3B : ANTI-MYCOBACTERIUM Flashcards

1
Q

exerts its effects by reversibly inhibiting DNA-dependent RNA polymerase, which
further inhibits bacterial protein synthesis and transcription.

A

Rifampin

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2
Q

a pro-drug that is converted to its active form metabolite by catalase-peroxidase
and exerts its action by further inhibiting the biosynthesis of mycolic acid.

A

Isoniazid

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3
Q

converted to its active form and exerts its effect by inhibiting
trans-translation
and possibly coenzyme A synthesis needed for the bacteria to survive.

A

Pyrazinamide

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4
Q

inhibits the enzyme arabinosyltransferases and prevents the biosynthesis of the
mycobacterial cell wall.

A

Ethambutol

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5
Q

binding to the 30S subunit of ribosomes and inhibiting the protein synthesis of the mycobacteria.

A

Aminoglycosides (Streptomycin, Kanamycin, Amikacin)

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6
Q

inhibiting DNA gyrase and topoisomerase IV, further inhibiting DNA synthesis within the bacteria.

A

Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin)

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7
Q

ADMINISTRATION

oral

A

Rifampin, Isoniazid, Pyrazinamide, and Ethambutol

Fluoroquinolones such as moxifloxacin, gatifloxacin, and levofloxacin

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8
Q

ADMINISTRATION
parenteral

A

Streptomycin is usually administered daily as a single intramuscular injection

Aminoglycosides are usually administered by intravenous infusion or intramuscular
injection

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9
Q

Adverse Effects

Rifampin:

A
  • Hepatotoxicity,
  • Thrombocytopenia,
  • Neutropenia,
  • Orange/Red discoloration of bodily
    fluids
    ,
  • CYP450 Inducer
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10
Q

Adverse Effects

Isoniazid:

A
  • Hepatotoxicity,
  • Vitamin B6 deficiency,
  • Peripheral Neuropathy

Isoniazid can interfere with the activity of vitamin B6. Vitamin B6 supplementation
is recommended, especially in people with poor nutritional status, to prevent the
development of isoniazid-induced peripheral neuritis (inflamed nerves).

INH metabolites directly attach to and inactivate pyridoxine species. The
combination of isoniazid and pyridoxine form a hydrazone which is excreted in
the urine.

INH inhibits the enzyme pyridoxine phosphokinase; this enzyme is necessary
to activate pyridoxine to pyridoxal 5’ phosphate, the cofactor in many
“pyridoxine-dependent” reactions

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11
Q

adverse effect

Pyrazinamide:

A
  • Hepatotoxicity,
  • Hyperuricemia,
  • Arthralgia
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12
Q

ADVERSE EFFECT

Ethambutol:

A
  • Optic neuropathy,
  • Hepatotoxicity
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13
Q

ADVERSE EFFECT

Aminoglycosides (Streptomycin, Kanamycin, Amikacin):

A
  • Ototoxicity,
  • Nephrotoxicity
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14
Q

ADVERSE EFFECT

Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin):

A
  • Tendonitis,
  • Tendon rupture,
  • Arthropathy
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15
Q

During pregnancy, all anti-tubercular medications are useful for treatment except for

A

AMINOGLYCOSIDES.

Aminoglycosides such as streptomycin, amikacin, and kanamycin may
exhibit ototoxic effects on the developing fetus

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16
Q

thioamide derivative with antitubercular activity
Used to treat MDR TB

A

PROTIONAMIDE

17
Q

MOA of protionamide

A

Forms a covalent adduct with bacterial nicotinamide adenine dinucleotide (NAD),
PTH-NAD, which competitively inhibits 2-trans-enoyl-ACP reductase (inhA), an enzyme
essential for mycolic acid synthesis
; results in increased cell wall permeability and decreased
resistance against cell injury eventually leading to cell lysis.

18
Q

ADVERSE EFFECT OF PROTIONAMIDE

A
  • Most commonly associated with nausea and vomiting.
  • It may cause depression and hallucinations.
  • Rarely, prothionamide will cause jaundice, menstrual disturbances and peripheral neuropathy.

Not recommended for pregnant women as it has been shown to be teratogenic in animal
studies

19
Q

analog of the amino acid D-alanine with broad-spectrum antibiotic activities

A

CYCLOSERINE

20
Q

an excitatory amino acid and partial agonist at the glycine
binding site of the NMDA receptor in the central nervous system (CNS); binding to the
central NMDA receptor may result in amelioration of neuropathic pain

A

D-cycloserine

21
Q

a broad spectrum antibiotic used as a second line agent for treatment of drug
resistant tuberculosis
, always in combination with other antituberculosis agents.

A

CYCLOSERINE

22
Q

Symptoms of acute toxicity of cycoloserine generally involve

A

the CNS and include
* headache,
* vertigo,
* confusion,
* drowsiness,
* hyperirritability,
* paresthesias,
* dysarthria, and
* psychosis.

Paresis, seizure, and coma may occur with large cycloserine overdosages; alcohol ingestion
may increase the risk of seizures.

23
Q

Member of a new class of drugs called the diarylquinolines

Blocks the proton pump for ATP synthase of mycobacteria

A

BEDAQUILINE

24
Q

Resistance bedaquiline

A
  • The specific part of ATP synthase affected by bedaquiline is subunit c which is
    encoded by the gene atpE. Mutations in atpE can lead to resistance.

Mutations in drug efflux pumps have also been linked to resistance

25
Q

Most common side effects of bedaquiline

A

include nausea, joint and chest pain, and headache

26
Q

black box warning of bedaquiline

A
  • increased risk of death and arrhythmias, as it may prolong the QT
    interval by blocking the hERG channel
27
Q

considerations in giving bedaquiline

A

can also cause hepatotoxicity

Should** not be co-administered with other drugs that are strong inducers or inhibitors
of CYP3A4**, the liver enzyme responsible for oxidative metabolism of the drug

Example:

Rifampicin - strong CYP3A4 inducer

Ketoconazole - strong CYP3A4 inhibitor

Approved for use in multidrug-resistant tuberculosis, and the more resistant extensively
drug resistant tuberculosis

28
Q

FREQUENCY OF QT INTERVAL MONITORING AND MANAGEMENT OF QT
INTERVAL PROLONGATION

A