Pharmacology of Respiratory Disease Flashcards
Tx of blastomyces
Itraconazole or ketoconazole
NOT fluconazole or amphotericin
DO NOT combine with antacids…need low pH to dissolve the capsule
MOA of amphotericin
Inhibiton of ergosterol
Itraconazole MOA
Inhibition of lanosterol demthylase
Progression to meningeal dz
Itraconzaole shifted to amphotericin
Itera nad keto distribution
Both highly protein bound but fluconzole cors BBB readily
Pregnancy and azoles
p450s
steroid hormones
Coccidiomces
Amphotericin is the mainstay of tx
How would tx of coccidio be changed if student was also taking acyclovir
Kidney toxicity through two different mechansis ms
Aspergillosis
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
If aspergilosis therapies fail
Then caspfungin (echinocandins) can be added to voriconazole
Tx of histo
Itraconzaole…can’t use amphotericin if kidney problems
Fluconazole activity and pharm
Itraconzsole
Flu - yeasts yes, molds no…good CSF
Itra-
borader spectrum, poor availabiloty…good for histo…long T1/2
VOriconazole activity and pharm
Asp yes, mucor no
Side effects (vision, neuron, rash)
P450 sub and inhibitor
Itraconzole and ovoriconazole uptake
Effected by food
Flu - NOT
Mucor tx
Amphotericin B
Voriconazole and fluconoizole NOT
LP drugs
Isonizaid
Rifampin
Pyrazinamide
Ethambutol
Needs to be treated for about 6 months…this is because waxy coat that makes it difficult
Isonizaid
Prophylactially and for HIV infected patients
Interferes with synthesis of mycolic acid
Pro-drug converted by mycobacterial catalase (KatG)…adds specificty
Resistance to isonizid
Mutations to enoyl reductase
Mutations in KatG
Mutations in other virulence genes
PKs isoniazid
Well absorbed
Slow acetylation - dose adjusemnt reuirement in most white
If patients has slow acetylation, then you need to decrease the dose
Toxicity of ison
Neuritis, heptotoxicty
This could be problem in TB population because of alcohol problems/hepatitis
Rifmapin
Targets RNA polymerase
Resistance through mutations in the target
Rfimapin toxicty
Hepatotoxicty
Orange secretions and urine
Rifmapin interactions
P450 inducer
Pyrazinamide MOA
Unknown
Inhibits mycolic acid biosynthesis
Pro-drug converted by pyrazinamidase…mutations are resistacne
Hepatitis is main toxocity
Ethambutol MOA
UNknown…interferes with mito rep
Well-tolerated
Optic neuritis
Why is hepatoxocity important
Why is bacteirocidal for divding and bacteriostatic for dormant important
When to discontnue
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
MDR resistance
Resitance to isoniazid and rifampin (poor adherence)
If MDR, then tx with pyrazinamide, ehtambutol, and ethionamide for 24 months
Ethionamide
Prodrug
Inhibits enoyl reductase (similar to isoni) but different mechanism
GI probs
Inhibits mycolic acid synthesis
Practial considerations of TB therapy
Neuritis, orange, hepato, P450
Adding ethionamide introduces GI and hypotension
