• Antimycobacterials
  • Pharmacology

Drugs Used in Treatment of Tuberculosis

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  • Revised on: 2020-08-04

Tuberculosis is an infectious bacterial disease caused by mycobacterium tuberculosis. Drugs used in the treatment of tuberculosis are known as antiTBs. Also, Mycobacterium avium complex (MAC) especially in HIV positive patients.

The people who are at most at risk include:

  • Alcoholics and drug misusers
  • Immunocompromised people e.g. HIV/AIDS
  • Populations in overcrowding conditions
  • Patients suffering from debilitating diseases such as diabetes.

Common symptoms of tuberculosis

  • Swollen lymph nodes
  • Loss of weight and appetite
  • Chronic non-productive cough
  • Haemoptysis (coughing of blood)
  • Night sweats

Classification of drugs used in the treatment of tuberculosis

Anti TB drugs are classified into two groups as the first line and second-line drugs which are used after the first-line drugs have proved to be inefficient.

1st Line drugs

  •  
    • Isoniazid (H)
    • Rifampicin (R)
    • Ethambutol (E)
    • Pyrazinamide (Z)
    • Streptomycin (S)

2nd line drugs

  •  
    • Ethionamide (ETM)
    • Paraaminosalicylic acid
    • Kanamycin (Kmc)
    • Amikacin
    • Capreomycin (Cpr)
    • Ofloxacin
    • Protionamide

First-Line Anti-TB Drugs

Isoniazid (H)

Fast multiplying organisms are rapidly killed, but slow multiplying ones are only inhibited. It acts on extracellular as well as intracellular.

Isoniazid is bacteriostatic (inhibits bacterial multiplication) and possibly bactericidal (kills bacteria) therefore it kills mycobacterium tuberculosis. It is rapidly absorbed from the intestines and largely excreted by the kidneys.

The drug diffuses widely throughout the body and crosses the meningeal barrier to the cerebrospinal fluid in amounts adequate to inhibit the growth of tuberculosis.

It is metabolized in the liver. There are fast and slow isoniazid metabolizers; depending upon how the rate of isoniazid metabolism.

Adverse effects

Isoniazid causes Peripheral neuropathy which is a burning sensation in feet, numbness. Patients who develop peripheral neuropathy are given pyridoxine prophylactically 10 mg/day; for treatment 100-200mg/day.

The drug also causes Hepatotoxicity or injury to the liver cells.

Drug interactions

Isoniazid inhibits the metabolisms of the following: phenytoin, Carbamazepine, diazepam, warfarin; their blood levels may rise.

Rifampicin (R)

Rifampicin is well absorbed orally, taken once a day and is excreted mainly in bile.

This drug acts best on slowly or intermittently (spurters) dividing organisms. Both extra- and intracellular organisms are affected. It has good sterilizing and resistance preventing action.

Adverse effects

Adverse effects are uncommon with rifampicin, but it should not be used in patients with liver disease as it can also cause hepatotoxicity.

It causes red discoloration of urine and sputum.

Other Uses of rifampicin

  • Leprosy
  • Combination with doxycycline in the treatment of brucellosis.

Drug interactions

It increases the metabolism of other drugs, thereby reducing the plasma concentration of the concerned drugs, for example, nevirapine and oral contraceptives.

Ethambutol (E)

Adverse effects

Patient acceptability of Ethambutol is very good and side effects are few.

Damage to the optic nerve, leading to the deterioration of visual acuity and color vision. The use of correct doses reduces this risk. If possible the vision should be tested before starting treatment and at 6 monthly intervals. It should not be used in young children because they may be unable to report early visual impairment. With early recognition and stoppage of therapy, visual toxicity is largely reversible.

Caution is required in its use in patients with renal disease.

Pyrazinamide (Z)

Pyrazinamide is a powerful and effective drug with good penetration into tuberculous lesions and the cerebrospinal fluid.

It is weakly tuberculocidal but more active in acidic medium.

It is absorbed orally, widely distributed, has good penetration in CSF, extensively metabolized in the liver and excreted in the urine.

Adverse effects

Hepatotoxicity but this effect is dose-related

Hyperuricemia is common due to inhibition of uric acid secretion in the kidney.

Light sensitivity.

Streptomycin (S)

Streptomycin is very effective against m.tuberculosis, but resistant strains develop in about 6 weeks if it is used as monotherapy. This resistance is prevented if it is combined with other drugs.

It is given as an injection once daily.

Adverse effects

It has a low margin of safety.

Ototoxicity (damage of the 8th cranial nerve) – the symptoms include high pitched tinnitus and vertigo.

Sensitization may occur.

Second-line anti-TB drugs

Second-line drugs in the treatment of tuberculosis are:

  • Kanamycin,
  • Amikacin,
  • Capreomycin

Kanamycin and amikacin are aminoglycosides. These drugs are more toxic antibiotics, therefore, they are used as reserve drugs especially in case of drug resistance. Anyone of these is used in combination with the commonly employed drugs to which resistance has not developed.

Because all of them can cause ototoxicity and nephrotoxicity they are not combined amongst themselves or with streptomycin. None of them is orally effective, none penetrates the meninges.

Para-amino salicylic acid (PAS)

Related to sulfonamides. It is not active against other bacteria. PAS is tuberculostatic and one of the least active drugs: It does not add to the efficacy of more active drugs that are given with it. It only delays the development of resistance. PAS formulations interfere with the absorption of rifampin.

Ethionamide (Etm)

It is a tubeculostatic drug, it acts on both the extra-and intracellular organisms. Resistance totem develops rapidly and some cross-resistance with Tzn is reported.

Adverse drug reactions are anorexia, abdominal upsets, rashes.

Thiacetone (Tzn)

It is tuberculostatic with low efficacy. It is added to the TB therapy to mainly delay resistance development to the other drugs.

Cycloserine (Cys)

It diffuses all over CSF. The CNS toxicity is high. It causes sleepiness, headache, tremor, and psychosis.

Tuberculosis treatment drug regimens

At least 2 drugs are used at the same time to prevent the emergence of resistant organisms. Then the treatment is continued for as long as possible to eradicate the infection completely.

The choice of drugs is determined by the sensitivity of the infective M.tuberculosis.

Variation in the drugs used is due to their differing penetration of tissue, their effectiveness against the dividing organisms and their ability to sterilize the lesions.

Resistance by M.tuberculosis to one or other drugs may require a change in regimen.

Multidrug resistance (MDR) TB is the resistance to both isoniazid and rifampicin and may be any number of other anti-TB drugs. Treatment is difficult using one or more 2nd line drugs for 12-24 months.

Extensively Drug-Resistant (XDR) TB occurs when Bacilli that are resistant to at least 4 most effective cidal drugs.