Antitubercular drugs

Drugs of choice are isoniazid, rifampin, and ethambutol, along with streptomycin and pyrazinamide. Less well tolerated, second-line agents include p-aminosalicylic acid, cycloserine, viomycin, kanamycin, amikacin, capreomycin, and ethionamide. 

Isoniazid is bactericidal against growing M. tuberculosis. Its mechanism of action remains unclear. In the bacterium it is converted to isonicotinic acid, which is membrane impermeable and hence likely to accumulate intracellularly. Isoniazid is rapidly absorbed after oral administration. In the liver, it is inactivated by acetylation. Notable adverse effects are peripheral neuropathy, optic neuritis preventable by administration of vitamin B6 (pyridoxine), and liver damage. 

Rifampin. Source, antibacterial activity, and routes of administration are described on p.276. Although mostly well tolerated, this drug may cause several adverse effects Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms 

Pyrazinamide exerts a bactericidal action by an unknown mechanism. It is given orally. Pyrazinamide may impair liver function hyperuricemia results from inhibition of renal urate elimination. 

Streptomycin must be given i.v. like other aminoglycoside antibiotics (p. 280). It damages the inner ear and the labyrinth. Its nephrotoxicity is comparatively minor 

Optic neuritis, fever, pruritis, headache, nausea, anorexia, dermatitis, hypersensitivity, p chic disturbances Peripheral neuropathy, nausea, vomiting, epigastric distress, jaundice, hepatitis, pyridoxine deficiency, skin eruptions, hypersensitivity 

Hepatotoxicity, nausea, vomiting, diarrhea, myalgia, rashes 

Hypersensitivity reactions, nephrotoxicity, hepatic impairment, pain and induration at injection site, ototoxicity Convulsions, somnolence, confusion, renal impairment, sudden development of congestive heart failure, psychoses 

Most aiititubercular dni are bacteriostatic (slow or retard the growtli of bacteria) against tlie M. tuberculosis bacillus. These dni usually act to inhibit bacterial cell wall syntliesis, which slows tlie multiplication rate of the bacteria. Only isoniazid is bactericidal, with rifampin and streptomycin having some bactericidal activily. 

Tuberculosis is a major health problem throughout the world, infecting more than 8 million individuals each year. It is die world s leading cause of death from infectious disease Individuals living in crowded conditions, those widi compromised immune systems, and individuals widi debilitative conditions are especially susceptible to tuberculosis. 

GENERIC NAME TRADE NAM E USES ADVERSE REACTIONS DOSAGERANGES 

Aiititubercular drug s are used in combination with other aiititubercular dm to treat active tuberculosis. Isoniazid (INH) is the only aiititubercular drug used alone While isoniazid is used in combination with other drains for the treatment of primary tuberculosis, a primary use is in preventive therapy (prophylaxis) against tuberculosis. For example, when a diagnosis of tuberculosis is present, family members of the infected individual must be given prophylactic treatment with isoniazid for 6 months to 1 year. Display 12-1 identifies prophylactic uses for isoniazid. 

Of increasing concern is the development of mutant strains of tuberculosis that are resistant to many of the aiititubercular drug s currently in use. Bacterial resistance develops, sometimes rapidly, with the use of anti-tubercular drag s. Treatment is individualized and 

Rifamycin is found to afford induction of the specific hepatic drug-metabolizing enzyme system and, therefore, accelerates the metabolism of digitoxin, methadone, phenytoin, 3-blockers, verapamil, oral contraceptives, chloramphenicol, theophylline, besides—oral anticoagulants, estrogens, tolbutamide, barbiturates and itself 

The drug has proved to be teratogenic in laboratory animals and, hence, must be refrained particularly in pregnancy. 

It is absorbed almost 100% after oral administration however, the food present in the stomach may delay its absorption considerably. It gets widely distributed in the body and even into the CSF. In plasma almost 98% is protein-bound. The volume of distribution (v/ ) stands at 0.9 mL.g Biotransformation in the liver helps in the elimination of almost 85% of the drug . An active and primary metabolite, deacetylrifampin, gets secreted right into the bile where it is effective therapeutically. 

Cautions (1) Risk of hepatotoxicity gets increased when used in combination with INH. 

A plethora of drugs are known that are found to be affecting the force of cardiac contractions. These drugs find there enormous use for the treatment of congestive heart failure by prolonging the life span of patients through pumping sufficient blood to sustain body requirements. 

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Discuss the uses, general drug action, contraindications, precautions, interactions, and general adverse reactions associated with the administration of the antitubercular drugs. 

Discuss important preadministration and ongoing assessment activities the nurse should perform on the patient taking an antitubercular drug. 

Discuss ways to promote an optimal response to therapy, how to manage adverse reactions, and important points to keep in mind when educating patients about the use of the antitubercular drugs. 

When administering die antitubercular drug by die parenteral route, die nurse is careful to rotate the injection sites. At die time of each injection, die nurse inspects previous injection sites for signs of swelling, redness, and tenderness. If a localized reaction persists or if die area appears to be infected, it is important to notify die primary health care provider. 

Monitoring and Managing Adverse Reactions Managing adverse reactions in patients taking antitubercular drug s is an important responsibility of die nurse The nurse must continuously observe for signs of adverse reactions and immediately report them to tlie primary health care provider. Some information specific to die different antitubercular drug s is provided below. 

Older adults are particularly susceptible to a potentially fatal hepatitis when taking isoniazd, especially if they consume alcohol on a regular basis. Two other antitubercular drugs rifampin and pyrazinamide, can cause liver dysfunction in the older adult. Careful observation and monitoring for signs of liver impairment are necessary (eg, increased serum aspartate transaminase, increased serum alanine transferase, increased serum bilirubin, and jaundice). 

The nurse reviews the dosage schedule and adverse effects associated with the prescribed antitubercular drug with the patient and family. Information that applies to all patients taking these drugs includes ... 

The nurse includes the following information in the teaching plan when a specific antitubercular drug is prescribed ... 

Which of the following drugs is the only antitubercular drug to be prescribed alone ... 

Which of the following antitubercular drugs is contraindicated in patients with gout ... 

Against this backdrop, researchers reported evidence that iproniazid, the antitubercular drug that was to become the first antidepressant, might increase norepinephrine and serotonin levels in the brain. How did it have this effect Recall that some of the neurotransmitter molecules released by a neuron are destroyed by enzymes in the synaptic cleft between the sending presynaptic neuron and the receiving postsynaptic neuron. When the neurotransmitter is a monoamine - like norepinephrine and serotonin - this process is called monoamine oxidase (MAO). As early as 1952 researchers at the Northwestern University Medical School in Chicago reported that iproniazid inhibited the oxidation of monoamines. This meant that iproniazid was a... 

Ethambutol is administered concurrently with other antitubercular drugs in the treatment of TB in order to... 

Irradiation of an alcoholic solution of the antitubercular drug isoniazid (261) with a low-pressure mercury lamp by Ninomiya and Yamamoto gave isolated yields of the hydrazone (262, 60%) and the hydrazide (264, 17%). Nicotinic and picolinic acid hydrazides reacted similarly, as did other alcohols. The production of (262) was easily understood since it was known that photolysis of ethanol gave acetaldehyde which would react spontaneously with the... 

The elimination rate constants of an antitubercular drug in normal and a renally impaired patient were found to be 0.2 and 0.08 hour1, respectively. It is usually administered once daily in a dose of 300 mg. How can the dose be adjusted in the renally impaired patient to provide similar plasma levels as in the normal patient by maintaining the same dosing interval of 24 hours ... 

Some substances, such as carbon monoxide and barbiturates, can deprive brain cells of oxygen or glucose - they produce anoxia - with potentially serious consequences for gray matter. Other substances, such as lead, hexachlorophene, and the antitubercular drug isoniazid, are capable of causing loss of myelin, a coating or sheath for the axon and dendrites that extend from the central unit (cell body) of neurons. Demyelination can occur in either the CNS or PNS. 

Rifampin is a first-line antitubercular drug used in the treatment of all forms of pulmonary and extrapul-monary tuberculosis. Rifampin is an alternative to isoniazid in the treatment of latent tuberculosis infection. Rifampin also may be combined with an antileprosy agent for the treatment of leprosy and to protect those in close contact with patients having H. influenza type b and N. meningitidis infection rifampin is also used in methicillin-resistant staphylococcal infections, such as osteomyelitis and prosthetic valve endocarditis. 

Ethambutol has replaced aminosalicylic acid as a first-line antitubercular drug. It is commonly included as a fourth drug, along with isoifiazid, pyrazinamide, and rifampin, in patients infected with MDR strains. It also is used in combination in the treatment of M. avium-intracellulare infection in AIDS patients. 

All mycobacteria produce (3-lactamase. In vitro, several (3-lactamase-resistant antibiotics or a combination of a (3-lactam with (3-lactamase inhibitors, such as clavulanic acid, are active against M tuberculosis and nontubercu-lous mycobacteria. However, the activity of (3-lactam agents against intracellular mycobacteria is generally poor. The (3-lactam agents may be useful in the treatment of MDR tuberculosis in combination with other antitubercular drugs but never as monotherapy. 

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