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Cology 2 Exam 2 > Mycobacterium agents (Tuberculosis) > Flashcards

Mycobacterium agents (Tuberculosis) Flashcards

1
Q

Is isoniazid static or cidal?

A

Static for latent

Cidal for active/dividing bacteria

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2
Q

How does isoniazid work?

A

Inhibits mycolic acid production (which inhibits the waxy cell coat)

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3
Q

How is isoniazid excreted?

A

75-95% excreted as acetylated metabolite

Fast acetylators (eskimos) 70 minute t1/2
Slow acetylators (caucasians) 3.3 hr t 1/2
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4
Q

Which TB drug has dif half lives for dif populations

A

Isoniazid

75-95% excreted as acetylated metabolite

Fast acetylators (eskimos) 70 minute t1/2
Slow acetylators (caucasians) 3.3 hr t 1/2
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5
Q

How does isoniazid work in the body?

A

It is metabolically activated by bacterial catalase-perioxidase

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6
Q

How does resistance to isoniazid occur?

A

Resistance occurs by point mutation in DNA coding for activation enzyme

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7
Q

True or False: Isoniazid enters the CNS

A

True

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8
Q

What is isoniazid used for?

A

Prophylactic for TB - used alone

Active TB - used in combination

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9
Q

What are the adverse effects of Isoniazid?

A

Allergic reactions - lupus like syndrome
Hepatitis - increased risk in alcoholics/older age
Peripheral neuritis - pyridoxine deficiency

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10
Q

How to treat isoniazid toxicity?

A 
Can only treat the peripheral neuritis
Use pyridoxine (B6)
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11
Q

What happens with Isoniazid overdose?

A

Seizures, euphoria, psychosis, memory impairment, coma

Happens due to decreased pyridoxyl-5-phosphate reactions which decreases GABA

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12
Q

What drug interactions do you worry about with Isoniazid?

A

Potent inducer of CYP2C19, CYP3A4
Weak inhibitor of CYP2D6

Worry about theophylline, phenytoin, diazepam, APAP, etc

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13
Q

What do you use Rifampin for?

A

Rifampin, Rifapentine, and RIfabutin are all BROAD spectrum (gram + and gram -, used in all mycobacterium)

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14
Q

What are the semi-synthetic forms of rifamycin B?

A

Rifampin
Rifapentine
Rifabutine

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15
Q

How does Rifampin work?

A

Inhibits the DNA dependent RNA polymerase (forms complex with the enzyme)

No effect on human enzyme!

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16
Q

When is Rifampin used alone?

A

NEVER

Rapid tolerance can occur due to mutations in DNA repair enzymes

17
Q

What is Rifampin used for?

A

Primary use is TB
Can also be used as prophylaxis for meningitis
Can also be used in endocarditis caused by gram - only

18
Q

How is rifampin excreted?

A

Metabolized by microsomal-B-esterases and cholinesterases

19
Q

What are the adverse effects of Rifampin?

A

Induces P450 enzymes so worry about antichoagulants, contraceptives, digoxin, etc

Jaundice, hepatitis (chronic liver disease)

Secretions are colored orange-tan (tears, sweat, urine)

Hypersensitivity - flu like symptoms in 20% of patients

GI disturbances

20
Q

Which drug can cause secretions to turn orange-tan?

A

Rifampin

21
Q

Which drug can cause flu like symptoms?

A

Rifampin

22
Q

How does Pyrazinamide work?

A

It is converted to pyrazinic acid, activated at LOW pH at necrotic edges of cavities

Inhibits fatty acid synthesis (interferes with mycolic acid production)
Reduces pH
Disrupts membrane transport

23
Q

Why do we use Pyrazinamide?

A

It decreases duration of the combined therapy

24
Q

What are the adverse effects of Pyrazinamide?

A

Hepatitis (15%)
Inhibits uric acid excretion, all hyperuricemic, may induce gout
Nausea, vomiting, anorexia, arthralgias
Avoid in pregnancy

25
Q

What drug can cause gout

A

Pyrazinamide

26
Q

What drug should be avoided in pregnancy

A

Pyrazinamide

27
Q

What causes resistance in Pyrazinamide?

A

Decreased conversion to pyrazinic acid

28
Q

What is Ethambutol?

A

Bacteriostatic drug

Inhibits arabinosyl transferase 3 which disrupts mycolic acid incorporation into membranes

Weakens the cell wall to allow other agents better access

29
Q

Why do we use Ethambutol?

A

It weakens the cell wall to allow other agents better access

Only use for 2 months

30
Q

How is Ethambutol excreted?

A

75% excreted unchanged

Adjust dose in renal disease

31
Q

What causes resistance in Ethambutol?

A

Resistance develops quickly if used alone, mutations in arabinosyl-transferase 3

32
Q

What are the adverse effects of Ethambutol?

A

Visual disturbances (limited in children)
Decreased red green discrimination
Decreased visual acuity
Increased uric acid levels

33
Q

What drug causes visual disturbances

A

Ethambutol

E=EYE

Cology 2 Exam 2 (18 decks)

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