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Pharmacology -AM > TB and Leprosy drugs > Flashcards

TB and Leprosy drugs Flashcards

1
Q

Naftifine

A

Squalene Epoxidase Inhibitors

Antifungals for cutaneous mycoses

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2
Q

Nystatin

A

Antifungals for cutaneous mycoses

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3
Q

Isoniazid

A

1st line Antimycobacterial used to treat TB
Most commonly used for latent TB (also active)
9 month treatment or 12 once-weekly doses of Isoniazid + rifapentine
Prodrug; inhibits mycelia acid in bacteria -> disruption in cell wall
M tuberculosis and M kansasii (at higher levels)
Most non-TB mycobacteria are resistant
effective against fast growing bacilli
Active against intracellular organisms
Cross resistance possible with ethionamide
PO- well absorbed (decreased w/ food, esp high fat meals)
Distributes to all body fluids, cells, caseous material, CSF
Metabolism is genetically variated- some faster w/ short 1/2 life, some slower w/ longer 1/2 life
Metabolized in liver
Renal excretion
AE: Hepatitis (can be fatal, MC in >35, + rifampin, or w/ alcohol), peripheral neuropathy (parasthesia of hands/feet = pyridoxine deficient -> supplement w/ pyridoxine (B6), CNS effects (convulsions), Hypersensitivity
*inhibits metabolism of carbamazepine and phenytoin - CYP450, causing nystagmus, ataxia, etc.
Monitor baseline hepatic enzymes

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4
Q

Macrolides

A

2nd line Antimycobacterial used to treat TB

Used in several non-TB mycobacterial infections (MAC)

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5
Q

Clofazimine

A

Anytimycobacterial used to treat Leprosy
Phenazine dye
MOA not fully known, may bind to bacterial DNA and/or cause generation of toxins
Some anti-inflammatory and anti-immune activity
Covers M leprae and maybe M tuberculosis and non-TB mycobacterium
PO- absorbed
Distribution: accumulates in tissues and allow intermittent therapy
No CSF
AE: typical to develop pink to brownish-black discoloration of skin, eosinophilic and other form of enteritis (sometimes surgery, rare)

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6
Q

Butoconazole

A 
Imidazoles
Antifungals for cutaneous mycoses
Topical
Tinea corporis, cruris, pedis
Oropharyngeal candida
Vulvovaginal candida
Trichophyton,epidermophyton, microsporum, candida, malassezia

AE: contact dermatitis, vulvar irritation, edema

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7
Q

Pyrazinamide

A

1st line Antimycobacterial used to treat TB
MOA unclear, but covers TB
Prodrug
Most benefit early in Tx, d/c after 2 months
Combo with Isoniazid, Rifampin, or Ethambutol
Covers tuberculosis bacilli in acidic lesions and macrophages
PO- distributes through body + CSF
Monitor baseline hepatic enzymes and uric acid levels
AE: liver toxicity, hepatitis, hyperuricemia, nausea, rash, joint ache, uric acid retention (but does not cause gout)

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8
Q

Capreomycin

A

2nd line Antimycobacterial used to treat TB
Inhibits protein synthesis
Only MDR-TB Tx
Parenteral only
Monitor vestibular, auditory, and renal toxicity
Risks of ototoxicity, nephrotoxicity

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9
Q

Sertaconazole

A 
Imidazoles
Antifungals for cutaneous mycoses
Topical
Tinea corporis, cruris, pedis
Oropharyngeal candida
Vulvovaginal candida
Trichophyton,epidermophyton, microsporum, candida, malassezia

AE: contact dermatitis, vulvar irritation, edema

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10
Q

Flucytosine (5-FC)

A

Antimetabolite Antifungal
(5-FC)
Use for candida UTI if fluconazole not appropriate.
Usually only used in combo.
Combo with Amphotericin B- covers systemic mycoses, meningitis caused by C. neoformans and C albicans, and cryptococcosis.
Combo with itraconazole- chromoblastomycosis.
Enters cell w/ fungal-specific enzyme, then is converted to compounds (5-FU and others) disrupt nucleic acid and protein synthesis.
Fungistatic
Amp B increases cell permeability through pores, allowing more 5-FC into cell.
Metabolized by converting to 5-FU in fungal cell.
Renal elimination- adjust dose w/ dys.
AE: reversible neutropenia or thrombocytopenia, dose-related bone marrow suppression (caution w/ radiation or chemo), reversible hepatic dysfunction + elevation of serum transaminases and alkaline phosphatase, Gi disturb, severe enterocolitis

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11
Q

Tioconazole

A 
Imidazoles
Antifungals for cutaneous mycoses
Topical
Tinea corporis, cruris, pedis
Oropharyngeal candida
Vulvovaginal candida
Trichophyton,epidermophyton, microsporum, candida, malassezia

AE: contact dermatitis, vulvar irritation, edema

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12
Q

Dapsone

A

Anytimycobacterial used to treat Leprosy
Similar structure to sulfonamides
Caution if sulfa allergy
Inhibits folate synthesis, interfering with bacterial cell growth/replication
Covers M leprae, Pneumocystis jirovecii (pneumonia in immunosuppressed patients)
PO
Distributes widely, and has high concentrations in the skin
Hepatic metabolism
Renal elimination
AE: Hemolysis (esp if G6P deficient), methemoglobinemia, peripheral neuropathy

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13
Q

Itraconazole

A

Triazoles Azole Antifungal

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14
Q

M. Tuberculosis, M avian-intracellulare, M chelonae, M abscesses, M kansasii, M fortuitous, M leprae

A

Types of mycobacteria
Rod shaped, aerobic
Multiply slowly (q18-24h)

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15
Q

Streptomycin (Aminoglycosides), Para-aminosalicylic acid, capreomycin, cycloserine, ethionamide, fluoroquinolones, macrolides

A

2nd line against TB

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16
Q

Sulconazole

A 
Imidazoles
Antifungals for cutaneous mycoses
Topical
Tinea corporis, cruris, pedis
Oropharyngeal candida
Vulvovaginal candida
Trichophyton,epidermophyton, microsporum, candida, malassezia

AE: contact dermatitis, vulvar irritation, edema

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17
Q

Terbinafine

A

Squalene Epoxidase Inhibitors

Antifungals for cutaneous mycoses

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18
Q 
Amphotericin B
Anidulafungin
Caspofungin
Fluconazole
Flucytosine
Intraconazole
Ketoconazole
Micafungin
Posaconazole
Voriconazole
A

Antifungals for systemic/subcutaneous mycoses

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19
Q

Micafungin

A

Echinocandin antifungal

20
Q

Anidulafungin

A

Echinocandin antifungal

21
Q

Amphotericin B

A

Antifungal drug of choice to treat life threatening subcutaneous mycoses
Very toxic, Low TI!
Binds to plasma membrane, forms pores that disrupt membrane function, allowing electrolytes and other molecules to leak into cell, causing death
Fungicidal or fungistatic
Broad spectrum: Candida albicans, histoplasmosis capsulatum, cryptococcal neoformans, coccidloides immitis, blastomyces dermatitidis, and many strains of aspergillus.
Also covers protozoal infection: leishmaniasis
Must be slow IV admin
water insoluble and coformulated with sodium deoxycholate (conventional) or artificial lipids (forms liposomes)
Liposomal preparations are reserved to pts who cannot tolerate conventional. $$$, but reduces renal and infusion toxicity- Dosing very different!
Distribution: binds to plasma proteins, throughout body, inflammation increase penetration into bodily fluids, does not cross CSF, vitreous humor, amniotic fluid. Crosses placenta
Elimination: some in urine, bile. No dose adjust for hepatic dysfunction. If renal dysfunction + conventional Amp B = must decrease dose 50%
AE: Renal impairment- decrease in GFR, etc- minimize with sodium loading w/ infusions of NS and lipid based Amp B. Fever/chills -1-3 hrs after starting IV- premed w/ corticosteroid or antipyretic. HypoTN - shock like fall of BP + hypokalemia- K supplement (caution if also on Digoxin). Thrombophlebitis- add heparin to infusion.
Interacts with nephrotoxic drugs- ensure adequate hydration: aminoglycosides, cyclosporine, pentamidine, vancomycin. Also drugs that cause K fluctuations (digoxin)

22
Q

Fluoroquinolones

A

2nd line Antimycobacterial used to treat TB

Used in multi drug resistant TB

23
Q

Para-Aminosalicyclic acid (PAS)

A

2nd line Antimycobacterial used to treat TB
One of the original TB meds
Streptomycin + Isoniazid + PAS was standard in 50-60’s
Some use in some MDR-TB regimens

24
Q

Posaconazole

A

Triazoles Azole Antifungal

25
Terconazole
``` Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia ``` AE: contact dermatitis, vulvar irritation, edema
26
Oxiconazole
``` Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia ``` AE: contact dermatitis, vulvar irritation, edema
27
Rifampin
Rifamycin 1st line Antimycobacterial used to treat TB or Leprosy *Important TB drug Blocks RNA transcription/ prevents cell growth and replication Broader than isoniazid Covers intra and extra cellular mycobacteria: M tuberculosis, M Kansasii, mycobacterium avium complex (MAC), Gram (+) (-), meningitis exp (meningococci or H. influenzae, M leprae PO- all body fluids and organs, 10-20% CSF Metabolized in liver- CYP450, auto induction: shortened 1/2 life for 1-2 wks Eliminated in bile, feces, small amt in urine (urine, feces, other secretions have orange-red color) AE: well-tolerated, common: n/v, rash; rare: hepatitis, death due to liver failure. With intermittent dosing: flu Sx + acute renal failure, hemolytic anemia, shock Caution in older pts, alcoholics, chronic liver disease Monitor baseline hepatic function and CBC Interactions possible with Isoniazid, plus CYP450
28
Miconazole
``` Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia ``` AE: contact dermatitis, vulvar irritation, edema
29
Bedaquiline
``` 2nd line Antimycobacterial used to treat TB First drug in new class to treat MDR-TB PO administration Covers many kinds of mycobacteria QT prolongation- monitor with ECG's CYP3A4 (Rifampin, etc- AVOID) ```
30
Ketoconazole
``` Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia ``` AE: contact dermatitis, vulvar irritation, edema
31
Capsofungin
Echinocandin antifungal
32
Cycloserine
2nd line Antimycobacterial used to treat TB Disrupts bacterial wall synthesis Distributes well into fluids, including CSF Renal/urine excretion Adjust dose for renal insufficiency AE: CNS related (lethargy, difficulty concentrating, anxiety, suicidal tendency), seizures Monitor for depression, anxiety, confusion, seizures, serum creatinine
33
Tolnaftate
``` Antifungal Stunts fungal growth Various topicals Tinea pedis, cruris, corporis Epidermophyton, microsporum, maassezia *no candida ```
34
Rifapentine
Rifamycin 1st line Antimycobacterial used to treat TB Used for latent TB in 12 once-weekly doses of Isoniazid + rifapentine Similar to Rifampin, but greater activity and longer half life Dose once weekly in combo w/ Isoniazid for latent TB Can be used in specific HIV-neg pts with minimal pulmonary TB
35
Rifampicin
Anytimycobacterial maybe used to treat Leprosy
36
Voriconazole
Triazoles Azole Antifungal
37
Butenafine
Squalene Epoxidase Inhibitors | Antifungals for cutaneous mycoses
38
Clotrimazole
``` Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia ``` AE: contact dermatitis, vulvar irritation, edema
39
Ethambutol, Isoniazid, Pyrazinamide, Rifabutin, Rifampin, Rifapentine
1st line against TB
40
Aminoglycosides- Streptomycin
2nd line Antimycobacterial used to treat TB One of 1st drugs to treat TB TB resistance is common now
41
Griseofulvin
Antifungals for cutaneous mycoses
42
Ciclopirox
Antifungals for cutaneous mycoses Various Topicals Disrupts synthesis of DNA & RNA in fungal cell Seborrheic dermatitis Tinea pedis, corporis, cruris, versacolor Cutaneous candidiasis Trichophyton, epidermophyton, microsporum, candida, malassezia
43
Fluconazole
Triazoles Azole Antifungal Least active of triazoles Covers yeasts, some dimorphic fungi (not aspergillosis, zygomycosis), C. albicans, C. parasilosis, vulvovaginal candidiasis, prophylaxis against invasive fungal in bone marrow transplant, Coccidioidomycosis. Resistance to C. krusei and C. glabrata Drug of choice for crytococcus neoformans after induction therapy with amp B and flucytosine. PO, IV Distributes widely to fluids and tissues, and CSF Excreted in urine, adjust dose for renal dysfunction AE: n/v, headache, skin rashes Caution if liver dysfunction
44
Econazole
``` Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia ``` AE: contact dermatitis, vulvar irritation, edema
45
Ethambutol
1st line Antimycobacterial used to treat TB Bacteriostatic, inhibits synthesis of mycobacterial cell wall Combo with Pyrazinamide, Isoniazid, or Rifampin (may d/c if organism susceptible to these) Covers mycobacteria Distributes through body, minimal CSF (questionable for TB meningitis Caution for Renal impairment AE: Optic neuritis (visual acuity, discriminate red/green) Monitor visual acuity/color discrimination before and during Uric acid excretion diminished- caution w/ gout
46
Rifabutin
Rifamycin 1st line Antimycobacterial used to treat TB Preferred if TB + HIV Similar to Rifampin: AE (+ uveitis, skin hyper pigmentation, neutropenia), MOA Interactions with CYP450 (less than Rifampin)
47
Ethionamide
2nd line Antimycobacterial used to treat TB Similar MOA to isoniazid Widely distributed in body & CSF Metabolized by the liver AE are bad and limits use: GI intolerance, n/v, hepatotoxicity, hypothyroidism, gynecomastia, alopecia, impotence, CNS effects Monitor LFT's, TSH, and GI intolerance

Pharmacology -AM (4 decks)

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