Tuberculosis+(Mycobacterium+tuberculosis)

=__**Disease/Drug of interest** : __ Mycobacterium Tuberculosis / rifampin (RIF)=

**Motivation and Background** :
Tuberculosis (TB), also known as consumption, is a disease caused by a bacteria that usually targets the lungs but can attack any part of the body for instance the kidney, spine, and brain [2]. There are two different tests that are used to determine if a person is infected with the TB bacteria: the tuberculin skin test and the TB blood tests [2]. The TB skin test, also called the Mantoux tuberculin skin test, is done by injecting a small amount of fluid called tuberculin into the skin in the lower part of the arm [2]. Once given the tuberculin skin test you must return within 48 to 72 hours to have a qualified health care worker examine for a reaction on the arm. If the area where the injection took place is swollen, the test is positive meaning that the person’s body was somehow infected or exposed to the bacteria. Another way to test for infection is the TB blood test. TB blood tests, also called interferon-gamma release assays or IGRAs, gauge how the immune system responds to the bacteria that cause TB [2]. If both the blood and skin tests are positive then additional tests are needed to determine if the person has latent TB infection or the active disease. The TB bacteria can live in the body without showing any symptoms. This is called latent TB infection. People exposed by the disease can fight the bacteria to stop them from growing. People with latent TB infection cannot spread TB bacteria to others. On the other hand, if the TB bacteria were to become active in the body and spread, the person will go from having latent TB infection to being sick with the disease. TB bacteria becomes active if the immune system can't stop them from growing any longer. People with active Tuberculosis are able to spread the bacteria to people they spend time with daily. There are cases where people who have latent TB infection never develop TB disease whereas some people develop TB disease within a few weeks of becoming infected, before their immune system can react. Other people may get sick years later when their immune system is weakened from another cause [2].

Tuberculosis can spread through the air from one person to another [2]. It is an airborne bacteria. The TB bacteria are put into the air when a person with TB disease of the throat or lungs coughs, speaks, sneezes or sings [2]. People nearby may breathe in these bacteria and become infected. This makes this disease a big threat towards large populations especially people who have weak immune systems. TB is one of the most common infectious diseases worldwide and a well-known household name. While noteworthy progress has been made toward the eradication of TB in the United States, this disease remains a critical public health problem in many other parts of the world. In 2013, 65% of all TB cases and 90% of multidrug–resistant TB cases in the United States happened among people born in other countries. Nearly 50% of these individuals were born in just five countries [2].

[1] Alsayyed, B.; Adam, H. M. Rifampin. // Pediatrics in Review // 2004, // 25 // (6), 216–217. [2] Tuberculosis (TB) http://www.cdc.gov/tb/topic/default.htm (accessed Feb 7, 2016). [3] Rifampin|tuberculosis https://clinicaltrials.gov/ct2/results/details?term=rifampin (accessed Feb 7, 2016). [4] Generic Rifadin Availability - Drugs.com http://www.drugs.com/availability/generic-rifadin.html (accessed Feb 7, 2016). [5] Howard, P.; Twycross, R.; Grove, G.; Charlesworth, S.; Mihalyo, M.; Wilcock, A. Rifampin (INN Rifampicin). // Journal of Pain and Symptom Management // 2015, // 50 // (6), 891–895. [6] Mitchison, D. A. Shortening the Treatment of Tuberculosis. // Nat Biotechnol Nature Biotechnology // 2005, // 23 // (2), 187–188. [7] Rifampicin http://pubchem.ncbi.nlm.nih.gov/compound/5458213#section=bioassay-results (accessed Feb 7, 2016). [8] Rifampin: Indications, Side Effects, Warnings - Drugs.com http://www.drugs.com/cdi/rifampin.html (accessed Feb 7, 2016). [9] Rifadin (Rifampin) Drug Information: Description, User Reviews, Drug Side Effects, Interactions - Prescribing Information at RxList http://www.rxlist.com/rifadin-drug.htm (accessed Feb 7, 2016).
 * References: **

**External links:**
RNA Polymerase image: http://f.emf.fr/confs2010/2010-03-10_journee_d_etudes_nanos/Lewalle/rna%20polymerase.jpg

=__**Target Information** : __= Rifampin inhibits DNA-dependent RNA polymerase activity in vulnerable cells[1,5,7,8]. Specifically, it interrelates with bacterial RNA polymerase but does not constrain the mammalian enzyme [7]. It is bactericidal and has a very wide-ranging spectrum of activity against most gram-positive and gram-negative organisms and specifically Mycobacterium tuberculosis [1].  Figure 1: RNA polymerase synthesizing messenger RNA normally.

** Location: **
Bacterial DNA-dependent RNA-polymerase.

** Function in a normal cell: **
Synthesizes RNA which in turn synthesizes protein that the bacteria needs to survive. =__**Drug Information**** : **__=

Figure 2: Schematic figure of Rifampin (Rifampicin) along with other drugs on a bacteria cell [6].
 * Schematic figure of drug ** :



Figure 3: Molecular structure of Rifampin.
 * Formula ** : C43H58N4O12


 * Molecular weight ** : 822.95g/mol
 * CAS Number ** : 13294-46-1


 * Delivery method ** : Intravenous (IV), injection, pill
 * Side effects ** :

Call your doctor at once if you have:


 * flu symptoms (fever, chills, body aches, headache, dizziness);
 * easy bruising or bleeding (nosebleeds, bleeding gums);
 * diarrhea that is watery or bloody;
 * little or no urinating;
 * liver problems--upper stomach pain, tired feeling, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes); or
 * severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:


 * heartburn, gas, upset stomach, loss of appetite;
 * nausea, vomiting, diarrhea, stomach cramps;
 * headache, dizziness, drowsiness, weakness, tired feeling;
 * muscle weakness, pain in your arms or legs;
 * vision problems;
 * flushing (warmth, redness, or tingly feeling); or
 * confusion, changes in behavior, trouble concentrating.

Rifampicin; Benemycin; Rifampin; Dipicin; Rimycin; Rifamicin AMP; Rifadin; Rifadin IV
 * Other names ** :
 * Maker or company ** : SANOFI AVENTIS US
 * Is it patented ** ? Yes, f or manufacturer SANOFI AVENTIS US the oral drug was patented in 1982 whereas the other manufacturers have different approval dates and it also depends on its delivery form [4].


 * Clinical Trials Info ** : 145 studies involve rifampin | tuberculosis.

__** Origin ** : __ Rifampin is a semisynthetic derivative of rifamycin B, a fermentation product of Streptomyces mediterrianei. Another common use for rifampin in pediatrics is to eradicate the carrier state in close contacts of patients who have meningitis from N meningitides or H inﬂuenzae. Rifampin is the drug of choice for chemoprophylaxis against both organisms[1].
 * Alternatives to this drug ** : (mentioned with the other names)
 * Miscellaneous ** : Rifampin must not be taken alone, it must be taken along with isoniazid, ethambutol, or pyrazinamide.
 * Other uses ** : can this drug be used to treat other diseases/conditions?