Pharmacology Of TB Flashcards
What is unique about mycobacterium?
Cell-wall
- possesses lipid-rich cell wall that is very impermeable to drugs
- also possesses mycotic acids which causes acid-fast staining
Slow growth rates
- cant use B-lactam drugs since the cell wall grows so slowly that it wont be of use
Intracellular pathogen growth
- mycobacterium almost always cause granulomas to form, so a drug must be able to piece macrophages as well as mycobacterium
Notorious for developing quick resistance
- most common is up regulation of efflux pumps, mutates target receptors and alters pH
Can enter dormancy (latency)
- resistant to drugs that take a while to kill. Also can reemerge
Active vs latent TB
Active (primary)
- roughly 5% of patients experience symptoms
- less dangerous overall
- can be self-limiting
- can devolpment progressive primary TB
- can develop latency
Latent (Progressive secondary)
- roughly 10% of patients have this occur
- more dangerous
- most commonly caused by weakened immune system of HIV
- can progress to miliary TB (systemic spread similar to sepsis) and almost always kills if so
Is combination therapy or monotherapy more common for TB treatment?
Combination is preferred
- is required for active infections
- this is required in order to combat mycobacterium very high resistance development rates.
Monotherapy
- ONLY for latent TB that is confirmed to be latent
First line agents in TB
- Isoniazid
- Rifampin/ Rifapentine/ Rifabutin
- ethambutol
- Pyrazinamide
Are the first choice of treatment in non-resistant TB infections
- make sure to always use combination therapy based on patient
Length of treatment is usually 3-9 months
All are given PO
- can range from daily -> 2x weekly
- requires direct observation therapy
second-line agents are only used in resistant TB infections
What first line TB agents can be used in both active and latent TB?
Isoniazid and the Rifa family drugs
note that ethambutol and pyrazinamide are 1st line agents in active infections only
When should latent infections of TB be treated
1) People who have a (+) TB test w/ 5mm or greater diameter and include in any of the following populations
- organ transplant
- HIV
- immunosupression
- elderly (>65yrs)
- have had recent contacts with other TB patients
- fibrotic changes are noted on xrays that are comparable to TB infections
2) People with a 10mm or greater and include any of the following
- IV drug users
- work or from countries where TB is common
- work in mycobacteria labs
- children under 4 yrs or that are exposed to adults from the 5mm category
3) anyone with a 15mm or greater diameter
Most common and best treatments for latent TB thanked bets to worst
1) Isoniazid & rifapentine
- takes only 3 months and requires only once weekly so high compliance rates
2) Rifampin monotherapy
- is a monotherapy so isnt as effective
- lasts 4 months and requires daily dosing so poor adherence
3) Isoniazid & rifampin
- lasts 3-6 months and requires daily dosing so poor adherence
4) isoniazid monotherapy
- is a monotherapy so isnt as effective
- takes forever 9 months and requires twice a week so poor adherence
- not as good as rifampin
Two phases in treatment for active TB
Intensive phase
- all first 4 line agents for 2 months (RIPE)
- after 2 months, if levels have dropped can move on to the next phase
Continuation phase
- isoniazid and rifampin for 4-7 months
- will take longer if patient has a cavitation and/or a positive culture
When do you use second line anti-TB agents?
- capreomycin
- cycloserine
- Bedaquiline
- streptomycin/amikacin (Aminoglycosides)
- macrolides
- fluroqunialones
1) case of resistance TB to first line agents
2) failure of 1st line therapies
3) serious adverse side effects occur
Classes of drug-resistant TB
1) Drug resistant TB (DR-TB)
- resistant to only one 1st line agent
2) multi drug-resistant TB (MDR-TB)
- resistant to more than one 1st line agent and is resistant to at least isoniazid and rifampin
3) Extensively drug- resistant TB (XDR-TB)
- super rare
- resistant to isoniazid, rifampin, fluroquinolones and at least 1 of the following 2nd line agents
- amikacin
- kanamycin
- capreomycin
- more likely to development in patients who have already been infected with TB or fail to adhere to regiments*
- Note: because drugs resistance emergence is high in failing treatments, NEVER add another drug without consulting a TB-expert*
How to limit toxicity effects of TB combo therapies?
Try to limit the combo therapy to 6 months or less (if possible)
- also can try to not overlap identical toxicity, but this is difficult to do sometimes.
Leprosy (Hansen’s disease)
Disfiguring disease that affects skin nerves and mucous membranes
- caused by Mycobacterium leprae and is most often carried in armadillos and reptiles
Left untreated, causes the following symptoms: - numbness - muscle weakness - painless ulcers on soles of feet - discoloring of skin - paralysis - loss of toes/fingers through reabsorption - burning sensation nerve/skin pain - blindness -
what is the recommended 1st line therapy for leprosy
Dapsone, rifampin and clofazimine combination therapy
Erythema nodosum leporosum
A condition categorized by the following:
- fever and malaise
- tender, induration nodules
- if left untreated, chronic organ damage
Caused by idiopathic immune complex formation
Very often seen in dapsone treatment
Treatment of this condition is thalidomide with anticoagulant
- since thalidomide increases DVT chances as monotherapy
- CANT USE IN PREGNANT PATIENTS
Mycobacterium Avium complex (MAC)
A complex of at least the following two specifics of mycobacterium
- M. Intracellulare
- M. Avium
Often causes pneumonia
