Tuberculosis

=Tuberculosis and Rifampicin =

Motivation and Background:
Tuberculosis is a bacterial infection that is spread through the air, though activities like breathing, singing, spitting, and speaking with someone with active tuberculosis.1 The disease has been thought to have been around for more than 4,000 years, dating back to ancient Egyptian times. The populations of ancient Italy, Denmark, and Middle Eastern countries have produced many fossils providing tubercular deformities. 2 The symptoms of tuberculosis are a sustained cough, coughing up blood, chest pain and fatigue. If left untreated, the infection will spread to the central nervous system, kidneys, lungs, heart and brain of the infected individual, and could be potentially become fatal. Tuberculosis targets especially compromised immune systems. This can include populations of [|children, healthcare workers, those with HIV/AIDS, IV drug abusers, diabetics, organ transplant recipients, and those who live in African and Asian countries.]3 Tuberculosis continues to be a cause of mortality due to increasing antibacterial drug resistance that occurs in nearly all populations. Drug resistance leads to loss of efficacy due to the requirement of longer sessions of therapy needed for resistant individuals. Increasing the length of antibacterial treatment means that patients must take extended doses of antibacterial medication, when the infection symptoms often subside after a number of doses lesser than the prescribed regimen. Patients often stop taking treatment once symptoms subside, which leaves the drug user susceptible to becoming resistant to the treatment bacteria as well.4 Drug resistance is a current problem in the world of healthcare that has yet to be solved, and in turn effects many tuberculosis sufferers. The motivation to treat tuberculosis is that it is a major cause of death, especially in elderly populations, as the average age at death from tuberculosis complications was 74 years old in 2016. In the same study, the overall mortality rate was 12.3% of the cases from 2016. The majority of these deaths were said to have been from non-tuberculosis related reasons, meaning that tuberculosis is a deadly comorbidity. [[image:global.png width="800" height="465" caption="Fig 2. Global numbers causing drug resistant tuberculosis.1 "]]



=Target Information: =

Location:
DNA Dependent RNA polymerase ====**Function in a normal cell**: DNA dependent RNA polymerase is the enzyme that produces the initial tRNA. This means there must be something to inhibit the replication of bacterial DNA in order to cure tuberculosis. This mechanism, found in the drug rifampin which is explored further below, works in the bacterial DNA dependent RNA polymerases to suppress the initiation of RNA synthesis, which means that the RNA polymerase cannot properly synthesize mRNA, but still keeps the normal enzyme intact, not effecting the human enzyme. This kills the replication process for the harmful mycobacteria, meaning the strain as a whole cannot be kept alive under most circumstances in the presence of this drug. Production will cease and it will leave the cells inhospitable for the mycobacteria to continue to repopulate itself. ====

=Drug Information: =



**Formula**:
C43H58N4O12 Molecular weight: 822.953 g/mol 13292-46-1 and 62534-43-4 **Delivery method:** Rifampicin can be ingested orally or taken intravenously <span style="font-family: 'Times New Roman',Times,serif;">**Side effects:** Side effects include but are not limited to itching, flushing, headache, drowsiness, dizziness, lack of coordination, lack of concentration, confusion, change in normal behavior, muscle weakness, intermittent pain in the extremities, diarrhea and vision change
 * <span style="font-family: 'Times New Roman',Times,serif;">CAS Number: **

<span style="font-family: 'Times New Roman',Times,serif;">**Other names:** Other names for rifampicin are Rifadin and Rinactane

<span style="font-family: 'Times New Roman',Times,serif;">**Maker or company**: Sanofi-Aventis

<span style="font-family: 'Times New Roman',Times,serif;">**Is it patented?** Rifampicin is patented by Sanofi-Aventis <span style="font-family: 'Times New Roman',Times,serif;">**Clinical Trials Info:** There are currently 130 clinical trials with rifampin and tuberculosis that have been completed, and many more that are still in progress or have been halted premeditatedly. <span style="font-family: 'Times New Roman',Times,serif;">Alternatives to this drug: Similar treatments include isoniazid and pyrazinamide
 * <span style="font-family: 'Times New Roman',Times,serif;">Origin: **<span style="font-family: 'Times New Roman',Times,serif;">Rifampin originated in the soil bacterium Amycolatopsis rifamycinica. It is thought that the bacteria that causes tuberculosis was also found in the soil and transmitted by the domestication of livestock
 * <span style="font-family: 'Times New Roman',Times,serif;">Miscellaneous: **<span style="font-family: 'Times New Roman',Times,serif;">The mycobacteria have evolved to inhibit their own cell death, but that mechanism is not known. 2 Another unique feature of the mycobacteria is that there is no true determinant of virulence factors, meaning it does not take the standard approach to the major causes of death other bacterial infections like diphtheria and cholera use.

<span style="font-family: 'Times New Roman',Times,serif;">**Other uses:** Rifampicin can also be used to treat bacterial anthrax infections and bacterial leprosy infections.


 * <span style="font-family: 'Times New Roman',Times,serif;">References: **

<span style="font-family: 'Times New Roman',Times,serif;">1.Zumla, A.; Raviglione, M.; Hafner, R.; von Reyn, C. F., Tuberculosis. N Engl J Med 2013, 368 (8), 745-55. <span style="font-family: 'Times New Roman',Times,serif;">2.Smith, I., Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence. Clinical Microbiology Reviews: 2003; Vol. 16, pp 263-296. <span style="font-family: 'Times New Roman',Times,serif;">3. Latent TB Infection and TB Disease. <span style="font-family: 'Times New Roman',Times,serif;">4.van Ingen, J.; Aarnoutse, R. E.; Donald, P. R.; .Diacon, A. H.; Dawson, R.; Plumper van Balen, G.; Gillespie, S. H.; Bore, M. J., Why Do We Use 600 mg of Rifampicin in Tuberculosis Treatment?. Clin Infect Dis: 2011; Vol. 52, pp e194-199. <span style="font-family: 'Times New Roman',Times,serif;">

<span style="font-family: 'Times New Roman',Times,serif; font-size: 14px;">External links: https://www.cdc.gov/tb/topic/basics/tbinfectiondisease.htm