MT6314 SULFONA/TRIMETH/QUINO/ANTIMYCOBACTERIALS Flashcards
(218 cards)
1
Q
Antifolate Drugs include?
A
*Sulfonamides
*Trimethoprim and Trimethoprim Sulfamethoxazole Mixtures
2
Q
DNA Gyrase Inhibitors include?
A
Fluoroquinolones
3
Q
What are the different antimetabolites?
A
SULFONAMIDES
TRIMETHOPRIM
TRIMETHOPRIM-SULFAMETHOXAZOLE
4
Q
What are the different quinolones?
A
NARROW SPECTRUM - 1st Gen
WIDE SPECTRUM - 2nd-4th Gen
5
Q
One of the earliest and successful antibiotics ever developed
A
Sulfonamides
6
Q
When were Sulfonamides introduced and by who?
A
1935 by Gerhard Domagk
7
Q
Sulfonamides were marketed as?
A
Prontosil
8
Q
Sulfonamides are similar to what substance?
A
p-aminobenzoic acid (PABA)
9
Q
Sulfonamides physical, chemical and pharmacologic properties are produced by?
A
attaching substituents to the amido group (-SO2, -NH, -R) or the amino group (-NH2 group) of the sulfanilamide nucleus
10
Q
One of the most inexpensive antibiotics today
A
Sulfonamides
11
Q
Examples of Sulfonamides and PABAs?
A
Sulfanilamide
PABA
Sulfadiazine
Sulfamethoxazole
12
Q
Sulfonamides inhibit what?
A
Dihydropteroate synthase and folate production
13
Q
Sulfonamides are bacteriostatic or bactericidal?
A
Static
14
Q
Sulfonamides are usually given in combination with?
A
Trimetophrim or Pyrimethamine
15
Q
Action of Sulfonamides and Trimethoprim?
A
PABA and sulfonamides compete in dihydropteroate synthase to form dihydrofolate reductase
Dihydrofolate reductase through Trimethoprim will become tetrahydrofolic acid
Tetrahydrofolic acid -> Purine
Purines -> DNA
16
Q
Sulfonamide is anti-_____
A
folate
17
Q
Sulfonamide is bacteriostatic inhibitor of?
A
folic acid synthesis
18
Q
SULFONAMIDES are antimetabolites of?
A
PABA
19
Q
SULFONAMIDES are competitive inhibitors of?
A
dihydropteroate synthase
20
Q
Sulfonamides act as substrates for enzyme synthesis of?
A
nonfunctional forms of folic acid
21
Q
Inability of mammalian cells to synthesize folic acid is due to what characteristic of Sulfonamide?
A
Selective toxicity and preformed folic acid in diet
22
Q
TRIMETHOPRIM is a selective inhibitor of?
A
bacterial dihydrofolate reductase
23
Q
TRIMETHOPRIM prevents the formation of?
A
active tetrahydro form of folic acid
24
Q
TRIMETHOPRIM and SULFAMETHOSAXOLE combination results to?
A
sequential blockade of folate synthesis
25
TRIMETHOPRIM and SULFAMETHOSAXOLE are bactericidal or bacteriostatic?
Bactericidal
26
Synergistic action against a wide spectrum of microorganisms
SULFONAMIDES and TRIMETHOPRIM
27
T or F: Resistance occurs but development is slow in sulfonamides only
F, in combination SULFONAMIDES and TRIMETHOPRIM
28
What kind of drugs are not affected by the anti folate drugs?
bacteria that depends on exogenous sources of folate
29
Resistance is also caused by mutations in?
* Overproduction of PABA
* Production of a folic acid synthesizing enzyme that has low affinity for sulfonamides
* Impaired permeability to the sulfonamides
* Antibiotic efflux
30
Resistance to antifolaxe drugs is common in?
sulfonamides
31
Why is resistance to antifolaxe drugs is common in sulfonamides?
* Plasmid mediated
* Decreased accumulation of the drug
* Increase production of PABA by bacteria
* Decrease in the sensitivity of
dihydropteroate synthase
32
Resistance is trimethoprims are due to the production of?
dihydrofolate reductase that has reduced affinity for the drug AND an altered reductase with reduced drug binding
33
Resistance in trimethoprim is also due to [increased/decreased] cell permeability
decreased
34
Resistance is trimethoprims are due to the OVERproduction of?
dihydrofolate reductase
35
3 major groups of sulfonamides based on ROA?
* Oral, absorbable
* Oral, non-absorbable
* Topical
36
What major group of sulfonamides based on ROA are absorbed from the stomach and small intestine, distributed widely including
CNS, placenta and fetus?
Oral absorbable
37
Oral absorbable sulfonamides are absorbed from what part of the body and distributing where?
stomach and small intestine, distributed widely including CNS, placenta and fetus
38
Sulfonamide protein binding ranges from?
20% to 90%
39
Sulfonamides are metabolized in?
Liver
40
Sulfonamides are excreted in?
Urine, adjusted in renal failure
41
SULFONAMIDES have [weak/strong] acidic compounds
Weak
42
Sulfonamides have [modest/major] tissue absorption
Modest
43
SULFONAMIDES undergo what type of metabolism?
Hepatic
44
What form of SULFONAMIDES are seen in the urine excretion?
Both intact drug and acetylated metabolites
45
_____ may decrease in acid urine for sulfonamide excretion
Solubility
46
Solubility may decrease in acid urine for sulfonamide excretion due to the?
Precipitation of the drug/metabolites
47
SULFONAMIDES bind where?
to plasma proteins at sites shared by bilirubin and other drugs
48
Combination of 3 separate sulfonamides is called?
Triple sulfa
49
Triple sulfa is used to?
reduce the likelihood to precipitate
50
SULFONAMIDES based on duration of action is classified into?
* Short-acting (sulfisozaxole)
* Intermediate-acting (sulfamethosaxole)
* Long-acting (sulfadoxine)
51
Short acting sulfonamide
sulfisozaxole
52
Intermediate-acting sulfonamide
sulfamethosaxole
53
Long-acting sulfonamide
sulfadoxine
54
TRIMETHOPRIM is structurally similar to?
folic acid
55
TRIMETHOPRIM is a [weak/strong] base
Weak
56
TRIMETHOPRIM is usually trapped in [acidic/basic] environments
ACIDIC
57
TRIMETHOPRIM is high in concentration in what body fluids?
prostatic and vaginal fluids
58
TRIMETHOPRIM excretion is mainly in?
excreted unchanged in urine
59
t1/2 of TRIMETHOPRIM
10-12hrs
60
CLINICAL USES of SULFONAMIDES include?
* Gram (+)
* Gram (-) organisms
* Chlamydia
* Nocardia
* Simple urinary tract infection
* Ocular infection
* Burn infections
* Ulcerative colitis, rheumatoid arthritis
61
Sulfonamide used for simple urinary tract infection
Oral (triple sulfa, sulfisoxazole)
62
Sulfonamide used for Ocular infection
Topical (sulfacetamide)
63
Sulfonamide used for Burn infections
Topical (mafenide, silver sulfadiazine)
64
Sulfonamide used for Ulcerative colitis, rheumatoid arthritis
Oral (sulfasalazine)
65
Clinical Uses of Non-absorbable Agents
Ulcerative colitis, Enteritis and other Inflammatory Bowel Diseases (IBDs)
burn wounds
66
What Non-absorbable Agents is used for Ulcerative colitis, Enteritis and other Inflammatory Bowel Diseases (IBDs)?
Sulfasalazine (Salicylazosulfapyrine)
67
What Non-absorbable Agents is used for burn wounds for prevention of infection?
Silver sulfadiazine
68
What Non-absorbable Agents is used for burn wounds but can cause metabolic acidosis?
Mafenide acetate
69
Mafenide acetate can cause what condition?
metabolic acidosis
70
Oral Absorbable Agents Clinical Uses
Acute Toxoplasmosis (1st line) and second line antimalarial agent
71
first line for Acute Toxoplasmosis
Sulfadiazine + Pyrimethimine
72
second line antimalarial agent
Sulfadoxine + Pyrimethamine (Fansinadir)
73
CLINICAL USES of TRIMETHOPRIM SULFAMETHOSAXOLE (TMP-SMX)
* Urinary tract
* Respiratory
* Ear
* Sinus infections caused by H. influenzae
and M. catarrhalis
74
TMP-SMX is the DOC for?
* Pneumocystis pneumonia
* Toxoplasma
* Nocardiosis
75
TMP-SMX is the back-up drug for?
* Cholera
* Typhoid fever
* Shigellosis
76
TMP-SMX is used for the treatment of infections caused by?
* MR staphylococci
* L. monocytogenes
77
TOXICITY OF SULFONAMIDES includes?
Hypersensitivity
Gastrointestinal
Hematoxicity
Nephrotoxicity
Drug interactions
78
What is COMMON in the hypersensitivity toxicity of sulfonamides?
Skin rash and fever
79
What is RARE in the hypersensitivity toxicity of sulfonamides?
Exfoliative dermatitis, polyarteritis nodosa
and Stevens-Johnson syndrome
80
In sulfonamide hypersensitivity, there is cross-allergenicity between?
individual sulfonamides and chemically related drugs
81
In sulfonamide hypersensitivity, there is _______________ between individual sulfonamides and with chemically related
drugs
cross-allergenicity
82
In sulfonamide GI toxicity, what is common?
Nausea, vomiting, and diarrhea
83
In sulfonamide GI toxicity, what is UNcommon?
Mild hepatic dysfunction, hepatitis
84
What is the rare kind of toxicity in sulfonamides?
Hematoxicity
85
Hematoxicity in sulfonamides includes?
Granulocytopenia, thrombocytopenia, and
aplastic anemia
Acute hemolysis in G-6PD
86
In nephrotoxicity, Sulfonamide may precipitate in ____ causing _______ and _________
acid urine
Crystalluria and hematuria
87
SULFONAMIDES have competitive drug interactions with?
warfarin and methotrexate for plasma binding
88
SULFONAMIDES also displaces ____ from plasma proteins causing _______
Displace bilirubin from plasma protein
Kernicterus (3rd trimester of pregnancy)
89
TOXICITY OF TRIMETHOPRIM
* Megaloblastic anemia, leukopenia, and
granulocytopenia
* HIV patients given TMP-SMX experience Fever, Rashes, Leukopenia, Diarrhea
* Mild elevation of blood creatinine
90
Megaloblastic anemia, leukopenia, and
granulocytopenia in trimethoprim toxicity is due to?
Supplementary folinic acid
91
What causes the mild elevation of
blood creatinine in trimethoprim?
inhibition in the secretion of creatinine at the distal renal tubule
92
Earliest Fluoroquinolone is?
Nalidixic Acid
93
Synthetic fluorinated derivatives include?
Ciprofloxacin,
Levofloxacin
94
Fluoroquinolones are bactericidal or bacteriostatic?
Bactericidal
95
Examples of Fluoroquinolones
Nalidixic Acid
Ciprofloxacin
Moxifloxacin
Gemifloxacin
Norfloxacin
Levofloxacin
96
1st generation FLUOROQUINOLONE
Norfloxacin
97
Norfloxacin is derived from?
nalidixic acid
98
Norfloxacin is used for?
Common pathogens that cause UTI
99
2nd generation FLUOROQUINOLONE
Ciprofloxacin
100
Ciprofloxacin is used for?
* Gonococcus
* Gram (+) cocci
* Mycobacteria
* Atypical organisms (M. pneumoniae)
101
Ciprofloxacin has a greater activity against G(-) or G(+)?
-
102
3rd generation FLUOROQUINOLONES
Levofloxacin, gatifloxacin, sparfloxacin
103
Levofloxacin, gatifloxacin, sparfloxacin have more activity against G[-/+] and less activity against G[-/+]
More activity for +
Less activity for -
104
Levofloxacin, gatifloxacin, sparfloxacin mainly acts of what bacteria?
* Streptococci
* S. pneumoniae
* Staphylococci
* MRSA
* Some strains of enterococci
105
4th generation FLUOROQUINOLONES
Moxifloxacin, trovafloxacin
106
Moxifloxacin, trovafloxacin have enhanced activity against?
anaerobes
107
Fluoroquinolones are well absorbed through what ROA?
Orally
108
Degree of distribution of Fluoroquinolones?
Wide
109
Long half-lives of what Fluoroquinolones permits 1x daily dosing?
Levofloxacin, Gemifloxacin and Moxifloxacin
110
Levofloxacin, Gemifloxacin and Moxifloxacin are dosed how often in a day?
1x
111
Fluoroquinolones have impaired absorption when combined with?
antacids, divalent and trivalent cations
112
Fluoroquinolones should be taken how many hours before and after the antacids, divalent and trivalent cations?
2 hours before or 4 hours after
113
Fluoroquinolones mode of excretion is mainly through?
Most are renally excreted (requiring renal dose adjustment) except for Moxifloxacin (liver)
114
Fluoroquinolone with the highest oral F
Ofloxacin
115
Oral F of Ciprofloxacin and Gemifloxacin
70%
116
Fluoroquinolones with the longest half-life
Moxifloxacin
117
Does not achieve adequate plasma levels
for use in systemic infections
Norfloxacin
118
Moxifloxacin, sparfloxacin, travofloxacin are eliminated partly by?
hepatic metabolism and biliary excretion
119
FLUOROQUINOLONES interfere with?
Bacterial DNA synthesis and inhibits topoisomerase II (DNA gyrase)
120
FLUOROQUINOLONES block the relaxation of?
supercoiled DNA catalyzed by DNA gyrase
121
FLUOROQUINOLONES are bactericidal or bacteriostatic?
Bactericidal
122
FLUOROQUINOLONES also exhibit what effects?
postantibiotic effects
123
Fluoroquinolone-resistant organisms appears in every?
10^7-10^9 especially notable among Staphylococci, P. aeruginosa and S. marcesens
124
Fluoroquinolone resistance can also be brought about by the mutation in?
in the quinolone binding region of the target enzyme or to a change in permeability
125
FLUOROQUINOLONES resistance emerged rapidly from what generation?
2nd
126
FLUOROQUINOLONES resistance emerged rapidly from 2nd generation, causing resistance in what bacteria?
* C. jejuni and gonococci
* Gram (+) cocci (MRSA)
* Pseudomonas and Serratia
127
FLUOROQUINOLONES resistance mechanisms include?
* Production of efflux pumps
* Changes in porin structure
* Changes in sensitivity of the enzyme via
point mutations in the antibiotic binding
regions
128
FLUOROQUINOLONES CLINICAL USE
* Urogenital and gastrointestinal tract
infection
* Gram (-) organisms
* Gonococci, E. coli
* K. pneumoniae, C. jejuni
* Enterobacter, P. aeruginosa
* Salmonella, Shigella
129
FLUOROQUINOLONES effectiveness is variable due to?
resistance in respiratory tract skin and soft tissue infection
130
FLUOROQUINOLONE alternative to 3rd generation cephalosporin
Ciprofloxacin and ofloxacin
131
Ciprofloxacin and ofloxacin are used for?
* N. gonorrhea (single oral doses)
* Ofloxacin will eradicate accompanying
organisms like Chlamydia (7 day course)
132
FLUOROQUINOLONES used for CAP and Atypical pneumonia (M. pneumoniae)
Levofloxacin
133
FLUOROQUINOLONES for Gram (+) organisms Penicillin-resistant pneumococci
Sparfloxacin
134
Moxifloxacin and trovafloxacin clinical uses
* Gram (+)
* Gram (-) organisms
* Anaerobic bacteria
* Used in meningococcal carrier state
* Tuberculosis
* Prophylactic management of neutropenic
patients
135
Fluoroquinolones most common adverse effect?
Nausea, vomiting and diarrhea
136
Fluoroquinolones most occasional adverse effect?
headache, dizziness, insomnia, skin rash or
abnormal LFTs
137
Lomefloxacin, Pefloxacin have what adverse effects?
Photosensitivity
138
Gatifloxacin, Levofloxacin, Gemifloxacin
and Moxifloxacin have what adverse effects?
QT Prolongation
139
Gatifloxacin has what adverse effects?
Hyperglycemia when given alone or Hypoglycemia when given with oral hypoglycemic agents
140
Fluoroquinolones may damage growing cartilage and cause?
arthropathy, Tendinitis and tendon rupture
141
Fluoroquinolones must be avoided in?
pregnancy
142
Fluoroquinolones are temporary to?
Permanent Peripheral Neuropathy
143
FLUOROQUINOLONES cause superinfection caused by?
C. albicans and streptococci
144
FLUOROQUINOLONES also have increased levels of what in toxicity?
theophylline and other methylxanthines
145
FLUOROQUINOLONE that causes risk for cardiac arrhythmia and Photosensitivity
Sparfloxacin
146
FLUOROQUINOLONE with Hepatotoxic potential
Trovafloxacin
147
Mycobacteria appearance?
Rod-shaped, aerobic bacteria and a cell wall with peptidoglycolipids, fatty acids, waxes,
and mycolic acid
148
Growth, acid staining and reactance of mycobacteria
Slow growth, acid fast, resistant to detergents / antibiotics
149
Mycobacteria infecting humans and their causes
M. tuberculosis - Pulmonary tuberculosis,
extrapulmonary TB
M. leprae - Leprosy
M. bovis - Tuberculosis-like illness
Mycobacterium avium complex - Disseminated infection, pulmonary infections, common in immunocompromised states/HIV
150
DRUG COMBINATIONS are used in ANTIMYCOBACTERIAL DRUGS for?
*To delay emergence of resistance
*To enhance antimycobacterial efficacy
151
COMPLICATIONS OF CHEMOTHERAPY in the use of ANTIMYCOBACTERIAL DRUGS
* Limited information about the MOA
* Development of resistance
* Intracellular location of mycobacteria
* Chronic nature of the disease (protracted therapy and drug toxicities)
* Patient compliance
152
What other organs besides the lungs can TB affect?
Liver, CNS, Bone, GI, Kidneys
153
First line drugs against TB?
Isoniazid (H)
Rifampicin (R)
Pyrazinamide (Z)
Ethambutol (E)
154
Second line drugs against TB?
Levofloxacin
Moxifloxacin
Bedaquiline
Linezolid
Clofazimine
Cycloserine
Ethambutol
Delamanid
Pyrazinamide
Imipenem – Cilastatin
Meropenem
Amikacin
Streptomycin
Prothionamide
P-amino salicyclic acid
155
Isoniazid is a structural congener of?
pyridoxine
156
In Isoniazid, the inhibition of enzymes required for?
the synthesis of mycolic acid
157
Is isoniazid bactericidal or bacteriostatic?
Bactericidal
158
T or F: Resistance can emerge rapidly in Isoniazid if used alone
T
159
Isoniazid resistance involves which substances?
katG gene -catalase peroxidase bioactivation of INH
inhA gene – enzyme acyl carrier reductase
160
Isoniazid is well absorbed in what ROA?
orally
161
Isoniazid is metabolized by what process in which organ?
acetylation in the liver
162
Metabolism of Isoniazid in the liver is affected by?
genetic control of acetylation which can be fast or slow
163
Clinical use of Isoniazid
Single most important drug used for TB, making it a component of drug combination regimen
Latent tuberculosis infection (LTBI); close contacts (sole drug)
164
Toxicity with the use of Isoniazid
* Peripheral neuritis, restlessness, muscle
twitches, insomnia
̶ Pyridoxine (25-50mg/d)
* Hepatotoxic
* CYP 450 enzyme inhibitor
* Hemolysis in G6PD deficient patients
165
Rifampin / Rifampicin is bacteriostatic or bactericidal?
Bactericidal
166
Rifampin / Rifampicin inhibits _______.
DNA-dependent RNA polymerase
167
Resistance to Rifampin / Rifampicin results from?
changes in drug sensitivity of polymerase
168
Clinical Uses of Rifampin / Rifampicin
* Used in combination with drugs
* Can be used as sole drug in LTBI or close contacts with INH-resistant strains
* In leprosy – it delays resistance to dapsone
* Used for MRSA, PRSP
169
Toxicities and Interactions observed in Rifampin
* Can impair antibody responses
* Skin rashes, thrombocytopenia, nephritis, liver dysfunction
* Flu-like symptoms, anemia
* Induces liver drug-metabolizing enzymes
170
What other rifamycin is equally effective as anti mycobacterial agent; less drug interactions?
Rifabutin
171
What other rifamycin is preferred over rifampin in AIDS patients taking some antiretrovirals?
Rifabutin
172
What other rifamycin is not absorbed from GI tract, used in traveler’s diarrhea?
Rifaximin
173
Ethambutol inhibits what substance needed for what process?
arabinosyltransferase enzyme needed for cell wall synthesis
174
Ethambutol resistance is due to?
mutation in emb gene if drug is used alone
175
Ethambutol is well absorbed in what ROA?
orally
176
Ethambutol is [limitedly/widely] distributed in most tissues including CNS
Widely
177
Ethambutol is mainly excreted through?
unchanged in urine with dose reduction in renal impairment
178
Ethambutol clinical use
Mainly for TB, in combination with other drugs
179
Ethambutol Toxicities include?
* Dose-dependent visual disturbances
̶ Decrease in acuity, color blindness, optic neuritis, retinal damage
* Headache, confusion, hyperuricemia, peripheral neuritis
180
Pyrazinamide is bactericidal or bacteriostatic?
Bacteriostatic action – through pyrazinamidases
181
Pyrazinamide has a [well-known/unknown] MOA
Unknown
182
Pyrazinamide resistance is due to?
mutations in genes that encode enzymes; drug-efflux systems esp. when used alone
183
Pyrazinamide is well absorbed through what ROA?
Oral
184
T or F: Pyrazinamide penetrates most body tissues, including CNS
T
185
Pyrazinamide is partly metabolized by?
Pyrazinoic acid
186
Pyrazinamide t1/2 is [prolonged/shortened] with liver or kidney failure
Prolonged
187
Pyrazinamide t1/2 is prolonged due to?
liver or kidney failure
188
Pyrazinamide clinical use is in combination with?
other drugs for MTB
189
Pyrazinamide toxicities include?
* Joint pains
* Asymptomatic hyperuricemia
* Myalgia, GI irritation, rash, hepatic dysfunction
* Should be avoided in pregnancy
190
Used in combination for life-threatening TB (meningitis, miliary TB, other EPTB)
Streptomycin
191
For TB caused by streptomycin- resistant or MDR-TB
Amikacin
192
Active against strains of MTB resistant to first-line agents; used in combination
Ciprofloxacin and ofloxacin
193
Congener of INH; major effect – severe GI irritation & neurologic toxicity
Ethionamide
194
The intensive phase of TB treatment lasts for how long?
2months
195
Continuation or maintenance phase of TB treatment lasts for?
≥4 months
196
Refers to MTB strains in which resistance to both isoniazid and rifampicin has been confirmed in vitro
Multidrug-resistant TB (MDR-TB)
197
Multidrug-resistant TB (MDR-TB) refers to MTB strains which are resistant to?
both isoniazid and rifampicin
198
Fixed-dose combination is composed of?
anti TB pills containing 2 or more drugs
199
Diagnostic and therapeutic unit that caters patients diagnosed with TB or suspected of having TB
TB-DOTS
200
DOTS stands for?
The Directly Observed Treatment Strategy
201
Drugs for Leprosy include?
DAPSONE (Diaminodiphenylsulfone)
Sulfones - ACEDAPSONE
Clofazimine
202
DAPSONE is the most active drug against?
M. leprae
203
DAPSONE MOA includes the inhibition of?
folic acid synthesis
204
Dapsone resistance can develop if [low/high] doses are given, usually in combination with __________.
Low
Rifampin and / or Cloafazimine
205
Dapsone ROA and excretion
Orally
Urine
206
Dapsone toxicity?
* GI irritation
* Fever
* Skin rashes
* Methemoglobinemia
* Hemolysis in patients with G-6PD
207
Repository form of dapsone
ACEDAPSONE
208
ACEDAPSONE provides what for several months?
inhibitory plasma concentrations
209
ACEDAPSONE is an alternative drug for?
P. carinii pneumonia in HIV patients
210
Phenazine dye for used for multibacillary leprosy
Clofazimine
211
T or F: Clofazimine MOA is well-known
F, not clearly defined
212
t1/2 of Clofazimine can last as long as?
2months
213
Most prominent adverse effect of Clofazimine?
discoloration of skin and conjunctivae
214
What kind of drugs are less susceptible to anti-TB drugs?
Nontuberculous Mycobacteria (NTM) Drugs
215
What drugs are active for NTM?
Tetracyclines, macrolides, sulfonamides
216
What bacterium are common among AIDS patients?
M avium complex: M avium and M intracellulare
217
M avium complex infections are treated with?
Azithromycin/Clarithromycin + Ethambutol, or Rifabutin
218
Prophylaxis against M avian includes?
Azithro/Clarithromycin
