(Ch 41) Antimycobacterial Drugs (Tuberculosis & Leprosy) Flashcards
- Drugs for Tuberculosis*
- Name 5 Drugs:*
- Isoniazid
- Rifampin (RIFADIN)a
- Ethambutol (MYAMBUTOL) • Pyrazinamide
- Streptomycin
- Amikacin
- Drugs for Mycobacterium avium-intracellulare Infections*
- name 1:*
• Azithromycin (ZITHROMAX)b
- Drugs for Leprosy*
- Name 4:*
- Dapsone
- Rifampin (RIFADIN)
- Clofazimine (LAMPRENE) • Thalidomide (THALOMID)
- Effective treatment of TB required*
- -the drug regimen and Protocol is used ?*
- and*
- -How long?*
Multidrug Therapy
Protocol: (DOT) directly obsereved therapy (observe each drug administration for adherence of Pt’s)
and
at least 6 months to eradocate the pathogen
Define Mycobacteria
What diseases does it cause
“acid-fast bacilli”
cause a variety of diseases:
TB, leprosy, and localized or disseminated
M. avium-intracellulare infections
- The goals of TB therapy*
- Name: 3*
- to kill tubercle bacilli rapidly
- to eliminate persistent bacilli and prevent relapse
- to prevent disease transmission
- Is Isolation of patients with TB in single-person rooms important:*
- yes/no?*
- how long?*
Isolation of patients with TB in single-person rooms is essential until sputum cultures are negative
and
extended isolation may be required to prevent the spread of drug-resistant strains
Which organism causes tuberculosis?
- bacterium*
- Mycobacterium tuberculosis.*
What makes tuberculosis difficult to treat?
Name 3 major complicating factors:
- Mycobacterium tuberculosis is an intracellular organism.
- Theorganism grows very slowly. Consequently infections are often chronic, and therapy may be required for as long as 2 years.
- Resistance to drugs develops rapidly.
Why is tuberculosis treated with multiple drugs?
Multiple drugs are used to delay the emergence of resistant strains of the organism.
- What are the five first-line pharmacological treatment options fortuberculosis?*
- “RIP ESther”*
- Isoniazid (INH)
- Rifampin
- Pyrazinamide
- Ethambutol
- Streptomycin
ISONIAZID (Laniazid)
How does it work: MOA
- Isoniazid is believed to act by inhibiting the enzymes enoyl acyl carrier protein reductase (InhA) and a β-ketoacyl ACP synthase (KasA).*
- These enzymes are essential for the synthesis of mycolic acids, which are unique to the mycobacterial cell walls.*
ISONIAZID (Laniazid)
ROA:
The drug is readily absorbed orally and parenterally. Absorption is impaired, however, if isoniazid is taken with aluminum-containing antacids.
ISONIAZID (Laniazid)
How does resistance to the drug occur?
A mutation or deletion of the katG gene results in underproduction of the mycobacterial enzyme needed for isoniazid to become biologically active. A mutation in the InhA enzyme can also cause resistance.
ISONIAZID (Laniazid)
What is this drug’s distribution?
Isoniazid penetrates all body fluids, cells, and caseous material. Therefore it is able to act on intracellular mycobacteria.
- ISONIAZID*
- State the metabolism of the drug.*
metabolized in the liver by N-acetylation.
The rate of acetylation shows a genetic variance among humans; it can be as fast as 1 hr or as slow as 3 hr.
ISONIAZID
How does isoniazid affect the cytochrome P-450 system?
inhibits this system;
the drug therefore increases plasma levels of drugs such as:
phenytoin,
benzodiazepines,
warfarin.
- ISONIAZID*
- adverse effects.*
1. Peripheral neuritis—Most commonly paraesthesias of the hands and feet.
This is thought to be caused by isoniazid’s action in binding and inactivating pyridoxine (vitamin B6).
Vitamin B6 supplementation can minimize this problem.
2. Hepatotoxicity—Jaundice and hepatitis
can be severe. LFTs must be monitored.
3. Rashes and skin eruptions
- Neurological problems such as convulsions in patients prone to seizures
ISONIAZID
When is isoniazid given alone?
In most cases isoniazid is given along with other drugs.
However, for prophylactic treatment of skin test converters and for close contacts of patients who have active disease, isoniazid is given alone.
-Isoniazid-
Can you use isoniazid in pregnant patients?
No!
- This drug crosses the placenta*
- and*
- may cause peripheral neuritis in newborns.*
Peripheral Neuritis
Define:
disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord.
Damage to peripheral nerves may impair sensation, movement, gland or organ function depending on which nerves are affected; in other words, neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms.
RIFAMPIN (Rifadin)
MOA?
Rifampin inhibits the β-subunit of DNA- dependent RNA polymerase.
It suppresses RNA synthesis by blocking chain initiation.
NOTE: Rifabutin and rifapentine are in the same family of drugs as rifampin and work similarly to rifampin.
- RIFAMPIN (Rifadin)*
- What is the metabolism of this drug?*
Rifampin is metabolized by and induces the cytochrome P-450 system.
Therefore other drugs such as ketoconazole and warfarin may require higher dosages to maintain therapeutic concentrations.
- Does* Rifabutin induce cytochrome P-450
- Why or why not?*
Rifabutin does not induce the cytochrome P-450 system as much as rifampin and therefore is used in tuberculosis-infected HIV patients
who are taking
protease inhibitors.
