Keep in mind that Isonaizd(INH) is the established treatment for preventive therapy , and the usual regimen is up to 300mg daily for adults. You can keep pts on for 6 months or 12 months with a positive CXR. Always give vitB6 when treating pts with INH. If there is a suspected resistance then use Rifampin (RIF) alone or in combo with the said INH. How do we treat current CLASSES III & IV diseases.
The first line medications are used in combinations since these tend to delay the development of resistance and to enhance activity.
INH(p.o. or IM) 300mg. inhibits synthesis of mycolic acid in the bacterial cell wall thus making it easy to kill the organism in the dividing stage. The drug is however, bacteriostatic for the bacilli in the stationary phase. The drug is metabolized by N-acetyl transferase. Some of side effects include paresthesia, fever, convulsions, hepatotoxic, optic neuritis and Hemolysis in G6PD deficient pts. High level resistance involves deletion in the katG gene that codes for catalase, and low-level resistance involves deletions in the inhA gene that codes for the target acyl carrier protein. Keep in mind that genotypic variability exists with FAST ACETYLATORS needing high doses of INH. Remember for the boards that Vit B6 will offset the neurotoxicity.
RIFAMPIN(RIF) GOOD against Mycobacterium tuberculosis very bacteriocidal against it. Also against M. leprae. Can be used prophylactically in meningitis. The drug suppress the initial step of RNA synthesis by inhibiting DNA dependent RNA polymerase, and resistance occurs via change in polymerase sensitivity to inhibition. The drug undergoes hepatic metabolism to red-orange colored metabolites. So let the patient know that the urine and feces will be red-orange in color. Nausea ,vomiting, rashes, fever, jaundice and flu like symptoms with high doses. This drug will reduce the efficacy of anticonvulsants,contraceptive steroids and warfarin so take note for your boards and clinical treatment.
PYRAZINAMIDE(PZA): Good for short term use and initial therapy with INH and RIF. The precise target of this drug is not well understood. Works well when bacteria is dividing very bacteriocidal at that point. The drug requires bioactivation. Can cause gouty attacks, liver dysfunction, phototoxicity, hyperuricemia, exacerabation of porphryia, polyarthralgia.
ETHAMBUTOL(EMB): Great against M.tuberculosis and kansasii. The drug inhibits synthesis of arabinogalactan a component of mycobacterial cell wall. The side effects are dose dependent, and most common are optic neuritis,and gout.
So we have looked at the first line drugs for treating TB, but keep in mind that daily intake of Alcohol increases the risk of hepatitis in patients on INH. In females on oral contraceptives increase the dosages or change to another form of contraceptive. RIF will also decrease methadone activity in pts on it so increase the methadone dosage by 50% . In treating pregnant patients the initial combination
should be INH, RIF and EMB along with B6. Do not use PZA it is TERATOGENIC, do not use STREPTOMYCIN also will cause deafness. In fact let me mention some antibiotics to be AVOIDED IN PREGNANCY.: Aminoglycosides – ototoxic in developing fetus, Clarithromycin-embryotoxic
Erythromycin estolate- increases incidence of cholestasis in the pregnant patient.
Fluoroquinolones- deleterious effect on collagen metabolism
Tetracyclines- interfere with bone and tooth formation via calcium chelation
Sulfonamides- not to be used in third trimester can displace bilirubin from plasma proteins in the fetus and neonate causing KERNICTERUS. Metronidazole – mutagenic.
OK let me get back to TB treatment. The second line drugs are Aminosalicylic acid, Ethionamide, Cycloserene, Streptomycin, ciprofloxacin, Oflofloxacin, Kanamycin or Capreomycin
Amniosalicyclic acid: This is a bacteriostatic drug used...