I had a friend who had tuberculosis, and I remember that he had to separate his spoon, cup, and plate, and he was keeping his distance. It took him months to get treated, and today he is fine. In our pharmacology post, I will be talking about Anti-Tubercular drugs.
Tuberculosis is a very infectious chronic disease that is caused by Mycobacterium Tuberculosis which is treated over a long period of time and could take months or years. Tuberculosis lesion is fibrotic preventing the penetration of the drug. Tuberculosis drugs can be divided into First-line Tuberculosis Drug and Second-line Tuberculosis Drug. First-line tuberculosis drugs are the first, cheap, and very effective, with decreased dose toxicity. These drugs include Isoniazid, Rifampin, Streptomycin, pyrazinamide, and Ethambutol.
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Isoniazid inhibits mycolic acid synthesis which is important to the bacteria's cell wall. The drug uses bacteria catalase for its activation and if the bacteria catalase is mutated, then the bacteria can become resistant to the drug. It has pharmacokinetic properties are the ability to cross the CFS barrier, the placenta, and tubercular cavities. Acetylation is used to metabolize it in the liver and excretion is done via Urine. The side effect of Isoniazid includes Hepatotoxicity, as a result of the drug being metabolized by the liver which could lead to an increase in LFT level, Sideroblastic anaemia, SLE, and Heamolytic anaemia.
Rifampin is a stabilizing agent that act on both intracellular and extracellular bacteria. It inhibits the DNA-Dependent RNA-polymerase. It is bactericidal against bacteria such as Gonococcus, mycobacterium tuberculosis, H.influenza, Staphylococcus aureus, and E.coli. It is metabolized in the liver by acetylation, also food reduces its absorption. Its metabolized waste is excreted via the Urine while the unmetabolized waste undergoes entero hepatic recycling and is excreted in the bile. Rifampin is used to treat tuberculosis, leprosy, and meningococcal. Since the liver metabolizes it, it can lead to hepatotoxicity as a side effect, also it can lead to itches, skin rash, and can lead to unwanted pregnancies in females.
Pyrazinamide is another first line drug that inhibits mycolic acid synthesis similar to Isoniazid but not with the same mechanism. taking the medication can lead to dose-dependent hepatic toxicity, and hyperuricemia as it competes for secretion in the Kidney with Uric Acid.
Ethambutol inhibits arabinogalactan synthesis, and Cell wall inhibition. It is bacteriostatic with no cross resistance with other anti-tuberculosis drug and it can cross the blood-brain barrier. It can be used to treat meningitis, and it combacts Mycobacterium avium complex. Its side effect include optic neuritis, and hyperuricemia. Tubercolosis patients can be treated with Streptomycin as a first-line tuberculosis drug. It is administered via IV or IM.
Second-line tuberculosis drugs are used if the first-line drugs. They are expensive and have increased toxicity. Second-line tuberculosis drug includes Fluoroquinolones, amikacin, cycloserine, Ethionamide, and Capromicin.
Floroquinolones are flourinated form of nalidixic acid which include ciprofloxacin, Norfloxacin, Levofloxacin,etc. The inhibit Topoisomerase 2 in gram negative bacteria and Topoisomerade 4 in gram positive bacteria. These drugs inhibits bacteria DNA-synthesis making them bactericidal drugs. Floroquinolone have high activity against E.coli, Enterobacter, Shiegella, Campalobacter jejuni, Neisseria and a lot of gram negative bacteria. It also has high activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. It can be used to treat UTI and STIs, and it is bactericidal in nature.
Amikacin is another secon-line tuberculosis drug that is bactericidal and given through IV. Cycloserine is another drug which is obtained from Strptomyces orchidaceus or Streptomyces garyphaius and it can also be obtained synthetically. It is a part of the multidrug regimen for tuberculosis but has a broad sprectrum of action against gram positive and gram negative organisms. Cycloserin can cross blood-brain barrier. It inhibits cell wall synthesis but can exhibit side effects which are neurologic such as convulsion, tremor, headache, depression, suicidal tendencies, vertigo, drowsiness, paresis, dysarthria, paraesthesia, coma, and psychosis. It can cause heart failure in patients that use excessively.
Ethionamide is another drug that has similar structures to Isoniazid but has reduced efficacy.
The regimens of treating tuberculosis involve multidrug therapy, so as to get rid of the bacteria, prevent resistance, prevent relapse, and to shorten the therapy period. The first course of the Therapy is about 6 to 8 eight months which has both an intensive and continuation phase. The intensive phase is between 2 to 3 months with 4 drugs combined while the continuation phase is between 4 to 6 months with 2 drugs combined. The intensive phase is to ensure the patient is non-contagious while treating while the continuation phase will prevent relapse.
https://www.niaid.nih.gov/diseases-conditions/tbdrugs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663953/
https://www.cdc.gov/tb/education/corecurr/pdf/chapter6.pdf
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https://www.webmd.com/drugs/2/drug-1054/cycloserine-oral/detail