(Ch 41) Antimycobacterial Drugs (Tuberculosis & Leprosy) Flashcards

1
Q
  • Drugs for Tuberculosis*
  • Name 5 Drugs:*
A
  • Isoniazid
  • Rifampin (RIFADIN)a
  • Ethambutol (MYAMBUTOL) • Pyrazinamide
  • Streptomycin
  • Amikacin
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2
Q
  • Drugs for Mycobacterium avium-intracellulare Infections*
  • name 1:*
A

• Azithromycin (ZITHROMAX)b

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3
Q
  • Drugs for Leprosy*
  • Name 4:*
A
  • Dapsone
  • Rifampin (RIFADIN)
  • Clofazimine (LAMPRENE) • Thalidomide (THALOMID)
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4
Q
  • Effective treatment of TB required*
  • -the drug regimen and Protocol is used ?*
  • and*
  • -How long?*
A

Multidrug Therapy

Protocol: (DOT) directly obsereved therapy (observe each drug administration for adherence of Pt’s)

and

at least 6 months to eradocate the pathogen

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5
Q

Define Mycobacteria

What diseases does it cause

A

“acid-fast bacilli”

cause a variety of diseases:

TB, leprosy, and localized or disseminated

M. avium-intracellulare infections

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6
Q
  • The goals of TB therapy*
  • Name: 3*
A
  1. to kill tubercle bacilli rapidly
  2. to eliminate persistent bacilli and prevent relapse
  3. to prevent disease transmission
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7
Q
  • Is Isolation of patients with TB in single-person rooms important:*
  • yes/no?*
  • how long?*
A

Isolation of patients with TB in single-person rooms is essential until sputum cultures are negative

and

extended isolation may be required to prevent the spread of drug-resistant strains

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8
Q

Which organism causes tuberculosis?

A
  • bacterium*
  • Mycobacterium tuberculosis.*
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9
Q

What makes tuberculosis difficult to treat?

Name 3 major complicating factors:

A
  1. Mycobacterium tuberculosis is an intracellular organism.
  2. Theorganism grows very slowly. Consequently infections are often chronic, and therapy may be required for as long as 2 years.
  3. Resistance to drugs develops rapidly.
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10
Q

Why is tuberculosis treated with multiple drugs?

A

Multiple drugs are used to delay the emergence of resistant strains of the organism.

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11
Q
  • What are the five first-line pharmacological treatment options fortuberculosis?*
  • RIP ESther”*
A
  1. Isoniazid (INH)
  2. Rifampin
  3. Pyrazinamide
  4. Ethambutol
  5. Streptomycin
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12
Q

ISONIAZID (Laniazid)

How does it work: MOA

A
    1. Isoniazid is believed to act by inhibiting the enzymes enoyl acyl carrier protein reductase (InhA) and a β-ketoacyl ACP synthase (KasA).*
    1. These enzymes are essential for the synthesis of mycolic acids, which are unique to the mycobacterial cell walls.*
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13
Q

ISONIAZID (Laniazid)

ROA:

A

The drug is readily absorbed orally and parenterally. Absorption is impaired, however, if isoniazid is taken with aluminum-containing antacids.

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14
Q

ISONIAZID (Laniazid)

How does resistance to the drug occur?

A

A mutation or deletion of the katG gene results in underproduction of the mycobacterial enzyme needed for isoniazid to become biologically active. A mutation in the InhA enzyme can also cause resistance.

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15
Q

ISONIAZID (Laniazid)

What is this drug’s distribution?

A

Isoniazid penetrates all body fluids, cells, and caseous material. Therefore it is able to act on intracellular mycobacteria.

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16
Q
  • ISONIAZID*
  • State the metabolism of the drug.*
A

metabolized in the liver by N-acetylation.

The rate of acetylation shows a genetic variance among humans; it can be as fast as 1 hr or as slow as 3 hr.

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17
Q

ISONIAZID

How does isoniazid affect the cytochrome P-450 system?

A

inhibits this system;

the drug therefore increases plasma levels of drugs such as:

phenytoin,

benzodiazepines,

warfarin.

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18
Q
  • ISONIAZID*
  • adverse effects.*
A

1. Peripheral neuritis—Most commonly paraesthesias of the hands and feet.

This is thought to be caused by isoniazid’s action in binding and inactivating pyridoxine (vitamin B6).

Vitamin B6 supplementation can minimize this problem.

2. Hepatotoxicity—Jaundice and hepatitis

can be severe. LFTs must be monitored.
3. Rashes and skin eruptions

  1. Neurological problems such as convulsions in patients prone to seizures
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19
Q

ISONIAZID

When is isoniazid given alone?

A

In most cases isoniazid is given along with other drugs.

However, for prophylactic treatment of skin test converters and for close contacts of patients who have active disease, isoniazid is given alone.

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20
Q

-Isoniazid-

Can you use isoniazid in pregnant patients?

A

No!

  • This drug crosses the placenta*
  • and*
  • may cause peripheral neuritis in newborns.*
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21
Q

Peripheral Neuritis

Define:

A

disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord.

Damage to peripheral nerves may impair sensation, movement, gland or organ function depending on which nerves are affected; in other words, neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms.

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22
Q

RIFAMPIN (Rifadin)

MOA?

A

Rifampin inhibits the β-subunit of DNA- dependent RNA polymerase.

It suppresses RNA synthesis by blocking chain initiation.

NOTE: Rifabutin and rifapentine are in the same family of drugs as rifampin and work similarly to rifampin.

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23
Q
  • RIFAMPIN (Rifadin)*
  • What is the metabolism of this drug?*
A

Rifampin is metabolized by and induces the cytochrome P-450 system.

Therefore other drugs such as ketoconazole and warfarin may require higher dosages to maintain therapeutic concentrations.

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24
Q
  • Does* Rifabutin induce cytochrome P-450
  • Why or why not?*
A

Rifabutin does not induce the cytochrome P-450 system as much as rifampin and therefore is used in tuberculosis-infected HIV patients

who are taking

protease inhibitors.

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25
Q

RIFAMPIN (Rifadin)

In what other setting is rifabutin used?

A

It is used as prophylaxis against

Mycobacterium Avium Complex (MAC).

MAC also can be treated with a combination of ethambutol

rifabutin

clarithromycin

azithromycin.

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26
Q
  • RIFAMPIN (Rifadin)*
  • State the clinical indications for rifampin*
  • in addition to the treatment of*

tuberculosis.

A

Prophylaxis of meningitis caused by Haemophilus influenzae and Neisseria meningitidis

Leprosy—used in combination with dapsone

Legionnaires’ disease—used in combination with erythromycin

27
Q

RIFAMPIN (Rifadin)

  • What is the absorption and distribution*
  • of the drug?*
A

is orally absorbed.

It easily penetrates into all tissue cells and fluids, including the CNS.

28
Q

RIFAMPIN (Rifadin)

A

Through decreased permeability

or

a mutation in the mycobacterial DNA- dependent RNA polymerase.

29
Q

Rifampin

State the adverse effects.

A

Urine, sweat, tears, and other secretions may become red-orange in color.

(Rifampin—Red-orange)

Rash, fever, nausea, and vomiting are common.

A flu-like syndrome with chills, fever, and myalgias may develop in patients who use rifampin once or twice weekly.

30
Q

PYRAZINAMIDE

When is this drug used?

A

For short-course (≤ 6 months)

treatment of tuberculosis in combination with

isoniazid** and **rifampin

31
Q

Pyrazinamide

What is the absorption and distribution

of this drug?

A

Pyrazinamide is

orally absorbed and distributed to most body tissues, including the CNS.

32
Q

Pyrazinamide

State the MOA.

A

The target of pyrazinamide appears to be the mycobacterial fatty acid synthase I gene

involved mycolic acid synthesis.

33
Q
  • Pyrazinamide*
  • What are pyrazinamide’s adverse effects?*
A
  • Hepatotoxicity*
  • Gout* due to the inhibition of uric acid

secretion

and
Arthralgia and myalgia (most common)

34
Q

Arthralgia

Define:

A

literally means joint pain

35
Q

Define

Myalgia

A

Muscle pain

36
Q

ETHAMBUTOL (Myambutol)

What is the clinical use of this drug?

A

Ethambutol is almost always used against

M. tuberculosis,

also used against

M. avium and M. kansasii

37
Q

ETHAMBUTOL (Myambutol)

How does it work?

A

Ethambutol inhibits the enzyme arabinosyl transferase,

which is involved in the synthesis of

arabinogalactan (an essential component of the mycobacterial cell wall)

38
Q
  • ETHAMBUTOL (Myambutol)*
  • State the absorption and distribution of the drug.*
A

It is well absorbed orally

and

distributes into all cells, including the CNS.

39
Q
  • ETHAMBUTOL (Myambutol)*
  • Is this drug bacteriostatic or bacteriocidal?*
A

Ethambutol

is the only first-line drug

that is bacteriostatic.

40
Q

Ethambutol

What are the adverse effects?

A
  • Optic neuritis* or other visual disturbances (decreased visual acuity, red-green color blindness)
  • Gout* due to a decrease in uric acid secretion

Rash, fever

41
Q
  • STREPTOMYCIN*
  • What is the classification of this drug?*
A

Streptomycin is an aminoglycoside

42
Q

STREPTOMYCIN

What is the MOA?

A

Streptomycin binds to the 30S ribosomal subunit, causing

a misinterpretation of the genetic code.

43
Q

Streptomycin

State the clinical indication for streptomycin.

A

Treatment of life-threatening tuberculosis in combination with other first-line drugs

44
Q

Streptomycin

What are streptomycin’s adverse effects?

A

Ototoxicity

Nephrotoxicity—usually reversible

45
Q

What is the preferred recommendation

for the initial treatment of

active TB?

A

A 2-month regimen of

pyrazinamide

INH

rifampin

and

4- month regimen of INH and rifampin

for a total of 6 months

46
Q

Name the second-line agents used

in the treatment of

tuberculosis.

A
  1. Ethionamide
  2. Aminosalicylicacid (PAS)
  3. Cycloserine
  4. Fluoroquinolones (moxi or gatifloxacin)
  5. Macrolides (Azithromycin)
47
Q

Why are second-line drugs considered

second line agents?

A

They are lower in efficacy and higher in toxicity* or they *are active against atypical strains of mycobacterium.

They are used only if the patient cannot tolerate the first- line drugs or if the strain is resistant to them.

48
Q

What organism causes leprosy?

A

Mycobacterium leprae

49
Q
  • What are the pharmacological treatment options*
  • for leprosy?*
A

Dapsone,

clofazimine,

rifampin.

Usually all three of them are used concomitantly.

50
Q

DAPSONE

How does dapsone work?

A

It is related to the sulfonamides

and

inhibits folate biosynthesis by

acting as a competitive antagonist of PABA.

51
Q

PABA

Define:

A

PABA - Para aminobenzoic Acid

is an intermediate in the synthesis of folate by bacteria, plants, and fungi.

52
Q

DAPSONE

What is this drug’s route of administration?

A

PO (orally)

53
Q

Dapsone

What is the metabolism of this drug?

A

It undergoes acetylation in the liver.

54
Q

Dapsone

How is it used?

A

Dapsone is used* in *combination with

rifampin and clofazimine to treat leprosy.

It is also used in the treatment and prophylaxis of Pneumocystis carinii pneumonia

55
Q

Pneumocystis carinii

define:

A

a yeast-like fungus of the genus Pneumocystis.

The causative organism of Pneumocystis pneumonia, it is an important human pathogen, particularly among immunocompromised hosts

S/S: may develop over several days or weeks

may include: shortness of breath and/or difficulty breathing (of gradual onset), fever, dry/non-productive cough, weight loss, night sweats, chills, and fatigue.

56
Q
  • DAPSONE*
  • What are the adverse reactions?*
A
  • GI irritation*
  • Methemoglobinemia*
  • Hemolysis* (dose-related) especially in patients with GGPD deficiency
  • Drug-induced lupus erythematosus*
57
Q

Methemoglobinemia

define:

A
  • -condition of elevated methemoglobin in the blood-*
  • Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis).
  • Complications may include seizures and heart arrhythmias.
58
Q

Methemoglobin

define

A

is a hemoglobin in the form of metalloprotein,

in which the iron in the heme group is in the Fe3+ (ferric) state,

not the Fe2+ (ferrous) of normal hemoglobin. Methemoglobin cannot bind oxygen,

which means it cannot carry oxygen to tissues

59
Q
  • G6PD deficiency*
  • define:*
A

Glucose 6 phosphate dehydrogenase (G6PD) deficiency is a hereditary condition in which red blood cells break down (hemolysis) when the body is exposed to certain foods, drugs, infections or stress.

60
Q

What causes G6PD deficiency?

A

It occurs when

a person is missing or has low levels of the enzyme glucose-6-phosphate dehydrogenase.

61
Q

What is the G6PD enzyme

responsible for?

A

This enzyme helps red blood cells work properly.

Symptoms during a hemolytic episode may include dark urine, fatigue, paleness, rapid heart rate, shortness of breath, and yellowing of the skin (jaundice)

62
Q

CLOFAZIMINE (Lamprene)

How does this drug work?

A

Clofazimine binds to DNA

and

inhibits its replication.

63
Q

Clofazimine

How is this drug given?

A

Orally

64
Q

Clofazimine

What are the adverse effects?

A

A distinctive reddish-brown discoloration of the skin

GI irritation (nausea, vomiting, diarrhea)