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Pharmacology > Antimicobacterial drugs > Flashcards

Antimicobacterial drugs Flashcards

1
Q

Drugs for Tuberculosis

  • Firstline?
  • Second line?
  • Tertatogenic
A

“RRIPE Tubercles for SALE”
First line: MOST are safe in prego
- Isoniazid (Bacteriostatic, Bacteriocidal)
- Rifampin (orange to red color)
- Rifabutin (1st line in HIV +ve patients)
- Ethambutol (Bacteriostatic)
- Pyrazinamide

Second line drugs: usually TERATOGENIC

  • Streptomycin
  • Ethionamide
  • Levofloxacin
  • Amikacin
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2
Q

When are Directly Observed Therapies (DOT) regimens recommended?

A

Recommended in noncompliant patients or resistant strains.

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3
Q

First line drug for TB?

A

Isoniazid - Narrow spectrum

  • Sole drug in tx. of latent infection
  • Part of combo therapy.
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4
Q

Isoniazid MOA

A

Pro-drug (activated by a mycobacterial catalase - peroxidase - KatG)
Targets enzymes involved in mycolic acid synthesis:
- enoyl acyl carrier protein reductase (InhA)
- B-ketoacyl-ACP synthase (KasA)

Note: bacteria can mutate these carriers–>resistance!
- cross resistance does NOT OCCUR

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5
Q

Isoniazid Antibacterial spectrum:

Resistance?

A
  • Bacteriostatic effects against bacilli in stationary phase.
  • Bactericidal against rapidly dividing bacilli
  • Specific for M. tuberculosis

If used alone resistant organism usually emerge!

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6
Q

Isoniazid PK

AE?

A

Oral, IV, IM
- diffuses into all body fluids, cells and caseous material

AE: (INH - Injury to Nerve and Hepatocytes)

  • Peripheral neuritis: corrected by pyridoxine (B6) supplementation
  • Hepatotoxicity: clinical hepatitis and idiosyncratic
  • CYP450 inibitor
  • Lupus like syndrome: rare
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7
Q

Isoniazid effects on pregnancy?

A

Safe in pregnancy (increased risk of hepatitis, pyridoxine supplementation is recommended)

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8
Q

Rifamycins

A

Rifampin, Rifabutin

  • First-line drugs for tx. of all susceptibe forms of TB*
  • Part of combo therapy
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9
Q

Rifampin

MOA

A

Bactericidal

  • Resistant strains rapidly emerge
  • Usually Given In Combination

MOA: Blocks transcription by binding to B-subunit of bacterial DNA-dependent RNA polymerase
–> leading to inhibition of RNA synthesis
STRONG CYP 450 inducer more superior to Isoniazid Inhibitory effects !

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10
Q

Rifampin: Antimicrobial spectrum

A

Bactericidal for intracellular AND extracellular mycobacteria

  • M. tuberculosis
  • M. kansasii

Gram +ve and Gram -ve organisms

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11
Q

Rifampin resistance:

A

Point mutations in rpoB, the gene for the B subunit of RNA polymerase

  • -> decreased affinity of bacterial DNA-dependent RNA polymerase for drug
  • decreased permeability
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12
Q

Rifampin clinical applications

A 
TB
Latent TB in INH intolerant patients
Leprosy
Prophylaxis for individuals exposed to meningitis
MRSA (with vancomycin)--> last option
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13
Q

Rifampin PK

A 
Oral and parenteral
well distributed (including CSF)
excreted mainly into feces
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14
Q

Rifampin AE

A
  • Light chain proteinuria
  • GI distress
  • Occasional effects: Thrombocytopenia, rashed, nephritis, liver dysfunction
  • Imparts harmless orange/red colot to bodily fluids
  • Strongly induces most CYP 450 isoforms
  • SAFE IN PREGNANCY
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15
Q

Rifabutin

A

Preferred drug for use in HIV patients (due to lesser effects on CYP enzymes).- TB

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16
Q

Ethambutol

A
  • First line treatment for susceptible forms of TB
  • specific for most strains of M. tuberculosis and M. kansasii
  • inhibits arabinosyl transferases
17
Q

Ethambutol AE

A
  • Dose-dependent visual disturbances (eg, red/green color blindness) - cannot be used in children too you to receive site tests
  • Headache, confusion, hyperuricemia, peripheral neuritis (rare)
  • safe in pregnancy
18
Q

Pyrazinamide

PK?

A

First-line agent

  • used in combo with isoniazid, rifampin and ethambutol
  • must be enzymatically hydrolyzed to active pyrazonoic acid

PK: well absorbed orally and well distributed (including CSF)

  • Renal or hepatic insufficiency may require dosage adjustment
19
Q

Pyrazinamide AE?

A

Nongouty polyarthralgia (~40%)
Acute gouty arthritis (rare unless predisposed)
Hyperuricemia
Hepatotoxicity, myalgia, GI irritation, porphyria, rash, photosensitivity
Recommended for use in pregnancy when benefits outweigh risks.

20
Q

Streptomycin

A
  • Used for drug resistant strains
  • Used in drug combinations for treatment of life-threatening tuberculous disease:
  • meningitis
  • miliary dissemination
  • severe organ tuberculosis

Increasing frequency of resistance to streptomycin limits use of drug!!

21
Q

Alternative Drugs (2nd line) for TB

A

Amikacin: used for streptomycin or multi drug resistant strains. Similar AE as strepto!
- TERATOGENIC

Levofloxacin: recommended for use against first line drug resistan strains. Should always be used in combination.
- Teratogenic

Ethionamide: Congener of INH (no cross resistance). Severe GI irritation and adverse neurologic effects. Also hepatotoxicity and endocrine effects.
- TERATOGENIC

22
Q

Treatment of Latent TB regimens

A

Isoniazid: 6-9 months
Rifampin: 4 months

23
Q

Anti drug regimens

Standard regimens for Empiric tx. of pulmonary TB:

A

Initiation
RIPE
- Rifampin, Isoniazid, Pyrazinamide, Ethambutol (4 drugs for 2 months)
RIE
- Rifampin, Isoniazid, Ethambutol ( 3 drugs for 2 months)

Continuation phase
- Isoniazid, Rifampin (2 drugs for 4 months- or 31 weeks)

24
Q

Leprosy (Hansen’s disease)

A

“Leprosy killed in the DRC”
Dapsone
Cloffazimin
Rifampin (rifabutin)

25
Q

Dapsone

A

Structurally related to sulfonamides
Bacteriostatic
Inhibits folate synthesis (via dihydropterate synthetase inhibition)
Also used in tx. of pneumonia (P. jiroveci) in HIV +ve patients.

PK: well absorbed and distributed (highlevels in skin)

Acedapsone = repository form of dapsone

26
Q

Dapsone - AE

A
  • Hemolysis (esp. G6PD def.)
  • Erythema nodosum leprosum (treated w/ corticosteroides or thalidomide)
  • Other effects - GI irritation, fever, hepatitis methemoglobinemia
  • CYP P450 inhibitor
27
Q

Clofazimine

MOA

A

Phenazine dye
Binds to DNA and inhibits replication
Redox properties may generate cytotoxic oxygen radicals
Bactericidals to M. leprae (some activity against M. avium-intracellulare complex)

28
Q

Clofazimine AE

what doesn’t develop with clofazimine

A

Red-brown discoloration of skin
GI irritation
Eosinophilic enteritis
Erythema nodosum does not develop (drug has anti-inflammatory action.)

29
Q

WHO tx. recommendations for leprosy types:

Pauci-bacillary (PB): 1-5 skin lesions:

Multi-bacillary: >5 skin lesions

A

PB:
- regimen of 2 drugs: Rifampin + dapsone (6 months)
Multi-bacillary:
- regimen of 3 drugs: Rifampin, clofazimine + dapsone (12 months)

30
Q

Tx options for infections w/ atypical mycobacterium

  1. M. Kansaii
  2. M. marinum
  3. M. avium complex
  4. M. chelonae
  5. M. fortuitum
A
  1. resembles TB: Isoniazid + rifampin + ethambutol
  2. Granulomatous cutaneous disease: 2 drug combo (rifampin, etahmbutol, clarithromycin, minocycline, doxycycline, sulfonamides)
  3. Pulmonary disease (clarithromycin + ethambutol +/- rifabutin)
  4. Abscess, sinus tract, ulcer; bone, joint, tendon infection (clarithromycin - monotherapy usually adequate )
  5. Abscess, sinus tract, ulcer; bone, joint, tendon (Amikacin, cefoxitin, levofloxacin, sulfonamides, impenem)

Pharmacology (27 decks)

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