Antitubercular Drugs

Question 1

Tuberculosis (TB)

Answer 1

Caused by Mycobacterium tuberculosis

TB is most commonly characterized by granulomas in the lungs: nodular accumulations of inflammatory cells (e.g., macrophages, lymphocytes) that are delimited (“walled off” with clear boundaries) and have a centre that has a cheesy or caseated consistency.

Question 2

Antitubercular drugs

Answer 2

treat all forms of Mycobacterium.

Question 3

Mycobacterium Infections common infection sites

Answer 3

Lung (primary site)
Brain (cerebral cortex)
Bone (growing end)
Liver
Kidney
Genitourinary tract
Virtually every other tissue and organ in the body

Question 4

Mycobacterium Infections

Answer 4

Aerobic bacillus

Tubercle bacilli is a common synonym for M. tuberculosis.

Passed from infected humans and (much less commonly) cows (bovine) and birds (avian)

Tubercle bacilli are conveyed by droplets.

Droplets are expelled by coughing or sneezing, and they then gain entry into the body by inhalation.

Tubercle bacilli then spread to other body organs via blood and lymphatic systems.

Tubercle bacilli may become dormant or walled off by calcified or fibrous tissue.

Question 5

Mycobacterium tuberculosis

Answer 5

tuberculosis a very slow-growing organism

More difficult to treat than most other bacterial infections

First infectious episode: primary TB infection

Re-infection: chronic form of the disease

Dormancy

Question 6

Dormancy

Answer 6

Dormancy: may test positive for exposure but are not necessarily infectious

Question 7

Incidence

Answer 7

Canada has one of the lowest rates of active TB internationally.

Decline is attributed to intensified public health efforts aimed at preventing, diagnosing, and treating TB as well as human immunodeficiency virus (HIV) infection.

In 2017 1, 796 cases in Canada

Higher incidence among Indigenous people

TB infects one third of the world’s population.

TB is second to HIV in the number of deaths caused by a single infectious organism.

A present concern is the increasing number of multidrug-resistant tuberculosis (MDR-TB) cases.

Question 8

Multidrug-Resistant Tuberculosis

Answer 8

Multidrug-resistant tuberculosis (MDR-TB) is TB that is resistant to both isoniazid (isonicotine hydrazine [INH]) and rifampin.

Close contacts of patients with MDR-TB need to be treated for 6 to 9 months.

Question 9

Isoniazid

Answer 9

Isoniazid is a primary drug and is widely used.

Primary (first-line) or secondary (second-line) drug categories

Question 10

Isoniazid

Therapy in two phases:

Answer 10

Initial intensive phase with two medications

Continuation phase with three or more medications

Question 11

Antitubercular Drugs

Four 1st line drugs

Answer 11

isoniazid: primary drug

ethambutol hydrochloride

pyrazinamide

rifampin

Question 12

Antitubercular Drugs

Three 2nd line drugs

Answer 12

amikacin sulphate

levofloxacin hemihydrate

moxifloxacin hydrochloride

Question 13

Protein wall synthesis inhibitors

Answer 13

rifampin

Question 14

Cell wall synthesis inhibitors

Answer 14

isoniazid

Question 15

Other mechanisms of action

Answer 15

ethambutol, isoniazid, pyrazinamide

Question 16

isoniazid (Isotamine®)

Answer 16

Primary drug of choice for TB

Resistant strains of Mycobacterium emerging

Metabolized in the liver through acetylation; watch for “slow acetylators.”

Used alone or in combination with other drugs

Contraindicated with previous isoniazid-associated liver injury or acute liver disease

Question 17

isoniazid (Isotamine®) AEs

Answer 17

Peripheral neuritis, hepatotoxicity, hyperglylcemia, discolouration of body fluids (see rifampin)

May need vitamin B6 for peripheral neuropathy

Question 18

What helps for peripheral neuropathy?

Answer 18

Vitamin B6

Question 19

Ethambutol hydrochloride

Answer 19

Considered part of first line therapy
Used in combination therapies to reduce risk of resistance

May be used to treat other mycobacterial diseases (i.e. leprosy)

Available only in oral form

Question 20

Ethambutol hydrochloride AEs

Answer 20

May cause visual changes (optic neuritis, blindness, altered colour perception)

Question 21

Ethambutol hydrochloride contraindication

Answer 21

Contraindicated in children under 13 years of age

Question 22

Pyrazinamide

Answer 22

Part of first line therapy

Used in combination with other first line drugs

Question 23

Pyrazinamide contraindication

Answer 23

Contraindicated in patients with gout and severe liver disease

Not normally used in pregnant patients as there is not enough teratogenicity data available

Question 24

Rifampin

Answer 24

Also effective against meningococcus, Haemophilus influenza B and leprosy

Used at least with one other first line drug

Belongs to rifamycin family of antibiotics

Question 25

Rifampin AEs

Answer 25

May experience discolouration of:

Skin, sweat, tears, urine, feces, sputum, saliva, cerebrospinal fluid, and tongue

hepatitis; hematological disorders

Question 26

INH adverse effects

Answer 26

peripheral neuropathy, hepatotoxicity, optic neuritis and visual disturbances, hyperglycemia

Question 27

ethambutol adverse effects

Answer 27

retrobulbar neuritis, blindness

Question 28

rifampin adverse effects

Answer 28

hepatitis; hematological disorders, red-orange-brown discoloration of urine, stools, sputum and tears

Question 29

Purified protein derivative (PPD) (Mantoux®)

Answer 29

A diagnostic injection given intradermally in doses of 5 tuberculin units (0.1 mL) to detect exposure to the TB organism

Positive indicated by induration (not erythema) at the site of injection

Question 30

Bacille Calmette-Guérin (BCG)

Answer 30

A vaccine injection derived from an inactivated strain of Mycobacterium bovis

Used mainly in First Nations communities in the Northwest Territories and used in much of the world to vaccinate young children against TB

Does not prevent infection but reduces active TB by 60 to 80%

Effective at preventing more-severe cases involving dissemination of infection throughout the body

Can cause false-positive results on the tuberculin skin test

Question 31

Antitubercular Drug TherapyConsiderations

Answer 31

Major effects of drug therapy: reduction of cough and thus reduction of the infectiousness of the patient

Normally occurs within 2 weeks of the initiation of drug therapy if TB strain is drug sensitive

Most cases of TB can be cured.

Successful treatment: several antibiotic drugs for at least 6 months and sometimes for as long as 12 months

Perform drug-susceptibility testing on the first Mycobacterium spp. that is isolated from a patient specimen, to prevent the development of MDR-TB.

Even before the results of susceptibility tests are known, begin a regimen with multiple antitubercular drugs (to reduce the chances of development of resistance).

Adjust drug regimen after the results of susceptibility testing are known.

Monitor patient compliance closely during therapy.

Problems with successful therapy occur because of patient nonadherence to drug therapy and the increased incidence of drug-resistant organisms.

Question 32

Major effects of drug therapy of antitubercular

Answer 32

reduction of cough and thus reduction of the infectiousness of the patient

Question 33

Antitubercular Therapy Effectiveness depends on:

Answer 33

Type of infection
Adequate dosing
Sufficient duration of treatment
Adherence to drug regimen
Selection of an effective drug combination

Question 34

Antitubercular Therapy problem

Answer 34

Drug-resistant organisms
Drug toxicity
Patient nonadherence

MDR-TB

Question 35

Nursing Implications

Answer 35

Obtain a thorough medical history and assessment.

Perform liver function studies in patients who are to receive INH or rifampin (especially older adult patients and those who use alcohol daily).

Assess for contraindications to the various drugs, conditions for cautious use, and potential drug interactions.

Patient education is critical.

Therapy may last for up to 24 months.

Have patient take medications exactly as ordered at the same time every day.

Emphasize the importance of strict adherence to the regimen for improvement of condition or for cure.

Remind patients that they are contagious during the initial period of illness—instruct them in proper hygiene and prevention of the spread of infected droplets.

Teach patients to take care of themselves, including getting adequate nutrition and rest.

Oral preparations may be given with food to reduce gastrointestinal upset.

Question 36

Patients should neither consume______ while taking these medications nor take other medications (including over-the-counter medications) unless they first check with their prescribers.

Answer 36

alcohol

Question 37

_________ causes oral contraceptives to become ineffective; another form of birth control is needed.

Answer 37

Rifampin

Question 38

Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become?

Answer 38

reddish orange; even contact lenses may be stained.

Question 39

________may be needed to combat neurological adverse effects associated with INH therapy.

Answer 39

Pyridoxine

Question 40

Observe for and monitor adverse effects.

Answer 40

Instruct patients about those adverse effects that should be reported to the prescriber immediately.

These effects include fatigue, nausea, vomiting, numbness and tingling of the extremities, fever, loss of appetite, depression, and jaundice.

Instruct patients to report any visual changes (e.g., altered colour perception, changes in visual acuity).

Question 41

Monitor patient for therapeutic effects.

Answer 41

Decrease in symptoms of TB, such as cough and fever

Laboratory study results (culture and sensitivity tests) and chest X-rays should confirm clinical findings.

Watch for a lack of clinical response to therapy, indicating possible drug resistance.