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Antimicrobials Flashcards

1
Q

Infections that cannot switch from parenteral to PO abts

A

Osteomyelitis

Endocarditis

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2
Q

Admin of most PCNs

A

Parenteral as they are unstable in the acidic environment of the stomach

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3
Q

Distribution of PCNs

A

Distributed widely and penetrate CSF in presence of inflammation

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4
Q

Half life of PCN in adults with normal renal function

A

30-90 min

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5
Q

PCN mech of action

A

Inhibition of bacterial cell growth by interference with cell wall synthesis

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6
Q

Agents of choice for gram+ infections

A

PCNs

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7
Q

High dose PCNs in severe renal dysfunction

A

Associated with seizures and encephalopathy

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8
Q

PCN adverse rxn when tx spirochetes (especially syphilis)

A

Jarisch-Herxheimer reaction:

Fever, chills, sweating, flushing

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9
Q

PCN drug interactions

A

Probenecid will increase half life

Parenteral carboxypenecillins have increased Na content (take care with sodium/fluid restrictions)

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10
Q

How does PCN resistance develop

A

Drug is inactivated by bacteria-produced penecillinases or beta-lactamases

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11
Q

Development of beta-lactam inhibitor combos

A

Inhibitor prevents breakdown of beta-lactam by organisms that produce the enzyme

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12
Q

Beta-lactamase producing organisms

A

S. Aureus
Haemophilus influenza
Bacteroides fragilis

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13
Q

Distribution of beta-lactam inhibitor combos

A

Most body tissue except brain and CSF

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14
Q

Beta-lactam inhibitor combos (Drugs)

A 
Amoxicillin-clavulanic acid (Augmentin)
Ampicillin-sulbactam (Unasyn)
Piperacillin-tazobactam (Zosyn)
Ticarcillin-clavulanic acid (co-ticarclav)
Ceftazidime-avibactam
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15
Q

Beta-lactam inhibitor combo half life

A

Approx 1h

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16
Q

Beta-lactam combo mech of action

A

Interfere with bacterial cell wall synthesis by binding to and in activating PBPs

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17
Q

Clinical uses of beta-lactam inhibitor combos

A

Polymicrobial infections
Extensively:
intra-abdominal and gynecologic infections
Skin/soft tissue infections (human/animal bites)
DM foot infections

Also used for aspiration pna, sinusitis, and lung abcess

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18
Q

Adverse events of beta-lactam inhibitor combos

A

Hypersensitivity rxns

GI SEs

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19
Q

Are cephalosporins a beta-lactam group

A

Yes

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20
Q

Beta-lactam groups

A

Cephalosporins
Monobactams
Carbapenems

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21
Q

How are cephalosporins divided

A

Into generations

1st-4th indicated increase in gram- coverage and decrease in gram+

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22
Q

Absorption of cephalosporins

A

Absorbed well through GI tract

2nd-4th penetrate CSF and play a role in tx of bacterial meningitis

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23
Q

Clinical uses for 1st generation cephalosporins

A

Gram+ skin infections, pneumococcal resp infections, UTI, surgical ppx

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24
Q

Clinical use of 2nd generation cephalosporins

A

Community acquired pna, other resp infections, skin infections

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25
Only cephalosporin that covers MRSA
``` Ceftaroline fossil (Teflaro) IV ```
26
Cephalosporin tx of bacterial meningitis
Typically 3rd generation like ceftriaxone or cefotaxime
27
Cephalosporin tx of nosocomial infections
Commonly ceftazidime or cefepime because broad spectrum covers gram- organisms (P. aeruginosa)
28
Most common SE with cephalosporin
GI: N/V, diarrhea
29
Cephalosporin drug interactions
Rare | Probenecid can increase half life
30
Monobactams
Aztreonam (Azactam) is the only one commercially available Primarily active against gram- organisms Safer alternative to aminoglycosides
31
Distribution of monobactams (Aztreonam)
Well into most tissues Penetration into CSF with inflamed meninges Not extensively bound to proteins
32
Half life of Aztreonam
2 hours
33
Aztreonam mech of action
Interferes with cell wall synthesis by binding to/inactivation PBPs Almost no action against gram+ Not active against anaerobic organisms
34
Clinical uses of aztreonam
Complicated and uncomplicated UTIs and resp tract infections (one, bronchitis) when needing aerobic gram-coverage
35
Cross allergy PCN, cephalosporin, Aztreonam
If all to PCN and cephalosporin should be able to take Aztreonam
36
Carbapenems
Bicyclal beta-lactams with a common carbapenem nucleus
37
Most broad spectrum agents available
Carbapenems
38
Administration of carbapenems
IV, not absorbed PO
39
Half life of carbapenems
Approx 1h
40
Distribution of carbapenems
Widely distributed | CSF penetration depends on degree of meningeal inflammation
41
Carbapenem mech of action
Interferes with cell wall synthesis by binding to PBPs
42
Drugs with the broadest spectrum of activity of all beta-lactam compounds
Imipenem, meropenem, doripenem
43
Carbapenem with no aignificant activity against P. aeruginosa
Ertapenem
44
Why use meropenum over imipenem in tx of CNS infections
Lower risk of causing seizures
45
Carbapenems adverse events
GI Neurotoxicity (seizures) Risk factors: impaired renal function Improper dosing Age Previous CNS disorder Meds that decrease seizure. threshold
46
Carbapenemen drug interactions
Probenecid causes decreased clearance and increased half life
47
Most commonly prescribed FQs
Ciprofloxacin Levofloxacin Moxifloxacin
48
Pharmacodynamics of FQs
``` Bacetericidal Excellent bioavailability (easy transition from IV to PO) Distributes well into most tissues except CNS ```
49
Half life of FQs
4-12h | Longest half lives: levofloxacin, gemifloxacin, moxifloxacin
50
FQ mech of action
Strong inhibitors of components of bacterial DNA, without which it cannot replicate
51
Only oral agents available to tx P. aeruginosa
Ciprofloxacin | Levofloxacin
52
Preferred agents for nosomial pna and other hospital acquired infections
Cipro or Levaquin
53
Recommended for meningococcal ppx
Cipro
54
Rare but serious SE of FQs
QT prolongation Tendon rupture Tendonitis Peripheral neuropathy
55
FQs may increase effects of...
Theophylline Warfarin Tizanidine Propranolol
56
What can decrease absorption of FQs
``` Antacids Sulcrafate Magnesium Calcium Iron salts ```
57
FQs with corticosteroids
Increased risk of tendonitis and tendon rupture
58
Only agent known as a ketolide
Telithromycin
59
Macrolides
Azithromycin Clarithromycin Erythromycin
60
Distributions of macrolides
Good tissue penetration Achieve high intracellular concentrations Exhibits minimal protein binding
61
Half life of erythromycin
2h
62
Half life of clarithromycin (Biaxin)
4-5h
63
Half life of azythromycin
50-60h
64
Clarithromycin and erythromycin with renal failure
Dosage adjustments are needed
65
Half life of telithromycin
Approx 10h
66
Macrolide mech of action
Inhibition of bacterial protein synthesis by binding to the 50s subunit of ribosome
67
FQ suffix
-Oxacin
68
Macrolides and atypical organisms
``` Chlamydia Mycoplasma Legionella Rickettsia Mycobacteria Spirochetes ```
69
Rare but serious SE of macrolides
Hepatotoxicity
70
Adverse rxn associated with telithromycin
Acute hepatic failure | Severe liver injury
71
Drug interactions of macrolides and ketolides
Inhibits CYP34A and interacts with an extensive list of meds including warfarin Take care when Admin with meds that prolong QT interval
72
Major drawback of aminoglycosides
Potential for nephrotoxicity and cytotoxicity Length of therapy is restricted
73
Absorption and distribution of aminoglycosides
Poorly absorbed through GI tract. Parenteral admin necessary for systemic infections Distributes into ECF
74
Absorption and distribution of aminoglycosides
Poorly absorbed through GI. Parenteral Admin needed for systemic infections Distributs into ECF (may be sig affected in ICU patients and in malnutrition, obesity, ascites)
75
Half life of aminoglycosides
Approx 1-3h | Increased with renal impairment
76
What is used to monitor therapy with aminoglycosides
Renal function and serum levels Narrow range between therapeutic and toxicity
77
Macrolides (drugs)
Azithromycin Clarithromycin Erythromycin Telithromycin (ketolide)
78
Aminoglycosides (drugs)
Gentamicin Tobramicin Streptomycin Amikacin
79
Aminoglycoside mech of action
Binds to 30s ribosomal unit of bacteria inhibiting bacterial protein synthesis
80
Activity of aminoglycosides
Aerobic gram- bacilli | Gram+ cocci (with cell wall active agent like ampicillin, ampicillin, vancomycin)
81
Clinical uses of aminoglycosides
Empiric tx of neutrogenic fever and nosocomial infections Routinely used in combo with other agents Monotherapy not recommended except with UTIs
82
How does nephrotoxicity occur with aminoglycosides
Accumulation of drug in proximal tubule cells of the kidney
83
Labs monitored with aminoglycosides
BUN/creat and serum levels
84
Forms of aminoglycoside ototoxicity
Auditory (healing loss, tinnitus) Vestibular (N/V, vertigo) Increases when admin with high dose loop diuretics, macrolides, or vancomycin
85
Aminoglycoside drug interactions
Increased risk of neuromuscular blockade when Admin with neuromuscular blockers, general anesthetic, calcium channel blockers Admin of calcium glucometer often reverses blockade
86
Tetracycline suffix
-cycline
87
Activity of tetracyclines
Gram+, gram-, atypical organisms
88
Adsorption of tetracyclines
GI tract Empty stomach increases absorption except with long acting (doxycycline, minocycline) Eliminated by glomerular filtration except for doxycycline
89
Tetracycline mech of action
Binds to 30s ribosomal unit to inhibit protein synthesis
90
Clinical uses for tetracyclines
When beta-lactams aren't an option Doxy for early Lyme disease and community acquired pna
91
Tx of SIADH
Demeclocycline (Declomycin)
92
Adverse events of tetracyclines
Anorexia, N/V, epigastric distress, gray-green discoloration of teeth (not for kids under 8) Sensitivity to the sun
93
Drug interactions with tetracyclines
Absorption decreased by iron, cholestyramine, sulcrafate, antacids, dairy Potentiate the effects of warfarin by impairing vitamin k synthesis by intestinal flora
94
Glycylcycline
Tigecycline Available IV only
95
Tigecycline dosage adjustments
Not for renal insufficiency but for severe underlying liver disease
96
Tigecycline mech of action
Binds to 30s subunit to inhibit bacterial protein synthesis Activity against MRSA and VRE
97
Clinical uses for Tigecycline
Complicated skin infections, intra-abdominal infections, community acquired pna
98
Adverse events Tigecycline
N/V, asymptomatic hyperbilirubinemia
99
Sulfonamides (drugs)
Sulfadiazine Sulfisoxazole Trimethoprim Trimethoprim-sulfamethoxazole (bactrim)
100
Absorption/distribution of sulfonamides
Readily absorbed through GI Distributed through all body tissues including CSF, plural fluid, synovial fluid
101
Half life of sulfonamides
Varies from hours to days
102
Sulfonamide mech of action
Inhibits the incorporation of para-aminbenzoic acid required for folic acid synthesis necessary for bacterial cell growth
103
Sulfonamide used to treat ulcerative colitis
Sulfasalazine | Lacks sig microbial activity
104
Why are sulfonamides typically used with other agents
Limited spectrum of activity and increasing resistance
105
Adverse events of sulfonamides
Rash (occurs within 1-2 wks), fever, GI Hemolytic anemia with G6PD deficiency
106
Sulfonamide drug interactions
Potentiates effect of warfarin, phenytoin, hypoglycemic agents, methotrexate
107
Glycopeptides (drugs)
Vancomycin Dalbavancin Oritavancin Telavancin
108
Monitoring glycopeptides
Monitor renal function | Serum monitoring with unpredictable kidney function, severe infection, when therapy exceeds 3-5 days
109
Clinical uses for vancomycin
Serious gram+ when allergic or unable to tolerate beta-lactams Drug of choice for MRSA and other resistant organisms
110
Adverse events of glycopeptides
Fever, chills, "red man" syndrome (associated with rate of infusion of vanc)
111
Red man syndrome
Pruritus, flushing of head, neck, and face, hypotension
112
Glycopeptide contraindicated during pregnancy
Telavancin
113
Drug interactions of glycopeptides
Unlikely as it does not undergo sig hepatic metabolism
114
Oxazolidinones available
Linezolid (Zyvox) | Tedizolid (Sivextro)
115
Absorption and administration of oxazolidinones
GI tract absorption Bioavailability greater than 90% Admin without regard to food Eliminated nonrenally
116
Oxazolidinone mech of action
Binds to 50s ribosomal subunit to disrupt bacterial protein synthesis Particularly good action against resistant organisms
117
Oxazolidinones drug interactions
Sympathomemtic agents like pseudoepinephrine, SSRI antidepressants, herbal products, and foods rich in tyramine
118
Lipopeptide available
Daptomycin
119
Daptomycin txs what
MDR Gram+ pathogens
120
Daptomycin dosing
6mg/kg x 7 days
121
Half life of daptomycin
Approx 8h
122
Daptomycin mech of action
Bonds to bacterial membranes and causes a rapid depolarization of membrane potential. Low membrane potential leads to cell death
123
Daptomycin activity
MRSA, VRE
124
Clinical uses of daptomycin
Complicated skin infections S. Aureus bacteremia R sided endocarditis caused by methicillin susceptible and methicillin resistive isolates
125
Daptomycin drug interactions
CPK levels weekly for concomitant use of stations and/or renal insufficiency
126
Streptogramins
Only available is quinupristin/dalfopristin (Synercid)
127
Administration of Synercid
IV, not absorbed through GI tract
128
Synercid mech of action/activity
Binds to 50s ribosomal subunit inhibiting bacterial protein synthesis Active against gram+ aerobic organisms
129
Clinical uses of Synercid
Skin infections, VRE
130
Administration of Synercid
Through a central line
131
Clindamycin
Anti anaerobic agent | Gram+ anaerobic bacterial infections
132
Distribution of clindamycin
Reaches most tissues and bone but distribution into CSF is limited
133
Clindamycin dosage adjustments
With liver impairment
134
Clindamycin mech of action
Binds to 50s subunit inhibiting protein synthesis
135
Clinical uses for clindamycin
Gram-/+ infections, toxoplasmosis, toxic shock
136
SE of clindamycin
Diarrhea assoc with c. Diff
137
Drug interactions with clindamycin
Skeletal muscle relaxants can potentiate neuromuscular blockade
138
Meteonidazole (flagyl) absorption and penetration
Completely absorbed through GI | Penetrates most tissues
139
Half life of flagyl
6-9h
140
Clinical uses for flagyl
Bacterial vaginosis Trichomoniasis C. Diff
141
Adverse events with flagyl
GI SE and metallic taste Seizures with high doses Peripheral neuropathy with prolonged therapy
142
Flagyl drug interactions
Enhances effect of warfarin | With alcohol disulfiram-like rxn (flushing, palpitations, nausea, vomiting)
143
What increases metabolism of flagyl leading to tx failure
Phenobarbital, phenytoin, and rifampin
144
Chloramphenicol
Wide spectrum of activity against gram+/-, and anaerobic organisms
145
Chloramphenicol limitation
Limited due to toxicity profile which includes gray baby syndrome, optic neuritis, and fatal aplastic anemia
146
Availability and penetrance of chloramphenicol
IV Penetrates into most tissues and body fluids including CSF Crosses the placenta
147
Chloramphenicol mech of action
Binds to 50s ribosomal subunit inhibiting protein synthesis
148
Half life of chloramphenicol
3-4h
149
Clinical usage of chloramphenicol
Alternative to tx meningitis when life threatening PCN allergy Rocky mountain spotted fever and typhoid fever in patients allergic to tetracyclines or in pregnant women
150
Adverse events of chloramphenicol
Gray baby syndrome Blood dyscrasias Aplastic anemia, Optic neuritis (assoc with long term use)
151
Chloramphenicol drug interactions
Prolongs half life of warfarin, phenytoin, and cyclosporine
152
Clinical usage of rifampin
1st line tx for TB | Post exposure ppx for n. Meningitidis and h. Influenza type b
153
Rifampin mech of action
Suppresses initiation of chain formation for RNA synthesis in susceptible bacteria by inhibiting DNA-dependent RNA polymerase
154
Absorption and distribution of rifampin
Completely absorbs | Distributes into most tissues and fluids including CSF
155
Half life of rifampin
Approx 3h
156
Adverse events of rifampin
Changes body fluids red-orange | Hepatotoxicity
157
Rifampin drug interactions
Increases clearance of antiarrhythmics, azole antifungals, clarithromycin, estrogens, most statins, warfarin, and many HIV meds
158
Macrobid
Only for uncomplicated UTIs
159
Half life of macrobid
Less than 30 min

Pharmacology (11 decks)

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