Pharmacology of Respiratory Disease

Question 1

Tx of blastomyces

Answer 1

Itraconazole or ketoconazole

NOT fluconazole or amphotericin

DO NOT combine with antacids…need low pH to dissolve the capsule

Question 2

MOA of amphotericin

Answer 2

Inhibiton of ergosterol

Question 3

Itraconazole MOA

Answer 3

Inhibition of lanosterol demthylase

Question 4

Progression to meningeal dz

Answer 4

Itraconzaole shifted to amphotericin

Question 5

Itera nad keto distribution

Answer 5

Both highly protein bound but fluconzole cors BBB readily

Question 6

Pregnancy and azoles

Answer 6

p450s

steroid hormones

Question 7

Coccidiomces

Answer 7

Amphotericin is the mainstay of tx

Question 8

How would tx of coccidio be changed if student was also taking acyclovir

Answer 8

Kidney toxicity through two different mechansis ms

Question 9

Aspergillosis

Answer 9

Voriconazole is new SOA compared to amphotericin

If pt is getting cyclophosphamide…then need to adjust dose because it could inhibt p450 and block activation of cyclo

Question 10

If aspergilosis therapies fail

Answer 10

Then caspfungin (echinocandins) can be added to voriconazole

Question 11

Tx of histo

Answer 11

Itraconzaole…can’t use amphotericin if kidney problems

Question 12

Fluconazole activity and pharm

Itraconzsole

Answer 12

Flu - yeasts yes, molds no…good CSF

Itra-
borader spectrum, poor availabiloty…good for histo…long T1/2

Question 13

VOriconazole activity and pharm

Answer 13

Asp yes, mucor no

Side effects (vision, neuron, rash)

P450 sub and inhibitor

Question 14

Itraconzole and ovoriconazole uptake

Answer 14

Effected by food

Flu - NOT

Question 15

Mucor tx

Answer 15

Amphotericin B

Voriconazole and fluconoizole NOT

Question 16

LP drugs

Answer 16

Isonizaid
Rifampin
Pyrazinamide
Ethambutol

Needs to be treated for about 6 months…this is because waxy coat that makes it difficult

Question 17

Isonizaid

Answer 17

Prophylactially and for HIV infected patients

Interferes with synthesis of mycolic acid

Pro-drug converted by mycobacterial catalase (KatG)…adds specificty

Question 18

Resistance to isonizid

Answer 18

Mutations to enoyl reductase

Mutations in KatG

Mutations in other virulence genes

Question 19

PKs isoniazid

Answer 19

Well absorbed

Slow acetylation - dose adjusemnt reuirement in most white

If patients has slow acetylation, then you need to decrease the dose

Question 20

Toxicity of ison

Answer 20

Neuritis, heptotoxicty

This could be problem in TB population because of alcohol problems/hepatitis

Question 21

Rifmapin

Answer 21

Targets RNA polymerase

Resistance through mutations in the target

Question 22

Rfimapin toxicty

Answer 22

Hepatotoxicty

Orange secretions and urine

Question 23

Rifmapin interactions

Answer 23

P450 inducer

Question 24

Pyrazinamide MOA

Answer 24

Unknown

Inhibits mycolic acid biosynthesis

Pro-drug converted by pyrazinamidase…mutations are resistacne

Hepatitis is main toxocity

Question 25

Ethambutol MOA

Answer 25

UNknown…interferes with mito rep

Well-tolerated

Optic neuritis

Question 26

Why is hepatoxocity important

Why is bacteirocidal for divding and bacteriostatic for dormant important

When to discontnue

Answer 26

IMportant if they have heptitis or other liver dz

Means tx means to be given longer bc over time some will break out

Side effects do not warrant disconitnuing

Question 27

MDR resistance

Answer 27

Resitance to isoniazid and rifampin (poor adherence)

If MDR, then tx with pyrazinamide, ehtambutol, and ethionamide for 24 months

Question 28

Ethionamide

Answer 28

Prodrug

Inhibits enoyl reductase (similar to isoni) but different mechanism

GI probs

Inhibits mycolic acid synthesis

Question 29

Practial considerations of TB therapy

Answer 29

Neuritis, orange, hepato, P450

Adding ethionamide introduces GI and hypotension