1 - TUBERCULOSIS

TUBERCULOSIS

• An infectious disease of humans and animals caused by the tubercle bacillus and characterized by the formation of tubercles on the lungs and other tissues of the body, often developing long after the initial infection

• mycobacterium tuberculosis

TB

• It is cause by s – a tubercle bacillus

LATENT TB INFECTION

• The bacteria lives in the body, but without making that person sick.

  • does not have any symptoms –-- they do not feel sick, they do not spread TB bacteria to others.

  • They need to receive a treatment to treat the latent TB infection – if not treated, the person can develop TB disease

RIPE • R – rifampicin • I – isoniazid (INH) • P – Pyrazinamide (PZA) • E – ethambutol

FIRST LINE AGENTS IN TB

RIFAMPIN

Semisynthetic derivative of rifamycin

MOA: inhibits DNA DEPENDENT RNA POLYMERASE

RIFAMPIN

Can be used as the sole drug in treatment of latent TB in INH-intolerant patients,

• PREVENT EMERGENCE OF DRUG-RESISTANCE MYCOBACTERIA

• Most active antimicrobial agent available

• Keystone of first line tuberculosis treatment

DAILY ADULT DOSE: 10 MG/KG ;

MAX: 600 MG (daily)

RIFAMPIN

• DAILY ADULT DOSE: —-

• MAX: —

ISONIAZID (INH)

• Fast acetylators (Asian) = 60-90 mins

• Slow acetylators (European/African) = 3-4 HOURS

A structural congener of pyridoxine (Vit B6)

Pkinetics: INH half-life

• Fast acetylators (—-) =

• Slow acetylators (——) =

ISONIAZID (INH)

MOA: inhibition of mycolic acid (component of cell wall)

DAILY ADULT DOSE: 5 MG/KG ;

MAX: 400 MG (daily)

ISONIAZID (INH)

• DAILY ADULT DOSE:

• MAX:

Pyridoxine (high dose)

– treatment for isoniazid poisoning

Isoniazid-induced Hepatitis

- Most common ADR of Isoniazid

PYRAZINAMIDE (PZA)

MOA: which is believed to act by inhibiting energy metabolism across the cell membrane, is a pro-drug requiring acidic conditions for activation.

PYRAZINAMIDE (PZA)

• Pyrazi noic Acid

Active form:

• Effective against slow replicating bacilli.

ETHAMBUTOL

• MOA: inhibits arabinosyl transferases (for the synthesis of mycobacterial cell wall)

TB Meningitis

ETHAMBUTOL

Pkinetics: dose reduction for renal impairment

Use: Higher dose is needed for ——

RETRO

BULBAR

NEURITIS

ETHAMBUTOL

• ADR

• (red-green color blindness, optic neuritis, possible retinal damage)

STREPTOMYCIN (in IV)

• For the treatment of life-threatening Tuberculosis disease including meningitis, miliary dissemination and severe organ TB.

• Treatment of drug-resistant strains

DAILY ADULT DOSE: 15 MG/KG,

MAX 1G*

• ototoxic and nephrotoxic

STREPTOMYCIN (in IV)

• DAILY ADULT DOSE:

• MAX:

• S/E:

PZA (Pyrazinamide), Rifampicin, INH

• Give drug with small meals or at bedtime

MINOR SIDE EFFECTS

• Anorexia, Nausea, Abdominal Pain

PZA

• Give aspirin or NSAID

MINOR SIDE EFFECTS

• Joint pain (from hyperuricemia)

INH (Isoniazid)

• Pyridoxine 100 mg daily for treatment/ 10 mg daily for prevention

MINOR SIDE EFFECTS

• Peripheral neuropathy

Rifampicin

• Reassure the patient

MINOR SIDE EFFECTS

• Orange/ redcolored urine

INH

• Reassure the patient and give the drug at bedtime

MINOR SIDE EFFECTS

• Drowsiness

Rifampicin

• Give antipyretic

MINOR SIDE EFFECTS

• Flu-like symptoms

• Ethambutol

MAJOR SIDE EFFECTS

• Visual impairment (optic neuritis)

• Streptomycin

MAJOR SIDE EFFECTS

• Deafness, tinnitus, and dizziness

• Streptomycin, Rifampicin

MAJOR SIDE EFFECTS

• Decreased urine output

• INH

MAJOR SIDE EFFECTS

• Psychosis and convulsion

• Rifampicin

MAJOR SIDE EFFECTS

• Thrombocytopenia, anemia, shock

Amikacin (Amikin DSC)

For TB caused by streptomycin-resistant or multidrugresistant mycobacterial strains

Ethionamide (Trecator)

Used in treatment of isoniazid-resistant tuberculosis Congener of INH,

• blocks synthesis of mycolic acid

• S/E: Gl irritation, neurologic effects, HEPATOTOXIC

p-Aminosalicylic Acid (PAS) (Granupas, Paser)

Folate synthesis blocker, similar to PABA

• Rarely used due to its primary resistance

• S/E: severe gastric irritation, crystalluria, ulceration

Capreomycin (Capastat sulfate)

For TB resistant to Streptomycin or Amikacin

• A peptide CHON (protein) synthesis inhibitor

• S/E: ototoxicity, renal dysfunction

Cycloserine (Seromycin)

Inhibits the cell wall synthesis

• S/E: peripheral neuropathy, CNS dysfunction

Linezolid (Zyvox)

● Considered as a drug of last resort

• Used in combination with other second-and third-line drugs to treat patients with multi-drug resistant tuberculosis

• S/E: bone marrow suppression and irreversible peripheral and optic neuropathy

Rifabutin (Mycobutin, Talicia)

Indicated in place of rifampin for treatment of TB in patients with HIV infection who are receiving antiretroviral therapy

Rifapentine (Priftin)

For treatment of tuberculosis caused by rifampinsusceptible strains during the continuation phase only

• Should not be used to treat patients with HIV infection because of an unacceptably high relapse rate with rifampin-resistant organisms

Kanamycin (Kantrex)

Treatment of TB caused by streptomycin-resistant strains.

• Levofloxacin (Levaquin)

Fluoroquinolones

• - More active than ciprofloxacin against TB

• Moxifloxacin (Avelox)

Fluoroquinolones

• Most active against TB by weight in vitro

• Ciprofloxacin (Ciprobay)

Fluoroquinolones

• More active against atypical TB

“multidrug-resistant TB” (MDR TB).

Strains that are resistant to at least isoniazid and rifampin are referred to as

Extensively Drug-Resistant TB (XDR-TB)

have appeared that are resistant to a very large number of products;

• those that are resistant to isoniazid, rifampin, to any fluoroquinolones,

• at least one of three secondline injectable drugs (capreomycin, kanamycin, and amikacin).

Beda quiline (Sirturo)

● First medication for pulmonary MDR-TB

• Used as part of combination therapy to treat adults with MDR TB when no other alternatives are available.

Bacillus-Calmette-Guerin

• BCG VACCINE

● The only vaccine available for the prevention of human forms of TB

• Normally given to children