ANTI-FUNGAL - ANTI-TUBERCULOSIS Flashcards
1
Q
are caused by microscopic organisms that can invade EPITHELIAL TISSUE caused by yeast, molds, etc.
A
FUNGAL INFECTIONS
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
3
Q
FUNGAL INFECTIONS CLASSIFICATION
TRANSMITTED from one host to another
A
DEEP-SEATED MYCOSES
4
Q
FUNGAL INFECTIONS CLASSIFICATION
- are caused by the INHALATION of SPORES affecting deeper tissues and organs and cause fungal pneumonia
A
SYSTEMIC INFECTIONS
5
Q
can FUNGAL PNEUMONIA be transmitted from human to human?
A
NO
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
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)
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
9
Q
- LARGEST ORGAN
- directly exposed to external environment
A
SKIN
10
Q
FORMIDABLE BARRIER to drug penetration
A
skin
11
Q
all FATTY ACID and FATTY ACID DERIVATIVES (salts) have antifungal properties due to ____ (part of innate immune system)
A
SEBUM FRACTION
12
Q
FATTY ACID & DERIVATIVES
what happens to SOLUBILTY if the MW increases
A
solubility decreases
INVERSE RELATIONSHIP
13
Q
FATTY ACID & DERIVATIVES
____ fatty acid have the advantage of having LOWER VOLATILITY
A
HIGHER MW
14
Q
FATTY ACID & DERIVATIVES
SALT form are ____
A
fungicidal
15
Q
TOPICAL ANTIFUNGAL AGENTS
- NON-IRRITATING and NON-TOXIC
- present in PERSPIRATION or SWEAT
- around 0.01% is fungicidal
A
PROPIONIC ACID
16
Q
TOPICAL ANTIFUNGAL AGENTS
PROPIONIC ACID:
how many % is fungicidal
A
0.01%
17
Q
TOPICAL ANTIFUNGAL AGENTS
used as fungicide on ADHESIVE TAPES
A
ZINC PROPRIONATE
18
Q
TOPICAL ANTIFUNGAL AGENTS
CREAM colored granules used topically to treat SUPERIFICAL DERMATOMYCOSES
A
SODIUM CAPRYLATE
19
Q
TOPICAL ANTIFUNGAL AGENTS
FINE WHITE powder and a topical fungicide and UNSTABLE to MOISTURE
A
ZINC CAPRYLATE
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
21
Q
TOPICAL ANTIFUNGAL AGENTS
UNDECYLENIC ACID:
is obtained from the ____ of CASTOR OIL (ricinoleic acid)
A
detructive distillation
22
Q
TOPICAL ANTIFUNGAL AGENTS
UNDECYLENIC ACID:
is obtained from the destructive distillation of ____
A
CASTOR OIL
23
Q
TOPICAL ANTIFUNGAL AGENTS
UNDECYLENIC ACID:
should NEVER be applied on
A
mucous membrane
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
25
# **TOPICAL ANTIFUNGAL AGENTS**
TRIACETIN:
release ____ upon **hydrolysis**
acetic acid
26
# **TOPICAL ANTIFUNGAL AGENTS**
TRIACETIN:
release **acetic acid** upon ____
hydrolysis
27
# **TOPICAL ANTIFUNGAL AGENTS**
* **CANNOT** be used **ALONE**
* anti**FUNGAL** and keratolytic
SALICYLIC ACID
28
# **TOPICAL ANTIFUNGAL AGENTS**
anti**SEPTIC** and keratolytic
RESORCINOL
29
# **TOPICAL ANTIFUNGAL AGENTS**
* **CANNOT** be used **ALONE**
* **ONLY** anti**fungal** that **CANNOT penetrate** the SKIN
* should be used **IN COMBINATION** to **provide therapeutic effect**
BENZOIC ACID
30
# **TOPICAL ANTIFUNGAL AGENTS**
MOA: **interfere** with **CELL MEMBRANE INTEGRITY** and function in **susceptible fungi**
Phenol and their derivatives
31
# **TOPICAL ANTIFUNGAL AGENTS**
**WHITE** to **PALE YELLOW** and **PHOTOSENSITIVE** 1% cream for the treatment superifical tine infection
HALOPROGIN
32
# **TOPICAL ANTIFUNGAL AGENTS**
* **SPONGY**, **LIGHT-SENSITIVE**, **YELLOWISH WHITE** powder
* substitute for **IODOFORM**
CLIOQUINOL
33
# **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**
CICLOPIROX OLAMINE
34
**nail bed** fungal infections
onychomycosis
35
# **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**
FLUCYTOSINE
5-FC
36
# **NUCLEOSIDE ANTIFUNGAL AGENTS**
FLUCYTOSINE:
incorporation ____ to fungal **RNA** following **selective deamination** of **5-fluouracil**
FLUORINATED PYRIMIDINE
37
# **NUCLEOSIDE ANTIFUNGAL AGENTS**
FLUCYTOSINE:
targets ____
nitrogenous bases
38
# **NUCLEOSIDE ANTIFUNGAL AGENTS**
* anti**METABOLITE**
* inhibits **THYMIDYLATE SYNTHETASE** and thus **DNA synthesis**
5-fluouracil
5-FU
39
# **NUCLEOSIDE ANTIFUNGAL AGENTS**
5-FLUOURACIL:
inhibits ____
thymidylate synthetase & DNA synthesis
40
# **NUCLEOSIDE ANTIFUNGAL AGENTS**
MOA of **5-FU**
* inhibition of DNA synthesis
* inhibition of PROTEIN synthesis
41
# **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
POLYENES
42
# **ANTIFUNGAL ANTIBIOTICS**
**LARGEST class** of antifungal antibiotics
POLYENES
43
# **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
POLYENES
44
# **ANTIFUNGAL ANTIBIOTICS**
**POLYENES** STRUCTURAL REQUIREMENT:
LACTONE RING: **NATAMYCIN**
26C
45
# **ANTIFUNGAL ANTIBIOTICS**
**POLYENES** STRUCTURAL REQUIREMENT:
LACTONE RING: **AMPHOTERICIN B** and **NYSTATIN**
38C
46
# **ANTIFUNGAL ANTIBIOTICS**
**POLYENE** STRUCTURAL REQUIREMENT:
series of ____ on the **acid portion** of the ring
OH groups
47
# **ANTIFUNGAL ANTIBIOTICS**
**POLYENE** STRUCTURAL REQUIREMENT:
**glycosidically linked** deoxyaminohexose sugar ____
MYCOSAMINE SUGAR
48
# **ANTIFUNGAL ANTIBIOTICS**
**POLEYENE** STRUCTURAL REQUIREMENT:
CONJUGATED DOUBLE BONDS: **NATAMYCIN**
PENTAENE
49
# **ANTIFUNGAL ANTIBIOTICS**
**POLEYENE** STRUCTURAL REQUIREMENT:
CONJUGATED DOUBLE BONDS: **NYSTATIN**
HEXAENE
50
# **ANTIFUNGAL ANTIBIOTICS**
**POLEYENE** STRUCTURAL REQUIREMENT:
CONJUGATED DOUBLE BONDS: **AMPHOTERICIN B**
HEPTAENE
51
can you consider **ALL** anti**bacterials** as anti**biotics**
NO, not all anibacterials are antibiotics
52
to be considered as anti**biotic**, what should be the requirement
it should come from a **NATURAL SOURCE**
53
# **ANTIFUNGAL ANTIBIOTICS**
POLYENES:
* **LAST line** for systemic fungal infections
* **NEPHROTOXIC**
AMPHOTERICIN B
54
# **ANTIFUNGAL ANTIBIOTICS**
use of POLYENES is **LIMITED** because of
| (3)
toxicity
low water solubility
poor chemical stability
55
# **ANTIFUNGAL ANTIBIOTICS**
POLYENES:
**LOW** water SOLUBILITY is due to
LARGE LACTONE RING
56
# **ANTIFUNGAL ANTIBIOTICS**
POLYENE:
**POOR** CHEMICAL stability: what is **EASILY HYDROLYZED**
AMINO SUGAR
57
# **ANTIFUNGAL ANTIBIOTICS**
MOA OF **POLYENES**:
binds with ____ in **cell membrane** as **"FALSE MEMBRANE"** component
STEROLS
58
# **ANTIFUNGAL ANTIBIOTICS**
MOA OF **POLYENES**:
____ at **LOW** concentration
-static
59
# **ANTIFUNGAL ANTIBIOTICS**
MOA OF **POLYENES**:
____ at **HIGH** concentration
-cidal
60
# **ANTIFUNGAL ANTIBIOTICS**
MOA OF **POLYENES**:
can form a **pore** in the membrane, creating a ____ resulting in the **LOSS of intracellular potassium ions**
transmembrane ion-channel
61
____ found in **cell membranes** of **FUNGI**
ergosterol
62
# **ANTIFUNGAL ANTIBIOTICS**
main MOA of **POLYENES**
cell membrane inhibitor
63
# **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**
AMPHOTERICIN B
64
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
isolated in ____
1956
65
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
isolated by ____
GOLD et al
66
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
isolated from ___
Streptomyces nodosus
67
# **ANTIFUNGAL ANTIBIOTICS**
AMPHOTERIC SUBSTANCE
polar & nonpolar
68
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
____ form is an **aqueous colloidal dispersion**
parenteral form
(except IM)
69
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
PARENTERAL form (except IM) is **stabilized** by ____
sodium deoxycholate
70
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
NSS is not used because ???
it disrupts colloidal dispersion that leads to unstability of solution
71
**antibiotics** are ____
secondary metabolites
72
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
____ on the cell membrane of fungi and some protozoa due to the **affinity** for **ERGOSTEROL** than cholesterol
SELECTIVE ACTION
73
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
SELECTIVE ACTION on the **cell membrane** of fungi and some protozoa due to the **affinity** for ____ than cholesterol
ERGOSTEROL
74
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
LIMITATIONS
* nephrotoxic
* toxic reactions
* hypolakemia, anemia
* pain at the injection site & thrombophlebitis
* hemolysis
* intrathecal route: neurotoxicity
75
# **ANTIFUNGAL ANTIBIOTICS**
**AMPHOTERICIN B**:
mode of RESISTANCE
LOW COUNT of ergosterol
76
# **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)
NYSTATIN
77
# **ANTIFUNGAL ANTIBIOTICS**
**NYSTATIN**:
patient counseling
swish & swallow
78
# **ANTIFUNGAL ANTIBIOTICS**
**NYSTATIN**:
isolated by ____
Hazen and Brown
79
# **ANTIFUNGAL ANTIBIOTICS**
**NYSTATIN**:
isolated from ____
Streptomyces noursei
80
# **ANTIFUNGAL ANTIBIOTICS**
**NYSTATIN**:
the **ring** (aglycone) is called
nystatinolide
81
# **ANTIFUNGAL ANTIBIOTICS**
**NYSTATIN**:
NATAMYCIN is obtained from
S. natalensis
82
# **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)
GRISEOFULVIN
83
# **ANTIFUNGAL ANTIBIOTICS**
**GRISEOFULVIN**:
was isolated from
Penicillum griseofulvum
84
# **ANTIFUNGAL ANTIBIOTICS**
**GRISEOFULVIN**:
dispensing notes
should be taken with **high fat meal**
shuld be bought for **1 month**
85
# **ANTIFUNGAL ANTIBIOTICS**
**GRISEOFULVIN**:
MOA
mitotic spindle poison
86
* 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
ALLYLAMINES & RELATED COMPOUNDS
87
# **ALLYLAMINES AND RELATED COMPOUNDS**
result of ____
random screening
88
# **ALLYLAMINES AND RELATED COMPOUNDS**
MOA:
interfere with the ____
early step of ERGOSTEROL biosynthesis
89
# **ALLYLAMINES AND RELATED COMPOUNDS**
MOA:
inhibition of ____
squalene epoxidase
90
# **ALLYLAMINES AND RELATED COMPOUNDS**
ACTIVITY:
____ against pathogenic **yeast**
-static
91
# **ALLYLAMINES AND RELATED COMPOUNDS**
ACTIVITY:
____ against **dermatophytes** and **filamentous fungi**
-cidal
92
# **ALLYLAMINES AND RELATED COMPOUNDS**
* **1% cream/gel** is used topically against **ringworm**, **athlete's foot** and **jock itch**
NAFTIFINE HCl
93
# **ALLYLAMINES AND RELATED COMPOUNDS**
use is **same** with **Naftifine** but active against **ONYCHOMYCOSIS**
Terbinafine HCl
94
# **ALLYLAMINES AND RELATED COMPOUNDS**
which is more active/effective:
Terbinafine or Naftifine
Terbinafine > Naftifine
95
# **ALLYLAMINES AND RELATED COMPOUNDS**
**THIOESTER** of **β-naphthol** that inhibits squalene epoxidasase (-cidal)
Tolnaftate
96
# **TISSUE REACTIONS OF FUNGAL DISEASE**
* targets **nucelic acid**
* **DNA synthesis** inhibitor
FLUCYTOSINE
97
# **TISSUE REACTIONS OF FUNGAL DISEASE**
target of **AZOLES**
14-α-demethylase
98
# **TISSUE REACTIONS OF FUNGAL DISEASE**
toxic to the cell
Lanosterol
99
**primary component** of fungus
ergosterol
100
# **TISSUE REACTIONS OF FUNGAL DISEASE**
* target **D14 reductases**
* **D7-8 isomerases**
Morpholines
101
# **TRIAZOLE NUCLEUS**
substitution must be in what position ONLY
N
| other positions will lose its activity
102
# **TRIAZOLE NUCLEUS**
**IMI**dazole
X = C
103
# **TRIAZOLE NUCLEUS**
**TRI**azole
X = N
104
# **TRIAZOLE NUCLEUS**
has **better** activity
TRIazole
105
# **TRIAZOLE NUCLEUS**
* **F**, **Cl**
* cause **phototoxicity**
* **increase** activity & **lipophilicity**
ELECTRON WITHDRAWING GROUP
106
# **MOA OF AZOLES**
inhibition of ____ that catalyzes **14-α-demethylation** of **LANOSTEROL** to **ERGOSTEROL**, accumulation of 14-methylated sterols cause **permeability disturbance**
CYP450
107
* **MOST TOXIC** sterol
* leads to **membrane stress**
ignosterol
108
# **MOA OF AZOLES**
CYP450 catalyzes **14-α-demethylation** of **LANOSTEROL** to ____
ergosterol
109
# **AZOLE ANTIFUNGALS**
* **broad-spectrum**
* SE: severe **GI disturbances**
* MOA: interferes with **AMINO ACID TRANSPORT** into the organism by an action of cell membrane
CLOTRIMAZOLE
110
# **AZOLE ANTIFUNGALS**
**1% cream** for the topical tx of **local** tinea infections & cutaneous candidiasis
Econazole nitrate
111
# **AZOLE ANTIFUNGALS**
**EXTREMELY broad spectrum**, active against C. albicans
Butoconazole nitrate
112
# **AZOLE ANTIFUNGALS**
**1% cream** is useful for **jock itch**, **athlete's foot**, and **ringworm**
Sulconazole nitrate
113
# **AZOLE ANTIFUNGALS**
treatment for **tinea pedis**, **tinea corporis**, and **tinea capitis**
Oxicanzole nitrate
114
# **AZOLE ANTIFUNGALS**
* useful for **vulvovaginal candidiasis**
* more effective against **Torulopsis glabrata**
Tioconazole
115
# **AZOLE ANTIFUNGALS**
**EXCLUSIVELY** for the **CONTROL** of **vulvovaginal monolialiasis**
Terconazole
116
# **AZOLE ANTIFUNGALS**
* tx for **systemic** fungal infection and **chronic** mucocutaneous candidiasis
* AE: **Thrombophlebitis**, **pruritus**, **fever**, **GI** upset
Miconazole nitrate
117
# **AZOLE ANTIFUNGALS**
* **1st ORALLY active BROAD SPECTRUM** (Imidazole)
* **HEPATOTOXIC**
* highly **PROTEIN BOUND**
KETOCONAZOLE
118
# **AZOLE ANTIFUNGALS**
**KETOCONAZOLE**:
dispensing note
should be taken with **EMPTY** stomach
119
# **AZOLE ANTIFUNGALS**
**KETOCONAZOLE**:
side effects
gynecomastia
120
# **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**
Itraconazole
121
ANTI-HISTAMINES:
**sedating**
1st gen
122
ANTI-HISTAMINES:
**non-drowse**
2nd gen
123
# **AZOLE ANTIFUNGALS**
* the ONLY **WATER SOLUBLE** azole with broad spectrum of activity
* excellent **ORAL BIOAVAILABILITY**
* plasma protein binding is <10%
Fluconazole
124
# **AZOLE ANTIFUNGALS**
* target market: FEMALE
* for **candidiasis**
Flunzela
(Fluconazole)
125
# **AZOLE ANTIFUNGALS**
**FLUCONAZOLE**:
plasma protein binding
<10%
126
# **AZOLE ANTIFUNGALS**
**ITRACONAZOLE**:
____% protein bound
99%
127
# **AZOLE ANTIFUNGALS**
* **NEWEST** in the market
* currently in **phase II**
Posoconazole
128
* a **CYCLIC DEPSIPEPTIDE** produced by **AUREOBASIDIUM PULLULANS**
* MOA: act as a **tight binding noncompetitive** inhibitor of the enzyme **inositol phosphorylceramide synthase**
AUREOBASIDINS
129
# **AUREOBASIDINS**
a **cyclic depsipeptide** produced by ____
Aureobasidium pullulans
130
# **AUREOBASIDINS**
MOA:
act as ____ of the enzyme **inositol phosphorylceramide synthase**
tight binding noncompetitive inhibitor
131
# **AUREOBASIDINS**
MOA:
act as **tight binding noncompetitive inhibitor** of the enzyme ____
inositol phosphorylceramide synthase
132
# **AUREOBASIDINS**
essential for **FUNGAL SPHINGOLIPID BIOSYNTHESIS**
IPC synthase
133
* obtained by **MOLECULAR MODIFICATION** on the basis of model compounds that is used as antibacterial agent for local, systemic and/or urinary tract infections
SYNTHETIC ANTIBACTERIAL AGENT
134
# **SYNTHETIC ANTIBACTERIAL AGENT**
obtained by ____
molecular modification
135
# **SYNTHETIC ANTIBACTERIAL AGENT**
inhibits **DNA GYRASE**
quinolones
136
patterned after **NALIDIXIC ACID** which is a **NAPHTHYRIDINE**
quinolones
137
# **QUINOLONES**
patterned after ____ which is a ____
nalidixic acid, naphthyridine
138
# **QUINOLONES | STRUCTURE**
enhances **absorption**
cyclopropyl
139
# **QUINOLONES**
* **HIGHLY** protein boound
* mostly used for **UTIs**
FIRST generation quinolones
140
# **QUINOLONES**
problem of **FIRST** generation quinolones
highly protein bound
141
# **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
FLUOROQUINOLONES
142
# **AZOLE ANTIFUNGALS**
**FLUCONAZOLE**:
agent of choice
cryptococcal meningitis
143
# **AZOLE ANTIFUNGALS**
**FLUCONAZOLE**:
DOC
fungal meningitis
144
* **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**
ECHINOCANADINS
145
# **QUINOLONES**
MOA
DNA gyrase inhibition
146
# **QUINOLONES**
MECHANISM OF RESISTANCE:
* by altering the target enzymes namely **DNA gyrase** and **topoisomerase IV**
CHROMOSOMAL
146
147
# **QUINOLONES**
MECHANISM OF RESISTANCE:
**CHROMOSOMAL** target enzymes
DNA gyrase
topoisomerase IV
148
# **QUINOLONES**
MECHANISM OF RESISTANCE:
* seen in some K. pneumoniae & E. coli
plasmid
149
# **QUINOLONES**
MECHANISM OF RESISTANCE:
* mutations in ____ of **gram negative**
outer membrane porins
150
# **QUINOLONES**
**circular extrachromosomal** structure
plasmid
151
# **SAR OF QUINOLONES**
PHOTOTOXICITY
X8
R5
F
152
# **SAR OF QUINOLONES**
**MOST PHOTOTOXIC**
halogen in X8
153
# **SAR OF QUINOLONES**
drug that has halogen in X8
Lomefloxacin
| take once daily
154
# **SAR OF QUINOLONES**
**LOWEST** phototoxicity
AMINO GROUP in R5 and X8
155
# **SAR OF QUINOLONES**
* **MORE FAVORABLE** for **DNA gyrase**
* **weakly** phototoxic
methoxy in R5
156
# **SAR OF QUINOLONES**
safest na nakakabit sa R5 and X8
hydrogen
157
# **SAR OF QUINOLONES**
replacement / modification
R2
158
# **SAR OF QUINOLONES**
drug interaction
complexation reaction w/ antacid & iron supplements
159
# **QUINOLONES | SPECTRUM OF ACTIVITY**
largely **confined** to ____
gram neg
160
161
* useful for **PENICILLIN** resistant gonococci
* **METHICILLIN** resistant Staph. aureus & **AMINOGLYCOSIDE** resistant P. aeuruginosa
QUINOLONES
162
# **QUINOLONES**
DRUG INTERACTION:
**DECREASE absorption** of ____, ____, and ____ **antacids**
Al, Mg, Ca
163
# **QUINOLONES**
DRUG INTERACTION:
____ inhibition
CYP450
164
# **QUINOLONES**
ADVERSE EFFECTS:
**GI**
N&V
165
# **QUINOLONES**
ADVERSE EFFECTS:
**cardiovascular**
torsades de pointes
166
# **QUINOLONES**
ADVERSE EFFECTS:
**muskoskeletal**
rupture tendon
167
# **QUINOLONES**
ADVERSE EFFECTS:
**neurologic**
polyneuropathy
168
# **QUINOLONES**
**Gram -** but NOT **pseudomonas** species
1st gen
169
# **QUINOLONES**
GEN:
**Nalidixic acid**
**Cinoxacin**
1st gen
170
# **QUINOLONES**
**Gram -** (including **pseudomonas**, **some** Gram + and **some** atypical MO
2nd gen
171
# **QUINOLONES**
GEN:
**Norfloxacin**
**Ciprofloxacin**
**Enoxacin**
**Ofloxacin**
2nd
172
# **QUINOLONES**
same as **2nd gen** with **extended G+** and **atypical** coverage
3rd gen
173
# **QUINOLONES**
GEN:
**Levofloxacin**
**Sparfloxacin**
**Moxifloxacin**
**Gemifloxacin**
3rd
174
# **QUINOLONES**
same with 3rd gen with **broad ANAEROBIC** coverage
4th
175
# **QUINOLONES**
GEN:
**Trovafloxacin**
4th
176
# **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**
CIPROFLOXACIN
177
# **QUINOLONES**
**CIPROFLOXACIN**:
AOC for ____
gastroenteritis caused by G- bacilli
178
# **QUINOLONES**
CIPROFLOXACIN:
with **CEFTRIAXONE**
disseminated gonorrhea
179
# **QUINOLONES**
CIPROFLOXACIN:
with **DOXYCYCLINE**
gonococal urethritis
180
# **QUINOLONES**
CIPROFLOXACIN:
binds ____
divalent cation
181
# **QUINOLONES**
CIPROFLOXACIN:
increase effect of ___
warfarin
182
# **QUINOLONES**
CIPROFLOXACIN:
targets ____
DNA gyrase
183
# **QUINOLONES**
CIPROFLOXACIN:
**enhance** activity with **pseudomonas**
piprazinyl
184
# **QUINOLONES**
* resembles ciprofloxacin in antibacterial spectrum and potency
* increased concentration in CSF
* **SUPERIOR ORAL ABSORPTION** and **BIOAVAILABILITY**
* food delays absorption
OFLOXACIN
185
# **QUINOLONES**
* SPECTRUM: **G-**, **G+**, **Legionella**, **atypical respiratory**, **M. tuberculosis**
* ADR: **blood glucose disturbances** in DM patients
LEVOFLOXACIN
186
# **QUINOLONES**
LEVOFLOXACIN:
relationship of generations with side effects
increase gen = increase SE
187
# **QUINOLONES**
* saftey and efficacy **NOT** established in patients <18 y/o
* SPECTRUM: **G-**, **atypical respiratory**, **M. tuberculosis**, **G- anaerobes**
MOXIFLOXACIN
188
# **QUINOLONES**
* ONLY quinolone that is taken **OD** (eye)
* **MOST PHOTOTOXIC**
LOMEFLOXACIN
189
# **QUINOLONES**
* HIGHER POTENCY against **G+** bacteria
* **skin** and **soft tissue** infection in LRT1 and PID
* bacterial **gastroenteritis** and **cholecystitis**
SPARFLOXACIN
190
# **QUINOLONES**
CLINICAL USES
UTI
Gonorrhea
Diarrhea
Respiratory infection
Osteomyelitis
191
* 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**
NITROFURANS
| 5 membered ring
192
# **NITROFURANS**
SAR:
**anti-microbial** property is present only when the **NITRO GROUP** is in the ____ position
5-position
192
193
# **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
reduction
(nitrofuran reductase)
194
# **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
formation of free radicals
195
# **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
ribosomal proteins
196
# **NITROFURAN**
MOA:
**overall effect**
inhibition of bacterial growth or cell death
197
# **NITROFURANS**
topically in the tx of **BURNS** and prevent bacterial infection associated with **SKIN GRAFTS**
NITROFURAZONE
198
# **NITROFURANS**
recommended for the **ORAL TREATMENT** of **bacterial** or **protozoal** **DIARRHEA**
FURAZOLIDONE
199
# **NITROFURANS**
* sutiable for **oral use** in the treatment of **UTI**
* **microcrystalline form** improve GI tolerance **without interfering oral absorption**
NITROFURANTOIN
200
# **NITROFURANS**
* prepared by **evaporating** a solution of **FORMALDEHYDE** and **STRONG AMMONIA** water to dryness
* prodrug
* promote the formation of formaldehyde
METHENAMINE
201
# **METHENAMINE**
MOA:
antibacterial activity depends on ____ and **enhanced** by **acidifying** with **sodium biphosphate** or **ammonium chloride**
liberation of formaldehyde
202
# **METHENAMINE**
MOA:
antibacterial activity depends on **liberation of formaldehyde** and **enhanced** by **acidifying** with ____ or ____
sodium biphosphate
ammonium chloride
203
# **METHENAMINE**
**INEFFECTIVE** for ____ containing microorganism
UREASE
| urease - ammonia - causes urine to be BASIC
204
* **alleviate pain** and **discomfort** caused by **UTI**
* **soluble** and concentrates in urine
* combined with UTI agents
URINARY ANALGESIC
205
# **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**
PHENAZOPYRIDINE HCl
(pyridium)
206
# **URINARY ANALGESIC**
PHENAZOPYRIDINE HCl:
may **tint** the urine ____
red orange
207
# **URINARY ANALGESIC**
PHENAZOPYRIDINE HCl:
the **stain** is **removed** by
sodium dithionite solution
208
* a **gram POSITIVE acid FAST** bacillus
* live **inside** the **macrophages** and **lysosomes**
* causative agent for tuberculosis
Mycobacterium tuberculosis
209
# **ANTI-TUBERCULAR AGENTS**
MANAGEMENT
shotgun therapy
| use of several drugs simultaenously
210
# **ANTI-TUBERCULAR AGENTS**
FIRST line of therapy **combination**
RIPE
Rifampin, Isoniazid, Pyrazinamide, Ethambutol
211
# **ANTI-TUBERCULAR AGENTS**
FIRST line **single agent**
streptomycin
212
# **ANTI-TUBERCULAR AGENTS**
BAN for Rifampicin
Rifampin
213
# **ANTI-TUBERCULAR AGENTS**
**SLOW** acetylator
isoniazid
214
# **ANTI-TUBERCULAR AGENTS**
INVESTIGATIONAL DRUG:
**TMC207** inhibits
ATP synthase = no energy = die
215
# **ANTI-TUBERCULAR AGENTS**
AIM OF THERAPY:
treatment must be for ____ because **response** is **SLOW**
longer period, 6 months
216
# **ANTI-TUBERCULAR AGENTS**
best drug for **ACTIVELY MULTIPLYING** bacteria
Isoniazid
217
# **ANTI-TUBERCULAR AGENTS**
**SEMI-DORMANT** bacilli that metabolize **SLOWLY** should be treated with
Pyrazinamide
Rifampicin
218
# **ANTI-TUBERCULAR AGENTS**
why **COMBINATION** therapy is given
| 3
* broaden the spectrum
* reduce toxicity
* prevent resistance
219
# **ANTI-TUBERCULAR AGENTS**
1st line drugs
RIPES
220
# **ANTI-TUBERCULAR AGENTS**
drugs for the **FIRST 2 MONTHS**
RIPE
221
# **ANTI-TUBERCULAR AGENTS**
drugs for the **NEXT 4 MONTHS**
RIP
222
# **ANTI-TUBERCULAR AGENTS**
why is **ETHAMBUTOL** not given for the next **4 months**
AE: color blindness
223
# **ANTI-TUBERCULAR AGENTS**
PROPHYLACTIC DOSE:
**Isoniazid**
**300mg/day**
224
# **ANTI-TUBERCULAR AGENTS**
PROPHYLACTIC DOSE:
**Isoniazid** for **IMMUNOCOMPROMISED**
900mg twice weekly for 6-12 months
225
# **ANTI-TUBERCULAR AGENTS**
PROPHYLACTIC DOSE:
**Isoniazid** consideration
should not have ACTIVE TB case
226
# **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
RIFAMPICIN
227
# **ANTI-TUBERCULAR AGENTS**
RIFAMPICIN can cause what color to **bodily fluids**
red orange
227
# **ANTI-TUBERCULAR AGENTS**
* **SAFEST**, **MOST POTENT** and **EFFECTIVE** against **ALL FORMS** of M. tuberculosis
* Bacteri**cidal**
* **readily absorbed** from the GIT
* does **NOT** bind with the **plasma protein**
* extensive ddistribution in the tissue and bodily fluids
ISONIAZID
228
# **ANTI-TUBERCULAR AGENTS**
ISONIAZID:
**toxic effects**
Insomnia
Neuropathy (peripheral)
Hepatotoxicity
| INH
229
# **ANTI-TUBERCULAR AGENTS**
ISONIAZID:
**metabolism** and **excretion**
acetylation, urine
229
230
# **ANTI-TUBERCULAR AGENTS**
ISONIAZID:
management of the TOXIC EFFECT: **neuropathy (peripheral)**
PYRIDOXINE
231
# **ANTI-TUBERCULAR AGENTS**
responsible for the synthesis of **MYCOLIC ACID**
FAS-1
| Fatty acid synthase 1
232
# **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**
ETHIONAMIDE
233
# **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**
PYRAZINAMIDE
234
# **ANTI-TUBERCULAR AGENTS**
PYRAZINAMIDE:
effective in ____ environment
low pH
235
# **ANTI-TUBERCULAR AGENTS**
PYRAZINAMIDE:
**can** kill TB bacilli in **acidic pH** up to ____
5.5
236
# **ANTI-TUBERCULAR AGENTS**
PYRAZINAMIDE:
**cannot** kill TB bacilli in the ____ because of **high pH**
blood
237
# **ANTI-TUBERCULAR AGENTS**
* associated with **gout**
* **hyperuricemia** effect
XANTHINE OXIDASE
238
# **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**
pyrazinoic acid
239
# **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**
pyrazinamidase
240
# **ANTI-TUBERCULAR AGENTS**
PYRAZINAMIDE:
**side effect**
interfere **uric acid secretion**
241
# **ANTI-TUBERCULAR AGENTS**
ETHAMBUTOL:
responsible for the synthesis of **arabinogalactan**
EmbA
242
# **ANTI-TUBERCULAR AGENTS**
ETHAMBUTOL:
target
EmbB
243
# **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
ETHAMBUTOL
244
# **ANTI-TUBERCULAR AGENTS**
an essential component of the **myobacterial cell wall**
arabino-galactan
245
# **ANTI-TUBERCULAR AGENTS**
ETHAMBUTOL MOA:
**inhibits** the **synthesis** of ____ which is an **essential component** of **myobacterial cell wall**
arabino-galactan
246
# **ANTI-TUBERCULAR AGENTS**
ETHAMBUTOL MOA:
**inhibition** of the ____ into the cell wall of the MO
incorporation of mycolic acid
247
# **ANTI-TUBERCULAR AGENTS**
ETHAMBUTOL ADVERSE EFFECT:
* **most common**
* **LOSS** of **visual acuity**
RETINOBULBAR OPTIC NEURITIS
248
# **ANTI-TUBERCULAR AGENTS**
should NOT be given to CHILDREN
ETHAMBUTOL
249
# **ANTI-TUBERCULAR AGENTS**
* **second AGENT** for TB
* MOA: prevents incorporation of **PABA** in **dehydrofolic acid** molecule
AMINOSALICYLIC ACID & AMINOSALICYLATE SODIUM
250
# **ANTI-TUBERCULAR AGENTS**
AMINOSALICYLIC ACID & AMINOSALICYLATE SODIUM MOA:
prevents incorporation of ____ in **dehydrofolic acid** molecule
PABA
251
# **ANTI-TUBERCULAR AGENTS**
* basic **RED DYE** that exerts a **SLOW** bacteri**cidal** effects on **M. leprae**
* anti-**inflammatory** and **immune-modulating** effects
CLOFAZIMINE
252
# **ANTI-TUBERCULAR AGENTS**
classification of **RIFAMPIN** & **STREPTOMYCIN**
antitubercular - antibiotic
253
# **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**
RIFAMPIN
(RIFAMPICIN)
254
# **ANTI-TUBERCULAR AGENTS**
RIFAMPIN:
produced by ____
Schmidtea mediterranea
255
# **ANTI-TUBERCULAR AGENTS**
RIFAMPINl:
powerful ____ of CYP450
inducer
256
# **ANTI-TUBERCULAR AGENTS**
RIFAMPIN:
when taken with ____, **APAP** is **inactivated**
paracetamol
257
# **ANTI-TUBERCULAR AGENTS**
RIFAMPIN:
can tint the **urine**, **stool**, **tears**, **saliva**, **skin** ____
RED ORANGE
258
# **ANTI-TUBERCULAR AGENTS**
RIFAMPIN:
**adverse effect**
hepatotoxicity
259
# **ANTI-TUBERCULAR AGENTS**
RIFAMPIN:
**metabolized** by ____
de-acetylation
260
# **ANTI-TUBERCULAR AGENTS**
RIFAMPIN:
mainly **excreted** by the ____ and ____
bile and feces
261
# **ANTI-TUBERCULAR AGENTS**
RIFAMPIN MOA:
**inhibits** ____ which is responsible for **RNA synthesis**
DNA dependent RNA polymerase
262
# **ANTI-TUBERCULAR AGENTS**
prophylaxis of **DISSEMINATED** MAC in **AIDS** patients
RIFABUTIN
263
# **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
CYCLOSERINE
264
# **ANTI-TUBERCULAR AGENTS**
CYCLOSERINE MOA:
**prevents** the **synthesis** of ____ in the formation of bacterial cell walls
cross linking peptide
265
# **ANTI-TUBERCULAR AGENTS**
* **aminoglycoside**
* strongly **basic** cyclic peptide isolated from Strep. capreolus
* **SECOND LINE agent**
* alternative to **STREPTOMYCIN**
STERILE CAPREOMYCIN SULFATE
266
# **ANTI-TUBERCULAR AGENTS**
alternative to **STREPTOMYCIN**
sterile capreomycin sulfate
267
# **ANTI-TUBERCULAR AGENTS**
ADVERSE EFFECT:
**Isoniazid**
peripheral neuropathy
268
# **ANTI-TUBERCULAR AGENTS**
ADVERSE EFFECT:
**Rifampicin**
Cholestatic jaundice + renal toxicity + flu like syndrome
269
# **ANTI-TUBERCULAR AGENTS**
ADVERSE EFFECT:
**Pyrazinamide**
hepatotoxicity + hyperuricemia
270
# **ANTI-TUBERCULAR AGENTS**
ADVERSE EFFECT:
**Ethambutol**
retinobulbar optic neuritis
