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antimycobacterial drug study

antimycobacterial drug study

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Published by Kath
antimycobacterial drug study, and mycobacteria
antimycobacterial drug study, and mycobacteria

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Published by: Kath on Jan 28, 2010
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Mycobacteria, the group of bacteria that contain the pathogens that cause tuberculosis and leprosy, are classified

on the basis of their ability to hold a stain even the presence of destaining agent such as acid. Because of this property, they are called “fast acid bacteria”. The mycobacteria have an outer coat of mycolic acid that protects them from many disinfectants and allows them to survive for long periods in the environment. These slow growing bacteria may need to be treated for several years before they can be eradicated. Mycobacteria cause serious infectious diseases. The bacterium Mycobacterium tuberculosis cause tuberculosis, the leading cause of death from infectious disease in the world. For several years the disease was thought to be under control, but with the increasing number of people with compromised immine systems and the emergence of resistant bacterial strains, tuberculosis is once again on the rise. Mycobacterium leprae causes leprosy, also known as Hansen’s disease, which is characterized to disfiguring skin lesions and destructive effects on the respiratory tract. Leprosy is also a worldwide health problem; it is infectious when the mycobacteruym invade the skin or respiratory tract of susceptible individuals. Mycobacterium avium-intracellulare which causes mycobacterium avium complex (MAC), is seen in patients with AIDS or in other patients who are severely immunocompromised. Rifabutin (Mycobutin) which was developed as an antituberculosis drug, is most effective agaisnt M. Avium intracelulare. Antituberculosis drug Tuberculosis can lead to serious damage in the lungs, the GU tract, bones and the meninges. Because M. Tuberculosis is so slow growing, the treatment muct be continued for 6 months to 2 years. The first- line drugs for treating tuberculosis are as follows: • • • • Isoniazid (INH) (Nydrazids) which affects the mycolic acid coating of the bacterium Rifampin (Rifadin, Rimactane) which alters DNA and RNA activity in the bacterium. Ethionamide (Trecator SC) which prevents cell division Rifapentine (Priffin), which alters DNA and RNA activity causing cell death.

These drugs are used in combination of two or more more agents until bacterial conversion occurs or maximum improvent is seen. If the patient cannot take one or more of these drugs, or if the disease continues to progress because of the emergence of a resistant strain, the cond-line drugs can be used: • Ethambutol (Myambutol) which inhibits cellular metabolism

Pyrazinamide (generic) which is both bactericidal and bacteriostatic

These drugs are used in combination with at least one other antituberculosis drug. If therapeutic success is still not achieved, a third line combination of two antituberculosis drugs can be tried • • Capreomycin (Capastat), whose mechanism of action is unknown Cycloserine (Seromycin) which inhibits cell all synthesis and lead to cell death Using the drugs in combination, helps to decrease the emergence of resistant strains and to affect the bacteria at various phases during their long and slow life cycle.

Leprostatic Drug Antibiotics used to treat leprosy include dapsone and clofazimine. Dapsone (generic) has been the mainstay of leprosy treatment for many years although resistant strains are emerging. Similar to the sulfonamide, dapsone inhibits folate synthesis in susceptible bacteria. In addition to tits use in leprosy, dapsone is used to reat P. Carinii pnemonia in AIDS patients and for a variety of infections caused by susceptible bacteria, as well as for brown recluse spider bites. Ciofazimine (Lamprene), which binds to bacterial DNA sites and causes cell death, has been useful in the treatment of dapsone-resistant leprosy. The drug is used as part of the initial leprosy treatment in combination with dapsone to prevent the development of resistant strains. Recently, the hypnotic drug thalidomide (Thalomid) was approved in use for a condition that ccurs after treatment for leprosy. Therapeutic Action and Indication: Most of the antimycobacterial agents act on the DNA of the bacteria leading to a lack of growth and eventually to bacterial death. INH specifically affects the mycolic acid coat around the bacterium. Although many of the antimycobacterial agents are effective against other species of susceptible bacteria, their primary indications are in the treatment of tuberculosis or leprosy. The antituberculosis drugs are always used in the combination to affect the bacteria at various stages and to help to decrease the emergence of resistant strains. Pharmacokinetics The antimycobacterial agents are generally well absorbed from the GI tract, metabolized in the liver and excreted in the urine. Caution should be used in patients with hepatic or renal dysfunction, which could interfere with the metabolism and excretion of the drugs. These drugs cross the placenta and enter

breast milk; they should be avoided during pregnancy and lactation unless the benefit to the mother clearly outweighs the potential risk to the neonate. DRUGS IN FOCUS: ANTIMYCOBACTERIAL DRUGS DRUG NAME DOSAGE/ ROUTE Antituberculosis Drugs Capreomycin Adult: 1g/ d IM for 60 – 120 (Capastat) d; followed by 1g IM 2 – 3 times per week for 18 – 24 mo; reduce dosage with renal impairment. Pediatric: 15mg/kg per day IM Cycloserine Adult: 250g PO b.i.d for 2wk, (Seromycin) then 500 mg to 1g/d PO in divided dose. Pediatric: safety not established Adult: 15mg/kg per day PO as a single dose Pediatric: not recommended for children <13y Adult: 15 – 20 mg/ kg per day PO in divided doese with pyridoxine Pediatric: 10 -20 mg/kg per day PO individual doses with pyridoxine Adult: 5mg/kg per day PO Pediatric: 10 – 20 mg/kg per day PO Adult and pediatric: 15 – 30 mg/g per day PO Adult: 300 mg PO q.d. Pediatric: safety not established Adult: 600mg PO or IV as a single daily dose Pediatroc: 10 – 20 mg/kg per day PO or IV Adult: 600mg PO 2 times per week for 2 mo Pediatric: safety not USUAL INDICATIONS Second-line drug for treatment of Mycobacterium tuberculosis

Second-line drug for treatment of Mycobacterium tuberculosis

Ethambutol (Myambutol)

Second-line drug for treatment of Mycobacterium tuberculosis

ethionamide (Trecator S.C.)

First-line drug for treatment of Mycobacterium tuberculosis

Isoniazid (INH) (Nydrazid) Pyrazinamide (generic) Ritabutin (Mycobutin)

First-line drug for treatment of Mycobacterium tuberculosis Second-line drug for treatment of Mycobacterium tuberculosis Treatment of Mycobacterium avium-intracellulare (MAC) in patients with advanced HIV infection First-line drug for treatment of Mycobacterium tuberculosis

Rifampin (Rifadin, Rimactane) Rifapentine (Priffin)

First-line drug for treatment of Mycobacterium tuberculosis

established Leprostatic Drugs Dapsone Adult: 50 – 100 mg/d PO (generic) Pediatric: 1 – 2 mg/kg per day PO for 3y

Clofazimine (Lamprene)

Adult: 100mg/ d PO for at least 2 y Pediatric: safety not established

Treatent of leprosy, Pneumocystis carinii pneumonia in AIDS patients, a variety of infections caused by susceptible bacteria and brown recluse spider bites Treatment for dapsone resistant leprosy

Contraindications and Caution Anitmycobacterial drugs are contraindicated for patients with any known allergy to these agents; in those with severe renal or hepatic failure that could interfere with the metabolism or excretion of the drug; in those with severe CNS dysfunction that could be exacerbated by the actions of the drugs and in pregnancy because of possible adverse effects on the fetus. If an antituberculosis regimen is necessary during pregnancy, the combination of isoniazid, ethmabutol and rifampin is considered the safest. Adverse Effects CNS effects such as neuritis, dizziness, headache, malaise, drowsiness and hallucinations are often reported and are related to direct effects of the drugs on the neurons. These drugs also are irritating to the GI tract, causing nausea, vomitting, anorexsia, stomach upset, and abdominal pain. Rifampin, rifabutin and rifapentine cause discoloration of the body fluids from urine to sweat to tears. Patients should be alerted that in many instances orange-tinged urine, sweat and tears may stain clothing and permanently stain contact lenses. This can be frightening if the patient is not alerted to the possibility that it will happen. As with other antibiotics, there is always a possibility of hypersensitivity reactions and the patient should be monitored on a regular basis. Clinically Important Drug to Drug Interaction When rifampin and INH are used in combination, the possibility of toxic liver reactions increases. Patient should be monitored closely. Increased metabolism and decreased drug effectiveness occur as a result of administration of quinidine, corticosteroid, oral contraceptives, oral antipropanolol, oral anticoagulants, oral antidiabetic agents, digoxin, theophylline, methadone, phenytoin, verapamil, cyclosporine, or ketoconazole, in combination with rifampin or rifabutin. Patients who are taking these drug combinations should be monitored closely and dosage adjustment as needed.

Nursing Managment’ Check culture and sensitivity reports. To ensure that this is the drug of choice for this patient and arrange repeated cultures if response is not anticipated. Monitor renal and liver function test resilts before and periodically during therapy. To arrange dosage reduction as needed. Ensure that the patient receives the full course of the drugs. To improve effectiveness and decrease the risk of development of resistand bacterial strains. These drugs are taken for years and often in combination. Period medical evaluation and reteaching are often essential to ensure compliance. Discontinue the drug immediately if hypersensitivity reactions occur. To avert potentially serious reactions. Encourage the patient to eat small, frequent meals as tolerated; perform frequent mouth care and drink adequeate fluids to ensure adequate nutrition and hydration. Monitor nutrition if GI effects become a problem.

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