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Pharmacology > Antimycobacterial Drugs > Flashcards

Antimycobacterial Drugs Flashcards

1
Q

Nicotinic acid derivative (isonicotinic acid hydrazide)

A

Isoniazid

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2
Q

Isoniazid - MoA

A

Inhibition of mycolic acid synthesis (needed for cell wall)

katG gene

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3
Q

Isoniazid - Clinical use

A

1st line TB.
Bactericidal: M.tuberculosis and M.kansaii
Little activity: M.avium-intracellulare.
Not active: M. leprae.

Given to prevent TB in neonates and children who have had close contact with persons in whom active TB was recently diagnosed

Active and latent TB

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4
Q

Isoniazid - Adverse effects

A

Hepatotoxicity (from metabolite acetylhydrazine)

Peripheral neuritis (paresthesias, numbness of fingers and toes, in vit B6 deficiency, effect individuals with slow acetylator phenotype)

Toxic encephalopathy
Seizures

Hematologic abnormalities (granulocytosis, anemia, thrombocytopenia)

Hepatitis (highest prevalence for persons over 50 years, elevated serum transaminase)

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5
Q

Isoniazid - Interactions

A

Alcohol + rifampin: increased risk of hepatotoxicity.

Increases carbamazepine and phenytoin levels.

Aluminum salts: inhibits absorption

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6
Q

Isoniazid - Special considerations

A

Genetically different rate of acetylation of drug causes different plasma concentrations.

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7
Q

Synthetic butanol derivative

A

Ethambutol

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8
Q

Ethambutol - MoA

A

Bacteriostatic for mycobacteria

Inhihits arabinosyl transferase and the synthesis of arabinogalactam required for mycobacterial cell wall formation

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9
Q

Ethambutol - Clinical use

A

1st line TB.
Bacteriostatic activity

M. avium-intracellulare infections

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10
Q

Ethambutol - Adverse effects

A

Dose dependent optic neuritis and impaired red-green color discrimination

Hyperuricemia
Gout
Hepatitis
Thrombocytopenia

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11
Q

Ethambutol - Special consideration

A

Monitor visual color discrimination regularly

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12
Q

Ethambutol - Contraindications

A

Children too young to permit assessment of visual acuity and red-green discrimination

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13
Q

Synthetic Nicotinamide derivatie

A

Pyrazinamide

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14
Q

Pyrazinamide - MoA

A

disrupts mycobacterial cell membrane metabolism and transport functions

M. tuberculosis: inhibits the growth by inhibiting fatty acid synthesis required for cell membrane function.

Inhibits also RNA

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15
Q

Pyrazinamide - Clinical use

A

1st line TB.

Rapid bactericidal action

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16
Q

Pyrazinamide - Adverse effects

A 
Hepatits
Hyperuricemia and gout
Arthalgia
Hematologic toxicity
Fever
Increase in Fe serum concentration
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17
Q

Rifamycin derivatives

A

Rifampin
Rifapentine
Rifabutin

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18
Q

Rifampin - MoA

A

Binds to DNA-dependent RNA polymerase, preventing DNA transcription and RNA synthesis

19
Q

Rifampin - Clinical use

A

Broad-spectum, gram (+), (-) and acid fast bacilli

1st line TB.
Combined with isoniazid, ethambutol, pyrazinamide to treat TB.
Combined with sulfone or clofazimine to treat leprosy.

Alternative to INH if resistance.

Meningitis prophylaxis
H. influenzae B inf
Prevent meningococcal disease
Tubercular meningtiis
Eliminate staph.coccal carriage,
Staph endocarditis (in comb. with vancomycin and gentamicin)
Legionella pneumphila (in comb with macrolide/fluoroquinolone)

20
Q

Rifampin - Special considerations

A

Penetrates inflamed meninges

Liver function tests must be done evere 2-4 weeks of treatment.

Never use alone in active infection

21
Q

Rifampin - Adverse effects

A

Impaired liver function
Elevate serum bilirubin and transaminase levels
Hepatitis
Hypersensitivity: chills, fever, fatigue, headache (50 % of patients!)
High dose: renal disease, leukopenia, thrombocytopenia, purpura
Reddish-orange to brown discoloration of saliva, tears, and urine
Light-chain proteinuria

If administered less often than twice weekly: flu-like syndrome (fever, chills, myalgias, anemia, thrombocytopenia)

22
Q

Rifampin - Interactions

A

Alcohol consumption appears to increase the risk of hepatitis and should be avoided in persons being treated for TB.

Rifampin induces cytochrome p450 isozymes, CYP1A2, CYP2C9 and CYP3A4, and can thereby accelerate the metabolism of other drugs and reduce their serum concentrations and therapeutic effectiveness

These drugs include: macrolides, benzodiazepines, Ca channel blockers, digoxin, estrogens, sulfonylureas, theophylline, warfarin.

23
Q

Rifapentine - Clinical use

A

Pulmonary TB by M. tuberculosis
Twice-weekly combined with isoniazid, ethambutol, and pyrazinamide for 2 months, and once-weekly with isoniazid for an additional 4 months.

24
Q

Rifabutin - Clinical use

A

Preferred for treating TB in HIV patients (protease inhibitors can be used).
M. avium intracellulare
M. fortuitum

25
Q

Rifabutin - Interactions and Adverse effects

A

Cytochrome P450 and GI irritation

26
Q

Streptomycin (antimycobacterial) - Clinical use

A

TB: Resistance to other TB drugs

Active against M. avium complex, M. kansasii

27
Q

Streptomycin (antimycobacterial) - Adverse effects

A

Nephrotoxicity, ototoxicity

28
Q

Amikacin (antimycobacterial) - Clinical use

A

2nd line TB

Multidrug resistant tuberculosis strains, atypical mycobacteria. Combined with at least one other drug

29
Q

Dapsone - MoA

A

Inhibits folic acid synthesis

30
Q

Dapsone - Clinical use

A

Leprosy (both types)

Bacteriostatic

31
Q

Dapsone - Adverse effects

A 
GI disturbances
Peripheral neuropathy
Optic neuritis and blurred vision
Proteinuria
Nephrotic syndrome
SLE-like syndrome
Hematologic toxicity
G6PD-def: hemolytic anemia
32
Q

Clofazimine - Clinical use

A

Bactericidal: M. tuberculosis
Bacteriostatic: M. leprae + avium-intracellulare.
Erythema nodosum leprosum (in lepromatous leprosy)

33
Q

Dapsone - Contraindications

A

Glucose 6 phosphate dehydrogenase deficiency

34
Q

Clofazimine - Adverse effects

A 
GI distress
Photosensitivity
Skin discolorations
Discoloration of body fluids
Elevation of hepatic enzyme levels
Hepatitis
35
Q

Clofazimine - Contraindications

A

Hepatic disease

36
Q

Thalidomide - Clinical use

A

TB
Leprosy
Erythema nodosum leprosum

37
Q

Antimycobacterial drugs - Administration

A

Generally Oral

Isoniazid: + IM
Rifampim: + IV
Streptomycin: Only IM

38
Q

Bedaquiline - MoA

A

Blocks the proton pump for ATP synthase in M. tuberculosis

39
Q

Bedaquiline - Clinical use

A

MDR-TB in adults and children when another effective treatment cannot be provided.

Adm. Once daily for 2 weeks, then 3 times per week for 22 weeks.

40
Q

Bedaquiline - Advers effects

A

Prolonged QT - arrhythmias, sudden death

Liver reactions; nausea, headache

41
Q

Bedaquiline - Special considerations

A

Used with at least 3 other drugs

Patients must have an electrocardiogram before treatment is begun, and at regular intervals thereafter

Patients should be monitored for adverse liver reactions

42
Q

Bedaquiline - Interactions

A

Cytochrome P450

43
Q

Isoniazid - Contraindications

A

Vitamin B6 deficiency

Pharmacology (55 decks)

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