Antimycobacteria Flashcards
1
Q
- Rod-shaped, aerobic bacteria
- Cell wall with peptidoglycolipids, fatty acids, waxes, and mycolic acid
- Slow growth, fast acid stain,resistsant to detergents/antibiotics
A
Mycobacteria
2
Q
Mycobacteria infecting humans
Pulmonary tuberculosis,
extrapulmonary TB
A
Mycobacteria Tuberculosis
3
Q
Mycobacteria infecting humans
Leprosy
A
Mycobacteria Leprae
4
Q
Mycobacteria infecting humans
Tuberculosis-like illness
A
Mycobacteria Bovis
5
Q
Mycobacteria infecting humans
Disseminated infection, pulmonary
infections, common in
immunocompromised states/HIV
A
Mycobacterium
Avium complex
6
Q
Mycobacteria infecting humans
Mycobacteria Properties
A
- Intrinsically resistant to most antibiotics
- Slow growing
- Cell wall is impermeable to many agents
-
Intracellular pathogens, inaccessible to drugs
that penetrate these cells poorly - Can also be dormant, resistant to many drugs or killed very slowly
7
Q
Mycobacteria infecting humans
USE OF DRUG COMBINATIONS is for ?
A
- To delay emergence of **resistance **
- To enhance antimycobacterial efficacy
8
Q
Mycobacteria infecting humans
What are the complications of chemotheraphy ?
A
- Limited information about the MOA
- Development of resistance (easily)
- Intracellular location of mycobacteria
- Chronic nature of the disease (protracted therapy and drug toxicities)
- Patient compliance ( minimum of 6 months cannot miss a day )
9
Q
- Commonly involves the lungs but can also infect other organs
- Liver, CNS, Bone, GI, Kidneys
- 6th leading cause of death in the Philippines
A
M. Tuberculosis
10
Q
Drugs for M. tuberculosis
First Line Drugs
A
Isoniazid (H)
Rifampicin (R)
Pyrazinamide (Z)
Ethambutol (E)
11
Q
- Structural congener of pyridoxine
- Inhibition of enzymes required for the synthesis
of mycolic acid - Bactericidal
-
Resistance can emerge **rapidly if used alone **
1. katG gene -catalase peroxidase bioactivation of
INH
2. inhA gene – enzyme acyl carrier reductase - **Oral **
- Metabolized by acetylation in the liver
- Affected by genetic control of acetylation (“fast” or “slow”)
- Majority of filipinos are SLOW
A
Isoniazid
12
Q
Clinical Use of Isoniazid
A
Single most important drug used for TB
13
Q
Toxicity of Isoniazid
A
- Peripheral neuritis, Restlessness, Muscle twitches, Insomnia
- CYP 450 enzyme inhibitor
- Hemolysis in G6PD deficient patients
14
Q
- Bactericidal
- Inhibits DNA-dependent RNA polymerase
- Resistance – from changes in drug sensitivity of polymerase
- can also be bacteriostatic
- side effect : turns every bodily fluid of patient into orange color
A
Rifampin / Rifampicin
15
Q
Clinical uses of Rifampin / Rifampicin
A
- Used in combination with drugs
- Can be used as sole drug in LTBI or close contacts
with INH-resistanc strains - In leprosy – it delays resistance to dapsone
- Used for MRSA, PRSP ( Penicillin Resistant Strepto Pseumoniae)
16
Q
Toxicities and Interactions of Rifampicin / Rifampin
A
- Can impair antibody responses
-
Skin rashes, Thrombocytopenia, Nephritis, liver
dysfunction - Flu-like symptoms, anemia
- Induces liver drug-metabolizing enzymes
17
Q
-
Equally effective as anti mycobacterial agent;
less drug interactions -
Preferred over Rifampin in AIDS patients taking
some antiretrovirals
A
Rifabutin
18
Q
- Not absorbed from GI tract, used in Traveler’s Diarrhea
A
Rifaximin
19
Q
- Inhibits arabinosyltransferase enzyme needed for cell wall synthesis
- Resistance due to mutation in emb gene if drug is used alone
- Orally
- Distributed most tissues
- Excrited in Urine
- Have Dose reduction in renal impairment
A
Ethambutol
20
Q
Uses for Ethambutol
A
Mainly for TBn, in combinatin with other drugs
21
Q
Toxicity of Ethambutol
A
- Dose-dependent visual disturbances
- Decrease in acuity, color blindness, optic
neuritis, retinal damage - Headache, confusion, hyperuricemia, peripheral neuritis
22
Q
- Not well known mechanism;
- Bacteriostatic action – through pyrazinamidases
- Resistance due to mutations in genes that encode
enzymes; drug-efflux systems esp. when used
alone - Oral
- Penetrate most body tissues, including CNS
- Recomendation “Don’t use alone”
A
Pyrazinamide
23
Q
Clinical use of Pyrazinamide
A
- In combination with other drugs for MTB
24
Q
Toxicity of Pyrazinamide
A
- Joint pains
- **Asymptomatic hyperuricemia **
- Myalgia, GI irritation, rash,** hepatic dysfunction**
- Should be avoided in pregnancy
25
# Second-line drugs for MTB
Used in combination for **life-threatening TB** (meningitis, miliary TB, other EPTB)
Streptomycin
26
# Second-line drugs for MTB
For TB caused by streptomycinresistant or MDR-TB
Amikacin
27
# Second-line drugs for MTB
Active against strains of MTB resistant
to first-line agents; **used in combination**
Ciprofloxacin
and Ofloxacin
28
# Second-line drugs for MTB
Congener of INH; major effect – severe
GI irritation & neurologic toxicity
29
# Treatment of TB
Intensive phase:
2 Months
30
# Treatment of TB
Continuation or maintenance phase:
more than 4 Months
31
refers to MTB
strains in which **resistance to both isoniazid and
rifampicin** has been confirmed in vitro
Multidrug-resistant TB (MDR-TB)
32
anti TB pills containing 2 or
more drugs
Fixed-dose combination
33
* Diagnostic and therapeutic unit that caters patients diagnosed with TB or suspected of having TB
* Is the most effective approach in the diagnosis, treatment, and control of TB
TB-DOTS ( Direct Observe Treatment Strategy )
34
# Drugs for Leprosy
Drug of Choice is ?
DAPSONE (Diaminodiphenylsulfone)
35
* Most active drug against M. leprae
* **Resistance** can develop **if low doses**
* usually in combination with
Rifampin and / or Cloafazimine
* Oral
* Eliminated in Urine
DAPSONE
36
Dapsone of Toxicity
* GI irritation
* Fever
* Skin rashes
* Methemoglobinemia
* Hemolysis in patients with G-6PD
37
* Repository form of dapsone
* Provides inhibitory plasma concentrations
for several months
* Alternative drug for P. carinii pneumonia
in HIV patients
Sulfones (ACEDAPSONE)
38
# Other drugs for Leprosy
*phenazine dye for used for multibacillary leprosy
*MOA not clearly established
*Stored widely in reticuloendothelial tissues and
skin
*T1/2 can be as long as 2 months
*Most prominent adverse effect – discoloration of
skin and conjunctivae
Clofazimine
39
# Drugs for Non-Tuberculous Mycobacteria (NTM)
Active for NTM
| NTM’s are less susceptible to anti-TB drugs
Tetracyclines, Macrolides, Sulfonamides
