Antimycobacterial Agents Flashcards
Antimycobacterial Agents are drugs for
tuberculosis
Micobacteria are
Slow growing microbes
infections Micobacteria cause
require prolonged treatment
prolonged therapy of micobacteria leads to
drug toxicity, poor patient compliance with treatment, and the emergence of drug-resistant mycobacteria
how many people are infected worldwide of TB
2 billion people
how many people die form TB each year
About 2 million (more than any other infectious disease)
when talking about TB how is the US compared to the rest of the world
In US new cases have declined since 1992, but in rest of world, new cases on the rise
In US how many people have latent TB
In US 9-14 million have latent TB
how many new cases of TB each year
9 million new cases each year, most in developing countries
Reasons for increase in TB number
AIDS with compromised immune system, increased incidence of crowded living conditions in urban areas, and multidrug-resistant mycobacteria
Those susceptible to TB
Alcohol addiction and IV drugs; Debilitative condition (malnourished, severe chronic disorder, cancer) ; AIDS
Tuberculosis caused by
by acid-fast bacillus Mycobacterium tuberculosis or tubercle bacillus
Tuberculosis transmitted
from one person to another by droplets dispersed in air through coughing & sneezing
The tubercle bacilli are inhaled
into the alveoli and can migrate to other organs via the blood and lymphatic system (so not just in the lungs, can go to other organs ex. kidneys but primarily in the lungs)
If body’s immune system is strong
phagocytes will stop the multiplication of the tubercle bacilli and the spread
Symptoms of Active TB
Anorexia and weight loss; Cough and sputum production; Increased fever; Night sweats; Positive acid-fast bacilli in the sputum ** (diagnostic qualifier)
In most cases of TB bacteria lie
dormant and the infected person has no symptoms
what will define the presence of TB
Sputum evaluation: microscopic smear and culture; Chest X-Ray
Latent TB is
Tubercle bacilli that are present, lying dormant but giving no evidence of signs & symptoms
Who should be tested for Latent TB?
hose who have had contact with TB patients; Residents & staff of high-risk populations: (prisons, nursing homes, hospitals, homeless shelters, residential facilities for AIDS patients); Persons who in last 5 years immigrated from country where TB is prevalent; Staff of mycobacteriology labs; Children & adolescents exposed to high-risk adults; Children under age of 4; Those at high risk of progression from latent to active TB
Those at high risk of progression from latent to active TB
HIV-infected persons; IV drug abusers; Patients on immunosuppressive drugs for 1 month or more; Patients with CXR findings indication changes consistent with prior TB; Patients with high-risk medical conditions (diabetes, chronic renal failure, leukemia or lymphoma); Clinical conditions associated with weigh loss, intestinal bypass surgery, chronic peptic ulcer disease, malabsorption syndromes, cancer of oropharynx & Upper GI tract, any disorder that inhibits nutritional intake
How Do We test for Latent TB?
Tuberculin Skin Test: purified protein derivative (PPD) - an antigen derived from M. tuberculosis
positive TB test information
If individual has an intact immune system and has been exposed to M. tuberculosis, the PPD will elicit a local immune response: a region of induration (hardness) around injection site within 48 – 72 hours
Before starting treatment for latent TB,
must rule out active TB with sputum, and CXR; Because Active TB requires multi-drug treatment to prevent drug resistance
Latent TB can be treated with
with one or two medications
Major impediment to successful therapy of TB:
Drug resistance
Drug resistance
some bacilli are resistant to just one drug; others to multiple drugs
Infection with a resistant organism may be acquired through:
- Contact with person who harbors a resistant bacillus 2. Repeated ineffectual course of therapy (didn’t finish therapy, sloppy technique, took meds longer than should have)
How bad is the problem of multi-drug resistance?
Increases risk of death from TB (especially among AIDS patients)
Cost of treating multi-drug resistant TB
$180,000 compared to $12,000 for nonresistant TB
biggest problem with treating TB
drug resistance
Drug combinations w/ treatment of latent TB
decrease risk of resistance and decrease incidence of relapse
Isoniazid and rifampin
very effective against actively dividing bacilli
Pyrazinamide
most active against intracellular, quiescent bacilli
By using combinations of drugs for treatment of TB
we increase chances of killing all bacilli, whether they are actively multiplying or dormant
Treatment for Active TB usually initiated w/
with a FOUR –DRUG regimen: Isoniazid and rifampin WITH pyrazinamide and ethambutol
Treatment for Active TB
Treatment includes an initial phase (Induction) to eliminate actively dividing bacilli (2 months long) and then a second phase to eliminate “persisters” (4 months) with 2 drugs isoniazid & rifampin
Treatment for multi-drug resistant TB
Treatment requires at least 3 drugs (maybe 5, 6 or 7); and should continue for 12 to 24 months after sputum converts to normal
Primary agent for treatment and prophylaxis of TB
isoniazid (INH) Laniazid, Nydrazid
isoniazid (INH) Laniazid, Nydrazid
Inhibits mycolic acid which necessary for building the mycobacterial cell wall; Bactericidal to mycobacteria that are actively dividing; Given orally or IM
Adverse effects of isoniazid (INH) Laniazid, Nydrazid **
Peripheral neuropathy: paresthesias (tingling, numbness, burning, pain in hands and feet) clumsiness, unsteadiness and muscle aches also occur (happens because INH induces a deficiency in pyridoxine, vitamin B6) * may need to supplement with Vitamin B6 (50 – 200 mg daily); Hepatotoxicity: due to production of a toxic metabolite; see in older population; Optic neuritis: blurred vision, constriction of visual field, disturbance of color discrimination *report any visual changes; Anemia
Use Ionizasid (INH) for
9 months for latent TB
combination of isoniazid and rifampim take
weekly for 3 months; both equally effective; combination is newer and has better response
pyriodoxine =
B6
optic neuritis
optic nerve become inflamed
INH: Drug Interactions
Phenytoin (Dilantin): INH can interfere with metabolism of phenytoin causing phenytoin to accumulate to toxic levels.; Concurrent use of ALCOHOL, Rifampin, & pyrazinamide increase risk of hepatotoxicity
if too much Dilantin then become
overly sedated and quit breathing, cardiac dysrythmias
if urine turns dark yellow then could be problem with
liver
AST and ALT both involved with
liver
INH-Teach patients to:
Be seen by MD if s/s of hepatitis: anorexia, fatigue, nausea, yellowing of skin or eyes-jaundice; Have serum aspartate aminotransferase (AST) levels drawn monthly; Take vitamin B6
Rifampin [Rifadin]
Broad spectrum antibiotic;inhibits protein synthesis of bacilli-bacteriocidal
Rifampin [Rifadin] best absorbed on
empty stomach; given po
Rifampin [Rifadin] eliminated by
hepatic metabolism; is a powerful inducer of P450 enzymes and can DECREASE levels of many other drugs
Rifampin [Rifadin] uses
Tuberculosis; Leprosy; Haemophilus influenzae; Legionella
Rifampin [Rifadin] adverse effects
Hepatotoxicity & Hepatitis (see MD if symptoms; check liver enzymes, avoid alcohol & hepatoxic drugs); Discoloration of body fluids: red-orange color to urine, sweat, saliva, tears, staining of soft contact lens
Rifampin [Rifadin] interactions
Through enzyme induction, may reduce effects of: oral contraceptives, warfarin, protease inhibiors & non-nucleoside reverse transcriptase inhibitors
woman on Rifampin [Rifadin] should
use a non-hormonal form of birth control; because it speeds up the metabolism of birth control, so more likely to become pregnant
for pt on Rifampin [Rifadin] coumadin dose may need to be
increased
Ethambutol [Myambutol]
bacteriostatic
Ethambutol [Myambutol] uses
tuberculosis ( active against bacilli that are resistant to INH & rifampin; must use WITH other anti-tubercular drugs
Ethambutol [Myambutol] adverse effects
Optic neuritis - blurred vision, constriction of visual field, disturbance of color discrimination *report any visual changes; Allergy; Hyperuricemia; gout; May take with food if GI upset occurs
Pyrazinamide used in
combination therapy
Pyrazinamide adverse effects
Hepatotoxicity-monitor Aspartate aminotransferase (AST) levels and alanine aminotransferase (ALT) levels; s/s of hepatitis; use with caution in patients taking other hepatotoxic drugs or alcohol
