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ANTI-FUNGAL & ANTI-TUBERCULAR Flashcards

1
Q

are caused by microscopic organisms that can invade EPITHELIAL TISSUE caused by yeast, molds, etc.

A

FUNGAL INFECTIONS

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2
Q

FUNGAL INFECTIONS CLASSIFICATION

  • caused by DERMATOPHYTES
  • these includes tinea infections affecting hair or hair follicles, flat areas of hairless skin and infection of the nails → incidence rate is high
  • causative microbes are SAPROPHYTES with unusual ability to digest keratin
A

SUPERFICIAL INFECTIONS

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3
Q

FUNGAL INFECTIONS CLASSIFICATION

TRANSMITTED from one host to another

A

DEEP-SEATED MYCOSES

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4
Q

FUNGAL INFECTIONS CLASSIFICATION

  • are caused by the INHALATION of SPORES affecting deeper tissues and organs and cause fungal pneumonia
A

SYSTEMIC INFECTIONS

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5
Q

can FUNGAL PNEUMONIA be transmitted from human to human?

A

NO

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6
Q

FUNGAL INFECTIONS CLASSIFICATION

can cause LIFE THREATENING infection to IMMUNOCOMPROMISED patients like patients with leukemia, cancer, HIV, diabetes, and patients currently using immunosuppresive agents, cytotoxins, irradiation and even steroids

A

OPPORTUNISTIC FUNGAL INFECTION

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7
Q

FUNGAL INFECTIONS CLASSIFICATION

  • cause infections of the SKIN by dermatophytes in the Microsporum, Trichophyton or Epidermophyton genera
  • these dermophytic infections are named for the site of infection rather than the causative organism
A

CUTANEOUS INFECTIONS
(dermatophytoses)

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8
Q

FUNGAL INFECTIONS CLASSIFICATION

  • refers to group of fungal disease which BOTH the SKIN and SUBCUTANEOUS TISSUES are involved
  • CHARACTERISTICS: soil saprophytes of very low grade virulence and invasive ability and they gain access as a result of trauma to the tissue
A

SUBCUTAENOUS MYCOSES

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9
Q
  • LARGEST ORGAN
  • directly exposed to external environment
A

SKIN

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10
Q

FORMIDABLE BARRIER to drug penetration

A

skin

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11
Q

all FATTY ACID and FATTY ACID DERIVATIVES (salts) have antifungal properties due to ____ (part of innate immune system)

A

SEBUM FRACTION

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12
Q

FATTY ACID & DERIVATIVES

what happens to SOLUBILTY if the MW increases

A

solubility decreases

INVERSE RELATIONSHIP

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13
Q

FATTY ACID & DERIVATIVES

____ fatty acid have the advantage of having LOWER VOLATILITY

A

HIGHER MW

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14
Q

FATTY ACID & DERIVATIVES

SALT form are ____

A

fungicidal

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15
Q

TOPICAL ANTIFUNGAL AGENTS

  • NON-IRRITATING and NON-TOXIC
  • present in PERSPIRATION or SWEAT
  • around 0.01% is fungicidal
A

PROPIONIC ACID

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16
Q

TOPICAL ANTIFUNGAL AGENTS

PROPIONIC ACID:
how many % is fungicidal

A

0.0001

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17
Q

TOPICAL ANTIFUNGAL AGENTS

used as fungicide on ADHESIVE TAPES

A

ZINC PROPRIONATE

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18
Q

TOPICAL ANTIFUNGAL AGENTS

CREAM colored granules used topically to treat SUPERIFICAL DERMATOMYCOSES

A

SODIUM CAPRYLATE

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19
Q

TOPICAL ANTIFUNGAL AGENTS

FINE WHITE powder and a topical fungicide and UNSTABLE to MOISTURE

A

ZINC CAPRYLATE

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20
Q

TOPICAL ANTIFUNGAL AGENTS

  • obtained from the destructive distillation of CASTOR OIL (ricinoleic acid)
  • viscous YELLOW liquid, a SEVERE IRRITANT and should NEVER be applied on mucous membrane
  • tx of athlete’s foot
A

UNDECYLENIC ACID

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21
Q

TOPICAL ANTIFUNGAL AGENTS

UNDECYLENIC ACID:
is obtained from the ____ of CASTOR OIL (ricinoleic acid)

A

detructive distillation

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22
Q

TOPICAL ANTIFUNGAL AGENTS

UNDECYLENIC ACID:
is obtained from the destructive distillation of ____

A

CASTOR OIL

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23
Q

TOPICAL ANTIFUNGAL AGENTS

UNDECYLENIC ACID:
should NEVER be applied on

A

mucous membrane

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24
Q

TOPICAL ANTIFUNGAL AGENTS

  • a fungicide, a COLORLESS OILY liquid that release ACETIC ACID upon hydrolysis
  • 3 acetic acid
  • like a prodrug
A

TRIACETIN

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25
Q

TOPICAL ANTIFUNGAL AGENTS

TRIACETIN:
release ____ upon hydrolysis

A

acetic acid

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26
Q

TOPICAL ANTIFUNGAL AGENTS

TRIACETIN:
release acetic acid upon ____

A

hydrolysis

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27
Q

TOPICAL ANTIFUNGAL AGENTS

  • CANNOT be used ALONE
  • antiFUNGAL and keratolytic
A

SALICYLIC ACID

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28
Q

TOPICAL ANTIFUNGAL AGENTS

antiSEPTIC and keratolytic

A

RESORCINOL

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29
Q

TOPICAL ANTIFUNGAL AGENTS

  • CANNOT be used ALONE
  • ONLY antifungal that CANNOT penetrate the SKIN
  • should be used IN COMBINATION to provide therapeutic effect
A

BENZOIC ACID

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30
Q

TOPICAL ANTIFUNGAL AGENTS

MOA: interfere with CELL MEMBRANE INTEGRITY and function in susceptible fungi

A

Phenol and their derivatives

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31
Q

TOPICAL ANTIFUNGAL AGENTS

WHITE to PALE YELLOW and PHOTOSENSITIVE 1% cream for the treatment superifical tine infection

A

HALOPROGIN

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32
Q

TOPICAL ANTIFUNGAL AGENTS

  • SPONGY, LIGHT-SENSITIVE, YELLOWISH WHITE powder
  • substitute for IODOFORM
A

CLIOQUINOL

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33
Q

TOPICAL ANTIFUNGAL AGENTS

  • a BROAD SPECTRUM antifungal agent used topically
  • SECOND LINE agemt for ONYCHOMYCOSIS
  • MOA:
    • LOW concentration: block the transport of amino acids into the cell
    • HIGH concentration: LOST of membrane integrity and cellular constituents
A

CICLOPIROX OLAMINE

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34
Q

nail bed fungal infections

A

onychomycosis

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35
Q

NUCLEOSIDE ANTIFUNGAL AGENTS

  • ORALLY ACTIVE, NARROW spectrum antifungal agent
  • MOA: incorporation of FLUORINATED PYRIMIDINE to fungal RNA following selective deamination of 5-fluouracil, which is an anti-metabolite that inhibits thymidylate sunthethase and thus DNA synthesis
A

FLUCYTOSINE
5-FC

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36
Q

NUCLEOSIDE ANTIFUNGAL AGENTS

FLUCYTOSINE:
incorporation ____ to fungal RNA following selective deamination of 5-fluouracil

A

FLUORINATED PYRIMIDINE

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37
Q

NUCLEOSIDE ANTIFUNGAL AGENTS

FLUCYTOSINE:
targets ____

A

nitrogenous bases

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38
Q

NUCLEOSIDE ANTIFUNGAL AGENTS

  • antiMETABOLITE
  • inhibits THYMIDYLATE SYNTHETASE and thus DNA synthesis
A

5-fluouracil
5-FU

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39
Q

NUCLEOSIDE ANTIFUNGAL AGENTS

5-FLUOURACIL:
inhibits ____

A

thymidylate synthetase & DNA synthesis

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40
Q

NUCLEOSIDE ANTIFUNGAL AGENTS

MOA of 5-FU

A
  • inhibition of DNA synthesis
  • inhibition of PROTEIN synthesis
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41
Q

ANTIFUNGAL ANTIBIOTICS

  • isolated from SOIL BACTERIUM Streptomyces
  • has MANY double bonds
  • large LACTONE ring
  • SERIES of OH ggroups on the acid portion of the ring
  • conjugated double bonds
  • glycosidically linked deoxyaminohexose sugar
A

POLYENES

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42
Q

ANTIFUNGAL ANTIBIOTICS

LARGEST class of antifungal antibiotics

A

POLYENES

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43
Q

ANTIFUNGAL ANTIBIOTICS

  • BROAD SPECTRUM antifungal agents against pathogenic yeast, molds, dermatophytes (with anti-protozoal properties)
  • use is LIMITED because: toxicity, LOW water solubility, POOR chemical stability
  • topical agents for superficial fungal infections
A

POLYENES

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44
Q

ANTIFUNGAL ANTIBIOTICS

POLYENES STRUCTURAL REQUIREMENT:
LACTONE RING: NATAMYCIN

A

26C

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45
Q

ANTIFUNGAL ANTIBIOTICS

POLYENES STRUCTURAL REQUIREMENT:
LACTONE RING: AMPHOTERICIN B and NYSTATIN

A

38C

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46
Q

ANTIFUNGAL ANTIBIOTICS

POLYENE STRUCTURAL REQUIREMENT:
series of ____ on the acid portion of the ring

A

OH groups

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47
Q

ANTIFUNGAL ANTIBIOTICS

POLYENE STRUCTURAL REQUIREMENT:
glycosidically linked deoxyaminohexose sugar ____

A

MYCOSAMINE SUGAR

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48
Q

ANTIFUNGAL ANTIBIOTICS

POLEYENE STRUCTURAL REQUIREMENT:
CONJUGATED DOUBLE BONDS: NATAMYCIN

A

PENTAENE

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49
Q

ANTIFUNGAL ANTIBIOTICS

POLEYENE STRUCTURAL REQUIREMENT:
CONJUGATED DOUBLE BONDS: NYSTATIN

A

HEXAENE

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50
Q

ANTIFUNGAL ANTIBIOTICS

POLEYENE STRUCTURAL REQUIREMENT:
CONJUGATED DOUBLE BONDS: AMPHOTERICIN B

A

HEPTAENE

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51
Q

can you consider ALL antibacterials as antibiotics

A

NO, not all anibacterials are antibiotics

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52
Q

to be considered as antibiotic, what should be the requirement

A

it should come from a NATURAL SOURCE

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53
Q

ANTIFUNGAL ANTIBIOTICS

POLYENES:
* LAST line for systemic fungal infections
* NEPHROTOXIC

A

AMPHOTERICIN B

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54
Q

ANTIFUNGAL ANTIBIOTICS

use of POLYENES is LIMITED because of

(3)

A

toxicity
low water solubility
poor chemical stability

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55
Q

ANTIFUNGAL ANTIBIOTICS

POLYENES:
LOW water SOLUBILITY is due to

A

LARGE LACTONE RING

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56
Q

ANTIFUNGAL ANTIBIOTICS

POLYENE:
POOR CHEMICAL stability: what is EASILY HYDROLYZED

A

AMINO SUGAR

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57
Q

ANTIFUNGAL ANTIBIOTICS

MOA OF POLYENES:
binds with ____ in cell membrane as “FALSE MEMBRANE” component

A

STEROLS

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58
Q

ANTIFUNGAL ANTIBIOTICS

MOA OF POLYENES:
____ at LOW concentration

A

-static

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59
Q

ANTIFUNGAL ANTIBIOTICS

MOA OF POLYENES:
____ at HIGH concentration

A

-cidal

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60
Q

ANTIFUNGAL ANTIBIOTICS

MOA OF POLYENES:
can form a pore in the membrane, creating a ____ resulting in the LOSS of intracellular potassium ions

A

transmembrane ion-channel

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61
Q

____ found in cell membranes of FUNGI

A

ergosterol

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62
Q

ANTIFUNGAL ANTIBIOTICS

main MOA of POLYENES

A

cell membrane inhibitor

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63
Q

ANTIFUNGAL ANTIBIOTICS

  • isolated in 1956 by Gold et. al from STREPTOMYCES NODOSUS
  • PARENTERAL form (except IM) is an aqueous colloidal dispersion stabilized by sodium deoxycholate
A

AMPHOTERICIN B

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64
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
isolated in ____

A

1956

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65
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
isolated by ____

A

GOLD et al

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66
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
isolated from ___

A

Streptomyces nodosus

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67
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERIC SUBSTANCE

A

polar & nonpolar

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68
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
____ form is an aqueous colloidal dispersion

A

parenteral form
(except IM)

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69
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
PARENTERAL form (except IM) is stabilized by ____

A

sodium deoxycholate

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70
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
NSS is not used because ???

A

it disrupts colloidal dispersion that leads to unstability of solution

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71
Q

antibiotics are ____

A

secondary metabolites

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72
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
____ on the cell membrane of fungi and some protozoa due to the affinity for ERGOSTEROL than cholesterol

A

SELECTIVE ACTION

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73
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
SELECTIVE ACTION on the cell membrane of fungi and some protozoa due to the affinity for ____ than cholesterol

A

ERGOSTEROL

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74
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
LIMITATIONS

A
  • nephrotoxic
  • toxic reactions
  • hypolakemia, anemia
  • pain at the injection site & thrombophlebitis
  • hemolysis
  • intrathecal route: neurotoxicity
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75
Q

ANTIFUNGAL ANTIBIOTICS

AMPHOTERICIN B:
mode of RESISTANCE

A

LOW COUNT of ergosterol

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76
Q

ANTIFUNGAL ANTIBIOTICS

  • isolated by HAZEN and BROWN (1951) from STREPTOMYCES NOURSEI
  • combination with TCN is used to prevent monilial overgrowth caused by TCN therapy (destruction of bacterial microflora)
A

NYSTATIN

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77
Q

ANTIFUNGAL ANTIBIOTICS

NYSTATIN:
patient counseling

A

swish & swallow

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78
Q

ANTIFUNGAL ANTIBIOTICS

NYSTATIN:
isolated by ____

A

Hazen and Brown

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79
Q

ANTIFUNGAL ANTIBIOTICS

NYSTATIN:
isolated from ____

A

Streptomyces noursei

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80
Q

ANTIFUNGAL ANTIBIOTICS

NYSTATIN:
the ring (aglycone) is called

A

nystatinolide

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81
Q

ANTIFUNGAL ANTIBIOTICS

NYSTATIN:
NATAMYCIN is obtained from

A

S. natalensis

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82
Q

ANTIFUNGAL ANTIBIOTICS

  • 1st reported by Oxford et. al and was isolated from Penicillum griseofulvum
  • very lipophilic
  • AE: rash/urticaria, GI upset, headache, dizziness, and insomnia
  • MOA: MITOTIC SPINDLE poison (binds with the tubulin dimes required for microtubule assembly)
A

GRISEOFULVIN

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83
Q

ANTIFUNGAL ANTIBIOTICS

GRISEOFULVIN:
was isolated from

A

Penicillum griseofulvum

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84
Q

ANTIFUNGAL ANTIBIOTICS

GRISEOFULVIN:
dispensing notes

A

should be taken with high fat meal
shuld be bought for 1 month

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85
Q

ANTIFUNGAL ANTIBIOTICS

GRISEOFULVIN:
MOA

A

mitotic spindle poison

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86
Q
  • result of RANDOM SCREENING
  • MOA: interfere early step of ERGOSTEROL BIOSYNTHESIS; inhibition of SQUALENE EPOXIDASE (increase squalene concentration destabilizes the fungal cell membrane)
  • ACTIVITY: -static against pathogenic yeast and -cidal against dermatophytes and filamentous fungi
A

ALLYLAMINES & RELATED COMPOUNDS

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87
Q

ALLYLAMINES AND RELATED COMPOUNDS

result of ____

A

random screening

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88
Q

ALLYLAMINES AND RELATED COMPOUNDS

MOA:
interfere with the ____

A

early step of ERGOSTEROL biosynthesis

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89
Q

ALLYLAMINES AND RELATED COMPOUNDS

MOA:
inhibition of ____

A

squalene epoxidase

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90
Q

ALLYLAMINES AND RELATED COMPOUNDS

ACTIVITY:
____ against pathogenic yeast

A

-static

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91
Q

ALLYLAMINES AND RELATED COMPOUNDS

ACTIVITY:
____ against dermatophytes and filamentous fungi

A

-cidal

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92
Q

ALLYLAMINES AND RELATED COMPOUNDS

  • 1% cream/gel is used topically against ringworm, athlete’s foot and jock itch
A

NAFTIFINE HCl

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93
Q

ALLYLAMINES AND RELATED COMPOUNDS

use is same with Naftifine but active against ONYCHOMYCOSIS

A

Terbinafine HCl

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94
Q

ALLYLAMINES AND RELATED COMPOUNDS

which is more active/effective:
Terbinafine or Naftifine

A

Terbinafine > Naftifine

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95
Q

ALLYLAMINES AND RELATED COMPOUNDS

THIOESTER of β-naphthol that inhibits squalene epoxidasase (-cidal)

A

Tolnaftate

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96
Q

TISSUE REACTIONS OF FUNGAL DISEASE

  • targets nucelic acid
  • DNA synthesis inhibitor
A

FLUCYTOSINE

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97
Q

TISSUE REACTIONS OF FUNGAL DISEASE

target of AZOLES

A

14-α-demethylase

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98
Q

TISSUE REACTIONS OF FUNGAL DISEASE

toxic to the cell

A

Lanosterol

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99
Q

primary component of fungus

A

ergosterol

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100
Q

TISSUE REACTIONS OF FUNGAL DISEASE

  • target D14 reductases
  • D7-8 isomerases
A

Morpholines

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101
Q

TRIAZOLE NUCLEUS

substitution must be in what position ONLY

A

N

other positions will lose its activity

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102
Q

TRIAZOLE NUCLEUS

IMIdazole

A

X = C

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103
Q

TRIAZOLE NUCLEUS

TRIazole

A

X = N

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104
Q

TRIAZOLE NUCLEUS

has better activity

A

TRIazole

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105
Q

TRIAZOLE NUCLEUS

  • F, Cl
  • cause phototoxicity
  • increase activity & lipophilicity
A

ELECTRON WITHDRAWING GROUP

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106
Q

MOA OF AZOLES

inhibition of ____ that catalyzes 14-α-demethylation of LANOSTEROL to ERGOSTEROL, accumulation of 14-methylated sterols cause permeability disturbance

A

CYP450

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107
Q
  • MOST TOXIC sterol
  • leads to membrane stress
A

ignosterol

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108
Q

MOA OF AZOLES

CYP450 catalyzes 14-α-demethylation of LANOSTEROL to ____

A

ergosterol

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109
Q

AZOLE ANTIFUNGALS

  • broad-spectrum
  • SE: severe GI disturbances
  • MOA: interferes with AMINO ACID TRANSPORT into the organism by an action of cell membrane
A

CLOTRIMAZOLE

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110
Q

AZOLE ANTIFUNGALS

1% cream for the topical tx of local tinea infections & cutaneous candidiasis

A

Econazole nitrate

111
Q

AZOLE ANTIFUNGALS

EXTREMELY broad spectrum, active against C. albicans

A

Butoconazole nitrate

112
Q

AZOLE ANTIFUNGALS

1% cream is useful for jock itch, athlete’s foot, and ringworm

A

Sulconazole nitrate

113
Q

AZOLE ANTIFUNGALS

treatment for tinea pedis, tinea corporis, and tinea capitis

A

Oxicanzole nitrate

114
Q

AZOLE ANTIFUNGALS

  • useful for vulvovaginal candidiasis
  • more effective against Torulopsis glabrata
A

Tioconazole

115
Q

AZOLE ANTIFUNGALS

EXCLUSIVELY for the CONTROL of vulvovaginal monolialiasis

A

Terconazole

116
Q

AZOLE ANTIFUNGALS

  • tx for systemic fungal infection and chronic mucocutaneous candidiasis
  • AE: Thrombophlebitis, pruritus, fever, GI upset
A

Miconazole nitrate

117
Q

AZOLE ANTIFUNGALS

  • 1st ORALLY active BROAD SPECTRUM (Imidazole)
  • HEPATOTOXIC
  • highly PROTEIN BOUND
A

KETOCONAZOLE

118
Q

AZOLE ANTIFUNGALS

KETOCONAZOLE:
dispensing note

A

should be taken with EMPTY stomach

119
Q

AZOLE ANTIFUNGALS

KETOCONAZOLE:
side effects

A

gynecomastia

120
Q

AZOLE ANTIFUNGALS

  • contains 2 triazole moieties
  • orally active, broad spectrum
  • mini capsules inside a capsule
  • ACIDIC environment requires for optimum absorption
  • food enhances absorption
  • 99% protein bound, increase plasma concentration of anti-histamines
  • important alternative to Ketoconazole
A

Itraconazole

121
Q

ANTI-HISTAMINES:
sedating

122
Q

ANTI-HISTAMINES:
non-drowse

123
Q

AZOLE ANTIFUNGALS

  • the ONLY WATER SOLUBLE azole with broad spectrum of activity
  • excellent ORAL BIOAVAILABILITY
  • plasma protein binding is <10%
A

Fluconazole

124
Q

AZOLE ANTIFUNGALS

  • target market: FEMALE
  • for candidiasis
A

Flunzela
(Fluconazole)

125
Q

AZOLE ANTIFUNGALS

FLUCONAZOLE:
plasma protein binding

126
Q

AZOLE ANTIFUNGALS

ITRACONAZOLE:
____% protein bound

127
Q

AZOLE ANTIFUNGALS

  • NEWEST in the market
  • currently in phase II
A

Posoconazole

128
Q
  • a CYCLIC DEPSIPEPTIDE produced by AUREOBASIDIUM PULLULANS
  • MOA: act as a tight binding noncompetitive inhibitor of the enzyme inositol phosphorylceramide synthase
A

AUREOBASIDINS

129
Q

AUREOBASIDINS

a cyclic depsipeptide produced by ____

A

Aureobasidium pullulans

130
Q

AUREOBASIDINS

MOA:
act as ____ of the enzyme inositol phosphorylceramide synthase

A

tight binding noncompetitive inhibitor

131
Q

AUREOBASIDINS

MOA:
act as tight binding noncompetitive inhibitor of the enzyme ____

A

inositol phosphorylceramide synthase

132
Q

AUREOBASIDINS

essential for FUNGAL SPHINGOLIPID BIOSYNTHESIS

A

IPC synthase

133
Q
  • obtained by MOLECULAR MODIFICATION on the basis of model compounds that is used as antibacterial agent for local, systemic and/or urinary tract infections
A

SYNTHETIC ANTIBACTERIAL AGENT

134
Q

SYNTHETIC ANTIBACTERIAL AGENT

obtained by ____

A

molecular modification

135
Q

SYNTHETIC ANTIBACTERIAL AGENT

inhibits DNA GYRASE

A

quinolones

136
Q

patterned after NALIDIXIC ACID which is a NAPHTHYRIDINE

A

quinolones

137
Q

QUINOLONES

patterned after ____ which is a ____

A

nalidixic acid, naphthyridine

138
Q

QUINOLONES | STRUCTURE

enhances absorption

A

cyclopropyl

139
Q

QUINOLONES

  • HIGHLY protein boound
  • mostly used for UTIs
A

FIRST generation quinolones

140
Q

QUINOLONES

problem of FIRST generation quinolones

A

highly protein bound

141
Q

QUINOLONES

  • 2nd to 4th generation
  • MODIFIED 1st generation quinolones
  • NOT highly protein bound – HIGHER BIOAVAILABILITY
  • wide distribution to urine and other tissue; limited CSF penetration
A

FLUOROQUINOLONES

142
Q

AZOLE ANTIFUNGALS

FLUCONAZOLE:
agent of choice

A

cryptococcal meningitis

143
Q

AZOLE ANTIFUNGALS

FLUCONAZOLE:
DOC

A

fungal meningitis

144
Q
  • LARGE cyclic peptides linked to a long fatty acid
  • MOA: inhibits the synthesis of 1,3-β-d-glucan synthase resulting to the disruption of the fungal cell wall and cell death
A

ECHINOCANADINS

145
Q

QUINOLONES

MOA

A

DNA gyrase inhibition

146
Q

QUINOLONES

MECHANISM OF RESISTANCE:
* by altering the target enzymes namely DNA gyrase and topoisomerase IV

A

CHROMOSOMAL

148
Q

QUINOLONES

MECHANISM OF RESISTANCE:
CHROMOSOMAL target enzymes

A

DNA gyrase
topoisomerase IV

149
Q

QUINOLONES

MECHANISM OF RESISTANCE:
* seen in some K. pneumoniae & E. coli

150
Q

QUINOLONES

MECHANISM OF RESISTANCE:
* mutations in ____ of gram negative

A

outer membrane porins

151
Q

QUINOLONES

circular extrachromosomal structure

152
Q

SAR OF QUINOLONES

PHOTOTOXICITY

153
Q

SAR OF QUINOLONES

MOST PHOTOTOXIC

A

halogen in X8

154
Q

SAR OF QUINOLONES

drug that has halogen in X8

A

Lomefloxacin

take once daily

155
Q

SAR OF QUINOLONES

LOWEST phototoxicity

A

AMINO GROUP in R5 and X8

156
Q

SAR OF QUINOLONES

  • MORE FAVORABLE for DNA gyrase
  • weakly phototoxic
A

methoxy in R5

157
Q

SAR OF QUINOLONES

safest na nakakabit sa R5 and X8

158
Q

SAR OF QUINOLONES

replacement / modification

159
Q

SAR OF QUINOLONES

drug interaction

A

complexation reaction w/ antacid & iron supplements

160
Q

QUINOLONES | SPECTRUM OF ACTIVITY

largely confined to ____

162
Q
  • useful for PENICILLIN resistant gonococci
  • METHICILLIN resistant Staph. aureus & AMINOGLYCOSIDE resistant P. aeuruginosa
A

QUINOLONES

163
Q

QUINOLONES

DRUG INTERACTION:
DECREASE absorption of ____, ____, and ____ antacids

A

Al, Mg, Ca

164
Q

QUINOLONES

DRUG INTERACTION:
____ inhibition

165
Q

QUINOLONES

ADVERSE EFFECTS:
GI

166
Q

QUINOLONES

ADVERSE EFFECTS:
cardiovascular

A

torsades de pointes

167
Q

QUINOLONES

ADVERSE EFFECTS:
muskoskeletal

A

rupture tendon

168
Q

QUINOLONES

ADVERSE EFFECTS:
neurologic

A

polyneuropathy

169
Q

QUINOLONES

Gram - but NOT pseudomonas species

170
Q

QUINOLONES

GEN:
Nalidixic acid
Cinoxacin

171
Q

QUINOLONES

Gram - (including pseudomonas, some Gram + and some atypical MO

172
Q

QUINOLONES

GEN:
Norfloxacin
Ciprofloxacin
Enoxacin
Ofloxacin

173
Q

QUINOLONES

same as 2nd gen with extended G+ and atypical coverage

174
Q

QUINOLONES

GEN:
Levofloxacin
Sparfloxacin
Moxifloxacin
Gemifloxacin

175
Q

QUINOLONES

same with 3rd gen with broad ANAEROBIC coverage

176
Q

QUINOLONES

GEN:
Trovafloxacin

177
Q

QUINOLONES

  • widely distributed in the body (CSF)
  • food DELAYS absorption
  • binds divalent cation (decrease absorption)
  • increase effect of warfarin
  • AOC for GASTROENTERITIS caused by G- BACILLI
A

CIPROFLOXACIN

178
Q

QUINOLONES

CIPROFLOXACIN:
AOC for ____

A

gastroenteritis caused by G- bacilli

179
Q

QUINOLONES

CIPROFLOXACIN:
with CEFTRIAXONE

A

disseminated gonorrhea

180
Q

QUINOLONES

CIPROFLOXACIN:
with DOXYCYCLINE

A

gonococal urethritis

181
Q

QUINOLONES

CIPROFLOXACIN:
binds ____

A

divalent cation

182
Q

QUINOLONES

CIPROFLOXACIN:
increase effect of ___

183
Q

QUINOLONES

CIPROFLOXACIN:
targets ____

A

DNA gyrase

184
Q

QUINOLONES

CIPROFLOXACIN:
enhance activity with pseudomonas

A

piprazinyl

185
Q

QUINOLONES

  • resembles ciprofloxacin in antibacterial spectrum and potency
  • increased concentration in CSF
  • SUPERIOR ORAL ABSORPTION and BIOAVAILABILITY
  • food delays absorption
186
Q

QUINOLONES

  • SPECTRUM: G-, G+, Legionella, atypical respiratory, M. tuberculosis
  • ADR: blood glucose disturbances in DM patients
A

LEVOFLOXACIN

187
Q

QUINOLONES

LEVOFLOXACIN:
relationship of generations with side effects

A

increase gen = increase SE

188
Q

QUINOLONES

  • saftey and efficacy NOT established in patients <18 y/o
  • SPECTRUM: G-, atypical respiratory, M. tuberculosis, G- anaerobes
A

MOXIFLOXACIN

189
Q

QUINOLONES

  • ONLY quinolone that is taken OD (eye)
  • MOST PHOTOTOXIC
A

LOMEFLOXACIN

190
Q

QUINOLONES

  • HIGHER POTENCY against G+ bacteria
  • skin and soft tissue infection in LRT1 and PID
  • bacterial gastroenteritis and cholecystitis
A

SPARFLOXACIN

191
Q

QUINOLONES

CLINICAL USES

A

UTI
Gonorrhea
Diarrhea
Respiratory infection
Osteomyelitis

192
Q
  • first NITROHETEROCYCLIC compound to be introduced into chemotherapy
  • derivatives of 5-nitro-2-furaldehyde, formed on reaction with the appropriate hydrazine or amine derivatiVe
  • AE: mutagenic and carcinogenic
A

NITROFURANS

5 membered ring

193
Q

NITROFURANS

SAR:
anti-microbial property is present only when the NITRO GROUP is in the ____ position

A

5-position

195
Q

NITROFURANS

MOA:
____ of the nitro group coupled with the formation of free radicals which cause damage to ribosomal proteins especially DNA, causing inhibition of DNA, RNA, protein, and cell wall synthesis

A

reduction
(nitrofuran reductase)

196
Q

NITROFURANS

MOA:
reduction (nitrofuran reductase) of the nitro group coupled with the ____ which cause damage to ribosomal proteins especially DNA, causing inhibition of DNA, RNA, protein, and cell wall synthesis

A

formation of free radicals

197
Q

NITROFURANS

MOA:
reeduction (nitrofuran reeductase) of the nitro group coupled with the formation of free radicals which cause damage to ____ especially DNA, causing inhibition of DNA, RNA, protein, and cell wall synthesis

A

ribosomal proteins

198
Q

NITROFURAN

MOA:
overall effect

A

inhibition of bacterial growth or cell death

199
Q

NITROFURANS

topically in the tx of BURNS and prevent bacterial infection associated with SKIN GRAFTS

A

NITROFURAZONE

200
Q

NITROFURANS

recommended for the ORAL TREATMENT of bacterial or protozoal DIARRHEA

A

FURAZOLIDONE

201
Q

NITROFURANS

  • sutiable for oral use in the treatment of UTI
  • microcrystalline form improve GI tolerance without interfering oral absorption
A

NITROFURANTOIN

202
Q

NITROFURANS

  • prepared by evaporating a solution of FORMALDEHYDE and STRONG AMMONIA water to dryness
  • prodrug
  • promote the formation of formaldehyde
A

METHENAMINE

203
Q

METHENAMINE

MOA:
antibacterial activity depends on ____ and enhanced by acidifying with sodium biphosphate or ammonium chloride

A

liberation of formaldehyde

204
Q

METHENAMINE

MOA:
antibacterial activity depends on liberation of formaldehyde and enhanced by acidifying with ____ or ____

A

sodium biphosphate
ammonium chloride

205
Q

METHENAMINE

INEFFECTIVE for ____ containing microorganism

A

UREASE

urease - ammonia - causes urine to be BASIC

206
Q
  • alleviate pain and discomfort caused by UTI
  • soluble and concentrates in urine
  • combined with UTI agents
A

URINARY ANALGESIC

207
Q

URINARY ANALGESIC

  • the ONLY URINARY ANALGESIC
  • formerly used as urinary antiseptic
  • local analgesic effect on the mucosa of the urinary tract
  • used in combination
  • may tint the urine red-orange
  • the stain is removed by sodium dithionite solution
A

PHENAZOPYRIDINE HCl
(pyridium)

208
Q

URINARY ANALGESIC

PHENAZOPYRIDINE HCl:
may tint the urine ____

A

red orange

209
Q

URINARY ANALGESIC

PHENAZOPYRIDINE HCl:
the stain is removed by

A

sodium dithionite solution

210
Q
  • a gram POSITIVE acid FAST bacillus
  • live inside the macrophages and lysosomes
  • causative agent for tuberculosis
A

Mycobacterium tuberculosis

211
Q

ANTI-TUBERCULAR AGENTS

MANAGEMENT

A

shotgun therapy

use of several drugs simultaenously

212
Q

ANTI-TUBERCULAR AGENTS

FIRST line of therapy combination

A

RIPE
Rifampin, Isoniazid, Pyrazinamide, Ethambutol

213
Q

ANTI-TUBERCULAR AGENTS

FIRST line single agent

A

streptomycin

214
Q

ANTI-TUBERCULAR AGENTS

BAN for Rifampicin

215
Q

ANTI-TUBERCULAR AGENTS

SLOW acetylator

216
Q

ANTI-TUBERCULAR AGENTS

INVESTIGATIONAL DRUG:
TMC207 inhibits

A

ATP synthase = no energy = die

217
Q

ANTI-TUBERCULAR AGENTS

AIM OF THERAPY:
treatment must be for ____ because response is SLOW

A

longer period, 6 months

218
Q

ANTI-TUBERCULAR AGENTS

best drug for ACTIVELY MULTIPLYING bacteria

219
Q

ANTI-TUBERCULAR AGENTS

SEMI-DORMANT bacilli that metabolize SLOWLY should be treated with

A

Pyrazinamide
Rifampicin

220
Q

ANTI-TUBERCULAR AGENTS

why COMBINATION therapy is given

3

A
  • broaden the spectrum
  • reduce toxicity
  • prevent resistance
221
Q

ANTI-TUBERCULAR AGENTS

1st line drugs

222
Q

ANTI-TUBERCULAR AGENTS

drugs for the FIRST 2 MONTHS

223
Q

ANTI-TUBERCULAR AGENTS

drugs for the NEXT 4 MONTHS

224
Q

ANTI-TUBERCULAR AGENTS

why is ETHAMBUTOL not given for the next 4 months

A

AE: color blindness

225
Q

ANTI-TUBERCULAR AGENTS

PROPHYLACTIC DOSE:
Isoniazid

226
Q

ANTI-TUBERCULAR AGENTS

PROPHYLACTIC DOSE:
Isoniazid for IMMUNOCOMPROMISED

A

900mg twice weekly for 6-12 months

227
Q

ANTI-TUBERCULAR AGENTS

PROPHYLACTIC DOSE:
Isoniazid consideration

A

should not have ACTIVE TB case

228
Q

ANTI-TUBERCULAR AGENTS

  • alternative
  • prophylaxis for the patients who are unable to take isoniazid
  • have a close contact with a case of active TB caused by an isoniazid resistant Rifampicin-susceptible strain
A

RIFAMPICIN

229
Q

ANTI-TUBERCULAR AGENTS

RIFAMPICIN can cause what color to bodily fluids

A

red orange

230
Q

ANTI-TUBERCULAR AGENTS

  • SAFEST, MOST POTENT and EFFECTIVE against ALL FORMS of M. tuberculosis
  • Bactericidal
  • readily absorbed from the GIT
  • does NOT bind with the plasma protein
  • extensive ddistribution in the tissue and bodily fluids
231
Q

ANTI-TUBERCULAR AGENTS

ISONIAZID:
toxic effects

A

Insomnia
Neuropathy (peripheral)
Hepatotoxicity

INH

232
Q

ANTI-TUBERCULAR AGENTS

ISONIAZID:
metabolism and excretion

A

acetylation, urine

234
Q

ANTI-TUBERCULAR AGENTS

ISONIAZID:
management of the TOXIC EFFECT: neuropathy (peripheral)

A

PYRIDOXINE

235
Q

ANTI-TUBERCULAR AGENTS

responsible for the synthesis of MYCOLIC ACID

A

FAS-1

Fatty acid synthase 1

236
Q

ANTI-TUBERCULAR AGENTS

  • SECONDARY DRUG for the treatment of TB
  • used in the txt of INH resistant TB
  • related to Ethambutol
  • AE: GI intolerance, visual disturbances, hepatotoxicity
A

ETHIONAMIDE

237
Q

ANTI-TUBERCULAR AGENTS

  • FIRST liine agent in SHORT TERM TB
  • effective in LOW pH environment
  • penetrate inflammed meninges
  • synthetic analogue of NICOTINAMIDE
  • can kill TB bacilli in acidic pH up to 5.5
  • cannot kill TB bacilli in the blood because of high pH
A

PYRAZINAMIDE

238
Q

ANTI-TUBERCULAR AGENTS

PYRAZINAMIDE:
effective in ____ environment

239
Q

ANTI-TUBERCULAR AGENTS

PYRAZINAMIDE:
can kill TB bacilli in acidic pH up to ____

240
Q

ANTI-TUBERCULAR AGENTS

PYRAZINAMIDE:
cannot kill TB bacilli in the ____ because of high pH

241
Q

ANTI-TUBERCULAR AGENTS

  • associated with gout
  • hyperuricemia effect
A

XANTHINE OXIDASE

242
Q

ANTI-TUBERCULAR AGENTS

PYRAZINAMIDE MOA:
drug is converted into ____ by pyrazinamidase in M. tuberculosis and kills the bacteria, the target and the MOA is unknown

A

pyrazinoic acid

243
Q

ANTI-TUBERCULAR AGENTS

PYRAZINAMIDE MOA:
drug is converted into pyrazinoic acid by ____ in M. tuberculosis and kills the bacteria, the target and the MOA is unknown

A

pyrazinamidase

244
Q

ANTI-TUBERCULAR AGENTS

PYRAZINAMIDE:
side effect

A

interfere uric acid secretion

245
Q

ANTI-TUBERCULAR AGENTS

ETHAMBUTOL:
responsible for the synthesis of arabinogalactan

246
Q

ANTI-TUBERCULAR AGENTS

ETHAMBUTOL:
target

247
Q

ANTI-TUBERCULAR AGENTS

  • active against DIVIDING MYOBACTERIA
  • stereospecific; in combination with other antitubercular drugs
  • MOA:
    • inhibits the synthsis of ARABINOGALACTAN which is an essential component of myobacterial cell wall
    • inhibition of the incorporation of mycolic acid into the cell wall of the microorganisms
A

ETHAMBUTOL

248
Q

ANTI-TUBERCULAR AGENTS

an essential component of the myobacterial cell wall

A

arabino-galactan

249
Q

ANTI-TUBERCULAR AGENTS

ETHAMBUTOL MOA:
inhibits the synthesis of ____ which is an essential component of myobacterial cell wall

A

arabino-galactan

250
Q

ANTI-TUBERCULAR AGENTS

ETHAMBUTOL MOA:
inhibition of the ____ into the cell wall of the MO

A

incorporation of mycolic acid

251
Q

ANTI-TUBERCULAR AGENTS

ETHAMBUTOL ADVERSE EFFECT:
* most common
* LOSS of visual acuity

A

RETINOBULBAR OPTIC NEURITIS

252
Q

ANTI-TUBERCULAR AGENTS

should NOT be given to CHILDREN

A

ETHAMBUTOL

253
Q

ANTI-TUBERCULAR AGENTS

  • second AGENT for TB
  • MOA: prevents incorporation of PABA in dehydrofolic acid molecule
A

AMINOSALICYLIC ACID & AMINOSALICYLATE SODIUM

254
Q

ANTI-TUBERCULAR AGENTS

AMINOSALICYLIC ACID & AMINOSALICYLATE SODIUM MOA:
prevents incorporation of ____ in dehydrofolic acid molecule

255
Q

ANTI-TUBERCULAR AGENTS

  • basic RED DYE that exerts a SLOW bactericidal effects on M. leprae
  • anti-inflammatory and immune-modulating effects
A

CLOFAZIMINE

256
Q

ANTI-TUBERCULAR AGENTS

classification of RIFAMPIN & STREPTOMYCIN

A

antitubercular - antibiotic

257
Q

ANTI-TUBERCULAR AGENTS

  • a complex semisynthetic derivative of Rifamycin produced by SCHIDMTEA MEDITERRANEA
  • MOST ACTIVE FIRST LINE agent against TB
  • powerful INDUCER of CYP450
  • when taken with paractemaol, APAP is inactivated
  • can tint the urine, stool, saliva, tears, skin - RED-ORANGE
  • AE: hepatotoxicity
  • HIGHLY protein bound
  • HIGHLY lipophilic
  • meetabolized by de-acetylation
A

RIFAMPIN
(RIFAMPICIN)

258
Q

ANTI-TUBERCULAR AGENTS

RIFAMPIN:
produced by ____

A

Schmidtea mediterranea

259
Q

ANTI-TUBERCULAR AGENTS

RIFAMPINl:
powerful ____ of CYP450

260
Q

ANTI-TUBERCULAR AGENTS

RIFAMPIN:
when taken with ____, APAP is inactivated

A

paracetamol

261
Q

ANTI-TUBERCULAR AGENTS

RIFAMPIN:
can tint the urine, stool, tears, saliva, skin ____

A

RED ORANGE

262
Q

ANTI-TUBERCULAR AGENTS

RIFAMPIN:
adverse effect

A

hepatotoxicity

263
Q

ANTI-TUBERCULAR AGENTS

RIFAMPIN:
metabolized by ____

A

de-acetylation

264
Q

ANTI-TUBERCULAR AGENTS

RIFAMPIN:
mainly excreted by the ____ and ____

A

bile and feces

265
Q

ANTI-TUBERCULAR AGENTS

RIFAMPIN MOA:
inhibits ____ which is responsible for RNA synthesis

A

DNA dependent RNA polymerase

266
Q

ANTI-TUBERCULAR AGENTS

prophylaxis of DISSEMINATED MAC in AIDS patients

267
Q

ANTI-TUBERCULAR AGENTS

  • rarely used as antibiotic due to toxic effects
  • isolated from Strep
  • recommended for patients who failed to respond to their anti-TB drugs or resistant TB
A

CYCLOSERINE

268
Q

ANTI-TUBERCULAR AGENTS

CYCLOSERINE MOA:
prevents the synthesis of ____ in the formation of bacterial cell walls

A

cross linking peptide

269
Q

ANTI-TUBERCULAR AGENTS

  • aminoglycoside
  • strongly basic cyclic peptide isolated from Strep. capreolus
  • SECOND LINE agent
  • alternative to STREPTOMYCIN
A

STERILE CAPREOMYCIN SULFATE

270
Q

ANTI-TUBERCULAR AGENTS

alternative to STREPTOMYCIN

A

sterile capreomycin sulfate

271
Q

ANTI-TUBERCULAR AGENTS

ADVERSE EFFECT:
Isoniazid

A

peripheral neuropathy

272
Q

ANTI-TUBERCULAR AGENTS

ADVERSE EFFECT:
Rifampicin

A

Cholestatic jaundice + renal toxicity + flu like syndrome

273
Q

ANTI-TUBERCULAR AGENTS

ADVERSE EFFECT:
Pyrazinamide

A

hepatotoxicity + hyperuricemia

274
Q

ANTI-TUBERCULAR AGENTS

ADVERSE EFFECT:
Ethambutol

A

retinobulbar optic neuritis

PMOC lec (13 decks)

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