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)