1
Q
Classification of Quinolones
A
- Nalidixic acid
- Cinoxacin
- Norfloxacin
- Enoxacin
- Ciprofloxacin
- Ofloxacin
- Lomefloxacin
- Sparfloxacin
2
Q
basis of Quinolones
A
Nalidixic acid
3
Q
reproduce by binary fission
A
Bacteria
4
Q
has circular shape
A
Bacteria
5
Q
cause the DNA strand to split into two.
A
DNA helicase
6
Q
point where 2 DNA separates to allow replication of DNA
A
Replication fork
7
Q
enzyme that put two strands in DNA strand
A
DNA Polymerase
8
Q
It will lead to supercoiling. That’s why to ______ will inhibit this supercoiling.
A
DNA gyrase (Topoisomerase II)
9
Q
DNA gyrase (Topoisomerase II) will turn to
A
Gram - Topoisomerase IV - gram +
10
Q
MOA of Quinolones
A
Inhibition of DNA - gyrase (Topoisomerase II) Ineffective to anaerobic gram negative (Bacillus and Clostridium)
11
Q
Highly polar quinolones enter through ___ (these
are the pores found in g (-) bacteria) into the cell
A
porins
12
Q
Porins are found in
A
g (-) bacteria
13
Q
Quinolones may also ________ in the ___ .
A
- Antagonize GABA receptors
- Brain
14
Q
CNS effects when GABA receptors were antagonize
A
- tremor
- sleep disorders
- anxiety
- convulsion
15
Q
GABA stands for
A
Gamma-Aminobutyric Acid
16
Q
Quinolones are designed mainly for
A
g (-) bacteria
17
Q
Most quinolones have the inability to
A
penetrate the BBB
18
Q
BBB stands for
A
Blood-Brain Barrier
19
Q
A subgroup because of the presence of 6-fluoro
A
Fluroquinolones
20
Q
Structure-activity relationships of Fluroquinolones
A
- Alkyl and Aryl substitution at position 1- better potency
- Piperazine (C-7) and the fluorine (C6) constituent extends its activity
21
Q
piperazine is ____, oftentimes associated to ____ when urine is too BASIC also)
A
- BASIC
- Crystalluria
22
Q
more potent, disrupt DNA binding complex enzyme
A
(+) cyclosporyl
23
Q
very close to the site of DNA gyras
A
R2
24
Q
Impact in PK, drug potency
A
R1
25
Carboxylate
R3
26
Carbonyl
R4
27
Structure-activity relationship of Quinolones
Fluoro Quinolone, high stability, activity
28
NH2, OH, CH3, increase activity in gram+. Decrease activity when halide and methoxy was attached.
R5
29
F increase activity
R6
30
direct activity in DNA gyrase
R7
31
aminopyrrolidine (gram +), piperazine gram-, ADE Crystalluria (Norfloxacin, Ciprofloxacin)
R7
32
spectrum activity affects overall molecular steruc configuration, +F, CI, CH3, OCH3 (anaerobic)
R8
33
In R5, _______ increase activity in gram+. Decrease activity when halide and methoxy was attached.
NH2, OH, CH3
34
In R5, it decrease its activity when ______ was attached.
halide and methoxy
35
Can form chelates with cations reducing bioavailability with quinolones
Quinolones
36
Can form chelates with cations reducing bioavailability with quinolones (thus, we should ____ antacids and all other _______)
1. Avoid
2. Metal ion sources (Fe+3)
37
It interferes with DNA gyrase
Nalidixic acid
38
inhibit DNA synthesis during bacterial replication.
Nalidixic acid
39
Active against gram (-) bacteria but not effective against pseudomonas organisms.
Nalidixic acid
40
Nalidixic acid is active against _____ bacteria but not effective against pseudomonas organism
1. gram (-)
2. pseudomonas organism
41
In Nalidixic acid this is more active
7-hydroxymethyl metabolite
42
p210
Nalidixic acid
43
How many generations does Quinolones have?
4 Generations
44
Have moderate gram-negative activity and minimal systemic distribution
First Generation
45
Example of First Generation
- Cinoxacin (Cinoxacin)
- Nalidixic acid (NegGam, Wintomylon)
- Oxolinic acid
46
NegGam and Wintomylon
Nalidixic Acid
47
Have expanded gram negative activity and atypical pathogen coverage, but limited grampositive activity
Second Generation
48
Example of Second Generation
Class I
- Lomefloxacin (Maxaquin)
- Norfloxacin (Noroxin)
- Enoxacin (Penetrex)
Class II
- Ofloxacin (Floxin)
- Ciprofloxacin (Cipro)
49
Retain expanded gram-negative and atypical intracellular activity but have improved gram positive coverage
Third Generation
50
Example of Third Generation
- Levofloxacin (Levaquin)
- Sparfloxacin (Zagam) *
- Moxifloxacin (Avelox)
51
Improve gram-positive coverage, maintain gram-negative coverage, and gain anaerobic coverage
Fourth Generation
52
Example of Fourth Generation
- Clinafloxacin
- Gemifloxacin (Factive)
- Moxifloxacin (Avelox, Vigamox)
- Gatifloxacin (Tequin)
- Sitafloxacin
- Trovafloxacin (Trovan) (withdrawn)
53
not available in the market due to CNS, Gl adverse effects
Cinoxacin
54
It is a close congener of oxolinic acid, an anti-bacterial agent no longer in the market.
Cinoxacin
55
It is more completely absorbed and less protein-bound than nalidixic acid
Cinoxacin
56
Higher concentration than nalidixic acid
Cinoxacin
57
It is a Broad-spectrum antibacterial agent, active against gram (+) and gram (-)
Norfloxacin
58
Fluoride atoms provide increase in potency against gram (+)
Norfloxacin
59
Activity generally is not effective against obligate anaerobic bacteria
60
Activity generally is not effective against obligate anaerobic bacteria
Norfloxacin
60
Activity generally is not effective against obligate anaerobic bacteria
Norfloxacin
61
It is used for uncomplicated gonorrhea in 800 mg single oral dose
Norfloxacin
62
The primary use is for the treatment of UTI and STD, for uncomplicated gonococcal urethritis and chancroid.
Enoxacin
63
The bioavailability is reduced by divalent metal ions present in antacids and hematinics
Enoxacin
64
Enzyme inhibitor (CYP1A2)
Enoxacin
65
b
66
The drug is active against many anaerobes including P. aeroginosa.
Ciprofloxacin
67
This is used for treatment of UTI, lower respiratory infections, sinusitis , diarrhea, bone, joint & skin structure infection.
Ciprofloxacin
68
It is used for gonococcal urethritis.
Ciprofloxacin
69
Agent of choice for bacterial gastroenteritis
Ciprofloxacin
70
Enzyme Inhibitor
Ciprofloxacin
71
It is incompatible with drugs that are alkaline
Ciprofloxacin
72
Food delays but does not prevent absorption.
Ciprofloxacin
73
For postexposure treatment of inhalational anthrax
Ciprofloxacin
74
Cipro + Doxycycline = gonococcal urethritis
Ciprofloxacin
75
Cipro + Doxycycline =
gonococcal urethritis
76
Ciprofloxacin & ceftriaxone = disseminated gonorrhea
Ciprofloxacin
77
Ciprofloxacin & ceftriaxone =
disseminated gonorrhea
78
Better than ciprofloxacin
Ofloxacin
79
Not effective in syphilis
Ofloxacin
80
Although food can slow the oral absorptions of the lower respiratory tract, including chronic bronchitis and pneumonia, caused by Gram-negative bacilli.
Ofloxacin
81
Although food can slow the oral absorptions of the lower
respiratory tract, including chronic bronchitis and
pneumonia, caused by _______
Gram-negative bacilli
82
Supplied as a racemate
Ofloxacin
83
A 2nd generation quinolone
Lomefloxacin
84
It is indicated for acute bacterial exacerbations of chronic bronchitis caused by H influenzae or moxarella catarrhalis
Lomefloxacin
85
The only quinolone for which once-daily oral dosing suffices
Lomefloxacin
86
C-8 with halogen causes Phototoxicity
Lomefloxacin
87
C-8 with halogen causes _______
Phototoxicity
88
With long elimination half-life, used for the treatment of bacterial gastroenteritis and cholecystitis.
Sparfloxacin
89
It shows lowest incidence of phototoxicity
Sparfloxacin
90
C-5: Amino portion decreases phototoxicity
Sparfloxacin
91
C-5: ______ decreases phototoxicity
Amino portion
92
Amino portion decreases phototoxicity
C-5
93
Halogen causes Phototoxicity
C-8
94
[p212, amino group on the 5th position]
Sparfloxacin
95
Adverse Effects of Quinolones
- QT prolongation
- Hepatotoxicity
- Abnormal or bitter taste
- Tendon rupture
96
Quinolones are not recommended for:
- Children
- Adolescents younger than 18 years of age
- In pregnant or breastfeeding women
97
Quinolones are not recommended for use in children and adolescents younger than 18 years of age, or in pregnant or breastfeeding women because it causes:
arthropathy and chondrotoxicity
98
Dermatologic Adverse Effects of Quinolones
- Rash
- PHOTOSENSITIVITY reactions,
- Pruritus
99
What are the nitrofuran antibacterial agents
- Nitrofurazone
- Furazolidone
- Nitrofurantoin
99
What are the Nitrofuran antibacterial agents
- Nitrofurazone
- Furazolidone
- Nitrofurantoin
100
Derivatives of 5-nitro-2-furaldehyde
Nitrofurans
101
Nitrofurans SAR
anti-microbial activity is present only when the nitro group is in the 5-positon
102
In Nitrofurans SAR, anti-microbial activity is present only when the _________________
nitro group is in the 5-positon
103
Has a broad spectrum of activity against Gram-positive and Gram-negative bacteria but not Fungi
Nitrofurazone
104
0.2 % usual concentration in solution, ointments and suppositories
Nitrofurazone
105
In Nitrofurazone, what is the usual concentration in solution, ointments and suppositories
0.2%
106
3'[(5-nitrofurylidene) amino]-2 oxazolodinone. It has bactericicdal activity and also antiprotozoal activity, specifically, against G. lamblia.
Furazolidone
107
It can inhibit aldehyde dehydrogenase. (avoid alcohol)
Furazolidone
108
In Furazolidone, 3'[(5-nitrofurylidene) amino]-2 oxazolodinone. It has bactericicdal activity and also antiprotozoal activity, specifically, _______
against G. lamblia.
109
Furazolidone can inhibit ___________________. (avoid ___)
1. Aldehyde dehydrogenase
2. Alcohol
110
disrupts bacterial enzyme system, active against gram(+) gram (-)
111
______ prevents and treats UTI. It colors the urine _____.
1. NITROFURANTOIN
2. Brown
112
To improve GI tolerance, the drug is designed using large crystalline form without interfering oral absorption
Nitrofurantoin
113
Brand name of Nitrofurantoin
Macrodantin
114
Antibacterial medication used to treat urinary tract infections, but it is not as effective for kidney infections.
Macrodantin
115
Methenamine aka
- Urothropi
- Uritone
116
Active agent: formaldehyde
Methenamine
117
What is the active agent of Methenamine
formaldehyde
118
Requires an Acidifying agent like ammonium chloride, sodium biphosphate
Methenamine
119
It is employed internally as urinary antiseptic
Methenamine
120
urease (enzyme that hydrolyzes urea to AMMONIA - too BASIC)
Methenamine
121
Urease inhibitor acetohydroxamic acid (Lithostat)
Methenamine
122
enzyme that hydrolyzes urea to AMMONIA - too BASIC
Urease
123
Urease inhibitor acetohydroxamic acid
Lithostat
124
It has the ability to furnish its own acidity
Methenamine Mandelate
125
It is effective with smaller amounts of mandelic acid and thus avoids the gastric disturbances
Methenamine Mandelate
126
Readily absorbed after oral administration and concentrated in the urinary bladder
Methenamine Hippurate
127
(AZO) Brick red in color
Phenazopyridine HCL
128
local analgesic effect
Phenazopyridine HCL
129
It is given in combination with urinary antiseptics
Phenazopyridine HCL
130
+ sulfisoxazole, it is available as Azo-Gantrisin
Phenazopyridine HCL
131
It gives an orange-red color stain
Phenazopyridine HCL
132
not for cure, only for management
Phenazopyridine HCL
133
What is the side effect of Phenazopyridine HCL
methemoglonemea
134
Family Mycobacteriaceae
Antitubercular Agents
135
Antituberculosis agents are drugs used to treat tuberculosis, an infectious disease caused by
Mycobacterium tuberculosis and Leprosy Mycobacterium leprae
136
M. tuberculosis is an acid fast, aerobic bacteria with an unusual cell wall, containing a large percentage of lipid content.
Antitubercular Agents
137
___________ is an acid fast, aerobic bacteria with an unusual cell wall, containing a large percentage of lipid content.
Mycobacterium tuberculosis
138
Aerobic bacteria with an unusual cell wall, containing a large percentage of lipid content. For this reason, the organism is resistant to alcohols, acids, alkali and some disinfectants.
Antitubercular Agents
139
Aerobic bacteria with an unusual cell wall, containing a large percentage of lipid content. For this reason, the organism is resistant to ______________
- Alcohols
- Acids
- Alkali
- Some disinfectants
140
Drugs that inhibit Mycolic Acid:
H - Isoniazid
E - Ethambutol
R - Rifampicin
Z - Pyrazinamiide
141
Reason why antibiotics are not potent to the body. hindi nagrereact
Mycolic acid
142
is a synthetic antibacterial agent which is bactericidal against replicating organisms, but bacteriostatic against nonreplicating organisms.
Isoniazid (INH)
143
Following exposure to INH, acid fast bacilli lose their acid
Isoniazid (INH)
144
fast characteristics, indicating that the agent interferes with cell wall synthesis.
Isoniazid (INH)
145
Isoniazid MOA
unknown, but it is thought that INH enters the cell wall and is metabolized to isonicotinic acid
146
(-) mycolic acid synthesis
Isoniazid (INH)
147
The major metabolite of INH is ___________
N-acetylisoniazid
148
In Isoniazid,
SLOW causes
FAST causes
1. Neuritis
2. Hepatoxicity
149
Have a higher concentration of this enzyme than slow acetylators
Fast acetylators
150
Acetylated isoniazid can be converted to isonicotinic acid and hydrazine, but it also gives rise to ________
1. Acetylated isoniazid
2. acetylhydrazide.
151
prevents peripheral neuritis
Pyridoxine
152
2nd class of tuberculosis drug
Ethionamide
153
It is used in the treatment of isoniazid resistant tuberculosis or when the patient is intolerant to isoniazid and other drugs
Ethionamide
154
Ethionamide is used in the treatment of _____________
isoniazid resistant tuberculosis
155
2 substitution increases potency
Ethionamide
156
Blocks mycolic acid synthesis, [p216]
Ethionamide
157
Pyrazinamide causes
Hepatotoxic, Uric Acid, Hyperuricemia
158
Pyrazinamide aka
Pyrazinecarboxamide (PZA)
159
Bioactivation of pyrazinamide to _____ (inh. = fatty acid synthesis) by an amidase present in mycobacteria
pyrazinoic acid
160
___ and its metabolites are reported to interfere with
uric acid excretion ...- p216
Pyrazinecarboxamide (PZA)
161
Bioactivation of pyrazinamide to pyrazinoic acid (inh. = fatty acid synthesis) by an __________
amidase present in mycobacteria
162
active only against dividing mycobacteria
Ethambutol
163
The dextro isomer is 16 times as active as the meso compound
Ethambutol
164
Not recommended for use alone
Ethambutol
165
- (-) arabinosyl transferase (polymerization of Arabinogalactan)
Ethambutol
166
Retrobulbar neuritis, Green red color blindness
Ethambutol
167
This agent was once quite popular, until significant resistance to the drug developed
p-Aminosalicylic acid
168
It interferes with the incorporation of p aminobenzoic acid into folic acid.
p-Aminosalicylic acid
169
(-) Folic acid synthesis
p-Aminosalicylic acid
170
- a basic red dye ("AZA") that exert a slow, bactericidal effect on M. leprae.
Clofazamine
171
This is used in the treatment of leprosy, including the dapsone-resistant forms.
Clofazamine
172
This was also used for treating skin lesions cause by M. ulcerans
Clofazamine
173
Rifampin is obtained from
Streptomyces mediterranei
174
Binds to bacterial DNA-dependent RNA polymerases
175
Most active agent in clinical use for the treatment of tuberculosis
176
The incidence of ____ was significantly higher when rifampin was combined with isoniazid
hepatoxicity
177
The incidence of hepatoxicity was significantly higher when rifampin was combined with _____
isoniazid
178
Enzyme inducer
Rifampin
179
Should be taken on an empty stomach
Rifampin
180
Orange to reddish brown crystalline powder
Rifampin
181
It is orally active against many Gram positive and Gram negative organisms, and is clinically effective against M. tuberculosis
Rifampin
182
greater potency against M. tuberculosis in vitro
Rifabutin
183
considered inferior to rifampin for the short-term therapy of tuberculosis because of its significantly lower plasma concentrations
Rifabutin
184
Rifabutin considered inferior to rifampin because of its
short-term theraphy of tubercuosis
185
natural product was isolated from Streptomyces orchidaceus as the D isomer
Cycloserine
186
is also active, and the racemic mixture is more potent than either isomer.
L-isomer
187
In enolic form, cycloserine is sterically and stereochemically _____ to D alanine.
analogous
188
What form, cycloserine is sterically and stereochemically analogous to D alanine.
Enolic form
189
(-) cell wall synthesis
Cycloserine
190
____ is the last resort for tuberculosis, because it causes CNS ____
1. Cycloserine
2. Depression
191
this antibiotic is a mixture of four cyclic polypeptides, where capreomycin la and 1b make up 90% of the mixture.
Capreomycin
192
Capreomycin MOA
Little is known about its mechanism of action, but it is thought to inhibit protein synthesis by binding to the 70S ribosomal unit.
193
(-) protein synthesis
Capreomycin
194
Capreomycin causes
- Oto toxicity
- Nephrotoxicity
195
Capreomycin is a mixture of four cyclic polypeptides, where capreomycin la and 1b make up __ of the mixture
90%
196
intramuscular administration
Streptomycin
197
sensitization dermatitis-wear gloves
Streptomycin
198
Binds to 12s and inhibits protein synthesis
Streptomycin
199
It is resistant
Streptomycin
200
Problems: crystalluria
Sulfonamides
201
pka 10.4 [sulfanilamide]
Sulfonamides
202
In what is the pka of sulfanilamide
pka 10.4
203
pH 6 [urine]
Sulfonamides
204
Insoluble, non-ionized form in the KIDNEY
Sulfonamides
205
presence of crystals in urine
Crystalluria
206
In Sulfonamides what is th pH number of urine
6
207
is necessary for activity and must not be substituted; para position
Sulfonamides
208
more soluble in acid urine
Sulfamethazine
209
kidney damage, from acetylsulfapyridine crystals deposited in the kidneys
Sulfapyridine
210
was the first drug to have an outstanding curative action on pneumonia
Sulfapyridine
211
is a sulfonamide drug closely related to sulfosoxazole in chemical structure and antimicrobial activity
Sulfamethoxazole
212
+ Trimethoprim =
Cotrimoxazole
213
For P. carinii
Tanong
214
because the sodium salt is highly soluble at the physiological pH of 7.4, it is specially suited, as a solution for repeated topical application
Sulfacetamide sodium
215
+ erythromycin =
Acute otitis
216
Sulfisoxazole Diolamine
Topical Sulfonamides
217
Drugs example for Topical Sulfonamides
- Triple Sulfa
- Sulfabenzamide
- Sulfacetamide
- Sulfathiazole
218
vaginal cream of Haemophilus vaginitis
Topical Sulfonamides
219
Topical Sulfonamides is a vaginal cream of
Haemophilus vaginitis
220
it is not a true sulfanilamide - type compound, as is not inhibited by PABA
Mafenide Acetate
221
PABA stands for
Para-aminobenzoic acid
222
Effective against Clostridium welchii
Non absorbable sulfonamides [BURN]
223
Silver Sulfadiazine
Non absorbable sulfonamides [BURN]
224
Against Pseudomonas spp
Non absorbable sulfonamides [BURN]
225
Sulfonamides are for
- Intestinal Infections
- Ulcerative Colitis
- Reduction of Bowel Flora
226
broken down in the body to m-aminosalicylic acid and sulfapyridine
Sulfasalazine
227
Sulfonamides Oral Absorbable are
- SULFISOXAZOLE
- SULFAMETHIZOLE
- SULFADIAZINE
- SULFAPYRIDINE
228
Sulfonamides Oral Non-Absorbable
SULFADIAZINE
229
Sulfonamides Topical are
- SULFACETAMIDE
- MAFENIDE
- SILVER SULFADIAZINE
230
Dihydrofolate Reductase Inhibitors example is
Trimethoprim
231
A mixture of trimethoprim (TMP) and sulfamethoxazole (SMX), also known as _______, is a widely used _______ combination to treat a variety of bacterial infections
1. Co-trimoxazole
2. synergistic antimicrobial
232
they are less effective than the sulfonamides
Sulfones
233
Cross resistance occur
Sulfones
234
DAPSONE causes
- Dermatitis
- Leprosy
235
Drug example of Sulfone
Dapsone
236
Adverse Effect of Sulfone
hemolytic anemia (G6PD deficient)
237
diaminodiphenyl sulfone, should not take
- Aspirin
- Quinine
238
Dapsone aka
diaminodiphenyl sulfone
239
It is effective orally against both acute and carrier states of the disease
METRONIDAZOLE
240
preferred drug for the tx of amebic dysentery, giardiasis, trichomoniasis
METRONIDAZOLE
241
active against all anaerobic cocci, gram (-) and the treatment of choice for C. defficile colitis infections
METRONIDAZOLE
242
carcinogenic in mice and exhibits disulfiram-type reaction when used with ethanol
METRONIDAZOLE
243
unstable for IV prep, reconstituted Metronidazole HCI is stable for 96 H, ready to use solutions for 24 H
METRONIDAZOLE
244
In metronidazole, carcinogenic in mice and exhibits ________________
disulfiram-type reaction when used with ethanol
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