Pharmacology Of TB Flashcards

1
Q

What is unique about mycobacterium?

A

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

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2
Q

Active vs latent TB

A

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
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3
Q

Is combination therapy or monotherapy more common for TB treatment?

A

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

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4
Q

First line agents in TB

  • Isoniazid
  • Rifampin/ Rifapentine/ Rifabutin
  • ethambutol
  • Pyrazinamide
A

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

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5
Q

What first line TB agents can be used in both active and latent TB?

A

Isoniazid and the Rifa family drugs

note that ethambutol and pyrazinamide are 1st line agents in active infections only

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6
Q

When should latent infections of TB be treated

A

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

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7
Q

Most common and best treatments for latent TB thanked bets to worst

A

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

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8
Q

Two phases in treatment for active TB

A

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
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9
Q

When do you use second line anti-TB agents?

  • capreomycin
  • cycloserine
  • Bedaquiline
  • streptomycin/amikacin (Aminoglycosides)
  • macrolides
  • fluroqunialones
A

1) case of resistance TB to first line agents
2) failure of 1st line therapies
3) serious adverse side effects occur

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10
Q

Classes of drug-resistant TB

A

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*
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11
Q

How to limit toxicity effects of TB combo therapies?

A

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.

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12
Q

Leprosy (Hansen’s disease)

A

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 
-
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13
Q

what is the recommended 1st line therapy for leprosy

A

Dapsone, rifampin and clofazimine combination therapy

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14
Q

Erythema nodosum leporosum

A

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
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15
Q

Mycobacterium Avium complex (MAC)

A

A complex of at least the following two specifics of mycobacterium

  • M. Intracellulare
  • M. Avium

Often causes pneumonia

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16
Q

1st line therapy for MAC

A

Rifampin, ethambutol and a macrolide combo therapy

Lasts for 12 months after last negative culture

17
Q

Disseminated MAC

A

A slight variation of normal MAC infection that is only seen in immunocompromised patients
- causes pneumonia as well as complete disabling of immune system (specifically kills CD4 T-cells the most)

Goal of tx = immune system rebound, negative cultures and suppression of symptoms

18
Q

Treatment of disseminated MAC

A

A combo therapy of at least 3 of the following:

  • Amikacin
  • Azithromycin
  • Clarithromycin
  • Ethambutol
  • Moxifloxacin
  • Rifabutin

Patients are to remain on their therapy until the following 3 criteria are met:

  • therapy lasts at least 12 months
  • CD4 count > 100/mm3 for at least 6 months
  • asymptomatic