Antibiotics Flashcards
1
Q
penicillin MOA
A
Cell Wall Synthesis Inhibitor
2
Q
penicillin adverse effects
A
nephrotoxicity, allergic interstitial nephritis, seizures (toxic levels due to renal dysfunction), diarrhea, C. difficile infection (with broader spectrum)
3
Q
penicillin ___ killing, half life
A
Time-dependent killing; most effective against microorganisms rapidly growing + dividing
* Very short half-life <2 hrs; dosed multiple times/day
4
Q
penicillin for special population
A
safe for infants and pregnancy
dose adjustment for renal dysfunction
5
Q
penicillin has sensitivity to
A
cephalosporins
6
Q
amoxicillin is __ spectrum
A
broad spectrum
7
Q
cephalosporin MOA
A
Cell Wall Synthesis Inhibiton
8
Q
adverse effects of cephalosporin
A
GI intolerance, seizures (high doses), interstitial nephritis, rare
blood dyscrasias,
***C. difficile infection
9
Q
cephalosporin is ___ killing
A
Time-dependent killing; most effective against microorganisms rapidly growing + dividing
- Renal elimination for all except ceftriaxone (liver) – adjust dose prn
10
Q
CSF penetration of cephalosporin
A
1st + 2nd Gen: low CSF penetration – do not use for bacterial meningitis
11
Q
special population for cephalosporin
A
Safe for use in infants/children (avoid ceftriaxone in neonates -> bilirubin displacement and kernicterus )
Crosses placenta + present in breastmilk Generally safe in pregnancy/breastfeeding
Adjust dose with renal dysfunction for older adults
12
Q
CARBAPENEMS MOA
A
Cell Wall Synthesis Inhibitor
13
Q
adverse effects of carbapenems
A
confusion, delirium, seizure, diarrhea, C. difficile infection anemia, ↑LFT’s
14
Q
carbapenems ____ killing
_____ CSF
A
Time-dependent killing
* Post-antibiotic effect
* Penetrates CSF
15
Q
Drug interactions of carbapenems
A
valproic acid (reduced effect -> seizures)
16
Q
monitoring for carbapenems
A
renal/liver/hematologic function periodically
17
Q
penicillin monitoring for
A
renal function with renal disease
18
Q
cephalosporin monitoring for
A
c. diff symptoms
19
Q
monobactams MOA
A
Cell Wall Synthesis Inhibitor
20
Q
adverse effects of monobactams
A
thrombophlebitis at injection site, neutropenia + ↑lft’s in peds, C. difficile infection
21
Q
monobactams are___ killing
____ CSF
A
Time-dependent killing
* Penetrates CSF
22
Q
beta lactam antibiotics metabolism and elimination
except
A
- Minimal hepatic metabolism
- Renal elimination (adjust dose prn)
except ceftriaxone (liver) – adjust dose prn
23
Q
monobactams special population
A
Not recommended in pediatric CNS infections due to seizure risk
Crosses placenta + present in breastmilk Use only if safer alternative not available.
Adjust dose with renal dysfunction for older adults
24
Q
__ generations of cephalosporin
A
There are 5 generations and as they proceed from the 1st to the 5th generation, there is more gram negative and anaerobic coverage, less resistance to beta lactamases and more CSF penetration.
25
vancomycine MOA
Cell Wall Synthesis Inhibitor
26
vancomycine is reserved for ___
Reserve for Gram (+) infections where B-lactams cannot be used
27
adverse effects of vancomycin
renal toxicity,
ototoxicity (tinnitus, hearing loss, vertigo/dizziness),
neurotoxicity, hypersensitivity/anaphylaxis,
C. difficile (IV use),
thrombocytopenia, neutropenia, pancytopenia, thrombophlebitis, infusion reaction with rapid administration (red man syndrome)
28
pharmacokinetics of vancomycin
____ killing
metabolism and elimination
Time-dependent killing
* Post-antibiotic effect
* No B-lactam ring
* Poor GI absorption; minimal hepatic metabolism
* Renal elimination (adjust dose prn)
29
special population for vancomycin
Caution in neonates/infants due to renal immaturity
Crosses placenta + present in breastmilk. Limited data. Use only if safer alternative not available.
Caution with older adults due to nephrotoxicity, ototoxicity, + neurotoxicity
30
Drug of choice for MRSA and C. difficile and severe infections
vancomycin
31
monitoring of vanco
renal function, serum drug levels, hydration
32
Oral formulation of vanco only indicated for
C. Diff
33
FOSFOMYCIN
MOA
___ killing
____ metabolism and elimination
Concentration-dependent killing
* Bactericidal in the urine
* Minimal hepatic metabolism
* Renal elimination (adjust dose prn)
34
FOSFOMYCIN indication
Only indicated for acute uncomplicated cystitis in females >18 yrs caused by E. coli or E. faecalis
35
fosfomycin should be taken
take without food
can cause dizzy and drowsy
36
Protein Synthesis Inhibitors
30s
antibiotics
Aminoglycosides
Tetracyclines
37
Protein Synthesis Inhibitors
50s
antibiotics
Macrolides
Lincosamides
Oxazolidinones
38
Aminoglycosides e.g.
* gentamycin
* tobramycin
* neomycin
* streptomycin
39
Aminoglycosides MOA
Binds bacterial 30S ribosomal subunit, causing production of abnormal protein synthesis + interruption of usual protein synthesis = cell death
40
adverse effects of Aminoglycosides
nephrotoxicity, ototoxicity, neurotoxicity (neuromuscular blockade + respiratory paralysis
41
drug interactions with Aminoglycosides
Drug Interactions: loop diuretics (↑ototoxicity), nephrotoxic drugs (i.e., NSAIDs, cephalosporins, vancomycin, cyclosporine, amphotericin B)
42
drug monitoring Aminoglycosides
Monitoring: serum drug levels (peak levels high to kill bacteria, trough levels low to reduce oto/nephrotoxicity
43
PK and PD of aminoglycosides
____ killing
_____ CNS penetration
elimination
Concentration-dependent killing
* Post-antibiotic effect
* Poor GI absorption + CNS penetration
* Renal elimination (adjust dose prn)
* Serum drug levels can vary widely between patients
44
special population aminoglycosides
safe for children
not safe for pregnancy
caution for older adults with renal impairment
45
TETRACYCLINES MOA
Binds bacterial 30S ribosomal subunits, causing cessation of usual protein synthesis to prevent bacterial growth + multiplication
46
adverse effects of tetracycline
renal toxicity,
hepatoxicity
GI (esophageal irritation, n/v, diarrhea, abd pain),
C. difficile,
Teeth discolouration/enamel hypoplasia (binds to calcium in teeth), Photosensitivity
47
PK/PD of tetracycline
____ killing
CNS penetration
elimination
Time-dependent killing
* Post-antibiotic effect
* Food may affect absorption (individual drug dependent)
* Poor CNS penetration
* Renal elimination (tetracycline) or hepatic elimination (doxycycline, minocycline)
48
tetracycline can cause_____
esophageal irritation
take full glass of water and remain upright for 1-2 hours after
49
special population consideration tetracycline
Avoid under 8 yrs: permanent teeth discolouration
Hepatotoxicity risk in pregnancy, crosses placenta -> staining of deciduous teeth of fetus, long bone growth suppression (reversible with discontinuation); use only if benefit >risks; avoid in breastfeeding
Dose adjustments prn with renal impairment
50
examples of macrolides
erythromycin
* azithromycin
* clarithromycin
51
MOA of macrolides
Binds bacterial 50S ribosomal subunits, causing blockage of new amino acids to the peptide chain to prevent bacterial growth + multiplication
52
adverse effects of macrolides
sudden cardiac death from QT prolongation -> torsades de pointes (small risk with high drug concentrations), GI (epigastric pain, n/v, diarrhea), transient ↑ LFT’s
53
contraindications of macrolides
hypersensitivity, congenital QT prolongation, antiarrhythmic drugs (class IA or III),
concurrent CYP3A4 inhibitors (i.e., Ca++ channel blockers,
Antifungals -> “azoles,” HIV protease inhibitors)
54
PK/PD of macrolides
____killing
CNS penetration
metabolism and elimination
* Time-dependent killing
* Post-antibiotic effect
* Food may affect absorption
* Poor CNS penetration
* Hepatic metabolization + elimination (toxicity rare): metabolism by CYP3A4 (isoenzyme of
cytochrome P450)
55
special population macrolides
Risk of infantile hypertrophic pyloric stenosis in neonates
Crosses placenta but no adverse fetal risks with erythromycin/azithromycin. Potential fetal adverse effects with clarithromycin. Low transfer to breastmilk, generally safe in breastfeeding
Potential for reversible ototoxicity (tinnitus, hearing loss) with large doses or renal/hepatic impairment
56
LINCOSAMIDES e.g.
clindamycin
57
MOA of lincosamides
Binds bacterial 50S ribosomal subunits, causing blockage of new amino acids to the peptide chain to prevent bacterial growth + multiplication
58
PD/PK of lincosamides
Time-dependent killing
* Post-antibiotic effect
* No CNS penetration
* Hepatic metabolism + renal elimination (adjust dose prn hepatic dysfunction, no renal
dose adjustment required)
* Metabolism by CYP3A4 (isoenzyme of cytochrome P450) but not significant
59
adverse effects with lincosamides
fatal C. Diff
60
special population of lincosamides
Caution with severe hepatic impairment
Crosses placenta + present in breastmilk Generally safe in pregnancy + breastfeeding
Caution in older adults with renal or hepatic impairment
61
OXAZOLIDINONES e.g.
linezolid
tedizolid
62
MOA of oxazolinones
Binds bacterial 50S ribosomal subunits, causing blockage of new amino acids to the peptide chain to prevent bacterial growth + multiplication
63
Drug interaction of oxazolinones
MAO inhibitors + sympathomimetic/vasopressive/dopaminergic drugs ->
hypertensive crisis, SSRIs/triptans/opiods -> ↑risk serotonin syndrome
64
Reserve for treatment of MRSA and VRE to delay emergence of resistance
oxazolinones
e.g.
linezolid
tedizolid
65
significant food interaction of linozalid
food/drinks high in tyramine, dopamine, tyrosine,
phenylalanine, tryptophan + caffeine -> hypertensive crisis or serotonin syndrome
66
FLUOROQUINOLONES
e.g.
ciprofloxacin
* levofloxacin
* moxifloxacin
67
FLUOROQUINOLONES MOA
Inhibits DNA gyrase + DNA topoisomerase IV enzymes to impair DNA replication + cell division = cell death
68
contraindication of fluoroquinolones
myasthenia gravis -> neuromuscular blocking activity =death/respiratory failure
69
adverse effects of fluoroquinolones
tendinopathy/tendon rupture (esp. Achilles)
QT prolongation
C. diff
70
PK/PD of fluoroquinolones
Concentration-dependent killing
* Post-antibiotic effect
* Upper GI absorption
* CYP450 inhibition (Cipro)
* Minimal hepatic metabolism; renal elimination (adjust dose adjustments prn)
71
special populations for fluoroquinolones
Avoid due to potential MSK toxicity (cartilage + joint damage)
Crosses placenta + present in breastmilk
Avoid (use only if safer alternative not available)
Caution in older adults due to risk altered mental status, psychosis, + vision disturbances
72
NITROIMIDAZOLES e.g.
metronidazole
73
MOA of NITROIMIDAZOLES
Enters bacteria through passive diffusion. Damages+breaks helical DNA structure, inhibiting DNA synthesis = cell death
74
NITROIMIDAZOLES contraindications
Caution in CNS disease
75
adverse effects of NITROIMIDAZOLES
potential carcinogen
76
PK/PD of NITROIMIDAZOLES
______Killing
______ CNS penetration
metabolism and elimination
Concentration-dependent killing
* Post-antibiotic effect
* Good GI absorption with oral
* Penetrates CSF
* Extensive hepatic metabolism (adjust dose prn hepatic dysfunction)
* Renal elimination + small percentage fecal elimination (no dose adjustment required)
77
what causes metalic taste and GI upset and should be taken with food?
NITROIMIDAZOLES
e.g. metronadazole
78
NITROFURANTOIN e.g.
nitrofurantoin
79
NITROFURANTOIN MOA
MOA: DNA/RNA Synthesis Inhibitor
Bacteriostatic (low concentrations) Bactericidal (therapeutic concentrations)
80
contraindications for NITROFURANTOIN
G6PD deficiency, pregnancy, infants <1
month
81
PK/PD of NITROFURANTOIN
Bactericidal in urine only at therapeutic concentrations
* Time-dependent killing
* Short post-antibiotic effect
* Good GI absorption
* Minimal hepatic metabolism; rapid renal elimination leading to high concentrations in urine
82
special population for NITROFURANTOIN
Avoid in infants <1 month due to risk of hemolytic anemia
Potential teratogen. Contraindicated in 3rd trimester, during L+D, and breastfeeding in premature or <1 month of age infants due to risk of hemolytic anemia
Avoid in older adults with renal impairment
83
it's important to avoid ___ when taking NITROIMIDAZOLES
avoidance of alcohol during treatment and at least 72 hours following completion
84
3 types of ABX DNA synthesis inhibitors
Fluoroquinolones
Nitroimidazoles
Nitrofurantoin
85
Folic Acid Synthesis Inhibitors
Sulfonamides
86
adverse effects of sulfonamides
photosensitivity, Stevens-Johnson syndrome, hemolytic anemia (with G6PD deficiency), megaloblastic anemia (with concurrent folate deficiency), renal damage,
87
MOA of sulfonamides
Sulfonamides: Inhibits synthesis of tetrahydrofolate, causing inhibition of DNA, RNA, and protein synthesis to prevent bacterial growth + multiplication
88
PK/PD of Folic Acid Synthesis Inhibitors
Time dependent killing
* Well absorbed orally
* Hepatic metabolism
* Renal elimination (adjust dose prn)
89
special population for Folic Acid Synthesis Inhibitors
Avoid in infants <2 months due to kernicterus (potentially fatal)
Avoid in pregnancy: may cause birth defects (1st trimester) and kernicterus (near term)
Caution in breastfeeding: can cause kernicterus in breastfeeding infants <2 months
Caution in older adults due to more severe adverse effects (can be life-threatening)
90
Cell Membrane Disruptor
daptomycin
91
daptomycin MOA
Binds to cell membrane, causing rapid depolarization of membrane potential, disrupting vital intracellular processes (such as DNA, RNA + protein synthesis) = cell death
92
adverse effects of daptomycin
DRESS (Drug Reaction with Eosinophilia + Systemic Symptoms), TIN (Tubulointerstitial nephritis), anaphylaxis, myopathy/↑CPK, peripheral neuropathy, GI upset, C. difficile
93
drug interaction of daptomycin
statins
94
“Last-resort” antibiotic
daptomycin
95
Drug Interaction of sulfonamides
warfarin, phenytoin, sulfonylurea hypoglycemics (glipizide, glyburide) -> ↑ effect for all;
ACE inhibitors/ARBs -> hyperkalemia
