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Infectious Diseases (CM) > Antimycobacterials Med Chem > Flashcards

Antimycobacterials Med Chem Flashcards

1
Q

Which of the following bacteria cause Tuberculosis?

A. MRSA

B. Legionella

C. S. Aureus

D. Mycobacteriaceae

A

D

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2
Q

Which of the following statements regarding Mycobacteriaceae are true? (Select All)

A. Anaerobic bacteria, not requiring oxygen to multiply

B. Aerobic bacteria, requires an aerobic, oxygen-rich environment to multiply.

C. Require acid fast staining (Zeil-Neelsen Stain)

D. Does not have a cell wall

E. Cell wall consists of fatty acids known as mycolic acid

A

B, C, E

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3
Q

Which of the follwing bacteria:disease statements is incorrect?

A. M. tuberculosis: Tuberculosis

B. M. leprae: Leprosy

C. M. avium-M. Intracllular complex (MAC):Opportunistic AIDs infection: lung infection like TB

D. M. kansasii: Opportunistic AIDs infection: lung infection like TB

A

D

M. Kansasii is only an opportunistic lung infection.

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4
Q

Why are the lungs a perfect environment for mycobacteria to multiply?

A. The lungs provid an anaerobic environment that allows the bacteria to multiply

B. The lungs contain an essential substance known as surfactant that the bacteria require for growth and reproduction

C. The lungs provide an aerobic environment that allows the bacteria to multiply

D. The lungs allow for large amounts of CO2 exchange and thus promotes an acidic environment for the bacteria to grow.

A

C

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5
Q

Tuberculosis infections are commonly present in the lungs. When the infection spreads beyond the lungs (such as the kidneys) it will be known as an ____ infection.

A. Interpulmonary

B. Intrapulmonary

C. Pulmonary

D. Transpulmonary

E. Extrapulmonary

A

E

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6
Q

Regarding the pathophysiology of Tuberculosis: Where do the bacteria multiply within the lungs?

A. On the surface of the lunbs

B. Within the surfactant

C. Within the neutrophils that have engulfed the bacteria

D. Within the macrophages that have engulfed the bacteria

E. Within the dendritic cells that have engulfed the bacteria

A

D

When the bacteria enters the lungs the pulmonary marophages will engulf the bacteria in order to destroy it. However, if the bacteria survives the proces then it will stay within the macrophage and multiply itself.

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7
Q

Once an infected macrohpage dies it releases the bacteria and the bacteria will then form the:

A. Caseous center

B. Viral center

C. Viral load

D. Bacterial center

E. Bactericeace Mediae

A

A

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8
Q

The Mycobacterium cell wall consists of high molecular weight faty acids known as:

A. Arabino-galactam

B. Lipoarabinomannan

C. Porins

D. Mycolic Acids

A

D

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9
Q

Mycobacterium cell walls contain Arabino galactam that is a polymer of ___ and ___.

A. Mannose, Arabinose

B. Arabinose, Galactose

C. Mannose, Glucose

D. Arabinose, Glucose

A

B

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10
Q

The Mycobacterium cell wall consists of a molecule known as Lipoarabinomannan that consists is made from polymers of ___ and ___.

A. Arabinose, Mannose

B. Arabinose, Lipose

C. Mannose, Lipose

D. Arabinose, Glucose

A

A

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11
Q

Which of the following medications are Rifamycin medications? (select all)

A. Rifampin

B. Isoniazid

C. Rifabutin

D. Pyrazinamide

E. Rifapentin

A

A, C, E

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12
Q

Which of these medications are First-line agents used to treat tuberculosis? (select all)

A. Ethionamide

B. Isoniazid

C. Fluoroquinolones

D. Rifamycins (rifampin, rifabutin, rifapentin

E. Pyrazinamide

F. Ethambutol

A

B, D, E, F

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13
Q

Which of these medications are second-line agents? (Select All)

A. Ethionamide

B. Fluoroquinolones

C. Pyrazinamide

D. Ethambutol

E. Macrolides

A

A, B, E

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14
Q

If the bacteria M. tuberculosis exhibits MDR resistance, which of the following drugs will have decreased efectiveness towards the bacteria? (select all)

A. Ethionamide

B. Rifampin

C. Ethambutol

D. Isoniazid

E. Moxifloxacin

A

B, C, D

MDR (Multi Drug Resitant) M.tuberculosis will be resistant towards any first-line agents but NOT second-line agents.

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15
Q

If the bacteria Mycobacterium. Tuberculosis exhibits XDR (Extensive Drug Reistant) resistance which of the following agents will have decreased effectiveness?

A. Isoniazid

B. Ethambutol

C. Ethionamide

D. Moxifloxacin

E. Rifamycins

F. All of the above

A

F

XDR (extensive drug resistance) is a type of resistance with m.tuberculosis that makes the bacteria resistant to first line AND second line medications

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16
Q

What are the general PK properties of first-line antimycobacterial agents? (select all)

A. Poor oral absorption

B. Low volume of distribution, stays in the blood for activity

C. High oral absorption

D. Typically given IV

E. Widely distributed throughout the body tissue and fluid

A

C, E

E especially makes sense since TB can spread to other organs and cause extrapulmonary infections in other tissues. As a result you need the drug to be able to distribute itself widely throughout the body

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17
Q

What is the other name for Isoniazid?

A. Isonprozole

B. Isonitrate

C. Isonicotinic acid hydrazide (INH)

D. Isonicotinic anhydrate (INA)

A

C

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18
Q

Isoniazid is a isostere of ____.

A. Nicotinic acid

B. Nitric acid

C. Glutamate

D. Guanidine

A

A

Remember Isoniazid’s other name: Isonicotinic acid Hydrazide (INH). Also there is some structural similarity between the two, hence the term isostere.

19
Q

Of the first-line agents, which of the following has the MOST activity against TB?

A. Rifampin

B. Rifabutin

C. Ethambutol

D. Pyrazinamide

E. Isoniazid

A

E

20
Q

Based on the picture provided, what is needed in order for mycolic acid to synthesize its long fatty acid chain?

A. ADP

B. ATP

C. NADH + H+

D. Acetyltransferase

A

C

21
Q

What enzyme is responsible for catalyzing the reduction of the double bond of mycolic acid?

A. NADPH-reductase

B. InhA

C. Mycolicase

D. NADPH-synthase

A

B

22
Q

What is the MOA of Isoniazid?

A. Inhibits the sythesis of long chain faty acids

B. Insertes itself in the existing viral DNA and terminate chain elongation

C. Lyses the cell wall by forming pores

D. None of the above

A

A

This is important because mycolic acid is a major part of the M.Tuberculosis bacterial cell wall. It consists of a long fatty acid chain and Isoniazid will inhibit the formation of the longer portion of the chain. This stops the synthesis of the cell wall.

23
Q

Isoniazid will specifically inhibit the synthesis of long chain fatty acids greater than __ carbons in length

A. 16

B. 22

C. 24

D. 26

A

D

24
Q

Isoniazid is a prodrug that requires activaiton by the bacterial enzyme ____.

A. Reverse Transcriptase

B. Polymerase

C. KatG

D. KatQ

A

C

25
Q

The prodrug Isoniazid is activated and changed to its nicotinyl radical form. The radical form of the drug then ____ binds to ___ and prevents the reduction of the doulble bond in mycolic acid.

A. Ionically, NAD+

B. Covalently, NAD+

C. Ionically, NADPH

D. None of the above

A

B

Remember the function of NADH is to reduce the double bond of mycolic acid so the fatty acid chain can form. If NAD+ is unable gain its H ion and become NADH then it can’t reduce the double bond on mycolic acid. This stops the synthesis of the fatty acid chain. (look at slide 12 to confirm)

26
Q

What are the mechanisms of bacterial resistance to Isoniazid? (select all)

A. Lactamase development

B. Overexpression of inhA

C. Overproduction of NAT

D. Mutation or deletion of katG

E. Cell wall thickening

A

B, D

Remember that Isoniazid is a prodrug that requires the bacterial enzyme KatG in order to become activated. If the bacterial cell mutates or deletes katG then isoniazid won’t become activated and it will not have any effect on the bacterial mycolic acid synthesis.

27
Q

What enzyme is responsible for the metabolism of Isoniazid?

A. NAT

B. UGT

C. NAC

D. SULT

A

A

28
Q

If someone is a fast acetylator they will have ___ drug levels of Isoniazid.

A. Increased

B. Decreased

A

B

Remember NAT metabolizes Isoniazid to an inactive form so if you are a fast acetylator then you will have less prodrug in the body and more inactive.

29
Q

All of the following statements about Isoniazid are true EXCEPT:

A. Patients should take with food

B. Fast acetylators will have an INH half-life of 1 hour

C. Slow acetylators will have an INH half-life of 3 hours

D. Slow acetylators are at higher risk for hepatotoxicity than fast acetylators

E. Overdosing on INH can cause seizures

A

A

Patients should take on an empty stomach because gastric emptying time is shorter (meaning faster).

Everything written in the answer choices were all written in red.

30
Q

Isoniazid can cause peripheral neuropathy because it depletes a certain B-vitamin in the body. As a result INH should be administerd with the B-vitamin____.

A. Thiamine

B. Cobalamin

C. Folic Acid

D. Pyridoxine

A

D

31
Q

What is the mechanism of action of Rifampin and other Rifampin analogs?

A. Inhibition of Mycolic acid synthesis

B. Inhibition of Cell wall formation

C. Inhibition of DNA-Dependent RNA Polymerase (DDRP)

D. Inhibition of RPO

A

C

32
Q

What makes Rifampin and rifampin analogs selectively toxic?

A. Binds to bacterial DDRP at lower concentrations of Rifampin

B. Binds to mammalian RNA Polymerase at lower concentrations of Rifampin

C. Binds to mammalian RNA Polymerase at higher concentrations of Rifampin

D. Both A and C

A

D

She said she will ask this on the exam.

33
Q

Resistance to Rifampin and rifampin analogs involves the mutation in the bacterial ___ gene.

A. DAPG

B. dAG

C. rpoB

D. NAT

A

C

When the rpoB bacterial gene is mutated it will cause the expression of a structurally different DDRP instead. As a result the rifampin and rifampin analogs will be unable to bind to it as effectively.

34
Q

Which of the following statements is true regarding rifampin and rifampin analogs?

A. When eliminated through the tears, saliva and urine it can cause a red-orange discoloration.

B. Strongly induces many CYP enzymes.

C. Strongly inhibits many CYP enzymes

D. Can decrease concentrations of NNRTIs and PIs in HIV patients

E. Rifampin is preferred over Rifabutin

A

A, B, D

C is incorrect because it does not inhibit CYP enzymes.

D is incorrect because Rifabutin is more preferred in comparison to rifampin because it doesn’t induce CYP enzymes as much as rifampin does.

Look up slide 19 to see specific DDIs with oral contraceptives, warfarin, azoles etc.

35
Q

The medication Pyrazinamide is a bio-isostere of ____

A. Nicotinic acid

B. Nicotinamide

C. Sulfonic acid

D. Guanidine

A

B

Remember Isoniazid (INH- Isonicotinic acid hydrazide) is a derivative of Nicotinic acid

Pyrazinamide is a bio-isostere of Nicotinamide.

36
Q

In order for Pyrazinamide to become activated it needs the bacterial enzyme _____.

A. katG

B. NAT

C. katQ

D. Pyrazinamidase

A

D

37
Q

Resistance to pyrazinamide is caused by bacterial mutation of the ____ gene.

A. inhA

B. rpoB

C. aDAG

D. pncA gene

A

D

The pncA bacterial gene is responsible for the expression of pyrazinamidase and if that gene is mutated then the mutated version of pyrazinamidase will not be able to activate the drug Pyrazinamide.

38
Q

All of the following are suspected MOAs of Pyrazinamide EXCEPT:

A. Forms pores in bacterial membranes, leaking bacterial contents

B. Inhibition of mycolic acid synthesis

C. Reduction of intracellular pH

D. Disruption of membrane transport

A

A

39
Q

Pyrazinamide can decrease the excretion of uric acid from the body. In turn this can cause:

A. Hypouricemia

B. Hyperuricemia

C. Kidney damage

D. Discoloration of bodily fluids

A

B

Because it causes hyperuricemia it can cause gout and gout flare-ups

40
Q

What is the mechanism of action of Ethambutol?

A. Inhibits mycobacterial cell-wall synthesis.

B. Inhibits mycolic acid synthesis

C. Inhibits bacterial DDRP

D. Reduces intracellular pH, causing bacterial destruction.

A

A

41
Q

What bacterial enzyme does Ethambutol inhibit?

A. katG

B. Pyrazinamidase

C. Arabinosyltransferase

D. NAT

A

C

Arabinosyltransferase is a bacterial enzyme that is responsible for incorporating arabino in the arabino-galactam structure of the cell wall in M. Tuberculosis. If you block this enzyme it cannot incorporate arabino into the cell wall and as a result it stops bacterial cell-wall synthesis.

42
Q

T/F Ethambutol can cause an irreversible optic neuritis, causing loss of color discrimination. (cant see certain colors)

A

F

It causes optic neuritis but it is reversible. Patient should have visual exams while on this drug.

43
Q
A

Infectious Diseases (CM) (10 decks)

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