Antimycobaterial Drugs Flashcards
(102 cards)
1
Q
Traditional first-line agents for treatment of tuberculosis
A
Isoniazid (INH)
Rifampin
Pyrazinamide
Ethambutol
2
Q
The most active drugs in treating TB
A
Isoinazid and rifampin
3
Q
Combination of this drug for 9 months will cure 95-98% of cases of tuberculosis
A
Isoniazid-rifampin
4
Q
In practice, therapy is usually initaited with a??? Until susceptibility of the clinical isolate has determined.
A
Four-drug regimen of isoniazid, rifampin, pyraziamide and ethambutol
5
Q
Most active drug for the treatment of tuberculosis caused by susceptible strains
A
Isoniazid
6
Q
Isoniazid inhibits most ___ bacteria and less effective against??
A
Tubercle bacilli
Nontuberculous mycobacteria
7
Q
What does isoniazid inhibits?
A
Inhibits mycolic acids , which are essential components of mycobacterial cell wall
8
Q
What is a mycolic acid?
A
An esential component of mycobacterial cell wall
9
Q
____ a prodrug that is activated by KatG, the mycobacterial catalase-peroxidase
A
Isoniazid
10
Q
Activated form of isoniazid forms a covalent complex with an?
A
Acyl carrier protein (AcpM) and KasA, a beta-ketoacyl carries protein synthetase WHICH BLOCKS MYCOLIC ACID SYNTHESIS.
11
Q
Resistance to isoniazid is associated with mutations resulting in?
A
- Overexpression of inhA, which encodes an NADH0-dependent acyl carrier protein reductase
- Mutation or deletion of the katG egne
- promoter mutation resulting in overexpression of aphC, gene involved in protection from oxidative stress
- mutation in kasA
12
Q
___ or more active agents should ALWAYS be used to treat active tuberculosis to prevent ___ during therapy
A
At least two
Emergence of resistance
13
Q
In taking isoniazid, should you take with meal or without meal?
A
Without meal (optimally on an empty stomach)
Because peak concentration with decrease up to 50% when taken with a fatty meal
14
Q
Typical adult dose and children dose of isoniazid in
A
300mg
5mg/kg
15
Q
Metabolism of isoniazid
A
Acetylation by liver N-acetyltransferase
16
Q
Average HL of isoniazid
A
Less than 1hr and 3hrs
17
Q
Isoniazid metabolites and a small amounts of unchanged drug are excreted in?
A
Urine
18
Q
Isoniazid dose in children
A
5mg/kg/d
19
Q
Is recommended for those with conditions predisposing to neuropathy, an adverse effect of isoniazid
A
Pyridoxine
20
Q
Isoniazid as a single agent is also indicated for treatment of?
A
Latent tuberculosis
21
Q
Duration of taking isoniazid in treating TB
A
9 months
Dosage 300 mg/d or 900mg twice weekly
22
Q
The most common major toxic effect of isoniazid
A
Isoniazid-induced hepatitis
23
Q
Adverse effects of isoniazid
A
Hepatoxicity, peripheral neuropathy
24
Q
What drug should you give in patients taking isoniazid to prevent peripheral neuropathy
(PN = adverse effect of isoniazid)
A
Pyridoxine
25
A semisynthetic derivative of rifamcyin, an antibiotic produced by amycolatopsis rifamycinica, formerly named streptomyces mediterranei
Rifampin
26
Rifampin is active against what organism?
GRAM + ORGANISMS
Some gram - org, like neisseria and haemophilus
27
This drug has no cross resistance, but there is a cross-resistance to its other derivatives
Rifampin
28
Derivatives of rifampin
Rifabutin and rifapentine
29
Binds to the B subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis
Rifampin
30
MOA of rifampin
Binds to the b subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis.
31
What causes resistance to rifampin
Mutations in rpoB gene for the B subunit of RBA polymerase
32
Excretion of rifampin
Liver into bile
The bulk is excreted as a deacylated metabolite in feces and small amount excreted in the urine.
33
What cytochrome P450 isoforms does rifampin strongly induces
CYP1A2
CYP2C9
CYP2C19
CYP2D6
CYP3A4
34
Oral dose of rifampin
600mg in adult
10 mg/kg/d in children
35
Alternative drug for patients with latent TB that has isoniazid resistant strain
Rifampin. 600mg daily for 4 months as a single drug.
36
____ must be administered with isoniazid or other antituberculous drug to patients with active TB to prevent emergence of drug-resistant mycobacteria.
Rifampin
37
Oral dose of 600mg twice aday for 2 days can eliminate meningococcal carriage
Rifampin
38
Treatment of serious staphylococcal infections
Rifampin
39
20mg/kg once daily for 4 days, used as prophylaxis in contacts of children with haemophilus influenzae type b disease
Rifampin
40
Adverse effects of rifampin
Harmless orange color to urine, sweat and tears.
Rashes, thrombocytopenia and nephritis.
Flu-like syndrome with intermittent dosing.
41
Similar to rifampin but less cytochrome p450 induction and fewer drug interactions
Rifabutin. PO
42
Long acting analog of rifampin that may be given once weekly in select cases during the continuation phase of TB treatment or for treatment of latent TB
Rifapentine. PO
43
MOA of ethambutol
Inhibits mycobacterial arabinosyl transferase, which are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall
44
EmbCAB operon encodes?
Arabinosyl transferases
45
Essential component of the mycobacterial cell wall.
Arabinoglycan
46
Involved in the polymerization reaction of arabinoglycan
Arabinosyl transferases
47
Ethambutol is well absorbed from the?
Gut
48
Excretion of ethambutol
20% in feces
50% in urine
49
Resistance to ethambutol if due to?
Overexpressio of embgene products or within the embB structural gene
50
Resistance to ethambuol emerges rapidly when?
The drug is given alone. Therefore, ethambutol is always given in combination with other antiTB drug
51
Ethambutol is also used in combination with other agents for the treatment of nonTB mycobacterial infections such as
Mycobacterium avium complex (MAC) or M. Kansasii
52
Most common adverse effect of ethambutol
Retrobulbar neuritis - loss of visual acuity and red-green color blindness
53
Ethambutol is relatively contraindicated to?
Children who aretoo young to permit VAC test and red-green color discrimination
54
A relative of nicotinamide, and it is used only for the treatment of TB
Pyrazinamide
55
What pH level is pyrazinamide inactive and active
Inactive = neutral pH
Active = 5.5 - inhibits tubercle bacilli
56
This drug is taken up by macrophages and exerts its activity against mycobacteria residing within the acidic environment of lysosomes
Pyrazinamide
57
Active form of pyrazinamide
Pyrazinoic acid
58
most tubercle bacilli are inhibited by
streptomycin
59
route of administration of streptomycin sulfate
IM or IV
60
most common adverse effect of streptomycin
vertigo and hearing loss
61
is related to isoniazid and similarly blocks the synthesis of mycolic acids
ethionamide
62
route of administration of ethionamide
only PO
63
ethionamide is metabolized by the?
liver
64
most tubercle bacilli are inhibited in vitro by
ethionamide
65
a peptide protein synthesis inhibitor antibiotic obtain from streptomyces capreolus
capreomycin
66
route of administration of capreomycin
IM
67
____ (15 mg/kg/d) is an important injectable agent for treatment of drug-resistant tuberculosis.
Capreomycin
68
___ penetrates into macrophages and is active against both extracellular and intracellular organism
Isoniazid
69
____ is observed in 10-20% of patients given isoniazid with greater than 5mg/kg/d but it is infrequently seen with the standard 300-mg adult dose
Peripheral neuropathy
70
Oral dosage of rifampin 600mg twice daily for 2 days can eliminate?
Meningococcal carriage
71
Rifampin, 20 mg/kg (maximum 600 mg) once daily for 4 days, is used as prophylaxis in contacts of children with?
Haemophilus influenzae type b disease
72
a synthetic, water-soluble, heat-stable compound, dispensed as the dihydrochloride salt.
Ethambutol
73
Resistance to ethambutol emerges rapidly when the drug is used alone or with combination?
Alone
74
Pyrazinoic acid disrupts mycobacterial cell membrane metabolism and transport functions
Pyrazinamide
75
Parent compound of PZA is metabolized by the ___ but metabolites are ___ cleared
Liver
Renally
76
An important front-line drug used in conjunction with isoniazid and rifampin in short course regimen as a “sterilizing agent” active against residual intracellular organisms that may case relapse
Pyrazinamide
77
Major adverse effect:
Hepatoxicity, photosensitivity and hyperuricemia
78
Penetrates into cells poorly and is active mainly against extracellular tubercle bacilli
Streptomycin
79
a structural analog of d-alanine—inhibits cell wall synthesis,
Cycloserine
80
Most serious toxic effects of cycloserine
Peripheral neuropathy and CNS dysfunction, including depression and psychoses
81
a folate synthesis antagonist that is active almost exclusively against M tuberculosis. It is structurally similar to p-amino-benzoic acid (PABA) and is thought to have a similar mechanism of action to the sulfonamides
Aminosalicylic acid PAS
82
Very high concentrations of aminosalicylic acid are reached in the urine, which can result in
Crystalluria
83
is indicated for treatment of tuberculosis suspected or known to be caused by streptomycin-resistant or multidrug- resistant strains. This drug must be used in combination with at least one and preferably two or three other drugs to which the isolate is susceptible for treatment of drug-resistant cases.
Amikacin
84
had been used for treatment of tuberculosis caused by streptomycin-resistant strains, but it is no longer available in the USA
Kanamycin
85
are an important addition to the drugs avail- able for tuberculosis, especially for strains that are resistant to first- line agents.
Fluoroquinolones
86
4 kinds of fluoroquinolones
Ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin
87
The most active fluoroquinolones against M tuberculosis in vitro
Moxifloxacin
88
A fluoroquinolones that tends to be slightly more active than ciprofloxacin
Levofloxacin
89
has been used in combination with other second- and third-line drugs to treat patients with tuberculosis caused by multidrug-resistant strains.
Linezolid
90
What drug has this adverse effect?
Bone marrow suppression, irreversible peripheral and optic neuropathy
Linezolid
91
should be used only for multidrug-resistant strains that also are resistant to several other first- and second-line agents
Linezolid
92
is often used in place of rifampin for treatment of tuberculosis in patients with HIV infection who are receiving antiretroviral therapy with a protease inhibitor
Rifabutin
93
A derivative of rifampin that can cause leukopenia, thrombocytopenia and optic neuritis
Rifampin
94
used for treatment of tuberculosis caused by rifampin- susceptible strains during the continuation phase (first 2 months of therapy)
Rifapentine
95
a diarylquinoline, is the first drug with a novel mech- anism of action against M tuberculosis to be approved since 1971.
Bedaquiline
96
What does bedaquiline inhibits?
Inhibits ATP synthase in mycobacteria
97
The most common adverse effect if this drug are nausea, arthralgia and headache. This has been associated with both hepatoxicity and cardiac toxicity
Bedaquiline
98
Nontuberculous mycobacteria are formerly known as ???
Atypical mycobacteria
99
The most widely used drug in treatment of leprosy
Dapsone (diaminodiphenylsulfone)
100
may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients.
Dapsone
101
Suflones can cause erthyhema nodosum leprosum, what drug can it suppress the adverse effect?
Thalidomide
102
a phenazine dye used in the treatment of multi- bacillary leprosy, which is defined as having a positive smear from any site of infection
Clofazimine
