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Chemotherapy > 5 - Antituberculosis & Antifungal > Flashcards

5 - Antituberculosis & Antifungal Flashcards

1
Q

What are properties of mycobacteria ?

A
  • Immobile,Slow-grow,Gram +
  • Contain lipid in cell walls called mycolic acids and
  • Acid-fast bacilli
  • Lipid-rich cell wall = impermeable to many agents.
  • Can develop resistance, use drug combinations
  • Intracellular pathogen , anti-TB drug need to penetrate until macrophages.
  • slow response to antibiotics
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2
Q

Mycobacteria classification

A
  1. Mycobacterium tuberculosis complex (TB)
  2. NonTuberculousMycobacteria.
  3. Mycobacterium Leprae (Leprosy)
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3
Q

Duration of standard regimen for TB sensitive

A
  • treatment in 6 months ( 2 intense , 4continuation)
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4
Q

Intensive treatment for TB sensitive

A

– Isoniazid (H)
– Rifampicin (R)
– Pyrazinamide (Z)
– Ethambutol (E)

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5
Q

Continuation treatment for TB sensitive

A

– Isoniazid (H)

– Rifampicin (R)

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6
Q

What is DOT and its purpose ?

A

Directly Observe Treatment,Ensuring compliance of patients that consume TB treatment.

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7
Q

Standard treatment regimen TB divided into 3 based on Diagnostic category which are ?

A
  1. Category 1 : New smear-positive patients; new smear- negative PTB/positive rongent with extensive parenchymal involvement; concomitant HIV disease or severe forms of extra-pulmonary TB.
  2. Category 2: Previously treated sputum smear-positive PTB (relapse/discontinue of treatment); treatment failure of category I
  3. Category 3 : New smear-negative PTB/positive rontgen mild illness; less severe forms of extra- pulmonary TB
  4. Insertion : (given to patients after 2 months regimen still have positive result)Sputum smear-positive on the last phase of treatment for new smear-positive patients of category I or smear-positive of retreatment of category 2
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8
Q

Regimen for category 1, 2, 3 and Insertion ?

A
  • C1 : 2 HRZE/4 H3R3 = 2 months all anti-TB once daily & 4 months , 3 times a week consumption for isoniazid and rifampicin.
  • C2 : 2 HRZES / 5H3R3E3 = 2 months anti-TB once daily via injection & 5 months 3 times a week consumption of isoniazid , Rifampicin , Ethambutol
    or 1HRZE/5H3R3E3
  • C 3 : 2HRZ/4H3R3
    -Insertion : 1 HRZE
    note : - front is intense & back is continuation , number = how many consumption per week
    -letter reffer to name of drug in the intense and continuation treatment flash card.
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9
Q

Medicines recommended for Multiple Drug Resistance TB

A

Group A : Fluoroquionone
Group B : Second- line agents
Group C : Other core second-line agents
Groyp D : d1 , d2, d3

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10
Q

2 types of MDR-TB Treatment with confirmed rifampicin-resistant or MDR-TB

A
  1. Shorter MDR-TB Regimen

2. Individual (conventional) MDR/RR-TB regimens

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11
Q

Standard MDR TB Regimen (“conventional”) characteristic

A
  • MINIMUM 20 MONTHS (6 mon intensive & 18 mon continuation)
  • 6Z-(E)-Kn-Lfx-Eto-Cs/18Z-(E)-Lfx-Eto
  • (E) & Z add on agents
  • (E) not given if there is resistance occurs
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12
Q

How to read 6Z-(E)-Kn-Lfx-Eto-Cs/18Z-(E)-Lfx-Eto-Cs ?

A

6 months intensive treatment with the letter given and 18 months continuation treatment with the abbreviations letter
note. refer the letter to MDR treatment slide

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13
Q

Shorter MDR TB Regimen characteristic ?

A

1.Treatment duration of 9-12 months
2.Patients with rifamipicin resistance (RR) or MDR TB who have not been treated with 2nd line TB drug and who have not develop resistance to fluoroquinolone and anti-TB injection 2nd line
3.Standardized shorter MDR-TB regimen with seven drugs
4. 4-6 Km-Mfx-Pto-Cfz-Z-Hhigh-dose-E / 5 Mfx-Cfz-Z-E
– Exclusion criteria: extrapulmonary disease and pregnancy

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14
Q

FUNGI CHARACTERISTIC

A
  • OPPORTUNISTIC MICROORGANISM
  • CELL WALLS CONTAIN GLUCANS AND CHITIN
  • INFECTION : SUPERFICIAL AND DEEP
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15
Q

Common Fungal Pathogen

A
  • Dermatophytes
  • Candida
  • Aspergilus
  • Cryptococcus
  • Rhizopus
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16
Q

-

A

-

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17
Q

Classification of Antifungal drug

A
  1. Systemic drugs ( amphotericin B , Flucytosine,Azoles,Echinocandins )
  2. Oral systemic ( Griseofulvin ,Terbinafine )
  3. Topical Drug ( Nystatin , Topical azoles , Topical allylamines )
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18
Q

PWhat are the properties of amphotericin B ?

A
  1. Produced by Steptomyces nodosus
    2.Amphoteric polyene macrolide
    3.Insoluble in water:
    – lipid formulations amphotericin B
    – Complexing with the bile salt deoxycholate for i.v
  2. Poorly absorbed from GIT→oral form is for local infection
  3. The drug is widely distributed in most tissues, but only 2–3% of the blood level is reached in CSF
19
Q

Amphotericin B mechanism of action ?

A

Amphotericin B binds with ergosterol, a component of fungal cell membranes, forming pores that cause rapid leakage of monovalent ions (K+, Na+, H+ and Cl−) and subsequent fungal cell death.

20
Q

clinical uses and anti fungal activity of amphotericin B

A 
1.Broadest spectrum of antifungal & fungicidal→agent for nearly all
life-threatening fungal infection
2.Clinical activity:
– Candidaspp.
– Cryptococcusneoformans
– Blastomycesdermatitidis
– Histoplasmacapsulatum
– Sporothrixschenckii
– Coccidioidesimmitis
– Paracoccidioides braziliensis – Aspergillusspp.
– Penicillium marneffei
– Mucormycosis
3.Local or topical administration: Mycotic corneal ulcers and keratitis
21
Q

Adverse effects of amphotericin B ?

A

A. Infusion-Related Toxicity
– Fever, chills, muscle spasms, vomiting, headache, and hypotension
B. Cumulative Toxicity
– Nephotoxic
• → renal tubular acidosis and severe potassium &
magnesium wasting
• Irreversible: prolonged administration (> 4 g cumulative dose)
– Abnormalities of liver function & anemia

22
Q

Properties of Flucytosine are ?

A
  1. 5-fluorocytosine
  2. Water-soluble pyrimidine analog
  3. Prodrug that has a narrow spectrum
  4. Eliminated by glomerular filtration→ accumulation leads to toxicity
23
Q

Mechanism action of flucytosine ?

A

ynergistic with amphotericin→enhanced penetration of flucytosine through amphotericin-damaged fungal cell membranes

24
Q

Clinical use and adverse effect of Fluocytosine are….

A
  1. ClinicalUse
    – Confined to combination therapy:
    • + amphotericin B = cryptococcal meningitis • + itraconazole = chromoblastomycosis
  2. AdverseEffect
    – Metabolized into toxic antineoplastic compound
    fluorouracil
    – Common: Bone marrow toxicity with anemia, leukopenia, and thrombocytopenia
    →Narrow IT: Monitoring drug concentration
25
Q

2 Classification of azoles are…

A
  1. Imidazole : ketoconazole, miconazole, and
    clotrimazole.
    2.Triazoles: itraconazole, fluconazole, voriconazole, and posaconazole
26
Q

Azoles mechanism of action …

A

+ Reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes (14α - sterol demethylase) which lead to the accumulation of 14α–methylsterols
– Disrupts the close packing of acyl chains of phospholipids
– Impairs the functions of certain membrane-bound enzyme systems (ATPase and enzymes of the electron transport system)

27
Q

Clinical Uses of azoles are…

A

Broad spectrum antifungal:
– Candida, C neoformans , the endemic mycoses (blastomycosis,
coccidioidomycosis, histoplasmosis), the dermatophytes
– Intrinsically amphotericin-resistant organisms such as P boydii – Itraconazole, voriconazole, posaconazole: aspergillus

28
Q

Adverse effect of azoles are…

A

The most common adverse reaction is minor GIT upset

– All azoles cause abnormalities in liver enzymes and, very rarely, clinical hepatitis

29
Q

Drug interactions of azoles are…

A
  • azoles relatively non-toxic

- Prone to drug interactions because they affect the mammalian cytochrome P450

30
Q

Properties of ketoconazole are…

A
  • Greater propensity to inhibit mammalian CYP enzymes→no longer used orally
  • First oral azole
31
Q

Properties of itraconazole are…

A

1.Absorption is increased by food and by low gastric pH
2.Important drug interaction: reduced bioavailability of itraconazole when taken with rifamycins (rifampin, rifabutin, rifapentine)
3.Does not affect mammalian steroid synthesis
4. Penetrates poorly into the cerebrospinal fluid
5. Indication:
• Dimorphic fungi:histoplasma,blastomyces,sporothix, dermatophytoses and onychomycosis

32
Q

Properties of fluconazole are…

A

1.Least effect of all the azoles on hepatic microsomal
enzymes→less common drug interaction
2.Fluconazole has the widest therapeutic index of the azoles
3. Clinical use:
•treatment and secondary prophylaxis of cryptococcal
meningitis
•Most commonly used treatment of mucocutaneous candidiasis
•Dimorphic fungi is limited to coccidioidal disease, in particular for meningitis
•Prophylactic use to reduce fungal disease in bone marrow transplant recipients and AIDS patients

33
Q

Properties of voriconazole are…

A

1.Bioavailability exceeding 90%
2.Similar spectrum of action to itraconazole
3. Inhibitor of mammalian CYP3A4→dose reduction of a number of medications is required when voriconazole is started
4.Less toxic than amphotericin B and is the treatment of choice for invasive aspergillosis
5.Adverse effect:
• Rashandelevatedhepaticenzymes
• Visual disturbances are common, occurring in up to 30% of patients receiving i.v voriconazole
•Photo sensitivity dermatitis is commonly observed in patients receiving chronic oral therapy1.

34
Q

Properties for posaconazole are…

A
  1. Absorption is improved when taken with meals high in fat
  2. Posaconazole is rapidly distributed to the tissues
  3. Inhibitor of CYP3A4→Increased levels of CYP3A4 substrates
  4. Posaconazole has the broadest spectrum among the azoles, with activity against most species of Candida and Aspergillus
  5. It is the only azole with significant activity against mucormycosis
  6. It is currently licensed for salvage therapy in invasive aspergillosis, as well as prophylaxis of fungal infections during induction chemotherapy for leukemia, and for allogeneic bone marrow transplant patients
35
Q

Properties of echinocandins….

A
  1. Newest class of antifungal agents to be developed
  2. Caspofungin, micafungin and anidulafungin are the only licensed agents
  3. Active against Candida and Aspergillus
  4. Available only in i.v formulations
  5. Dosage adjustments are required only in the presence of severe hepatic insufficiency
36
Q

Mechanism of action of echinocandinds…

A

Inhibiting the synthesis of β(1–3)-glucan →disruption of the fungal cell wall and cell death.

37
Q

clinical uses of echinocandinds…

A
  1. Caspofungin: mucocutaneous candidal infections, empiric antifungal therapy during febrile neutropenia, invasive aspergillosis only as salvage therapy in patients who have failed to respond to amphotericin B
  2. Micafungin:mucocutaneouscandidiasis,candidemia, and prophylaxis of candidal infections in bone marrow transplant patients
  3. Anidulafungin:esophagealcandidiasisandinvasivecandidiasis, including candidemia
38
Q

Adverse effect of echinocandinds…

A

1.Echinocandin agents are extremely well tolerated with minor gastrointestinal side effects and flushing reported infrequently
2.Elevated liver enzymes in several patients receiving caspofungin &
cyclosporine→this combination should be avoided
3.Micafungin has been shown to increase levels of nifedipine, cyclosporine, and sirolimus.

39
Q

Griseofulvin properties as oral systemic anti fungal drugs are…

A
  1. Very insoluble fungistatic→absorbed better with fatty foods
  2. Only use is in the systemic treatment of dermatophytosis
  3. Mechanism of action: deposited in newly forming skin where it binds to keratin, protecting the skin from new infection
  4. Griseofulvin must be administered for 2–6 weeks for skin and hair infections
    5.Adverse effects: an allergic syndrome much like serum sickness, hepatitis, and drug interactions with warfarin and phenobarbital
    – Griseofulvin has been largely replaced by newer antifungal medications such as itraconazole and terbinafine
40
Q

Terabifine properties …

A

– Belongs to allylamines group
– It is used in the treatment of dermatophytoses, especially onychomycosis
– Mechanism of action: Interferes with ergosterol biosynthesis by inhibiting the fungal enzyme squalene epoxidase→accumulation of the sterol squalene = toxic
– Adverse effects are rare, consisting primarily of gastrointestinal upset and headache

41
Q

Nystatin properties as topical anti fungal therapy are…

A
  1. Polyene macrolide similar to amphotericin B
  2. Really toxic systemically→limited to topical use
  3. Active against most Candida sp→most commonly used for local candidal infections
42
Q

Properties of topical azole are…

A

1.Most commonly used: clotrimazole and
miconazole for vulvovaginal candidiasis
2.Oral clotrimazole troches: oral candidiasis
3.In cream form, both agents are useful for dermatophytic infections, including tinea pedis, tinea cruris, tinea corporis
4.Topical and shampoo forms of ketoconazole: seborrheic dermatitis and pityriasis versicolor

43
Q

properties of topical allylamines are…

A
  1. Terbinafine and naftifine

2. Treatment of tinea cruris and tinea corporis

Chemotherapy (22 decks)

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