Antifungals and TB

Question 1

Steroid found in the cell membrane of fungi.

Answer 1

Ergosterol

Question 2

Binds to ergosterol in the fungal cell membrane, creating pores to increase cell permeability and thus cause death.

Answer 2

Amphotericin MOA

Question 3

Amphotericin mechanism of resistance.

Answer 3

The sterols (ergosterol) are altered in the membrane, so amphotericin cannot bind.

OR

There’s a decreased amount of sterols in the cell membrane.

Question 4

Adverse reaction of Amphotericin

Answer 4

1) Kidney toxicity, causing the patient to waste K and Mg.
2) Idiosyncratic hypotension and arrhythmias.
3) Fever, chills, and rigors.

Question 5

These antifungals bind to cyt P450 enzymes to inhibit 1,4-alpha demethylation of Lanosterol (fungal steroid found in cell membranes).

Answer 5

Azole antifungals

Question 6

Adequate hydration may decrease the toxicity caused by this drug.

Answer 6

Amphotericin

Question 7

Azole used for candida albicans.

Answer 7

Fluconazole

Question 8

This antifungal has the least drug-drug interactions of all the azoles.

Answer 8

Fluconazole

Question 9

Antifungal against Aspergillus (a fungus).

Answer 9

Voriconazole

Question 10

Another azole antifungal.

Answer 10

Posaconazole

Question 11

Need to be aware of this with all azole antifungals.

Answer 11

Drug-drug interactions!

Question 12

Antifungal that’s part of the Echinocandin family.

Answer 12

Caspofungin

Question 13

This antifungal inhibits beta 1,3-glucan.

Answer 13

Caspofungin

Question 14

This antifungal works at a different site of action from the azoles and amphotericin.

Answer 14

Caspofungin

Question 15

Also members of the Echinocandin family.

Answer 15

Micafungin

Anidulofungin

Question 16

These bacteria have chains of mycolic acid (types of fatty acids).

Answer 16

Mycobacteria

Question 17

Where does TB infection begin in the lungs?

Answer 17

Alveoli

Question 18

Large or small TB droplets lodge in the alveoli?

Answer 18

Small

Question 19

Why are the majority of TB bacilli destroyed or inhibited once inhaled?

Answer 19

Alveolar macrophages ingest them.

Question 20

T/F: A small number of TB molecules multiply in the alveolar macrophages (intracellularly), and are released when the macrophages die.

Answer 20

TRUE

Question 21

Immune responses soon develop to kill the bacilli.
Within how many weeks after infection does the immune system halt the multiplication of the tubercle bacilli, preventing further spread?

Answer 21

2-10 weeks

Question 22

When is a person INFECTED with TB?

Answer 22

When their immune system tries to halt the multiplication of the tubercle bacilli.

Question 23

What percent of people infected with TB will develop the disease?

Answer 23

10%

Question 24

The TB infection is controlled by the immune system in what percent of people? They will not develop CLINICAL TB.

Answer 24

90%

Question 25

What percent of the 10% infected that get the disease will develop it in the first two years?

Answer 25

5%

Question 26

What percent of the 10% infected that get the disease will develop it over the remaining lifetime?

Answer 26

5%

Question 27

What is latent TB infection?

Answer 27

When you're infected (have immune response against TB), but don't have the disease.

Question 28

If you're infected with TB, but don't have the disease, can you spread TB?

Answer 28

No

Question 29

Total body burden of tuberculosis bacilli in LATENT TB infection.

Answer 29

Less than 10 ^4

Question 30

Drug used for latent TB infection.

Answer 30

Isoniazid

Question 31

How many organisms are in ACTIVE TB disease?

Answer 31

10^9-10^10

Question 32

Isoniazid MOA

Answer 32

Inhibits mycolic acid synthesis in the cell wall.

Question 33

Isoniazid/INH is what kind of drug?

Answer 33

Prodrug

Question 34

This enzyme metabolizes isoniazid to its active form.

Answer 34

Catalase/peroxidase enzyme (katG) Cat activates the Ise; Nat breaks down the Ise.

Question 35

Strains which cannot break down Isoniazid bc they have a defective catalase/peroxidase are __________ to Isoniazid.

Answer 35

resistant

Question 36

What metabolizes Isoniazid and where is it metabolized?

Answer 36

N-acetyl transferase; Liver NAT breaks down ISE

Question 37

The rate of isoniazid acetylation is determined as what type of genetic trait?

Answer 37

Autosomal recessive.

Question 38

Does the rate of isoniazid acetylation alter therapy clinically?

Answer 38

No, just the weekly administration schedules

Question 39

Isoniazid adverse reactions.

Answer 39

1) Hepatitis | 2) Neurotoxicity

Question 40

Peak hepatitis incidence when using Isoniazid.

Answer 40

First 4-8 weeks Hepatic failure can occur, which then leads to death if you continue to take the drug.

Question 41

What percent of Isoniazid patients get elevated transaminases?

Answer 41

15%

Question 42

What causes neurotoxicity when using Isoniazid?

Answer 42

Increased pyridoxine excretion.

Question 43

Pyridoxine is what vitamin?

Answer 43

B6

Question 44

Concomitant administration of what vitamin is given when taking Isoniazid?

Answer 44

B6

Question 45

Clinical uses of Isoniazid

Answer 45

1) Treat latent TB (positive PPD, but no active disease). | 2) Combo therapy for active TB at any stage.

Question 46

Rifampin MOA

Answer 46

Inhibits DNA dependent RNA polymerase of mycobacterial cells.

Question 47

Human enzyme is insensitive to the effects of this tuberculosis drug.

Answer 47

Rifampin

Question 48

Rifampin mechanism of resistance.

Answer 48

Alteration of DNA-dependent RNA polymerase (rpoB). Occurs at about the same frequency as INH in the absence of drug 10^-6.

Question 49

Rifampin has excellent _____ absorption and wide distribution, including the __.

Answer 49

Oral; CNS

Question 50

How is Rifampin metabolized?

Answer 50

HEPATIC via cytochrome P450 (deacylation).

Question 51

This drug induces its own increased metabolism.

Answer 51

Rifampin

Question 52

Rifampin adverse reactions.

Answer 52

Hepatotoxicity is manifest as cholestatic changes (increase alkaline phosphatase, increased bilirubin), but can also be necroinflammatory with elevated transaminases. INH and rifampin may potentiate hepatotoxicity of the other agent.

Question 53

Marked drug interaction secondary to the induction of CYT P450 occurs with this drug.

Answer 53

Rifampin

Question 54

Increased metabolism of coumarin, oral contraceptives, and phenytoin may occur with this drug.

Answer 54

Rifampin

Question 55

Interaction with verapamil causes marked reduction in verapamil levels when using this drug.

Answer 55

Rifampin

Question 56

What do elevated transaminases in the blood indicate?

Answer 56

The liver cells are inflammed or damaged, and they leak liver enzymes, like transaminases.

Question 57

Pyrazinimide MOA

Answer 57

Used to treat tuberculosis, and inhibits fatty acid synthesis.

Question 58

M. tuberculosis has this enzyme, which activates pyrazinamide to its active form (pyrazinoic acid) at acidic pH.

Answer 58

Pyrazinamidase.

Question 59

Pyrazinamide mechanism of resistance?

Answer 59

Unknown

Question 60

Pyrazinamide adverse reaction.

Answer 60

Hepatotoxicity Gout

Question 61

Ethambutol MOA

Answer 61

An antimetabolite for tuberculosis, affecting RNA synthesis.

Question 62

Ethambutol Mechanism of Resistance

Answer 62

Unknown

Question 63

Most dangerous adverse reaction of ethambutol.

Answer 63

Retrobulbar neuritis.

Question 64

How does retrobulbar neuritis usually develop?

Answer 64

Decreased acuity and change in color vision (yellow and green). Associated with high doses; peripheral neuropathy can also occur.