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PHAR 255 > Tuberculosis > Flashcards

Tuberculosis Flashcards

1
Q

How many people globally have tuberculosis?

A

10 million people worldwide with active TB and 1.4 million people died from TB in 2020

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2
Q

What section of the Canadian population is disproportionately affected by TB?

A

Immigrants and Indigenous people

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3
Q

What age group forms the largest number of reported cases of TB?

A

Almost 20% of the people with TB are between 25 and 34

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4
Q

How concerning is TB in Saskatchewan?

A

It is spreading at an alarming rate within indigenous communities

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5
Q

What bacteria is responsible for the most TB?

A

Mycobacterium tuberculosis

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6
Q

What are some characteristics of Mycobacterium tuberculosis?

A

Acid fast bacillus (Ziehl-Neelson stain)

Impervious to gram-staining

Relatively slow growing, doubling in 20 hours

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7
Q

How is Mycobacterium tuberculosis spread in the community?

A
  • Spread airbone via coughing or sneezing
  • Host inhales droplet nuclei
  • Close contacts (family members, coworkers, co-residents of shelters, prisons, and nursing homes (co-habitating individuals are most likely to be infected)
  • With prolonged contact (risk of infection can be up to 30%)
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8
Q

Which patient groups have higher incidence rates of TB?

A
  • Foreign born from highly endemic areas
  • Canadian Indigenous people
  • Close contacts
  • Homelessness
  • Incarceration
  • Alcoholism, Intravenous Drug Users, malnutrition
  • Co-infection with HIV (accelerated decline of immunological functions)
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9
Q

What are some risk factors for TB infections?

A
  • Once infected with M. tuberculosis (lifetime risk of active TB is approx. 10%)
  • Greatest risk is during first 2 years after infection
  • Extremes of age (1-5x greater risk of active disease)
  • Immunosupression (4-16x greater risk)
  • HIV-infected (100x greater risk)
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10
Q

What does the likelihood of M. tuberculosis transmission to a new patient depend on?

A

The likelihood of a transmission event will depend on the number of infectious droplet nuclei per volume of air and the length of time that the uninfected perosn spends breathing that air

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11
Q

What are some factors that increase the probablity of M. tuberculosis transmission?

A
  • Bacterial burden
  • Upper lung-zone disease on CXR in source patient
  • Laryngeal disease in source patient
  • Amount and severity of cough in source patient
  • Duration of exposure
  • Crowding and poor room ventilation
  • Delayed diagnosis annd/or treatment
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12
Q

How does a patient get infected by M. tuberculosis for the first time?

A

Occurs by inhalation of droplet nuclei which reach alveoli

Progression to clinical disease depends on the following:
- Infecting dose (# of organisms inhaled)
- Virulence of the organism
- Cell-mediated immune response (is innate immune system of macrophages capable of controlling infection, or does that adaptive immune system need to respond)

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13
Q

What is TB reactivation disease?

A
  • Occurs in about 10% of cases
  • Organisms within granulomas emerge and infect the apices of the lungs (low host defences)
  • If untreated, the bacterial infection will destroy the lung (hypoxia, respiratory acidosis, and death)
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14
Q

What are some extrapulmonary manifestations of TB?

A
  • Lymphatic and pleural disease are most common
  • Vertebrae, joints, GU, and meninges can also be affected
  • If organism gets into blood, can cause miliary TB (medical emergency)
  • Can accelerate the progression of HIV via synergistic effect
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15
Q

What are some signs and symptoms associated with TB?

A
  • Gradual onset
  • Patients may not seek care until hemoptysis (coughing up blood)
  • Weight loss, fever, cough, fatigue, nightsweats
  • Frank hemoptysis
  • Chest exam (dullness to percussion, rales (crackling))
  • Moderate increase in WBC
  • Nodular infiltrates seen under CXR
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16
Q

What is the Mantoux test?

A

Also known as the TB skin test

  • 5 tuberculin unit dose is injected just below the dermis
  • Read size of the bump in 48-72 hours to determine if patient has been infected with TB or has an active infection
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17
Q

In addition to a postive Mantoux test result, what else needs to test positive to confirm TB diagnosis?

A

Sputum culture and sensitivity (3 consecutive days of positive results)

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18
Q

What are the three subpopulations of TB that cause disease?

A
  1. Extracellular (rapidly dividing within protective cavities)
  2. Within granulomas (semidormant, very slow replication with bursts of activity)
  3. Intracellular within macrophages
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19
Q

What are the best drugs for Extracellular TB?

A

Isoniazid
Rifampin
Streptomycin

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20
Q

What are the best drugs for TB within granulomas?

A

Pyrazinamide
Rifampin
Isoniazid

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21
Q

What are the best drugs for intracellular TB?

A

Rifampin
Isoniazid
Quinolones

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22
Q

What is the first line treatment for latent TB infection?

A

Rifampin OD for 4 months

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23
Q

What is the second-line treatment for latent TB infection?

A

Rifapentine and Isoniazid once weekly for 3 months

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24
Q

For patients who cannot tolerate rifamycin, what drugs are used to treat latent TB infections?

A

Isoniazid daily for 9 months, if cannot be tolerated this long then try 6 months

25
Q

What are the two most important drugs for treatment of active TB infection?

A

2 main drugs are isoniazid and rifampin (used together whenever possible)

26
Q

What is the standard treatment schedule for an active TB infection?

A

Quadruple therapy (isoniazid, rifampin, pyrazinamide, ethambutol) for 2 months, followed by isoniazid and rifampin for another 4 months

Drugs are dosed daily

6 month total anti-TB therapy

27
Q

How often are patients with HIV dosed for active TB infection treatment?

A

Thrice weekly

28
Q

If a patient with an active TB infection cannot tolerate isoniazid and rifampin, how long are ethambutol and pyrazinamide used to complete course?

A

2 years

29
Q

What is the mechanism of action for isoniazid in TB treatment?

A

They inhbit bacterial wall synthesis (similar effect as penicillins, but different mechanism)

30
Q

What are some dosing and administration instructions for isoniazid?

A
  • Take on an empty stomach
  • Polymorphisms exist for its metabolism (slow acetylators = higher risk of neurotoxicity)
  • Elevations in serum transaminases common (12-15%, so monitor liver function)
31
Q

What are some risk factors for hepatotoxicity while on isoniazid therapy for TB?

A
  • Age
  • Pre-existing liver dysfunction
  • Excess ethanol (alcohol consumption)
  • Pregnancy
  • Post-partum
32
Q

What are some risk factors for neurotoxicity while on isoniazid therapy for TB?

A
  • Pyridoxine deficiency
  • Pregnancy
  • Breastfeeding
  • Diabetes
  • CKD
  • HIV
  • Seizure disorders
  • Substance misuse
  • Children
33
Q

What are some drug interactions associated with isoniazid?

A

Inhibits metabolism of phenytoin, carbemazepine, primidone, and warfarin

34
Q

What is the mechanism of action for rifampin?

A

It inhibits bacterial RNA synthesis by binding to the beta subunit of DNA-dependent RNA polymerase, blocking RNA transcription

35
Q

How long does anti-TB treatment last without rifampin?

A

Treatment is minimum 12-18 months

36
Q

What is the cross-resistance between rifampin and other antibiotics used to treat active TB infections?

A

Rifampin resistant strains are often resistant to isoniazid

37
Q

What are some dosing and administration instructions for rifampin?

A
  • Empty stomach
  • Usual dose is 10mg/kg
38
Q

What are some side effects associated with the use of rifampin?

A
  • Rash, flu-like symptoms
  • GI
  • Gives body secretions an orange-red hue
  • Hepatoxicity (1%) - elevation in liver enzymes
39
Q

What are some drug interactions associated with rifampin?

A

It is a potent CYP3A4 inducer (macrolides, methadone, warfarin, steroids, phenytoin)

It also interacts with oral contraceptives (increased risk of unplanned pregnancy)

40
Q

What are some characteristics of rifabutin?

A
  • Fewer drug interactions than rifampin
  • Preferred with some antiretrovirals and immunosuppressives
  • Arthralgias, myalgia
  • Less common (hepatoxicity, neutropenia, thrombocytopenia)
41
Q

What are some characteristics of rifapentine?

A
  • Longer half-life than rifampin
  • Rash, hematologic (anemia, lymphocytopenia, thrombocytopenia)
  • More hypersensitivity reactions
42
Q

What is the impact of using pyrazinamide in anti-TB quadruple therapy?

A

When used in the first 2 months, shortens duration of therapy to 6 months instead of 9 months(preferred by HCPs and patients)

43
Q

What are some side effects associated with pyrazinamide?

A
  • GI, arthralgias, and increased uric acid
  • Hepatoxicity (major SE and dose-related)
44
Q

What are some characteristics of Ethambutol?

A

Generally bacteriostatic (not used alone, pair with other drugs to prevent resistance)

45
Q

What is a common side effect associated with the use of Ethambutol?

A

GI side effects are common (avoid concurrent use of antacids)

46
Q

What is a serious side effect associated with ethambutol?

A

Retrobulbar neuritis (decreased visual acuity or inability to see green or both)

Need regular eye exams to monitor for this side effect

47
Q

What is the role of fluoroquinolones in anti-TB therapy?

A

Levoflox. and moxiflox. are used as second line alternatives when first line options are d/c (due to hepatoxicity, neurotox., etc.)

48
Q

What are some side effects associated with the use of fluoroquinolones in anti-TB therapy?

A

Common:
- Nausea
- Headache
- Diarrhea
- Dizziness
- Insomnia

Serious:
- Tendinopathy
- QT prolongation
- Blood glucose alternations

49
Q

What are some second-line agents used for anti-TB therapy?

A
  • Streptomycin
  • P-aminosalicylic acid
  • Cycloserine
  • Ethionamide
  • Clofazamine
  • Quinolones (levoflox. and moxiflox.)
50
Q

What is the BCG vaccine?

A

Bacille Calmette-Guerin Vaccine

  • Contains an attenuated, hybridized live strain of M. bovis
  • Low efficacy rates, but still given to vulnerable populations
  • Can prevent severe forms of TB in children
51
Q

What is the main organisation that handles TB directly in Saskatchewan?

A

TB Prevention and Control Saskatchewan (TBPC SK)

They have a head office in Saskatoon, and offices in Regina and PA. They also have mobile clinical and provide telehealth services

52
Q

What is the division of scope between TB pharmacy and community pharmacies?

A

TB pharmacy:
- TB meds + relevant adverse effect management, check for interactions, efficacy, and safety

Community pharmacy:
- Directly observed therapy, manage new interactions (Rx and OTC), and report

53
Q

Review slide 42 for a treatment guideline for how TB is managed in Saskatchewan

A
54
Q

What is the interaction between rifamycins and hormonal birth control?

A

TB drug: Rifampin, rifapentine, rifabutin

All of the above drugs reduce efficacy of hormonal birth control (use condom during therapy)

55
Q

What is often done to resolve drug interactions with rifampin?

A

Because rifampin is such a potent enzyme inducer, doses of the victim drugs are often increased to ensure therapeutic benefit

56
Q

Review slide 45 for common drug interactions with isoniazid

A
57
Q

Review slide 46 for common adverse effects associated with anti-TB therapy

A
58
Q

What are some patient monitoring tips for anti-TB therapy?

A
  • Complete initial physical to determine baseline to which future readings will be compared against (ex. weight, visual acuity, colour vision, CXR, lab work)
  • Sputum (every 1-2 weeks until 2 consecutive negatives and repeat monthly until 2 consecutive negatives in 2-3 months)
  • Drug sensitivity testing
  • Adherence (directly observing therapy)
59
Q
A

PHAR 255 (15 decks)

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