophrenia.

Eating disorders: Involve extreme emotions, attitudes and behaviours involving weight and food e.g. anorexia nervosa, bulimia nervosa.

Impulse control and addiction disorders: Involve the inability to resist urges or impulses to perform acts that could be harmful to themselves and others e.g. pyromania (starting fires), kleptomania (stealing).

Personality disorders: Involve extreme and inflexible personality traits that are distressing to the person and/or problems in work, school or social relationships.

Some other very common illnesses include epilepsy , coma, dizziness, migraines, neurosis, amnesia, neuralgia.

Causes of mental illness

Although the exact cause of most mental illnesses is not known, it is becoming clear through research that many of these conditions are caused by a combination of biological, psychological and environmental factors;

i) Biological factors: Some mental illnesses have been linked to an abnormal balance of special chemicals in the brain called neurotransmitters. Neurotransmitters help nerve cells in the brain communicate with each other. If these chemicals are out of balance or are not working properly, messages may not make it through the brain correctly, leading to symptoms of mental illness. In addition, defects in or injury to certain areas of the brain have also been linked to some mental conditions. Other biological factors that may be involved in the development of mental illness include;

• Genetics: Susceptibility can be passed on in families through genes.
• Infections: Certain infections have been linked to brain damage
• Brain defects or injury: Defects in or injury to certain areas of the brain have been linked to some mental illness.
• Prenatal damage: Disruption of early fetal brain development or trauma that occurs at time of birth.
• Poor nutrition and exposure to toxins such as lead.

ii) Psychological factors:

• Severe psychological trauma suffered as a child, such as emotional, physical or sexual abuse.
• An important early loss, such as the loss of a parent
• Neglect
• Poor ability to relate to others.

iii) Environmental factors

• Death or divorce
• Living in poverty
• Feelings of inadequacy, low self-esteem, anxiety, anger or loneliness
• Changing jobs or schools
• Social or cultural expectations

Sometimes, mental problems may come as a result of excessive smoking of things like marijuana, tobacco, Indian hemp and many others.

Symptoms of mental disorders

Symptoms vary depending on the type and severity of the condition. They may also vary depending on the age group. Some general symptoms include:

In adults:

• Confused thinking
• Long-lasting sadness or irritability
• Excessive fear, worry or anxiety.
• Dramatic changes in eating or sleeping habits.
• Strong feelings of anger
• Delusions and hallucinations (seeing or hearing things that are not really there)
• Increase inability to cope with daily problems and activities
• Many unexplained physical problems
• Thoughts of suicide
• Denial of obvious problems

In older children and pre-teens

• Changes in sleeping and eating disorders
• Excessive complaints of physical problems.
• Intense fear of gaining weight
• Drug abuse and/or alcohol
• Frequent outbursts of anger
• Defying authority, skipping school, stealing or damaging property.

In younger children

• Changes in school performance
• Excessive worry or anxiety
• Persistent nightmares
• Persistent disobedience
• Hyperactivity

Classification of some medicinal plants used to treat mental disorders

Scientific name	Common name	Part of plant used	Major constituents	Diseases/uses	Side effects
Bocopa monnieri	Brahmi	Alcoholic extract of plant	Saponins, bacoside A, bacoside B, monnierin, hersoponin	Improvement of intelligence and memory Revitalizing of sense organs
Centella asiatica	Mandukoparni	Fresh leaves	Triterpenoid soponins, madecassides and asiaticoside and their aglycons Asiatic acid and madessic acid	Amnesia, hysteria, improves memory	Contact dermatitis
Valeriana officinalis	Valerian	Rhizomes	Volatile oil which includes valerianic acid, volatile alkaloids including chantinine and iridoids (valepotriates)	Tranquilizer, induces sleep and relieves anxiety	Gastrointestinal upset, contact allergies, headache, restless-sleep.
Withania somnifera	Ashwagandha	Roots, leaves		General debility, nervous exhaustion, brain-fatigue, andtidepressant, mood stabilizer
Piper methysticum	Kava	Water extracts	Kavapyrones Kavalactones	Antianxiety Sleeping pills	Oral and lingual dyskinesia, torticollis, painful twisting movements of the trunk, oculogyric crisis, increases Parkinson’s disease
Gingko biloba	Gingko	Leaves	Flavonoids, Terpenes	Fatigue, anxiety, depression, increases cerebral blood flow, Alzheimer’s disease	Headache, allergic, skin reactions, gastrointestinal upset
Panax ginseng	Ginseng			Maintains emotional balance, improves some aspects of mental function	Breast tenderness, postmenopausal, vaginal bleeding, menstrual abnormalities
Leonurus cardiaca	Motherwort			Increases blood circulation in the brain, anxiety, sleep, disorders, prevent melancholy	Diarrhoea, uterine bleeding, stomach, irritation.

Other herbs used in treatment of mental disorders include;

Platago asiatica, Scruphularia ningpoensis, Ilex pubescens which are traditional Chinese medicines prescribed for treating depression like ailments

Passiflora incarnata, Evolvulus alsinide, Scutellaria lateriflora are studied for their activity against irritation of the brain, nervousness, restlessness, sleeplessness.

Humulus lupulus, Convolvulus pluricaulis are considered for their activity against mild to moderate anxiety.

Celastrusa paniculatus, Acorus calamus, Piper longum are claimed as brain tonics.

Essential oils can be used in aromatherapy room diffuser to reduce depression and anxiety. The oils like that of Citrus bergamia (Bergamot), Juniperus virginiana (cedar wood), Anthemis nobilis (chamomile), Lavendula officinalis (lavender), Citrus lemon (lemon), Rosa centifolia (Rose), Santalum album (sandal wood) are mainly used in treatment of mild to severe depression, anxiety and stress. These oils are mainly used in the form of inhalation, bath, massage or steam treatments. However, their use is limited to external application. Some of them like Bergamot oil may cause phototoxicity, while others like lavender oil may result in skin irritation and rashes. Some like cedar wood oil and chamomile oil are restricted during pregnancy.

Even the layman can do much to reduce stress and sooth frayed nerves. Drinking chamomile , lemon balm or linden tea is preferable to coffee for anyone having sleeping difficulties or anyone who wishes to have a greater sense of inner calmness. Twenty minutes out-of-breath exercise (walking, swimming or cycling) will go a long way as a natural antidote to the tension that results from a stressful day at the office, and it will have the unexpected bonus of improving circulation, increasing metabolic rate and enhancing heart and liver function which are all associated with the nervous system.

The B-vitamins as found in whole-wheat bread, wheat germ, brewer’s yeast and liver (organically produced) provide ideal nourishment for the nervous system and can be wisely substituted for the stimulant foods such as white flour, sugar, junk foods and their harmful chemical additives.

Methods of preparation of medicinal plant extracts

Medicinal plants can be prepared in many different ways depending on the part of the plant being used, the illness being treated and the major constituents of the plant. Some methods used in preparing medicinal plants for use include;

1) Tinctures: They contain alcohol. In a tincture, alcohol is employed to extract and concentrate the active properties of the herb. Alcohol is also a very effective natural preservative. Because a tincture is easily assimilated in the body, it is a very effective way to administer herbal compounds. The full taste of the herb comes through very strongly in a tincture. Children and adults too may find the taste of some herbs unpleasant. Goldenseal for example is bitter-tasting

In order lesson, the amount of alcohol in a tincture, mix the appropriate dose with one -quarter cup of very hot water. After about five minutes, most of the taste of the alcohol will have evaporated.

2) Extracts: Extracts can be made with alcohol, like tinctures, or the essence of the herb can be leached out with water. Extracts offer essentially the same advantages and disadvantages that tinctures do. They are the most concentrated form of herbal treatment and therefore the most cost-effective. They are easy to administer, but have a strong herbal taste.

3) Capsules and tablets: They contain a ground or powdered form of raw herbs. In general, there are little differences between the two in terms of clinical results. Because finely milled herbs degrade quickly, it is important that herbs be freshly ground and then promptly encapsulated or tableted, within twenty four hours of being powdered. With the exception of certain herbal concentrates in capsule from, both capsules and tablets tend to be much less strong and potent than tinctures and extracts.

4) Decoctions: This involves boiling the plant parts in water for about 15-20 minutes

5) Infusions: Infusions make use of dried or fresh herbs in boiled water.

6) Pills: The dried and powdered drug is mixed thoroughly with honey and cooked.

7) Syrups: Cane sugar is dissolved in boiling water and the decoction fluid is added .

Poultice or paste: The plant material is ground with little oil, water and honey.

9) Juices: The fresh plant material is pounded, filtered and then squeezed to extract the juice.

Toxic effects of medicinal plants

Over the past decade, there have been certain cases of adverse effects produced by these plants which are sometimes life threatening. These toxic effects may come as a result of contamination with excessive use of banned pesticides during treatment and collection of plant materials, microbial contamination, heavy metals, chemical toxins. Chemical toxins may come from unfavourable or wrong storage conditions or chemical treatment due to storage.

Toxic effects may also come as a result of unprofessional practice of the manufacturer. Since plants contain many active ingredients, if not used properly, they can provoke adverse reactions.

CHAPTER TWO

EXPERIMENTAL

CASE STUDY: Bombe Health Centre for Mental Problems and other Chronic

Illnesses.

This is a centre run by Dr. Zack Maghang who is responsible for the treatment of people suffering from mental problems and other chronic diseases. He keeps his mental patients in a house which is divided into different sections depending on the intensity of the problem. Those whose cases are chronic are usually chained since they are very aggressive and dangerous while those with milder cases are kept in different rooms.

Treatment

Generally, treatment here is the same for all the patients irrespective of the cause of the illness and the intensity. The only thing that varies is the duration of treatment. If a patient is brought to the centre as soon as the problem starts, he can be treated within a week.

When a patient is first brought to the centre, he is given some snuff-like medicine to inhale. The purpose of this is to clear the patients brain. After a period of about 2 hours, the patient is administered some droplets through the nose in order that all the liquid in the patients head goes out. This liquid leaves through both the mouth and the nostrils. This calms down the patient and he is then allowed to sleep. The following morning , as soon as the patient wakes up, his hair is shaved to let it cool. Some leaves are boiled in water and then used to bath the patient. The patient is rubbed with some medicinal oil which is made up of a mixture of palm oil and some medicinal plant. This process is carried out every morning. The essence of this is just to let the patient to be conscious of the fact that he must take a bath every morning.

The patient is then given malaria and typhoid drugs alongside the other drugs that are being administered. The malaria medicine is prepared using tree bark and it is boiled with some other leaves. The patient receives this medicine in the morning while he is given a valium-like medication in the evening to allow the patient to sleep. This treatment goes on daily till the patient recovers.

Sometimes, these patients have nightmares and are unable to sleep. In this case, some dried leaves are burnt to produce incense. This causes them to sleep very well. The medications given to the patients are usually given through the ears, the eyes, the nose or the mouth. This is the ensure that when the patient recovers, he regains all his senses. This is because when the brain is affected, the various senses could also be affected. When a patient starts complaining of body pains and aches it implies that the patient is recovering. While the patients are receiving treatment, they are being taken care of by their relatives who provide food and clothing . sometimes, those who have recovered and are able to reason help in taking care of the others. When not treated at the early stage, like any other illness, it becomes chronic and more difficult to treat.

CHAPTER THREE

RESULTS

Analysis show that the majority of mad people are women. Women are the weaker sex and are generally less resistant to pain than men. When a woman undergoes a lot of stress or pain, the probability of having mental problems is greater than in men who are more resistant. An example is during child birth.

Results have shown that these medicinal plants are very effective in the treatment of mental problems because they are less toxic and have not produced any cases of death so far. All the patients receiving this treatment have been able to regain consciousness. Also, it is worth mentioning that when the patients are recovering, they are able to tell what led to the madness and sometimes they are able to tell at what time and place, though most of them feel very ashamed after recovery.

In cases where the problem was as a result of excessive smoking, most of the patients after recovery still desire going back to continue with the smoking.

Conclusion

Some of the most common causes of mental disorders are excessive smoking and drug abuse and the teenage age group are more exposed to these problems since most of these activities are carried out by teenagers.

As soon as it is discovered that an individual is showing any of the symptoms mentioned, he should immediately be taken for check up. This reduces the risk of the person’s situation becoming chronic and more difficult to treat.

Recommendations

There is need for a rigorous study of various traditionally but not scientifically proven herbs at the pre-clinical and clinical levels.

The environmental related factors can be controlled by implementing standard operating procedures which will lead to good agricultural practice, good laboratory practice, good supply practice and good manufacturing practice for producing these medicinal products from their natural sources.

Since mental illnesses are diverse and individual patients are biochemically unique, a larger number of drugs will increase the probability of finding a beneficial medication

References

http://www.skepticsfiles.org/weird/nerveshr.htm

http://www.webmd.com/anxiety-panic/mental -health-causes-mental-illness

The illustrated Encyclopedia of Natural Remedies, Norman Shealey

A consumer’s guide to avoiding Drug Induced Death or Illness, Sidney M. Wolfe

Presented by Mbuahme Margaret

University of Buea

Abstract

Tuberculosis (TB) is the leading cause of mortality due to a single infectious agent. The currently used combination drug regimens produce cure rates that exceed 95%, given good patient adherence during the multiple months treatment period. However the recent surge in HIV infections and the synergy between HIV and TB as well as the emergence of resistance resulted in an unforeseen increase in the number of TB cases, including multi-drug resistant (MDR) and extensively-drug resistant (XDR) forms of TB. Consequently, there is an urgent need to develop novel, fast acting antituberculosis drugs with high potency that can provide treatment options for all forms of TB. It is well known that the current TB drugs exhibit differences in their in vivo activity profile and these differences are largely determined by their pharmacodynamics (PD), i.e. intrinsic antibacterial activity, biopharmaceutical properties such as solubility and permeability, and pharmacokinetic (PK) properties such as drug exposure, tissue distribution, and protein binding. An understanding of the relationships among these properties is considered key for a rational use of antituberculosis therapeutics. The current review provides a comprehensive summary of physicochemical/biopharmaceutical, PK, and PD properties of currently used anti tuberculosis drugs and novel agents under development. Also, a brief review of PK/PD parameters of current TB drugs is given and properties of a desirable TB drug target and drug molecule are outlined. The information provided herewith may be useful in the optimization of biopharmaceutical and PK/PD characteristics in the development of novel TB therapeutics and in the design of optimal treatment regimens.

Introduction

Tuberculosis (TB) is a contagious disease caused by Mycobacterium Tuberculosis and occasionally by opportunistic microbacterial. It affects mostly areas in the body that are rich in blood and oxygen such as the lungs as pulmonary tuberculosis and can also affect other parts of the body such as the skin or other organs as extrapulmonary tuberculosis. Its primary reservoir host is in humans and occasionally in cattle within incubation of 4 to 12 weeks TB is also associated with HIV/AIDS which is the leading killer of HIV positive patients. TB can also manifest as primary or reactivated infection

Primary infection which is asymptomatic, is initiated by inhaling droplet of nuclei that contain tubercle bacilli which passes through the bronchiole tree and implants in the respiratory bronchiole beyond the mucocillary. It is engulfed by microphages and after entering the lungs, a Ghon’s complex could be formed later. The immune response also provide protection against additional tubercle bacilli that maybe inhaled at later time, but people with HIV infection are more likely to acquire activated TB which is also known as latent tuberculosis infection.

Reactivated TB, results from the activation of previously healed primary lesion that develops because of impaired body’s defense mechanism.

OBJECTIVES

· To identify the first line drugs employed in the treatment of tuberculoses.

· Identify the genetic factors that can affect the action of the drugs.

· To understand the pharmacokinetics and pharmacodynamics of antitubercular drugs in the treatment of tuberculosis.

· Identify the drug interactions that are associated with anti-tubercular drugs.

· Identify the adverse reaction of these drugs.

· Teach the patient with a mycobacterial infection about the disease and drug therapy.

· To know how to apply the nursing processes when caring for a patient who is receiving anti tubercular drugs.

SOME DEFINITIONS

Drug: It is a chemical substance that modifies the response of a tissues to its environment

Pharmacokinetics: It is the study of the factors that determine the concentration of a drug at its site of action at any given time after administration into the system by any route. In short pharmacokinetics is the study of what the body does to the drugs. The pharmacokinetic phases of drug actions are;

- Absorption: it is the transfer of chemicals from site of exposure into the systemic circulation.

- Distribution: Movement of drug from blood to the tissues.

- Metabolism: It is the Biotransformation of drugs to more hydrophilic molecules for easy passage through membranes.

- Excretion: It is the elimination of metabolic waste substances from the body.

Pharmacodynamics: It is the study of the interaction between the drug and the target (site of action) of the drug to bring about a biochemical responds. In simple terms it is the study of what the drug does to the body.

Causes of Tuberculosis

You can catch TB by breathing droplets in the air that contain the bacterium M. tuberculosis. These are spread through the air when someone with TB coughs or sneezes. TB is only infectious when it affects the lungs (See Symptoms). Although it is spread through the air, you need to be closely exposed to a person with TB for some time before you catch it. People most commonly catch TB from people they live or work with.

You are more likely to get TB if you:

• already have a weakened immune system (e.g. from HIV/AIDS or from taking medicines that suppress your immune system)
• have diabetes
• regularly come into contact with people who have TB lung infection
• are young or elderly
• are malnourished
• smoke or drink alcohol excessively
• live in overcrowded housing
• travel to, or come from, places where TB is common

Signs and Symptoms of Tuberculosis

Many people who become infected with TB don’t realize they have been exposed to the infection because their immune system successfully fights it off. When this happens, the bacteria become coated in tiny tubercles (round lesions), usually in the lungs. These can sometimes be seen on a chest X-ray. The bacteria are still in the body, but there are no symptoms and it can’t be passed on to other people. This is called latent TB. Depending on how effectively your immune system fights the infection, you may have:

• no symptoms at all
• minor symptoms for a few weeks, which then go as you fight the infection off
• no symptoms at first, but symptoms and active TB develop in the following weeks or months

If your immune system successfully fights the infection, you will be immune to TB. Sometimes latent tuberculosis becomes active years later. This is known as post-primary

TB, and is more likely to happen if your immune system is weakened by other problems such as HIV, poorly controlled diabetes, or if you are underweight. About one in 10 people infected with TB bacteria go on to develop active TB at some point in their life.

Active TB bacteria are not contained in tubercles, and a person with active TB will have symptoms, which may include:

• a persistent cough – there may also be lots of phlegm, sometimes containing blood
• fever
• swollen glands, especially in the neck
• tiredness
• loss of appetite
• weight loss
• night sweats
• chest pain when you breathe in, caused by inflammation of the membranes lining your lungs (pleurisy)

At first, a TB infection normally affects the lungs. This is called pulmonary TB. However, TB often spreads to the lymph nodes (glands throughout your body that are part of your immune system). It can also affect your bones, joints and kidneys, as well as cause meningitis (inflammation of the membranes surrounding the brain and spinal cord).

Diagnosis

The most common test for TB is the tuberculin test. The test detects latent TB and is also used as part of vaccination programmes.

There are two ways to do the test.

The most common one is called the Heaf test. A small device with six small needles is pressed onto the skin of your forearm. The needles carry tiny amounts of tuberculin protein, which comes from the bacteria that cause TB. One week later, a doctor or nurse will examine the skin at the site of the test to see if there has been a reaction.

An alternative, the Mantoux test involves injecting the tuberculin protein into your skin. You will get the results 48 hours after the test.

In either case, the doctor or nurse is looking for a raised red reaction on your skin. This is a positive result, meaning you have been exposed to the TB bacteria. The reaction is then graded.

A weak reaction suggests that you have developed some immunity to the disease. A strong reaction means the problem may need further investigation and diagnosis.

If you have no reaction, you haven’t been exposed to TB, which means you can be immunized (see Immunisation).

The test for active TB involves analysis of a sample of your phlegm. This can also identify which combination of drugs is likely to treat it successfully. A chest X-ray can also diagnose active TB.

Treatment

People with either active or latent TB are treated with a combination of antibiotic tablets to kill the bacteria. Treating latent TB prevents the infection becoming active.

You may need to go to hospital for the first week or so, especially if you are very ill or thought to be very infectious. However, some people can be treated at home.

Unlike most antibiotics antituberculosis drugs may need to be administered over many months or even years. This creates problems such as patient non compliance, the development of bacterial resistance and drug toxicity.

You will usually need to take antibiotics for six months. You may need a longer course of treatment if the bacteria are resistant to one or more of the antibiotics (See Drug resistant TB).

It’s very important to take the full six-month course of antibiotics and to take them regularly; otherwise the bacteria may develop resistance to the antibiotics. Treatment with antibiotics is usually effective, provided that the full course of medication is taken as prescribed. Some people may get side-effects from the antibiotics. These can include:

• visual disturbances
• nausea, vomiting or diarrhea
• dizziness
• skin flushes
• fever
• jaundice (yellowing of the skin and eyes)
• pins and needles
• depression or other mental disturbances

If you notice any of these symptoms, don’t stop taking the medication, but talk to your doctor as soon as you can – an alternative treatment may be needed.

Prevention

Immunization

In the UK, a large-scale immunisation programme is run to help prevent TB. Immunisation is given as the BCG (Bacillus Calmette-Guérin) vaccination. This protects between 70 and 80 percent of people who receive it. It lasts for at least 15 years. The vaccination strategy in the UK targets people who are most at risk of getting TB, such as:

• babies born in areas where TB is common
• people who have immigrated from a country where TB is common, or their children
• healthcare workers and laboratory staff
• people who intend to travel to a country where TB is common

The vaccination is not usually recommended for people over 45 unless they are in a high-risk group such as healthcare workers. Once you have had the immunization, you won’t need to have it again.

Before giving the vaccination, your doctor or nurse must first check whether you are already immune to TB. This is done with the tuberculin test (see Diagnosis).

If the test is positive, this means you have been exposed to the TB bacteria and you are already immune. You will not be given the BCG vaccination. Depending on the size of the skin reaction, you may be referred for more tests, such as an X-ray and a phlegm test, and possibly treatment for TB.

People who are not already immune are given the vaccination either as a single needle injection, or with a multiple needle device similar to the one used for the Heaf test. The injection is given to the top of the left arm (or the right arm in left-handed people).

It is rare to get a strong reaction to the vaccination, but a small ulcer on the skin of the arm often forms. This may take several weeks to heal properly. A flat scar often develops later. This is normal and a sign of successful immunisation.

ANTIMYCOBACTERIAL AGENTS (DRUGS)

Antitubercular And Antileprotic Agents

These are agents used to treat mycobacterial infections: tuberculosis which is caused by Mycobacterium tuberculosis and Hansen’s disease (previously called leprosy), which is caused by Mycobacterium leprae. These agents are also effective against less common mycobacterial infection caused by M. kansasii, M. aviun, M. fortuitun, M. intracellulare and other related organisms. These agents are not always curative but can halt the progression of a mycobacterial infection. Unlike most antibiotics, antitubercular and antiaprotic agents are administered over many months or even years. They create problems such as patient non compliant, development of bacterial resistance and drug toxicity. To help reduce these complications to the patient during long therapy, the nurse must be aware of these and other problems.

1. Antitubecular Agents

The most used antitubercular agents are ethambutol hydrochloride, isoniazid, rifampin and streptomycin sulfate. Other antitubercular agents which are less commonly used include amino salicylic acid, capreomycin sulfate, cycloserine, ethionamide and pyrizinamide. These agents are less commonly used because they are less effective and more toxic. They are used only when hypersensitivity, intolerance or bacterial resistance to the first line agent exist.

2. Antileprotic Agents

The primary agent used to treat Hansen’s disease (leprosy) is dapsone, a sulfa drug. However, refampin and clofazimine are also used. Clofazimine ane dapsone are mostly used. Ethonamides, an antitubercular agents is used to treat dapsone resistant Hansen’s disease and is usually combined with refampin or clofazimine.

Tuberculosis Treatment; Drug Therapy

The first line drug in the treatment of tuberculosis:

- The first option is a four drug regimen consisting of isoniazides, refampin, pyrazinamide and either ethambutol or streptomycin. This therapy may be given daily or two or three times weekly if directly observed. Ethambutol or streptomycine may be continued if susceptibility to isoniazide and refampin is documented. Pyrazinamide should be discontinued after eight weeks.

- The second option for treatment is to administer isoniazide, refampicin, pyrazinamide and streptomycin or ethambutol daily for two weeks followed by directly observed twice weekly administration of the same drug for six weeks, and followed by directly twice weekly administration of isoniazide and refampin for sixteen weeks.

- The third option is directly observed twice administration of ioniazide, refampin, pyrazinamide and ethambutol for six months.

Treatment of Special Cases of Tuberculosis

1. HIV infection cases: for patients with HIV infection, any of the three options can be used but therapy should be continued for nine months and at least six months after culture conversion.

2. Extrapulmonary Tuberculosis: treatment is the same as for pulmonary tuberculosis. However nine months of therapy is advised. Treatment of skeletal tuberculosis is enhanced by early surgical drainage and debridement of necrotic bone. Corticosteroids therapy is indicated in tuberculus pericardiatis and tuberculos meningitis.

3. Pregnancy case: it is treated with an initial regimen of isoniazide, refampin and ethambutol. Pyrazinamide should be used only if resistance to other drugs is document or likely and susceptibility to pyrazinamide is also likely. This is because the risk of theratogenecity with pyrazinamide has not been determined. Streptomycin is contraindicated in pregnancy because is causes congenital deafness.

A Table Showing The First Line Drugs And Other Anti Mycobacterial Agents

Used In The Treatment Of Tuberculosis.

DRUGS	ACTION	ROUTE AND ADULT DOSAGE	ADVERSE EFFECT
Isoniazid	Unknown, may block mycolic acid synthesis in mycobacterium buberculoses, resulting in either bacterostatic or bactericidal effect depending on dose	Oral or intramuscular 5mg/kg/dayin single dose with a maximum of 300mg daily for the treatment of active tuberculoses.	Peripheral neuritis, irritability, seizure, hyperglycemia, metabolic acidosis, allegic reactions, hypertoxicity
Rifampin	Inhibit bacteria RNA formation (bactericidal)	Oral 600mg once daily, 1hour before or 2hours after meal.	Gastrointestinal tract distress, central nervous system effects, hypertoxicity with intermittent therapy fever, chills, nausea, vomiting, trumbocitopemia, henolitic anemia, acute renal failure.
Ethambutol	Unknown, only effective against mycobacteria (bactericidal)	Oral 15microgram/kg single dose daily as initial treatment. Real treatment is 25mg/kg as a single oral dose every 24hours.	Retrobulbar neuritis, GI tract upset, allergic reaction, central nervous effect, acute gout peripheral neuritis.
Para aminosalicyclic acid	Blocks the synthesis of folic acid in mycobacterium tuberculoses (bacteriostatic)	Oral’ 10-12g/day in 2 or 3 divided doses.	GI irritation, allergic reactions, blood dyscrasias, fluid retention.
Cycloserine	Compete with alanine for use by bacteria thus preventing cell wall formation	Oral; 12mg/kg/day. 25mg every 4days until therapeutic serum levels are reached.	Central nervouse system toxicity.

Pharmacodynamics Of Antitubercular Agents

These agents are specific for mycobacteria. At usual doses, ethambutol and isoniazides are tuberculostatic inhibiting growth of mycobacterium tuberculosis bacteria. In contrast, refampin is tuberculocidal destroying the bacterial. Because bacterial resistance to isoniazide and refampin can rapidly develop, they are usually used with other antituberbacular agents.

Mechanism of action

Ethambutol is most active against mycobacterium tuberculosis and mycobacterium Kansasii but acts to varying degree against all mycobacteria. Although mycobacterial rapidly takes up ethambutol, the drug does not inhibit their growth significantly for approximately 24 hours. The exact mechanism of action remains unclear but may be related to inhibition of cell metabolism, arrest of multiplication and cell death. Ethambutol acts only against replicating bacteria.

Isoniazide mechanism of action is not exactly known but evidence suggest that the drug inhibits the synthesis of mycolic acid, an important component of the mycobacterium cell wall.

This inhibition alters the fastness of the cell and disrupts the cell wall. Because mycolic acid synthesis is unique to mycobacteria, this mechanism explains the high degree or specificity of isoniazides. Only isoniazide sensitive bacteria takes the drug and only replicating not resting bacteria are inhibited.

Rifampin inhibits ribonucleic acid (RNA) synthesis in susceptible organisms by acting on the beta subunit of the enzyme RNA polymerase. The drug is effective primarily in replicating bacteria but may have some effect on resting bacteria as well.

Para-Aminosalicylic Acid is structurally similar para-aminobenzoic acid.Its mechanism of action is claimed to be similar to that ofsulfanamide in that it prevent the synthesis of folic acid. however sulfonamide are insensitive in treating M.tuberculosis and PAS is inactive against sulfonamide sensitive bacteria.

Clocyrine is structurally similar to the amino acid alanine. By competing with alanine in the bacteria, it is believed to prevent the formation of bacteria cellwall.

Capreomycin sulfate is a polypeptide antibiotic whose mechanism of action isunknown. It is absorbed by the GI tract thus administered intra-muscularly.It half life is four to six hours unchanged in urine.

Pyrazinamide is a niacinamide derivative.It is highly specific for M.Tuberculosis. Mechanism of action isunknown.

Ethionamide(trecator-SC), aderivative of isonicotinic acid is use to treat tuberculosis and Hansen’s disease especially useful in dapsone-resistance M leprae. It mechanism of action is unknown

Streptomycin sulfate is the first egent recognized to effectively treat tuberculosis

It appear to enhance the activity of oral anti-tubercular agents and is of great value in the early weeks to month of therapy.

PHARMACOKENITIC

Antitubercular agents almost exclusively are administered orally. Isoniazid is commercially available parentarally. When this agent are administered orally they are absorbed well from the gastrointestinal tract and distributed through out the body. This drugs are metabolized primarily by the liver and excreted by the kidney.

Absorption, Distribution, Metabolism and Excretion of drugs.

Ethambutol

- After oral dose of ethambutol is administered, about 75 – 80% is absorbed rapidly from the GI tract.

- The drug is distributed widely into more body tissues and fluids and about twice as much appears in erythrocytes as that in the plasma. The erythrocytes can serve as a reservoir that slowly releases the drug into the circulatory system.

- Ethambutol crosses the placenta and appears in the breast milk in concentrations equal to those of plasma concentration.

- 50% of the drug is metabolized in the liver and the kidney excretes almost all of it primarily as an unchanged drug.

Isoniazids

- It is readily absorbed from the GI tract and the intra muscular injection site as it is administered both orally and intramuscularly.

- It is distributed into all body tissues and fluids and readily crossed the blood brain barrier and the placenta. It distributes into blood milk in concentration level similar to that of the maternal plasma concentration.

- It is metabulised almost completely by enzymatic acetylation and hydrolises in the liver. The rate of the acetylation is determined by race-linked genetic factors that produce significant variations in the rate of isoniazid elimination. Despite this, the drug is still effective when administered two of three times a week. It’s effectiveness is reduced for some patients (fast acytelators), when administered once weekly.

- About 75 -95% of isoniazid is excreted in the urine as metabolite and unchanged drug within 24hours after administration. Small amounts are excreted in the saliva, sputum and feaces.

Rifampin

- It is absorbed well from the GI tract although food in the stomach can reduce its rate and extend of absorption. The drug difusses freely into most body tissues and fluids such as the cerebrospimal fluids in concentrations of 10-20% that of the plasma.

- It crosses the placenta and appears in breast milk.

- Metabolism take place in the liver and is excreted primarily in the feaces, urine and bile.

- Aminosalicycylic acid is readily absorbed in the GI tract, distributed widely to the tissues and metabolized rapidely by the liver and excreted by the kidneys.

Capreomycin Sulphate

- It is absorbed by the GI tract thus administered intramuscularly. Its half life is four to six hour

- It is excreted unchanged in the urine.

Cycloserine

- After oral administration, it’s absorbed well in the GI tract, distributed widely and excreted by the kidney

Ethionamide

- It is absorbed well after oral administration and distributed widely. It is extensively metabolized in the liver and excreted in the urine.

Pyrazinamide

- It is absorbed well and distributed widely. It is metabolized by the liver.

Streptomycin Sulphate

- It is administered only intramuscularly and this limits its usefulness and long term therapy.

- It is rapidly absorbed from the IM injection site.

- It is excreted by the kidney as unchanged drug.

Onset, Peak and Duration of action of drug.

- After and oral dose of ethambutol, the plasma concentration peaks in 2-4hours in proportion to the size of the dose. The half life in a patient with normal renal function is three hours whereas that for a patient with renal impairment is longer an those the dosage is adjusted.

- Isoniazid after oral administration reaches a peak plasma concentration in 1-2hours. The half life of this drug ranged from 4-5hours but may be longer for patients with renal or hepatic impairment.

- Rifampin reaches a peak plasma concentration kin 2-4hours. Initially, it half life ranges from 1-5 as an averages 3hours but because of biliary excretion of rifampin increases during the first two weeks of therapy, the half life gradually decreases to about 2hours. Its plasma concentration is higher and more prolonged in patients with hepatic dysfunction but unaffected in patients with renal dysfunction.

DRUG INTERACTION

Anacids that contain aluminum hydroxide or other aluminum salts may decrease the GI absorption of ethambutol slightly. Some evidence suggest that isonaizid, cycloserine and ethionamide may produce additive CNS effect such as drowsiness, dizziness, heahach, lethargy, depression, tremor, anxiety, confusion and finnitus. Therefore this drugs should be administered cautiously in combination.

Isoniazid may increase plasma concentration of phenytoin, who are slow acetylators Aluminum hydroxide a common ingredient in antacid, significantly decreases isoniazids absorption. Isoniazid should be administered at least one hour before aluminum anacid. INH’s administration with a corticosteroid decreases its effect and increases the corticosteroid effect. Psychotic episodes and difficulty incordination have occurred when INH’s has be give with disufiram. Concomitant administration should be avoided.

Refampin can increase the rate of metabolism and consequently decreases the plasma concentration of some drugs including oral contraceptives. Ketoconazole, quinidine, cyclosporine, chloramphenicol estrogens, corticosteroids, methadone, oral hypoglycemics, warfarine, cardiac glycosides and dapsone. The dosage of these agents may need to be increased during refampin therapy. Aminosalicylic acid may inhabit refampin reaction.

ADVERSE DRUG REACTION

Adverse drug reaction to anti tubercular agent primarily occur in the GI tract, the peripheral nervous system and the hepatic system. Fortunately this reaction seldom are severe enough to necessitate interruption of tuberculosis therapy.

Optic neuritis is the significant reaction to ethambutol. Signs and syntoms include decrease visual aquity, lost of red-green colour discrimination visual field constriction, and central and peripheral scotomas. This adverse reaction occur in only 0.8% of patients receiving 15mg/kg, but its incidence increases in patients who receive higher dosage or who have renal dysfunction. Discontueing ethambutol usually reverses the optic neuritis, but if vision impairment is severe, recovering may be incomplete. Occasionally ethambutol therapy increases serom uric acid levels and precipitate and acute gouts episode. The most common hypersensitivity reaction to ethambutol are rash and fever.

Peripheral neuritis occurs in 20% of the patient receiving isoniazid daily and higher doses increase the incidence of this reaction. Usually preceded by paresthesia of the feet and hands. Peripheral neuritis is more likely to affect and alcoholic, a diabetic or a malnourished individual or one who is predisposed to peripheral neuritis.

Drug Resistant TB

The bacteria that causes TB can, in rare cases, become resistant to antibiotics, making it extremely difficult to treat. According to the World Health Organisation (WHO), multi drug resistant tuberculosis (MDR TB) has been found in most countries surveyed. Drug resistant TB is more likely to develop if you don’t finish your antibiotic treatment course for TB.

Some Common Nursing Diagnosis And Related Intervention

For Each Anti Tubercular Drug Class

Planning and Implementation

- Monitor the patient closely for hypersensitivity reaction.

- Monitor the patient’s liver function test for abnormalities with NIH or rifampin therapy, serum uric acid levels with ethambutol therapy and white blood count with rifampin and ethambutol therapy.

- Monitor hydration if the patient experiences nausea, vomiting, and anorexia, or diarrhea during rifampin ore ethaambutol therapy. Obtain a prescription for an antirnetic or anti diarrheal agent as needed.

- Administer an analgesic as prescribed if the patient experience a headache during ethambutol therapy of joint pain or muscle aches or cramps during rifampin therapy.

- Take safety measures if the patient experiences adverse CNS reactions such are confusion or coordination. For example, place the patients bed at a lower position, keep the bed rails raised, and supervise ambulation.

- Take seizure precaution when administering INH’s to a patient with a seizure disorder.

- Administer rifampin one hour before of two hours after the meal because food affect the rate and extent of absorption.

- Administer INH at least one hour before administering aluminum antacid to prevent a drug interaction.

- Monitor the patient closely for additive central nervous system effect during concomitant therapy with INH and cycloserine or ethionamide.

- Expect to increase the dosage of oral contraceptive, corticosteroids and warfarin because rifampin is not to accelerate their metabolism.

- Notify the physician if adverse reaction of drug interaction occur.

- Monitor the patient closely for peripheral neuritis when administering 6mg/kg of INH daily of higher.

- Administer pyeridozine concurrently with INH as prescribed to prevent peripheral neuritis.

- Monitor the patient closely for optic neuritis when administering INH of 50mg/kg or higher doses of ethambutol.

- Test the patient visual acuity before INH or ethambutol theraphy begins and monthly thereafter when the ethambutol dose excite 15mg/kg and throughout INH therapy.

- Notify the physician if visual disturbances occur.

CONCLUSION

Various chemically unrelated agents are used to treat myco bacterial infections. Although this agents show relatively high bacteria specificity and inhibition, myco bacterium tuberculosis and mycobacterium leprae require long term treatment. In almost all compliant patients, combination therapy can control this diseases effectively. Isonicotinic acid hydroxide (INH), streptomycin and PAS where formerly termed first line drugs but this phase now include ethambutol and rifampin with the later two drugs and isoniazids serving as a trio of powerful first line oral drugs suitable, for initial therapy for treating TB. Their low level of toxicity make them more acceptable to the patient than PAS with its gastrointestinal upset of the painful injection of streptomycin or its ototoxicity. Although this drugs vary in terms of specific regimens and length of treatment required, they produce similar therapeutic results. Anti tubercular agents have a favorable benefit to risk ratio. Significant adverse reaction do occir however usually produces neurotoxin of hypertotoxic effect. The development of bacteria resistance to this drugs is a constant threat but aggressive combination therapy can minimize it greatly.

Finally, the nurse must instruct the patient anf family in the administration effect of and possible adverse reaction to anti mycobacterial agents monitoring the patient throughout therapy and notify the physician it adverse reaction occur.

Reference

- Mackie and McCartney Medical Microbiology Volume 1: Microbial Infections, 13^th Edition. J.P DUGUID ET AL

- Chemotherapy of Infections W. B Pratt , Oxford Press (1977)

- The Choice of Anti Microbacterial drugs, The medical letter (24,21-28, March 5^th, 1982)