Tuberculosis , also known as consumption, is a systemic infectious disease caused by the bacterium Tuberculosis. It can occur all year round, with an incubation period of 4-8 weeks. The respiratory tract transmission between person to person is the main way that this disease infects, infecting source is the tuberculosis patient that contacts discharge bacterium. The human body except hair almost whole body all tissues can be infected with tuberculosis, wait like enteric tuberculosis, bone tuberculosis, lymphatic tuberculosis. But because tuberculosis basically undertakes through respiratory tract to spread, because this tuberculosis infection rate is higher than other organs, occupy the first place of human body tuberculosis. Tuberculosis early stage does not have obvious symptom, there can be systemic symptom after disease development, wait like tired, inappetence, emaciation, low heat, still have the local symptom of pathological change organ. Tuberculous bacterium after invading human body has to the whole body viscera spread sex and long-term latent sex in the organization. Tuberculosis usually occurs or recaps when the body’s resistance is low.
Drug treatment for tuberculosis
Tuberculosis person wants early to begin to treat, reasonable combine drug use, dose wants appropriate, reach the time of the requirement, this can make the patient is cured and recrudescence rarely, tubercle bacterium after treatment also won’t produce drug resistance.
The anti-tuberculosis drug treatment that uses chemical and biological agent calls chemical therapy again, it is modern tuberculosis most main treatment method. All other treatments are adjuvant. Chemotherapy is the only effective way to control the spread of TB. The commonly used bactericidal drugs for chemotherapy are rifampicin (din) and isoniazid. Sterilization drugs for pyrazinamide, streptomycin; Bacteriostatic drugs are ethambutol, sodium paraminosalicylate, thiourea; B (c) thioisomiamine, cycloserine, kanamycin, capreomycin and so on are only used in patients with drug resistance.
2.Classification of drug treatment for tuberculosis
For a long time, anti-TB drugs have been divided into first-line and second-line drugs based on: bactericidal activity, clinical efficacy, safety, and drug price.
Traditionally, there are two classes of first – and second-line antitb drugs. Isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin are classified as first-line drugs because of their good efficacy and low side effects. The rest are classified as second-line drugs, including rifapentine, rifaputine, kanamycin, amikacin, ofloxacin, levofloxacin, moxifloxacin, cycloserine, p-amino-salicylic acid, etc. (2) According to the bactericidal and bacteriostatic effects, it can be divided into bactericidal drugs and bacteriostatic drugs. Isoniazid and ripfampicin are total bactericidal drugs, while pyrazinamide and streptomycin are semi-bactericidal drugs, and other tuberculosis drugs are bacteriostatic drugs. (3) Classification by action and function According to the action and function of anti-tuberculosis drugs, drugs with early bactericidal effect such as isoniazid, drugs with bactericidal effect such as rifampicin.
Who classification The WORLD Health Organization divides drugs into five groups based on their efficacy, experience with use, and drug classification, which is useful for chemotherapy of drug-resistant TB. The first group was given first line oral anti-tuberculosis drugs isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z) and rifambutin (Rfb). The second group was injected with anti-tuberculosis drugs kanamycin (Km), amikacin (Am), capreomycin (Cm) and streptomycin (S). The third group of fluoroquinolones were moxifloxacin (Mfx), levofloxacin (Lfx) and Ofx. The fourth group was given the second-line antituberculous drugs: Eto, Pto, Cs, Trd and PAS. The fifth group was treated with clofazimine, linezolid, amoxicillin/clavulanic acid, imipenem/cilastatin, high-dose isoniazid and clarithromycin.
3.First-line anti-tb drugs
(1) Isoniazid INH: As one of the most powerful anti-tuberculosis drugs, INH is an essential drug for the treatment of tuberculosis. Its mechanism of action may be to inhibit the synthesis of sensitive bacteria mycolic acid and rupture the cell wall through the activation of bacterial endothixoenzyme — peroxidase. Inhibition of bacterial folate synthesis. This medicine can kill cell inside and outside growth metabolizes exuberant and almost static tuberculosis bacterium, it is a kind of full effect fungicide. Caution: Isoniazid can cause severe and sometimes fatal liver damage. Common side effects include vision problems, diarrhea and mild stomach upset. Serious side effects include numbness or tingling in the hands and feet, eye pain, sore throat, fever, swollen glands, abnormal bleeding or bruising, stomach pain or tenderness, seizures, and memory or mood changes. In addition, there may be signs of an allergic reaction, which may include hives, itching, difficulty breathing or swelling of the face, mouth, lips or tongue.
(2) Rifampin (meperifamamycin, Rifampin RFP) : AS a semi-synthetic broad-spectrum fungicide, RFP firmly binds to the β subunit of DNA-dependent RNA polymerase, inhibits the synthesis of bacterial RNA, prevents the enzyme from binding to DNA, and thus blocks the RNA transcription process. With isoniazid same, this article belongs to total effect fungicide, can kill cell inside and outside growth metabolism exuberant and almost static tuberculosis bacterium. Note: Common side effects of lifampin include heartburn, upset stomach and cramps, bloating, diarrhea, headache, drowsiness, fatigue, dizziness, difficulty concentrating, confusion, muscle weakness or body numbness and pain, vision changes, dyspenorrhea or irregular periods, flushing and itching, and loss of coordination. Go to the hospital immediately if you experience: fever, loss of appetite, anxiety, nausea and vomiting, dark urine, jaundice, joint pain or swelling.
Now with rifampicin as the representative of tuberculosis drugs are better, as long as people can improve the understanding of tuberculosis, timely detection of regular treatment, its efficacy can reach 95% – 100%.
(3) Streptomycin SM: SM belongs to aminoglycoside antibiotics. Its antibacterial mechanism is to inhibit the synthesis of bacterial proteins, and it has a strong antibacterial effect on tuberculosis bacteria. SM mainly inhibits 70S complex formation by interfering with the binding of amyl-trna and 30S subunit of the nucleosome, thus inhibiting the extension of the peptide chain, affecting the synthesis of protein, and finally leading to bacterial death. But it can kill the tuberculosis bacterium outside the cell only, play a role when pH is neutral, pass barrier of blood brain and penetrate into the cell not easily, belong to half effect fungicide.
(4) Pyrazinamide PZA: this product is a derivative of nicotinamide. It has bacteriostatic or bactericidal effects. The effect depends on drug concentration and bacterial sensitivity. This product has antibacterial activity only when pH is acidic (pH≤5.6), it is a semi-effective bactericide. Note: Pyrazinamide must be used with other TB drugs. If pyrazinamide is used alone, tuberculosis may become resistant to treatment. Common side effects of pyrazinamide include joint or muscle pain, nausea and vomiting, and loss of appetite.
(5) Ethambutol EMB: This product is a synthetic antibacterial and anti-tuberculosis drug. Its mechanism of action has not been fully elucidated, and may be inhibition of RNA synthesis. It is thought that it can increase the permeability of the cell wall, infiltrate into the bacteria and interfere with the synthesis of RNA, thereby inhibiting bacterial reproduction. This product is only effective against growing and breeding tuberculosis bacteria. Note: Ethambutol can cause serious vision problems or irreversible vision loss. If you have eye problems or vision problems, you may not be able to take the drug. To be safe, tell your doctor if you have any of the following: inflammatory eye diseases such as uveitis or iritis, eye problems caused by diabetes, cataracts, liver disease, kidney disease, gout.
(6) Thiosemicarbazone TB1: this product is an antibacterial agent, the mechanism of action is not very clear. There are studies that TB1 is easy to generate a complex with copper, tuberculosis lack copper ion, may also hinder the synthesis of nucleic acid, and make the bacteria morphology changes, such as the loss of normal size, granular degeneration, linear or coccal deformation, acid-fast staining reaction loss.
4.Second-line anti-TB drugs
Second-line drugs are mostly bacteriostatic drugs, can only inhibit tuberculosis, side effects will be more. Patients are more prone to gastrointestinal reactions, peripheral neuropathy (numbness of hands and feet), and liver damage.
(1) Para -aminosalicylic acid PAS: PAS has an inhibitory effect on tuberculosis. This product can inhibit the growth and reproduction of tuberculosis bacteria through the competitive inhibition of folic acid synthesis.
(2) Prothionamidam (1321TH,PTH) : Prothionamidam is a derivative of isonicotinic acid with a chemical structure similar to thiourea ammonia (TB1). It is a weak fungicide. The mechanism of action is not clear yet, and it may have an inhibitory effect on the synthesis of peptides. The action of propyl sulphur isomiacin to tuberculous bacterium depends on the drug concentration of infection site, low concentration only has bacteriostatic action, high concentration has bactericidal action.
(3) Amikacin (amikacin, amikacin, AMK, AK) : belongs to the aminoglioside drugs, in the test tube for tuberculosis bacteria is a highly effective bactericidal drugs. The mechanism of action of AMK is that it binds to 30S subunit ribosome and interferes with protein synthesis to produce antibacterial effect. It was still effective against SM resistant strains.
(4) Capreomycin CPM: CPM is a fungicide obtained from Streptomyces capreomycin. CPM is a polypeptide complex that is effective as an antituberculous drug and is still effective against bacteria resistant to SM, kanamycin (KM), or AMK. The mechanism of action is the same as aminoglycosides.
(5) Rifapentine (rifapentine, DL473, RPE, RPT) : a rifampicin drug with the same mechanism of action as rifampicin. In vitro, the antibacterial activity of rifampicin is 2-10 times higher than that of rifampicin, and the anti-tuberculosis effect in mice is better than that of rifampicin, and the elimination half-life time is 4-5 times longer than that of rifampicin. Therefore, RPE is a highly effective anti – tuberculosis drug.
(6) Rifabutin (RFB, RBU) : rifabutin, whose mechanism of action is the same as rifampin, is a semi-synthetic antibiotic derived from S class rifamycin. Rifampicin-resistant TB may also be resistant to RBU, but studies have shown that rifampicin-resistant TB still has a 31% sensitivity to RBU.