drugs for TB Flashcards
Tuberculosis risk
About 90% of individuals infected with Mycobacterium tuberculosis have asymptomatic, latent TB infection, with only a 10% lifetime chance that a latent infection will progress to active disease.
if untreated, the death rate for these active TB cases is more than 50%.
latent to active TB
When the disease becomes active, 75% of the cases present as pulmonary TB.
TB symptoms
Pulmonary symptoms include chest pain, persistent cough, and coughing up blood.
• Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, pallor, and often a tendency to fatigue very easily
Mycobacterium tuberculosis characteristics
aerobic bacterium that divides every 16 to 20 hours
has a cell wall but lacks a phospholipid outer membrane–> Gram-positive bacterium.
M. tuberculosis either stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolic acid content of its cell wall
small rod-like bacillus that can withstand weak disinfectants and survive in a dry state for weeks
retains certain stains after being treated with acidic solution, it is classified as an acid-fast bacillus
Ziehl-Neelsen stain, dyes AFBs a bright red that stands out clearly against a blue background
simple TB treatment duration
After two weeks of such treatment, people with non-resistant active TB generally have markedly reduced infectivity or cease to be contagious.
TB requires much longer periods of treatment (around 6 to 12 months) to entirely eliminate mycobacteria from the body.
Treating latent TB vs active
latent: usually consists of one or two antibiotics
active: TB disease is best treated with combinations of several antibiotics.
Current treatment recommendations for active TB involves the initial use of 4 or more drugs in order to reduce the risk of the bacteria developing further antibiotic resistance.
most common TB antibiotics
The two antibiotics most commonly used are Rifampin and Isoniazid.
Standard treatment of TB often includes:
- Rifampin/ Rifadin
- Isoniazid (INH) / Nitrazid
- Pyrazinamide/ Pyrazinamide
- Ethambutol/ Myambutol
Multi-drug resistant tuberculosis (MDR-TB)
defined as TB that is resistant at least to Isoniazid and Rifampin. Isolates that are resistant to any other combination of anti-TB drugs but not to INH and RMP are not classed as MDR-TB.
Isoniazid (INH) / Nitrazid overview
• Class: Antibiotic
• Indication: Tuberculosis
• MOA: Isoniazid is a pro-drug and must be
activated by bacterial catalase. The activated form of INH inhibits the synthesis of mycolic acid in the mycobacterial cell wall.
Char: PO. Rapid absorption. Potent drug for TB but always given with additional agents when treating active TB in order to reduce possible resistance. Metabolized by liver, thus lower doses should be given to patients with chronic liver disease.
Side effects: Rash, abnormal liver function tests, hepatitis, sideroblastic anemia, peripheral neuropathy and CNS effects.
• The possible hepatoxicity of INH is best avoided by close clinical monitoring of the patient, specifically for signs of nausea, vomiting, and abdominal pain as well as monitoring liver function tests.
Peripheral neuropathy from Isoniazid
Isoniazid competes with an enzyme that is needed to produce pyridoxine.
- Peripheral neuropathy is a common side effect when using Isoniazid and is caused by INH induced pyridoxine deficiency.
- Peripheral neuropathy may be reduced or avoided altogether by concurrent supplementation with pyridoxine (vitamin B6 – 10 to 50 mg/day).
Rifampin/ Rifadin
• Class: Antibiotic
• Indication: Tuberculosis, Methicillin-
resistant Staphylococcus aureus (MRSA) and prophylactic therapy against meningococcal infection from Neisseria meningitidis.
• MOA: Inhibits DNA-dependent RNA polymerase in bacterial cells thus preventing transcription of messenger RNA and subsequent translation to protein production.
Char: PO. Taking Rifampin can cause certain bodily fluids, such as urine and tears, to become orange-red in color. This may permanently stain soft contact lenses.
• Side effects: Fever, upset stomach, nausea, vomiting, rash. Hepatotoxicity with liver damage and jaundice can occur. Liver function tests must be followed.
risk factors for MDR-TB include
: HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse following standard TB treatment.
If treating a patient with suspected MDR-TB
SHREZ
Streptomycin + Hydrazine + Rifampin + Ethambutol + PyraZinamide (+ Moxifloxacin, a fluoroquinolone) and Cycloserine (a broad spectrum antibiotic), pending the result of laboratory sensitivity testing.
This regimen is often changed to a 4 or 5 drug regimen after sensitivity results are known.
Additional drugs for TB
Pyrazinamide is a nicotinamide analog with an unknown mechanism of action in the treatment of Mycobacterium.
• Ethambutol inhibits mycolic acid synthesis in the mycobacterial cell wall.
