MT6314 PROTEIN SYNTHESIS INHIBITORS AND AMINOGLYCOSIDES Flashcards
1
Q
T or F: Protein synthesis in microorganisms is identical to mammalian cells
A
F, NOT identical
2
Q
How many S ribosomal units are in bacteria and what are the subunits?
A
70S (50S and 30S)
3
Q
How many S ribosomal units are in mammalians and what are the subunits?
A
80S (40S and 60S)
4
Q
Protein Synthesis Inhibitors have a basis for (WHAT) against microorganisms without causing major effects on mammalian cells?
A
selective toxicity
5
Q
Differences in protein synthesis inhibitors are based on?
A
Chemical composition
Ribosomal subunits
Functional specificities of component nucleic acids and proteins
6
Q
What are the types of MOAs in protein synthesis inhibitors?
A
Bacteriostatic
Bactericidal
7
Q
What protein synthesis inhibitors are under the bactericidal MOA?
A
Oxazolidinones and Pleuromutilins
8
Q
All have a 50S ribosomal unit except?
A
Tetracycline
9
Q
A normal bacterial ribosomal complex is composed of what ribosomal units?
A
Entire structure - 70S
Larger - 50S
Smaller - 30S
10
Q
Can inhibit transpeptidation (part of the bacterial MOA structure) – acting on the cell wall
A
Chloramphenicol
11
Q
Blocks translocation of peptide tRNA from acceptor site
A
Macrolides
12
Q
Where are the tetracyclines located: 30S or 50S?
A
30S
13
Q
Blocks the binding of the charged tRNA to the acceptor site
A
Tetracyclines
14
Q
Constricts the channel and inhibits the entrance of other molecules which created a steric effect on the growing peptide chain
A
Streptogramins
15
Q
What protein synthesis inhibitors are under the broad spectrum?
A
Chloramphenicol and Tetracyclines
16
Q
What protein synthesis inhibitors are under the moderate spectrum?
A
Macrolides and Ketolides
17
Q
What protein synthesis inhibitors are under the narrow spectrum?
A
Lincosamides
Streptogramins
Linezolid
18
Q
Disadvantage of broad spectrum inhibitors?
A
Affect normal flora
19
Q
ROA of chloramphenicols?
A
Parenteral and oral
20
Q
MOA of chloramphenicols?
A
inhibits microbial protein synthesis
bacteriostatic against most susceptible organisms
binds reversibly to the 50S subunit of the bacterial ribosome and inhibits peptide bond formation
21
Q
Chloramphenicols readily cross the?
A
BBB
Placenta
22
Q
T or F: Chloramphenicols can be used in pregnant patients and NOT in patients with meningitis and encephalopathy.
A
F, CANNOT in pregnant and CAN in meningitis and encephalopathy
23
Q
Chloramphenicols under go ___ cycling
A
Enterohepatic
24
Q
T or F: Some fraction of chloramphenicols remains unchanged in the urine
A
T
25
The enterohepatic cycling of chloramphenicols is inhibited by?
Glucuronosyltransferase
26
Chloramphenicol's are active against?
G(+) nand G(-) bacteria
27
Bactericidal antimicrobial activity of chloramphenicols are effective against strains of?
H. influenzae
N. meningitidis
Some strains of Bacteroides
28
Chloramphenicols are NOT effective against?
Chlamydia
29
Resistance to chloramphenicols are ___ mediated through the formation of _______
Plasmid
Chloramphenicol acetyltransferases
30
Clinical Uses of chloramphenicols?
- Rickettsial infections: typhus and Rocky Mountain spotted
- Alternative to a β-lactam antibiotic for bacterial meningitis in patients who have major hypersensitivity reactions to penicillin
- Severe infections - Salmonella spp.
- Alternative to pneumococcal and meningococcal meningitis
- Anaerobic - B. fragilis
- Topical antimicrobial
31
IV formulation of chloramphenicol involves the hydrolysis of what component to form what component?
chloramphenicol succinate (prodrug) -> hydrolyzed to yield free chloramphenicol
32
Chloramphenicol is widely distributed, including?
CNA and CSF
33
T or F: Concentrations of chloramphenicol in the brain tissue may be equal to that in serum
T
34
Chloramphenicols are inactivated by?
(1) conjugation with glucuronic acid or
(2) reduction to inactive aryl amines
35
Excretion of chloramphenicols
Active chloramphenicol + inactive degradation products = urine
Small amount of active drug - bile and feces
36
Toxicity of chloramphenicols
1. Gastrointestinal disturbances
2. Oral or vaginal candidiasis due to alteration of normal flora
3. Bone marrow
4. Gray baby syndrome
37
What is a rare idiosyncratic reaction in the toxicity of chloramphenicols?
Aplastic anemia
38
T or F: Aplastic anemia is reversible
F, irreversible nad fatal
39
In gray baby syndrome, the baby lacks what?
Effective glucuronic acid conjugation mechanism for degradation and detoxification
40
T or F: Neonates and premature babies are more sensitive to the dosages of chloramphenicols to older infants
T
41
What are the drug interactions of chloramphenicols?
* Inhibits hepatic drug-metabolizing enzymes
* Increasing the elimination half-lives of drugs
42
Chloramphenicol increases the half life of what drugs?
Warfarin
Tolbutamide
Chlorpropamide
Phenytoin
43
What are the kinds of tetracyclines?
Tetracycline
Doxycycline
Minocycline
Tigecycline
Eravacycline
Omadacycline
44
Tetracyclines are bacteriostatic or bactericidal?
Bacteriostatic
45
MOA of tetracyclines?
bind reversibly to the 30S subunit of the bacterial ribosome, blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex and prevents addition of amino acids to the growing peptide
46
Oral absorption for tetracyclines include which kinds?
* 60–70% for tetracycline and demeclocycline
* 95–100% for doxycycline and minocycline
47
Which tetracyclines are exempt from being taken on an empty stomach?
Doxycycline and Minocycline
48
Tetracyclines which are taken intravenously
Tigecycline and eravacycline
49
Tetracycline is excreted in?
Feces
50
Tetracyclines absorption occurs mainly in the?
Upper small int.
51
Tetracycline absorption is impaired by?
Food, multivalent cations (Ca2+, Mg2+, Fe2+, Al3+); dairy products and antacids, and by alkaline pH
52
T or F: Tetracyclines cross the placenta
T
53
Tetracyclines have wide tissue distribution except in the?
CSF
54
Tetracyclines cross the placental barrier and excreted in?
breast milk
55
Tetracyclines excreted mainly in?
bile and urine
Except : Doxycycline and tigecycline (eliminated by nonrenal mechanisms and do not accumulate significantly in renal failure, requiring no dosage adjustment)
56
T or F: Tetracyclines also undergo enterohepatic cycling
T
57
Doxycycline and Tigecyclines are excreted in?
Feces/ fecal extraction
58
t1/2 of Tetracycline?
6-11h
59
t1/2 of doxycycline and minocycline?
15-23h
60
t1/2 of tigecycline?
30-36h
61
Shortest acting tetracycline?
tetracycline (oral)
62
Intermediate acting tetracycline?
demeclocycline (oral)
63
Long acting oral and IV tetracyclines?
doxycycline and minocycline
64
Tetracyclines with long half lives?
Tigecycline (IV),
Eravacycline (IV),
Omadacycline (oral and IV)
65
Antibacterial Activity of tetracyclines?
Active against gram-positive and gram-negative bacteria - certain anaerobes, rickettsiae, chlamydiae, and mycoplasmas (CRAM)
66
Resistance mechanisms for tetracyclines?
(1) impaired influx or increased efflux by an active transport protein pump
(2) ribosome protection due to production of proteins that interfere with tetracycline binding to the ribosome
(3) enzymatic inactivation
67
Primary clinical uses of tetracyclines?
Mycoplasma pneumoniae (in adults)
Chlamydiae
Rickettsiae*
Borrelia sp.*
Vibrios
Spirochetes
Anaplasma phagocytophilum
Ehrlichia sp
(CREAMBVS)
68
Secondary uses for tetracyclines include its use an alternative to treat?
CAP
Syphilis
Chronic bronchitis
Leptospirosis
Acne
(SLACC)
69
Selective use of tetracycline includes treating?
GI ulcers in H. pylori
70
Doxycycline selective uses includes treatment for?
Lyme disease
71
Minocycline includes selective use against?
meningococcal carrier state
72
Selective use of doxycycline is used for?
* Malaria prophylaxis
* Treat ameobiasis
73
Demeclocycline selective use is to?
* inhibits the renal actions of antidiuretic hormone (ADH)
* ADH-secreting tumors
74
Selective use includes Coagulase-negative staphylococci (CoNS), gram-positive cocci resistant to methicillin (MRSA strains) and vancomycin (VRE strains)
Tigecycline, eravacycline and omadacycline
75
Tigecycline, eravacycline and omadacycline has selective uses against?
Streptococci,
enterococci,
G(+) rods,
Enterobacteriaceae,
Acinetobacter sp,
anaerobes,
rickettsiae,
Chlamydia sp,
L. pneumophila; and
rapidly growing mycobacteria
76
Tetracyclines toxicity includes?
1. Gastrointestinal disturbances
2. Bony structures and teeth
3. Hepatic toxicity
4. Renal toxicity
5. Photosensitivity
6. Vestibular toxicity
77
Fetal exposure to tetracycline will cause?
* irregularities in bone growth
* tooth enamel dysplasia
78
Toxicities of tetracycline seen in the Bony structures and teeth in children are due to?
* enamel dysplasia
* crown deformation (permanent teeth)
79
Photosensitivity toxicity seen in tetracyclines is seen in?
demeclocycline
80
Vestibular toxicity in tetracyclines is prominent in?
Doxycycline and minocycline
81
Vestibular toxicity in tetracyclines is characterized by?
Dose-dependent reversible dizziness and vertigo
82
Macrolides includes?
Erythromycin
Azithromycin
Clarithromycin
(ACE)
83
Macrolides have what structure?
lactone ring with attached sugars
84
Prototype macrolide is?
Erythromycin (1952)
85
Semisynthetic derivatives of erythromycin include?
Clarithromycin and azithromycin
86
Macrolides MOA?
Inhibition of protein synthesis occurs via binding to the 50S ribosomal RNA
87
Macrolide antibiotics prolong the _______________ due to an effect on ________ channels: _______________
electrocardiographic QT interval
potassium channels
torsades de pointes arrhythmia
88
Macrolides has (good/bad) oral F
Good
89
Azithromycin absorption impeded by?
Food
90
Azithromycin is distributed mainly where?
tissues and phagocytes > plasma
91
T or F: Macrolides are distributed mainly in most body tissues
T
92
* Erythromycin (oral and IV) half-life: _____
* Clarithromycin (oral) half-life: ______
* Azithromycin (oral and IV) half-life: ______
2 hours
6 hours
2 to 4 days
93
Antibacterial activity of erythromycin includes?
Campylobacter
Chlamydia
Mycoplasma
Legionella
G(+) cocci and some G(-) organisms
94
Azithromycin and Clarithromycin antibacterial activity?
Greater activity against Chlamydia, Mycobacterium avian complex and Toxoplasma
95
Azithromycin is used as an alternative drug against?
Gonorrhea
96
Resistance in gram-positive bacteria in macrocodes are due to?
* efflux pump mechanisms
* production of a methylase
97
T or F: There is complete cross resistance between macrolides
T
98
In macrolide antibacterial activity, there is partial cross resistance between?
clindamycin and streptogramins.
99
Resistance in Enterobacteriaceae is caused by?
drug-metabolizing esterases.
100
Erythromycin is effective against G(+) cocci except?
penicillin-resistant Streptococcus pneumoniae [PRSP] strains
101
Erythromycin is effective against G(-) cocci except?
MRSA strains
102
Azithromycin more active against what bacterial infections?
* Haemophilus influenzae
* Moraxella catarrhalis
* Neisseria.
103
A single dose of azithromycin is useful against?
genitourinary infections - C trachomatis
104
A 4-day course of treatment by azithromycin is useful against?
CAP
105
What macrolide has the same spectrum as erythromycin?
Clarithromycin
106
Clarithromycin and erythromycin are used for what clinical uses?
* prophylaxis and treatment of M avium complex
* drug regimens for ulcers caused by H pylori.
107
What is a narrow-spectrum macrolide example and its uses?
Fidaxomicin used for gram-positive aerobes and anaerobes.
108
Fidaxomicin is as effective as what drug for what infection?
effective as vancomycin vs difficile colitis
109
Toxicity to erythromycin includes?
GI irritation
Skin rashes
Eosinophila
110
Acute cholestatic hepatitis is caused by?
Erythromycin estolate
111
Erythromycin estimate causes what condition?
Acute cholestatic hepatitis
112
T or F: Hepatic toxicity in erythromycin is common in children
F, rare
113
Who is at higher risk of erythromycin estolate?
pregnant women
114
Inhibits cytochrome p450
Erythromycin
115
T or F: Azithromycin inhibits cytochrome P450
F, does not
116
With the inhibition of cytochrome P450, erythromycin increases plasma levels of?
Anticoagulants, cisapride, carbamezapine, digoxin
117
Ketolide structurally related to macrolides.
Telithromycin
118
Telithromycin has the same spectrum and MOA as?
erythromycin
119
Telithrmycin is usually used to treat?
Community acquired bacterial pneumonia
120
What strains are susceptible to telithromycin?
Macrolide-resistant strains
121
Telithromycin is metabolized in?
the liver
122
Telithromycin is excreted in?
Bile and urine
123
How often is the dosing of telithromycin?
Once daily, 800mg
124
Telithromycin reversibly inhibits what in the enzyme system?
CYP34A
125
T or F: Telithromycin also prolongs the QTc intervals
T
126
Telithromycin is only used for the treatment of?
Community acquired bacterial pneumonia
127
Telithromycin can also cause what kind of toxicity?
Hepatitis and liver failure
128
Telithromycin contraindicated in patients with?
Myasthenia gravis
129
A fluoroketolide
Solithromycin
130
Solithromycin showed noninferiority with ______ in the treatment of ______
Moxifloxacin
Community acquired bacterial pneumonia
131
Solithromycin has in vitro activity against?
Macrolide resistant bacteria
Staphylococci, S. pneumoniae, Neisseria, Enterococci, Chlamydia
132
Solithromycin lacks what side chain group?
Pyridine imidazole
133
What is the role of pyridine-imidazole side chain to telithromycin?
Contributes to its hepatotoxicity
134
Solithromycin is also used against what infections?
STIs
135
What is still the DOC for STIs?
Ceftrizxone and Azithromycin
136
Gram-negative organisms erythromycin is effective against include?
Neisseria sp,
Bordetella pertussis,
Bartonella spp.
Rickettsia species
Treponema pallidum,
Campylobacter species
137
Erythromycin resistance mechanisms include?
(1) Reduced permeability of the cell membrane or active efflux
(2) Production (by Enterobacteriaceae) of esterases that hydrolyze macrolides
(3) Modification of the ribosomal binding site (so-called ribosomal protection) by chromosomal mutation or by a macrolide-inducible or constitutive methylase.
138
T or F: Food interferes with absorption in Erythromycin
T
139
Erythromycin is excreted mainly in?
bile (only 5% in the urine)
140
Erythromycin is distributed widely except to the?
Brain and CSF
141
Erythromycin is mainly taken up by what cells?
polymorphonuclear leukocytes and macrophages
142
Erythromycin also traverses the?
placenta and reaches the fetus
143
What is the main adverse reaction seen in Erythromycin?
Cholestatic hepatitis
144
Erythromycin has drug interactions with?
theophylline
warfarin
cyclosporine
methylprednisolone
digoxin
(MTW-DC)
145
Useful as a penicillin substitute in penicillin-allergic individuals with infections caused by staphylococci and streptococci
Erythromycin
146
Clarithromycin is more active against what strains of bacteria?
Mycobacterium avium complex
M leprae, T gondii, H influenzae.
147
Where is Clarithromycin metabolized mainly?
Liver
148
Where is Clarithromycin excreted mainly?
Partially in the urine, mainly in bile
149
What is the major metabolite seen in Clarithromycin that confers its antibacterial activity?
14-hydroxyclarithromycin
150
Where is 14-hydroxyclarithromycin eliminated?
Urine
151
What is the adverse reaction observed in Clarithromycin?
lower incidence of gastrointestinal intolerance
152
Clarithromycin has similar drug interactions with?
Erythromycin
153
Dosage reduction for Clarithromycin is recommended in patients with?
creatinine clearances less than 30 mL/min
154
Azithromycin penetrates into _____ and ______ really well
most tissues (except cerebrospinal fluid) and phagocytic cells extremely well
155
Azithromycin is rapidly absorbed and tolerated well in what ROA?
Oral
156
When taken with Azithromycin, these substances do not alter bioavailability but delay absorption and reduce peak serum concentrations
Aluminum and magnesium antacids
157
What are the effects of Aluminum and magnesium antacids on the absorption of Azithromycin?
do not alter bioavailability but delay
absorption and reduce peak serum concentrations
158
T or F: Azithromycin has drug interactions
F, none
159
What is the drug under Lincosamide?
Clindamycin
160
Clindamycin has similar MOA with?
Macrolides
161
T or F: Clindamycin is chemically related to Macrolides
F
162
Clindamycin is useful against?
* Streptococci, staphylococci, and pneumococci
* Bacteroides sp and other anaerobes
163
What strains are intrinsically resistant to Clindamycin?
Gram-negative aerobes due to poor penetration through the outer membrane.
164
MOA of Clindamycin
Oral and IV
165
When does good tissue penetration of Clindamycin occur?
after oral absorption
166
Mode of metabolism of Clindamycin?
Hepatic metabolism
167
Half life of Clindamycin?
6- 8hours
168
Excretion of Clindamycin happens through?
renal and biliary excretion
169
Clinical Use of Clindamycin includes?
* Severe anaerobic infections: Bacteroides, Fusobacterium, and Prevotella (BFP)
* Backup for gram-positive cocci: Community-acquired strains of MRSA
* Toxic shock syndrome (with penicillin G) or necrotizing fasciitis
* Penetrating wounds of the abdomen and gut (combined with aminoglycoside or cephalosporin)
* Septic abortion, pelvic abscesses, or pelvic inflammatory disease; and lung and periodontal abscesses
* Prophylaxis of endocarditis in valvular disease (patients allergic to penicillin)
* In combination with primaquine alternative vs P. jiroveci pneumonia in AIDS
patients
* In combination with pyrimethamine for AIDS-related toxoplasmosis
170
Toxicities commonly seen in Clindamycin include?
* GI irritation
* Skin rashes
* Neutropenia
* Hepatic dysfunction
* Superinfections C. difficile- pseudomembranous colitis
171
Dalfopristin is to streptogramin (A/B)?
A - 70%
172
Quinupristin is to streptogramin (A/B)?
B - 30%
173
Quinupristin-dalfopristin have the same ribosomal binding site as?
macrolides and clindamycin
174
Quinupristin-dalfopristin are bacteriostatic or bactericidal?
Bactericidal
175
T or F: Quinupristin-dalfopristin have post-antibiotic effects, wherein the effects still linger long after the serum concentrations have gone down
T
176
Quinupristin-dalfopristin are all bactericidal except combating which bacteria?
Enterococcus faecium
177
Quinupristin-dalfopristin is active against what bacterium?
Active against gram-positive cocci (multidrug-resistant strains of streptococci, PRSPs, methicillin-susceptible and resistant strains of staphylococci, and E faecium)
VRSA
178
What bacterium is intrinsically resistant via efflux transport system in Quinupristin-dalfopristin?
E faecialis
179
Resistance of Quinupristin-dalfopristin methods include?
* Modification of the quinupristin binding site (MLS-B type resistance)
* Enzymatic inactivation of dalfopristin
* Efflux
180
ROA of streptogramins?
IV
181
Which has a faster metabolism activity/more rapidly metabolized: Quinupristin or Dalfopristin?
Dalfopristin t1/2 = 0.7 hours
182
Elimination of Quinupristin-dalfopristin?
fecal route
183
Side effects of the IV ROA of Quinupristin-dalfopristin?
Pain
Arthralgia Myalgia syndrome
184
T or F: Dose adjustment for Quinupristin-dalfopristin is necessary for renal failure, peritoneal dialysis, or hemodialysis
F, not necessary
185
Quinupristin-dalfopristin has drug interactions with what substances due to the inhibition of what substance?
due to inhibition of CYP3A4:
warfarin, diazepam, quetiapine, simvastatin, and cyclosporine
186
Clinical uses of Quinupristin-dalfopristin include?
Infections caused by staphylococci or by vancomycin-resistant strains of E faecium
187
Adverse effects of Quinupristin-dalfopristin include?
Pain at infusion site and arthralgia-myalgia syndrome
188
Oxazolidinones include?
Linezolid
Tedizolid
189
Linezolid is active against?
Active against gram-positive organisms including staphylococci, streptococci, enterococci, anaerobics, corynebacteria, Nocardia sp, L monocytogenes, and Mycobacterium tuberculosis
190
Linezolids are mainly bacteriostatic or bactericidal?
Bacteriostatic but bactericidal against streptococci
191
MOA of Linezolid
preventing formation of the ribosome complex that initiates protein synthesis.
192
Where is the binding site of Linezolid?
23S ribosomal RNA of the 50S subunit
193
Resistance of Linezolid
mutation of the linezolid binding site on 23S ribosomal RNA
194
T or F: There is rare resistance with Linezolid
T
195
T or F: There is cross resistance between Linezolid and other protein synthesis inhibitors
F, none
196
Rare resistance in Linezolid involves a (decreased/increased) affinity to its binding site
Decreased
197
MOA of Linezolid
Oral and IV
198
t1/2 of Linezolid
4-6h
199
Method of metabolism of Linezolid
oxidative metabolism to form inactive metabolites
200
Linezolid is usually reserved for what kind of bacteria?
Multidrug resistant G(+) bacteria
201
Linezolid is mainly metabolized by what organ?
Liver
202
Clinical uses of Linezolid
vancomycin-resistant E faecium infections, HCAP, CAP, skin and soft tissue infections (gram-positive bacteria).
203
Off-label uses of Linezolid
treatment of MDR-TB and Nocardia infections
204
Adverse effects of Linezolid
thrombocytopenia, anemia, neutropenia; optic and peripheral neuropathy and lactic acidosis; serotonin syndrome
205
Tedizolid is an active prodrug against?
tedizolid phosphate
206
High potency against G(+) or G(-) bacteria?
G(+) - (MRSA, VRE, streptococci, gram-positive
anaerobes)
207
Bioavailability and t1/2 of Tedizolid
91% bioavailability; t1/2: 12 hours
208
T or F: Tedizolid is higher protein binding than Linezolid
T; Higher protein-binding (70–90%) than linezolid (31%)
209
Tedizolid penetrates well into?
muscle, adipose, and pulmonary tissues
210
T or F: Tedizolid requires no dose adjustment for renal or hepatic impairment
T
211
Clinical use of Tedizolid
skin and soft tissue infection
212
Adverse effects of Tedizolid
Lower risk of bone marrow suppression, lower risk of serotonergic toxicity
213
Pleuromutilins includes?
Lefamulin
214
MOA of Lefamulin
binding the 50S ribosome and inhibits bacterial protein synthesis; binding pocket closes around the drug molecule, preventing bacterial transfer RNA from binding appropriately
215
Is Lefamulin bactericidal or bacteriostatic?
Bactericidal
216
Lefamulin is Bactericidal against what infections?
lower respiratory tract infections (S. pneumoniae, H. influenzae)
atypical pathogens (L. pneumophila, M. pneumoniae, and C. pneumoniae)
aerobic gram-positive organisms (S. pyogenes, S. aureus, and E. faecium)
STIs (M. genitalium, N. gonorrhoeae, and C. trachomatis)
217
Lefamulin lacks activity against?
E. faecalis, P. aeruginosa, A. baumannii, and the Enterobacteriaceae group of gram-negative organisms (EPEA)
218
Mechanisms for resistance in Lefamulin
ribosomal target site alteration and active efflux from the site of action
219
Clinical use of Lefamulin
CAP
220
ROA of Lefamulin
Oral and IV
221
Bioavailability and protein binding availability of Lefamulin
25% bioavailability; 95-97%-protein bound
222
t1/2 of Lefamulin
T1/2: 8 hours
223
Method of excretion of Lefamulin
Excreted by hepatic metabolism (CYP3A4)
224
T or F: Dose adjustment for severe hepatic impairment is needed in Lefamulin
T
225
Adverse effects of Lefamulin includes?
infusion-site reactions, GI disturbances, congenital malformations
226
Aminoglycosides are used in the treatment of microbial infection with?
Antibiotics
227
The serum concentration levels of Aminoglycosides must be (above/below) the MIC
Above
228
As the plasma level of ahminoglycosides is increased (above/below) the MIC, the drug kills an (increasing/decreasing) proportion of bacteria at a more (rapid/slow) rate
Above
Increasing
Rapid
229
What antibiotics are time dependent?
Penicillin and Cephalosporins
230
Time is (directly/indirectly) related to the MIC
Directly
231
T or F: The duration of the antibiotic is independent of the concentration once MIC is reached
T
232
Event whenreim aminoglycosidesʼ killing action continues when the plasma levels have declined below measurable levels
POSTANTIBIOTIC EFFECT
233
Aminoglycosides have a greater efficacy when administered how often?
SINGLE LARGE DOSE than when given as multiple smaller doses
234
Toxicity of ahminoglycosides (in contrast to antibacterial activity) depends on?
critical plasma concentration and on that time such a level is exceeded
235
Time (above/below) such threshold of MIC is shorter with single large dose
Above
236
Aminoglycosides are structurally related to _______ attached by ______
amino sugars
glycosidic linkages
237
Aminoglycosides are polar or non polar?
Polar
238
Are aminoglycosides absorbed orally?
No
239
ROA of aminoglycosides
IM or IV for systemic effects
240
Penetration of Aminoglycosides: Widely distributed or limited
Limited
241
Do aminoglycosides cross the BBB?
No
242
Major mode of excretion of aminoglycosides
Glomerular filtration
243
Aminoglycoside plasma levels are affected by changes
in?
renal function
244
Aminoglycoside excretion is (directly/indirectly) proportional to?
Directly
creatinine clearance
245
With normal renal function, elimination of aminoglycosides is how long?
2-3h
246
Needed for safe and effective dosage selection and adjustment in aminoglycosides
Monitoring plasma levels
247
How often should aminolgycosides be given daily?
2-3x / day
248
When should peak serum levels for aminoglycosides be measured?
30-60 minutes after administration
249
When should trough serum levels for aminoglycosides be measured?
Measured just before the next dose
250
MOA of aminoglycosides
Bactericidal (irreversible) inhibitors of protein synthesis
251
Aminoglycoside penetration of bacterial cell wall is partly dependent on?
O2-dependent active transport
252
Aminoglycosides have minimal activity against?
strict anaerobes
253
Aminoglycoside transport is enhanced by?
cell wall synthesis inhibitors via antimicrobial synergism
254
Aminoglycosides bind to what ribosomal unit?
30S
255
How do aminoglycosides interfere with protein synthesis?
1. Block formation of initiation complex
2. Cause misreading of the code on the mRNA template
3. Inhibit translocation
256
Aminoglycosides are resistant to what bacterium?
- Streptococci, including S. pneumoniae
- Enterococci
257
Why are aminoglycosides resistant to Streptococci and Enterococci?
due to failure to penetrate into the cell
258
Aminoglycoside primary mechanism of resistance
Plasmid-mediated formation of inactivating enzymes
259
Catalyze the acetylation of amine functions
Group transferases
260
Transfer of phosphoryl or adenyl groups to the O2 atoms of hydroxyl groups on the aminoglycoside
Group transferases
261
Transferases produced by enterococci can inactivate what molecules?
Amikacin
Gentamicin
Tobramycin
(TAG)
262
Transferases produced by enterococci CANNOT inactivate what molecules?
streptomycin
263
Less susceptible to plasmid-mediated formation of inactivating enzymes and is active against more strains of organisms
Netilmicin
264
Receptor protein on the 30S ribosomal subunit may be deleted or altered as a result of?
a mutation
265
What are the different aminoglycosides and spectinomycins?
Gentamicin
Tobramycin
Amikacin
Streptomycin
Neomycin
Spectinomycin
266
MOA of aminoglycosides and spectinomycins
Bactericidal, inhibiting protein synthesis by binding to 30S ribosomal unit, concentration dependent action with post antibiotic effect
267
Aminoglycoside with least resistance
Amikacin
268
Aminoglycosides and spectinomycin are used against?
Aerobic G(-) - H. influenzar, M catarrhalis, Shigella
Can be used with beta lactase for gonorrhea (spectinomycin; IM) and TB (spectromycin; IM)
269
Main ROA of aminoglycosides and spectinomycins
IV with renal clearance
Once daily dosing
270
Oral and topical examples of aminoglycosides and spectinomycins
Neomycin and gentamicin
271
Toxicities of aminoglycosides and spectinomycins
Nephrotoxicity (reversible)
Ototoxicity (irreversible)
Neuromuscular blockade
272
CLINICAL USES of GENTAMICIN, TOBRAMYCIN, AMIKACIN
Serious infections caused by aerobic gram (-) bacteria (SKEEPPP)
Used for the following but is not DOC
H. influenzae
M. catarrhalis
Shigella species
273
Aminoglycosides and spectinomycins are not effective for G (+/-) cocci when used alone
+
274
Aminoglycosides are combined with _______ in the treatment of Pseudomonas, Listeria and Enterococcus
penicillin
275
Aminoglycosides are combined with penicillins to treat what conditions?
Pseudomonas, Listeria and Enterococcus
276
STREPTOMYCIN clinical uses
Tuberculosis
Plague
Tularemia
277
Multi-drug-resistant (MDR) strains of TB resistant to streptomycin maybe susceptible to?
amikacin
278
NEOMYCIN, KANAMYCIN, PAROMOMYCIN clinical uses
Neomycin – topical
Kanamycin and paromomycin – IM/IV/PO
* Active against: Gram-positive bacteria, Gram-negative bacteria, some mycobacteria
279
Kanamycin and paromomycin are resistant against?
P aeruginosa, Streptococci
280
NETILMICIN ROA
IM/IV/Topical/Ocular/Intrathecal
281
Netilmicin clinical uses
serious infections resistant to other aminoglycosides
282
SPECTINOMYCIN is a ____ related to aminoglycosides
Aminocylitol
283
T or F: Spectinomycin is a back up drug
T
284
SPECTINOMYCIN as a single dose is useful against?
Gonorrhea but NOT recommended for treatment of pharyngeal gonococcal infections
285
TOXICITY of AMINOGLYCOSIDES includes
OTOTOXICITY
NEPHROTOXICITY
NEUROMUSCULAR BLOCKADE
SKIN REACTIONS
286
Auditory impairment is caused by which aminoglycosides?
Amikacin and kanamycin
287
Vestibular dysfunction is caused by which aminoglycosides?
Gentamicin and tobramycin
288
Ototoxicity risk is (proportionate/disproportionate) to plasma levels
Proportionate
289
Ototoxicity is increased with the use of?
loop diuretics
290
Ototoxicity is contraindicated in?
Pregnancy
291
NEPHROTOXICITY includes what condition?
Acute tubular necrosis
292
Is nephrotoxicity in aminoglycosides reversible?
Yes
293
Most nephrotoxic AMINOGLYCOSIDES
Gentamicin
Tobramycin
294
Nephrotoxicity is common in which demographic?
More common in elderly patients
Patients concurrently receiving
Amphotericin B
Cephalosporins
Vancomycin
295
T or F: NEUROMUSCULAR BLOCKADE is a common toxicity in AMINOGLYCOSIDES
F
296
High doses of aminoglycosides can cause what blockade subsequently causing what condition?
Curare-like block may occur at high doses
Respiratory paralysis
297
Is Neuromuscular blockade reversible?
Yes
298
Treatment for neuromuscular blockade
Calcium
Neostigmine
Ventilatory support
299
SKIN REACTIONS are caused by?
Neomycin
300
AMINOGLYCOSIDES can cause allergic skin reactions like?
contact dermatitis
