Antitubercular Drugs
Question 1. Write Different Groups Of Antitubercular Drugs. Discuss Important Toxic Manifestations Of Streptomycin With Important Therapeutic Uses.
Answer:
Those drugs which are given against tuberculosis are known as antitubercular drugs.
Groups Of Antitubercular Agents
- First Line: These drugs have high antitubercular efficacy as well as low toxicity and are used routinely. The first line of drugs is isoniazid, streptomycin, rifampin, pyrazinamide, and ethambutol.
- Second Line: These drugs have low antitubercular efficacy or high toxicity or both and are used in special circumstances. The second line of drugs used are thiacetazone, para-aminosalicylic acid, ethionamide, cycloserine, kanamycin,amekacin, capeomycin.
Read And Learn More: Pharmacology Question And Answers
Newer Drugs: Ciprofloxacin, ofloxacin, clarithromycin, azithromycin, rifabutin.
Toxic Manifestations Of Streptomycin
- Streptomycin is avoided during pregnancy because if used in infants it causes fetal ototoxicity.
- It is avoided using other ototoxic drugs like minocycline and diuretics.
- It is avoided using nephrotoxic drugs like amphotericin B and cyclosporine.
- It should not be mixed with any other drug in the same syringe.
Antitubercular Drugs Therapeutic Uses
It is used in tuberculosis, plague, tularemia, brucellosis, urinary
tract infections, and septicemias.
Question 2. Discuss Isoniazid In Tuberculosis.
Or
Describe The Adverse Effects Of Isoniazid.
Answer:
Isoniazid is a fist-line antitubercular drug. It acts on extracellular as well as intracellular TB and is equally effective in alkaline and acidic medium.
Isoniazid Mechanism Of Action
Isoniazid Pharmacokinetics
Isoniazid is completely absorbed orally and penetrates all body tissues, tubercular cavities, and placenta. It is extensively metabolized in the liver by acetylation. The metabolites are excreted in the urine.
Isoniazid Adverse Reactions
- Hepatotoxicity: In chronic alcoholics, old people and rapid acetylators risk of hepatic damage is high. The effect is reversible on discontinuation of the drug.
- Peripheral neuritis: Dose-related toxicity is present. The drug promotes the excretion of pyridoxine.
- Various other side effects are fever, skin, rash, anemia, arthralgia, gastrointestinal disturbances, psychosis and rarely it causes convulsions.
Question 3. Write On Fist Line Antitubercular Drugs. Names And Their Adverse Effects.
Or
Enumerate First Line Antitubercular Drugs And A Characteristic Adverse Drug Reaction Seen With Each Of Them.
Answer:
Question 4. Describe First Line Antitubercular Drugs.
Or
Write Short Note On First Line Antitubercular Drugs.
Answer:
The following are the first-line drugs for the treatment of tuberculosis:
- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol
- Streptomycin.
First-Line Antitubercular Drugs Isoniazid
- Isoniazid is the most widely used antitubercular agent.
- It is very effective orally, cheap, and has high tuberculocidal activity.
- The drug is active for both intracellular and extracellular bacilli.
- It is used for chemoprophylaxis of tuberculosis.
- Isoniazid is a prodrug that enters inside mycobacteria and becomes active. It inhibits the synthesis of mycolic acid and acts as a bactericidal.
Isoniazid Adverse Effects
- Hepatotoxicity: In chronic alcoholics, old people and rapidacetylators risk of hepatic damage is high. The effect is reversible on discontinuation of the drug.
- Peripheral neuritis: Dose-related toxicity is present. The drug promotes the excretion of pyridoxine.
- Various other side effects are fever, skin, rash, anemia, arthralgia, gastrointestinal disturbances, psychosis and rarely it causes convulsions.
First-Line Antitubercular Drugs Rifampin
- Rifampin is bactericidal to M. tuberculosis.
- Bactericidal action covers all subpopulations of TB bacilli but acts best on slowly or intermittently dividing ones, as well as on many atypical mycobacteria.
- It has good sterilizing and resistance-preventing actions.
- Rifampin inhibits DNA-dependent RNA synthesis.
- It is well absorbed orally, and widely distributed in the body— penetrates cavities, caseous masses, placenta, and meninges.
- It is metabolized in the liver to an active deacetylated metabolite which is excreted mainly in bile, some in urine also.
Rifampin Adverse Effects
- Hepatitis, a major adverse effect, generally occurs in patients with preexisting liver disease.
- Respiratory syndrome—breathlessness which may be associated with shock and collapse.
- Flu-like symptoms, i.e. fever with chills, headache, and muscle and joint pain.
- Gastrointestinal disturbances, i.e. nausea, vomiting, and abdominal discomfort.
- Skin rashes, itching, and flushing
- Purpura, hemolysis, shock, and renal failure.
First-Line Antitubercular Drugs Pyrazinamide
- It is weakly tuberculocidal but more active in an acidic medium.
- It is more lethal to intracellularly located bacilli and to those at sites showing an inflammatory response (pH is acidic at both these locations).
- It is highly effective during the first 2 months of therapy when inflammatory changes are present.
- By killing the residual intracellular bacilli it has good ‘sterilizing’ activity.
- It inhibits mycolic acid synthesis, but by interacting with a different fatty acid synthase encoding gene.
- Pyrazinamide is absorbed orally, widely distributed, has good penetration in CSF, is extensively metabolized in the liver, and excreted in the urine.
Pyrazinamide Adverse Effects
- Hepatotoxicity is the most important dose-related adverse effect.
- Hyperuricemia is common
- Other adverse effects are arthralgia, flushing, rashes, fever, and loss of diabetes control.
First-Line Antitubercular Drugs Ethambutol
- Ethambutol is selectively tuberculostatic and clinically as active as S. Fast-multiplying bacilli are more susceptible as are many atypical mycobacteria.
- Ethambutol inhibits arabinose transferases involved in arabinogalactan synthesis and interferes with mycolic acid incorporation in the mycobacterial cell wall.
- It is used in combination with other antitubercular drugs to prevent the emergence of resistance and for faster sputum conversion.
- On oral administration it is well absorbed and is widely distributed inside the body, it is metabolized in the liver, crosses the blood-brain barrier in meningitis, and is excreted in the urine.
- Patient acceptability of ethambutol is very good and side effects are few.
Ethambutol Adverse Effects
- Loss of visual acuity/color vision, and field defects due to optic neuritis are the most important dose and duration of therapy-dependent toxicity.
- Ethambutol produces a few other symptoms—nausea, rashes, fever, and neurological changes are infrequent.
- Hyperuricemia is due to interference with urate excretion.
First-Line Antitubercular Drugs Streptomycin
- It was the first clinically useful antitubercular drug.
- It is tuberculocidal, but less effective than rifampin; acts only on extracellular bacilli. Thus, host defense mechanisms are needed to eradicate the disease.
- It penetrates tubercular cavities, but does not cross to the CSF, and has poor action in an acidic medium.
- Resistance developed rapidly when streptomycin was used alone in tuberculosis—most patients had a relapse.
Streptomycin Adverse Effects
- Most atypical mycobacteria are unaffected by streptomycin popularity of streptomycin in the treatment of tuberculosis had declined due to the need for IM injections.
- Ototoxicity and nephrotoxicity, especially in the elderly and in those with impaired renal function.
Question 5. Write Important Uses And Toxic/Side Effects Of Rifampin.
Answer:
It is an antimicrobial antitubercular drug.
Rifampin Uses
- It is the first antitubercular drug and is also used in chemoprophylaxis of tuberculosis.
- It is used in leprosy.
- Prophylaxis of meningococcal and H. influenza meningitis and carrier state.
- It is a second/third choice drug for diphtheroid and legionella infections.
- A combination of doxycycline and rifampin is used in first-line therapy of brucellosis.
- Rifampin in combination with β-lactam antibiotics is used in staphylococcal infections.
Rifampin Toxic/Side/Adverse Effects
- Hepatitis, a major adverse effect, generally occurs in patients with preexisting liver disease.
- Respiratory syndrome—breathlessness which may be associated with shock and collapse.
- Purpura, hemolysis, shock, and renal failure.
- Flu-like symptoms, i.e. fever with chills, headache, muscle and joint pain.
- Gastrointestinal disturbances, i.e. nausea, vomiting, and abdominal discomfort.
- Skin rashes, itching, and flushing.
Question 6. Classify Antitubercular Drugs. Discuss The Mechanism Of Action And Adverse Effct Of Fist Line Antitubercular Drugs.
Or
Classify Antitubercular Drugs. Mention The Mechanism Of Action And Adverse Effects Of Isoniazid (Inh) And Rifampicin.
Answer:
Classification Of Antitubercular Drugs
First-line drugs: Isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin
Second-line drugs: Thiacetazone, para-aminosalicylic acid, ethionamide, cycloserine, kanamycin, amikacin, and capreomycin.
Newer Drugs: Ciprofloxacin, ofloxacin, clarithromycin, azithromycin, rifabutin.
Mechanism Of Action And Adverse Effects Of First-Line Antitubercular Drugs
Question 7. Write A Short Note On Rifampin.
Answer:
Rifampicin (INH) or rifampin is a bactericidal antibiotic drug of the rifamycin group.
Rifampin Mechanism Of Action
Its lipophilic nature makes it a good candidate to treat the meningitis form of tuberculosis, which requires distribution to the central nervous system and penetration through the blood-brain barrier.
Rifampin Pharmacokinetics
This is given orally and is rapidly absorbed from the gastrointestinal tract but the presence of food decreases its absorption.
The drug is distributed widely throughout the body and is metabolized in the liver. The active deacetylated form is excreted in bile and undergoes enterohepatic recycling. The left out rest of the drug is excreted in the urine.
Rifampin Uses
- Rifampicin is typically used to treat Mycobacterium infections, including tuberculosis and Hansen’s disease. With multidrug therapy used as the standard treatment of Hansen’s Disease, rifampicin is always used in combination with dapsone and clofazimine to avoid eliciting drug resistance.
- Rifampicin also has a role in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in combination with fusidic acid.
- It is used in prophylactic therapy against Neisseria meningitidis (meningococcal) infection.
- It is also used to treat infection by Listeria species, Neisseria gonorrhoeae, Haemophilus influenza, and Legionella pneumonia.
- Rifampicin has some effectiveness against the vaccinia virus.
- Rifampicin is used with doxycycline for the treatment of brucellosis.
Rifampin Adverse Effects
- Hepatotoxic: Hepatitis, jaundice, liver failure in severe cases
- Respiratory syndrome: Breathlessness along with shock and collapse
- Cutaneous: Flushing, pruritus, rash, redness, and watering of eyes
- Abdominal syndrome: Nausea, vomiting, abdominal cramps with or without diarrhea
- Flu-like symptoms: With chills, fever, headache, arthralgia, and malaise. Rifampin has good penetration into the brain, and this may directly explain some malaise and dysphoria in a minority of users.
Rifampin Interactions
Rifampicin has significant interactions with warfarin, oral contraceptives, cyclosporine, itraconazole, digoxin, verapamil, nifedipine, simvastatin, midazolam, and HIV protease inhibitors.
Question 8. Write Short Note On ShortTerm Chemotherapy Of Tuberculosis.
Answer:
Short-term chemotherapy consists of short-course regimens of 6 to 9 months duration.
- All regimens have two phases, i.e. initial intensive phase and continuation phase
- Initial intensive phase: In this patient receives intensive treatment with 3 to 4 antitubercular drugs daily or thrice weekly for a period of 2 to 3 months. The main objective of this phase is to render the patient non-contagious.
- Continuation phase: The patient receives 2 to 3 drugs usually isoniazid and rifampicin daily or thrice weekly for a period of 4 to 6 months. This phase eliminates persistence and prevents relapse.
Categorywise Alternative Treatment Regimens For Tuberculosis (WHO-1997)
Erculosis Explanation Of Standard Code
- Each antitubercular drug has a standard abbreviation, i.e.
- Isoniazid (H)
- Rifampicin (R)
- Pyrazinamide (Z)
- Ethambutol (E)
- Streptomycin (S)
- Numerical before a phase is the duration of that phase in months.
- Numerical in the subscript is the number of doses of that drug per week. If there is no subscript numerical then the drug is given daily.
Question 9. Classify Antitubercular Drugs.
Answer:
Classification Of Antitubercular Drugs
Antitubercular Drugs First Line Drugs
These drugs have high antitubercular efficacy as well as low toxicity and are used routinely.
First-line drugs are:
- Isoniazid (H)
- Rifampin (R)
- Pyrazinamide (Z)
- Ethambutol (E)
- Streptomycin (S).
Antitubercular Drugs Second Line Drugs
These drugs have low antitubercular efficacy or high toxicity or both and are used in special circumstances.
Second-line drugs are:
- Thiacetazone Newer Drugs
- Paraamino salicylic acid Ciproflxacin
- Ethionamide Ofloxacin
- Cycloserine Clarithromycin
- Kanamycin Azithromycin
- Amikacin Rifabutin
- Capreomycin.
Question 10. Enumerate Primary Antitubercular Drugs.
Answer:
Enumeration of Primary Antitubercular Drugs
- Isoniazid
- Rifampicin
- Pyrazinamide
- Ethambutol
- Streptomycin.
Question 11. Enumerate Fist Line Antitubercular Drugs.
Answer:
Following are fist line antitubercular drugs:
- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol
- Streptomycin.
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