Anti-Mycobacterial Therapies Flashcards
Streptomycin
Works against Tb. Inhibits protein synth by targeting 30S ribosomal subunit
Isoniazid (INH) (pro drug), Ethionamind (ETA), p-Aminosalicyclic acid (PAS) (prodrug)
Targets mycolate acid synthesis
Ethambutol
Targets arabinogalactan synthesis
Fluoroquinolone
Inhibits DNA synth and supercoiling by targeting topoisomerase
Rifamycin
Inhibits RNA synth by targeting RNA polymerase
Macrolides
Targets 23S ribosomal RNA subunit
Pyrasinamide (he emphasized this)
First line drug. Inhibits protein synth in only dormant bacteria. pro drug.
First line drug for defense against Tb. When intensive phase is over, and continuation phase if being use, what 2 drugs are used?
(RIPE), use for 8 weeks (2 months) of 56 doses of the 4 drugs combined. Continusation phase is 4 months (18 weeks). The only difference between confirmed and unconfirmed cases is that in unconfirmed cases, the continuation phase is only 16 weeks instead of 18.
RIF
INH
PZA
EMB
Note that INH and RIF stay on in continuation phase, when intensive phase is over. In both phases, take each drug once daily
Isoniazid
Describe: Small, water soluble.
Action: Attachs extracelluelar and intramacrophage bacteria
Combinational use: High resistance. Must use with other drugs (unless you discover that the patient was just recently exposeed)
Mech: INH = prodrug activated by bacterial KatG enzyme. INH-NAD complex = active drug.
Target: FAS-2 (which lengthens carbon chains to greater than 52 carbons). Prevents double bond to single bond conversion in FAS-2 system, preventing Fa elongation
Adverse effects: Chance of Hepatitis development (fatal), peripheral neuropathy (CNS issue) (organ/gland dsyfunction, sensory screw ups, burning pain, muscle wasting). Reason for these side effects: INH LOOKS LIKE Vit. B6. Overcome L’s by giving B6.
Metabolism: Changes by genetics. Overcome by giving drug once daily.
Resistance: High
Rifampin (RIF) (rifampicin)
Function: RNA synth inhibition. Bactericidal for gram + and - bacteria, mycobacteria, chlamydia (Broad). Drug use is restricted to Tb use, due to prevent resistance.
Mech: Binds to RNA polymerase, parking it on the promoter redion of DNA, and preventing the RNA elongation. Bacteria dies soon after.
Action: Bactericidal against FAST growing mycobacteria, but works against slow ones too. Crosses bbb to treat meninges if inflammed. Treats lepracy. INCrEASES cytochrom P450 action, increasing elimination of other drugs, so if patient is on multiple drug therapy, can’t use this drug right..
Drawback:
Rifabutin and Rifapentine
Analogs of Rifampin, but higher potency, longer half life, better membrane permeability, so they can enter macrophages more easily, and they are more compatible with other drugs (HIV, arrythmia drugs), as it does not speed up P450 (CYP3A) as much. Rifabutin is the best of the 3.
Pyrazinamide (PZA)
Similar in structure to INH, BUT it’s a prodrug. (needs Pyrazinamidase (PcnA) in order to convert its Nh2 t OH.)
Pros: Works synergistically with rifampin, no cross-resistance with other Tb drugs, PERSISTENT killer against dormant Mtb, making therapy only 6 months, not 9 months.
Con: Needs to be used with at least 2 other drugs, its inexpensive, high rate if resistance due to PcnA mutations
Note: Trans RNA carries messenger RNA without reading frame. Only in harsh times.
Mech: PZA likes RPF A (high affnity). When RPF is hinibited, and starred bacteria proteins will fail, organism dies.
Ethambutol (EMB)
Targets: Embb A and EmbB arabinosyl trasferases, which incorporates arabinoes into arabinogalactan layer, weakening the cell wall.
About drug: if accummulated in kidney, dangerous. Crosses bbb if meninges is present and inflammed.
Con: can cause red-green color blindness
Asithromycin, clarthromycin
treats MAC infections
