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Antibiotics - Antimycobacterials: Nursing Pharmacology

Notes

Notes

ANTIBIOTICS: ANTIMYCOBACTERIALS, PART 1/5
DRUG NAME
isoniazid (INH)
ethambutol (EMB): Myambutol
rifapentine (RPT): Priftin
CLASS
Antimycobacterial antibiotics (first line)
MECHANISM of ACTION
Inhibition of the synthesis of cell wall components
Inhibits DNA-dependent RNA polymerase
INDICATIONS
Tuberculosis
ROUTE(S) of ADMINISTRATION
PO; IM
PO
IV (rifampin)
SIDE EFFECTS
  • Hepatotoxicity (boxed warning)
  • Peripheral neuropathy
  • Optic neuritis
  • CNS effects (memory impairment, agitation)
  • Hypersensitivity
  • Hepatotoxicity
  • Nephrotoxicity
  • Optic neuritis
  • Decreased visual acuity
  • Color blindness
  • Hypersensitivity
  • Hepatotoxicity
  • Hypersensitivity
  • Reddish-orange discoloration of urine, tears, saliva
CONTRA-INDICATIONS and CAUTIONS
  • Liver impairment
  • Liver impairment
  • Children < 13 yrs
  • Clients who cannot report visual changes
  • Liver impairment
  • Porphyria
ANTIBIOTICS: ANTIMYCOBACTERIALS, PART 2/5
DRUG NAME
rifampin (RIF): Rifadin
pyrazinamide (PZA)
streptomycin (SM)
CLASS
Antimycobacterial antibiotics (first line)
MECHANISM of ACTION
Inhibits DNA-dependent RNA polymerase
Inhibits bacterial fatty acid synthesis (not fully understood)
Inhibits bacterial protein synthesis at the ribosomal level
INDICATIONS
Tuberculosis
ROUTE(S) of ADMINISTRATION
PO
IV (rifampin)
IM, IV
SIDE EFFECTS
  • Hepatotoxicity
  • Hypersensitivity
  • Reddish-orange discoloration of urine, tears, saliva
  • Hepatotoxicity
  • Hypersensitivity
  • Hepatotoxicity
  • Neurotoxicity (boxed warning): optic neuritis, ototoxicity, peripheral neuritis
  • Hypersensitivity
CONTRA-INDICATIONS and CAUTIONS
  • Liver impairment
  • Liver impairment
  • Gout
  • Liver impairment
ANTIBIOTICS: ANTIMYCOBACTERIALS, PART 3/5
DRUG NAME
dapsone
bedaquiline: Sirturo
capreomycin: Capastat Sulfate
CLASS
Antimycobacterial antibiotics (first line)
Antimycobacterial antibiotics (second line)
MECHANISM of ACTION
Inhibits of folic acid pathway in bacteria
Inhibits bacterial ATP synthesis
Inhibits bacterial protein synthesis at the ribosomal level
INDICATIONS
Leprosy
Multidrug-resistant tuberculosis
ROUTE(S) of ADMINISTRATION
PO
IV, IM
SIDE EFFECTS
  • Hepatotoxicity
  • Hemolytic anemia
  • Aplastic anemia
  • Agranulocytosis
  • Hypersensitivity
  • Hepatotoxicity
  • QT prolongation (boxed warning)
  • Hypersensitivity
  • Nephrotoxicity (boxed warning)
  • Ototoxicity (boxed warning)
  • Hypersensitivity
CONTRA-INDICATIONS and CAUTIONS
  • Liver impairment
  • Renal impairment
ANTIBIOTICS: ANTIMYCOBACTERIALS, PART 4/5
DRUG NAME
cycloserine: Seromycin
ethionamide: Trecator
rifabutin: Mycobutin
CLASS
Antimycobacterial antibiotics (second line)
MECHANISM of ACTION
Inhibits bacterial cell wall synthesis
Inhibits DNA-dependent RNA polymerase
INDICATIONS
Multidrug-resistant tuberculosis
Mycobacterium avium Complex
ROUTE(S) of ADMINISTRATION
PO
SIDE EFFECTS
  • Confusion
  • Depression
  • Psychosis
  • Seizures
  • Hypersensitivity
  • Hepatotoxicity
  • Optic neuritis
  • Hypersensitivity

  • Hepatotoxicity
  • Neutropenia
  • Hypersensitivity
  • Reddish-orange discoloration of urine, tears, saliva
CONTRA-INDICATIONS and CAUTIONS
  • History of seizures
  • Psychosis
  • Excessive use of alcohol
  • Renal insufficiency
  • Liver impairment
ANTIBIOTICS: ANTIMYCOBACTERIALS, PART 5/5
DRUG NAME
amikacin: Amikin
aminosalicylic acid
CLASS
Antimycobacterial antibiotics (second line)
MECHANISM of ACTION
Inhibits bacterial protein synthesis at the ribosomal level
Inhibits bacterial cell wall synthesis
INDICATIONS
Multidrug-resistant tuberculosis
ROUTE(S) of ADMINISTRATION
IV; IM, INH (amikin)
PO (aminosalicylic acid)
SIDE EFFECTS
  • Nephrotoxicity (boxed warning)
  • Ototoxicity (boxed warning)
  • Hypersensitivity
  • Hypersensitivity
CONTRAINDICATIONS and CAUTIONS
Renal impairment
NURSING CONSIDERATIONS FOR ANTIBIOTICS: ANTIMYCOBACTERIALS
ASSESSMENT and MONITORING
isoniazid, rifampin, pyrazinamide, and ethambutol treatment regimen
  • Assessment
    • Weight
    • Vital signs
    • Lung sounds
    • SpO2
    • Current symptoms: productive cough, fatigue, night sweats, anorexia
  • Laboratory test results: CBC, renal and liver function tests, QFT-Plus, T-Spot, sputum smear and culture
  • Diagnostic test results: TB skin test, chest X-ray, ophthalmic examination

Monitoring
  • Side effects
  • Evaluate effectiveness of the medication regimen: resolution of their TB symptoms; absence of mycobacteria in sputum



CLIENT EDUCATION
  • Purpose of medications: combination therapy helps eliminate their TB infection
  • Take all four medications consistently at the same time each day, with a full glass of water. on an empty stomach
  • Drink plenty of fluids
  • Avoid alcohol during treatment
  • Importance of adherence
  • Side effects
    • Reddish-orange discoloration of urine, tears, or saliva
      • Harmless
      • May discolor soft contact lenses
    • GI symptoms: nausea and abdominal pain
      • Eat small, frequent meals throughout the day
    • Report
      • Peripheral neuropathy
        • Take the prescribed vitamin B6 supplement daily
        • Include dietary sources of B6: chickpeas, salmon, tuna, bananas, potatoes, fortified breakfast cereals
      • Fatigue, agitation, issues with memory
        • Take prescribed folic acid supplement daily
        • Include dietary sources of folate: dark green leafy vegetables, peanuts, whole grains
      • Hepatotoxicity
      • Nephrotoxicity
      • Optic neuritis
Transcript

Antimycobacterials are medications used to treat infections caused by the mycobacterium species. These include tuberculosis, caused by Mycobacterium tuberculosis; leprosy, also known as Hansen’s disease, caused by Mycobacterium leprae; and non-tuberculous lung infections caused by Mycobacterium avium complex or MAC, which includes Mycobacterium avium, Mycobacterium chimaera, and Mycobacterium intracellulare.

Antimycobacterial drugs can be divided into two broad categories. We have the first-line antimycobacterials, which are the standard initial therapy; and the second-line antimycobacterials, used when the first-line drugs aren’t suited, like when they have contraindications, they have failed to treat the infection, or with multi-drug resistant tuberculosis.

The first-line antimycobacterials include isoniazid or INH for short, which is administered orally or intramuscularly; as well as streptomycin or SM, which is given intravenously or intramuscularly; rifampin or RIF, which is given orally and intravenously; and rifapentine or RPT, ethambutol or EMB, and pyrazinamide or PZA, all of which are given orally.

On the other hand, the second-line antimycobacterials include bedaquiline, cycloserine, ethionamide, rifabutin, and aminosalicylic acid all of which are administered orally; as well as capreomycin which is administered intravenously or intramuscularly; and amikacin which can be administered intravenously, intramuscularly, or by inhalation. These medications are mainly used for treating active mycobacterial infections, except rifabutin, which is preferred as preventive treatment against Mycobacterium Avium complex in clients with advanced HIV infection, who are severely immunocompromised. Finally, antimycobacterials also include leprostatic medications, such as dapsone, which is administered orally to treat leprosy.

Now, antimycobacterials have different mechanisms of action by targeting various mycobacterial structures. Isoniazid, ethambutol, aminosalicylic acid, ethionamide, and cycloserine act mainly by disrupting the synthesis of essential components of the bacterial cell walls, which causes bacteria to burst out of osmotic pressure, and die.

On the other hand, rifampin, rifapentine, and rifabutin work by inhibiting the bacterial DNA-dependent RNA polymerase, which prevents the bacteria from synthesizing RNA, ultimately killing them. Next, streptomycin, amikacin, and capreomycin work by inhibiting bacterial ribosomes, stopping protein synthesis.

There is also bedaquiline, which inhibits the synthesis of bacterial ATP, making them run out of energy needed for their metabolic functions, and then ultimately die. The mechanism of action of some medications like pyrazinamide isn’t fully understood, but it is thought to interfere with bacterial fatty acid synthesis, which is needed for their growth. Finally, dapsone works by inhibiting the pathway of folic acid, ultimately disrupting bacterial proliferation.

Unfortunately, antimycobacterial medications can cause undesired side effects, ranging from mild side effects requiring dose adjustment and careful monitoring, to serious organ damage, which can require immediate discontinuation.

Clients taking antimycobacterials may present with gastrointestinal side effects, which include nausea, vomiting, anorexia, stomach upset, and abdominal pain. Other side effects include hypersensitivity reactions, ranging from skin rashes or hives to life-threatening anaphylaxis. This can occur with any of the antimycobacterial medications, but it is more commonly seen in isoniazid, rifampicin, pyrazinamide, ethionamide, cycloserine, ethambutol, aminosalicylic acid, and streptomycin.

Some of these medications can also cause neurotoxicity, most often associated with isoniazid, which is associated with peripheral neuropathy, optic neuritis, memory impairment, and agitation; ethambutol, which can cause optic neuritis, decreased visual acuity, or color blindness; capreomycin and amikacin, which have a boxed warning for ototoxicity; cycloserine which can cause confusion, depression, psychosis, and seizures; ethionamide, which can cause optic neuritis; as well as streptomycin, which has a boxed warning for neurotoxicity that can manifest as peripheral neuropathy, ototoxicity, and toxicity to the optic nerve. Clients on antimycobacterials can also develop hepatotoxicity, which is a boxed warning for isoniazid.

Next, bedaquiline has a boxed warning for QT prolongation; dapsone can cause hematological problems like hemolytic anemia, aplastic anemia, and agranulocytosis; while rifabutin can cause neutropenia. Nephrotoxicity is a side effect of ethambutol and capreomycin, and a boxed warning for amikacin. Finally, rifampin, rifapentine, and rifabutin can turn certain body fluids like urine, tears, and saliva a reddish-orange color.

As far as interactions with other medications are concerned, rifampin, rifapentine, and rifabutin are notable for their ability to induce a number of cytochrome P450 isoenzymes, meaning that by accelerating the metabolism of other medications, rifampin reduces the effectiveness of medications like warfarin, oral contraceptives, and medications used to treat HIV infection.

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  4. "Capreomycin"  (2018)
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