ANTIBIOTICS Flashcards
1
Q
vancomycin mechanism of action
A
prevents cell wall synthesis and promotes cell lysis
2
Q
vancomycin spectrum of activity
A
ONLY gram positive organisms
includes MRSA
3
Q
pharmacokinetics of vancomycin
A
- VERY poor oral absorption
- ONLY give PO when treating C. diff
4
Q
adverse effect of vancomycin
A
- nephrotoxicity
- red man syndrome
- Characterized by flushing, rash, pruritus, urticaria, tachycardia and possibly hypotension
- Treat symptomatically with anti-histamines
- SLOW the infusion rate
1 gram of vancomycin should be given over a minimum of 60 minutes
5
Q
if a person is allergic to pencillin you give them?
A
cephalosporins
6
Q
therapeutic index of vancomycin
A
Vancomycin has a narrow therapeutic index
7
Q
vancomycin monitoring
A
- Vancomycin levels must be monitored once drug is at steady state
- Trough levels are preferred
8
Q
mechanism of action of fosomycin
A
Prevents cell wall synthesis
9
Q
administration of fosfomycin
A
- Medication is a powder in a packet
- Educate patient to dissolve powder in water and drink the entire dose
10
Q
drugs of tetracylines
A
tetracyline
doxycycline
minocycline
doxy and amino are long lasting
11
Q
tetracylines mechanism of action
A
Inhibits growth of the peptide chain and production of vital proteins
12
Q
what are the beta-lactam antibiotics (bacteriocidal)
A
penicillins
cephalosporins
carbapenems
monobactams
13
Q
mechanisms of resistance of tetracycline
A
Increased drug inactivation
Decreased access to the ribosome
↓ accumulation of drug intracellularly
14
Q
contraindications of tetractclines
A
Pregnancy category D
Do NOT use in children < 8 years old
15
Q
monitoring/counseling points for taking tetracycline, doxycycline, minocycline
A
- Do NOT take tetracyclines with diary products, calcium, magnesium or aluminum containing products
- administer tetracycline 1 hour before or 2 hours after
16
Q
adverse effects of tetracycline, doxycycline, minocycline
A
- Discoloration of teeth if taken during pregnancy or childhood
- Superinfection
- Photosensitivity
17
Q
what drugs are macrolides
A
- Azithromycin
- Clarithromycin
- Erythromycin
18
Q
Mechanism of resistance:
of macrolides (Azithromycin
Clarithromycin
Erythromycin)
A
↓ intracellular concentrations of the drug – efflux pumps
Decrease access to the ribosome
19
Q
Monitoring/ Counseling Points for macrolide( azithromycin, clarithromycin, erythromycin)
A
- Avoid combining these agents with other QTc prolonging drugs
- Take with food to decrease GI upset
- Ensure erythromycin formulation can be taken with food
20
Q
Mechanism of action:
clindamycin
A
Inhibits growth of the peptide chain and production of vital proteins
21
Q
Mechanisms of resistance:
clindamycin
A
↓ intracellular concentrations of the drug – efflux pumps
Decrease access to the ribosome
22
Q
adverse effect of clindamycin
A
Clostridium difficile
- Clostridium difficile-associated diarrhea (CDAD)
- Leads to superinfection of the bowel
- Characterized by:
Profuse, watery diarrhea
10 to 20 stools per day
Abdominal pain
Fever - Can start as soon as 1 week after antibiotics treatment
- Educate patients on signs and symptoms of CDAD
23
Q
mechanism of action linezoid
A
- Inhibits growth of the peptide chain and production of vital proteins
24
Q
Spectrum of activity linezoid
A
- Gram positive organisms only
MRSA
Vancomycin-resistant enterococcus (VRE)
25
adverse effect of linezolid
Thrombocytopenia – typically occurs about 2 weeks after therapy
26
mechanism of action of tigecycline
- Bind to 30s ribosomal subunit
- Inhibit binding of transfer RNA to the messenger RNA
- Inhibits growth of the peptide chain and production of vital proteins
27
adverse effects of tigecycline
Nausea/vomiting
Photosensitivity
Black box warning for increased risk of mortality
28
Mupirocin
Topical antibiotic active against gram positive bacteria
29
INDICATION OF MUPIROCIN
elimination of MRSA
30
drugs for herpes simplex virus and varicella zoster virus
Acyclovir
Valacyclovir
Famciclovir
31
Famciclovir mechanism of action
- inhibits viral DNA polymerase and prevents replication of viral DNA
- Blocks further DNA strand growth after being incorporated into viral DNA
32
whats meant by valacyclovir being a prodrug?
it is converted to acyclovir after absorption from the GI tract
33
adverse effect of acyclovir
- IV therapy
| – phlebitis, nephrotoxicity
34
Monitoring/ Counseling Points
| for acyclovir
- Oral administration requires three to five doses daily
- Prevent nephrotoxicity:
Hydrate patient
Decrease other nephrotoxic medications
35
topical drugs for herpes labialis (cold sores)
- penciclovir cream
| - docosanol cream
36
drugs for cytomegalovirus
Ganciclovir
Valganciclovir
Cidofovir
Foscarnet
37
mehcanisms of actions for Ganciclovir and Valganciclovir
- Inhibits viral DNA polymerase
| - Blocks further DNA strand growth after being incorporated into viral DNA
38
what does it mean for Valganciclovir to be a prodrug?
After absorption from the GI tract it is converted to ganciclovir
39
adverse effects of ganciclovir
- Agranulocytosis
- Thrombocytopenia
- Reproductive toxicity
- Nausea
- Liver dysfunction
40
monitoring/ counseling points for ganciclovir
Monitor white blood cell count, platelets, liver function tests, serum creatinine (Scr)
Avoid use in pregnancy
Avoid pregnancy for 90-days following therapy
Handle with caution. Should be treated as a cytotoxic drug
41
mechanism of action of cidofovir
- inhibits viral DNA polymerase
| - Inhibits viral DNA strand growth after being incorporated
42
adverse effect of cidofovir
nephrotoxicity
43
monitoring/ counseling points of cidofovir
- Prevention of nephrotoxicity:
Hydrate patient with IL NS prior to dose
Avoid other nephrotoxic medications
44
foscarnet mechanism of action
- Inhibits viral DNA polymerase and reverse transcriptase
| - Inhibits synthesis of viral nucleic acids
45
foscarnet adverse effects
nephrotoxicity
46
prevention of nephrotoxicty
Hydrate patient with IL NS prior to dose
| Avoid other nephrotoxic medications
47
mechanism of action of interferon-alfa
- Interferon alfa binds to the host cell membranes
- Binding to the host cell membrane inhibits viral entry into the cell
- Interferon alfa stimulates cell to turn on genes for antiviral proteins
- Antiviral proteins block viral reproduction
48
clinical effects of interferon-alfa
- 30 to 40% response rate with sustained virologic response (SVR)
- Up to 50% of patients with - - SVR will relapse
- SVR is maintained only in 5-15% of patients
- Best effects when combined with another agent
49
mechanism of actions: nucleoside analogs
- Inhibits viral DNA strand growth after being incorporated
50
mechanism of actions of ribavirin
Interferes with RNA metabolism needed for viral replication
51
ribavirin is used in combination with inteferon BUT NEVER used as......
monotherapy for HCV
52
adverse effects for ribavarin
- Hemolytic anemia (10%)
( Develops in 1 to 2 weeks of therapy )
- Fetal injury
( Contraindicated during pregnancy )
- Pancreatitis
53
prevention with vaccination is.....
key
54
types of influenza vaccines
- Inactivated influenza vaccine
| - Live-attenuated vaccine
55
vaccine contraindications of everyone 6 months and older
- Prior history of anaphylactic reaction to influenza vaccine
56
Patients at high risk for influenza complications:
Children < 5 years
Pregnant women
Adults > 65
People living in long-term care facilities
American Indians or Alaskan Natives
Confirmed history of Guillain-Barre syndrome occurred within 6 weeks following previous vaccination and LOW risk for influenza complication
57
neuraminidase inhibitors drugs
Oseltamivir
Zanamivir
Peramivir
58
mechanisms of actions of neuraminidase ( Oseltamivir, Zanamivir. Peramivir ) inhibitors
Inhibit neuraminidase
59
adverse effects of Oseltamivir
- Nausea
| - Delirium or abnormal behavior in children
60
monitoring/ counseling point of oseltamivir
take with food to decrease nausea
61
respiratory syncytial virus (RSV)
- Ribavirin (inhaled)
| - Palivizumab
62
indications of respiratory syncytial virus (RSV)
Prevention of RSV in premature infants or children with chronic lung disease
63
AIDS is defined by:
- CD4 counts below a certain level
| - Contracting an AIDS defining illness
64
without CD4 helper T cells, the immune system experiences .
progressive decline
65
CD4 helper T cells are required for
production of antibodies by B lymphocytes, and activation of cytotoxic T cells.
66
HIV replication cycle
Co-receptors CCR5
HIV lipid bilayer fuses with the host cell membrane. Viral RNA is released into the cell.
67
Reverse transcriptase converts
single-strand DNA to double-strand
68
HIV DNA is integrated into host cell DNA by what enzyme
integrase
69
HIV RNA is transcribed into DNA by
reverse transcriptase
70
Protease cleaves large?
viral polyproteins.
71
Mutations may lead to
drug resistance
72
Higher viral loads increase the chance of
developing resistance
73
To combat resistance:
- Treat HIV infection with multiple agents
| - Ensure compliance with HAART therapy
74
what are the 5 classes of antiretroviral drugs
1. Reverse transcriptase inhibitors
- Nucleoside/nucleotide reverse transcriptase inhibitors
- Non-nucleoside reverse transcriptase inhibitors
2. Integrase strand transfer inhibitors
3. Protease inhibitors
4. Fusion inhibitors
5. Chemokine receptor 5 (CCR5) antagonists
75
ALL clinicians should check drug-drug interactions before ?
administering HAART therapy
76
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI)
DO NOT USE AS MONOTHERAPY
77
mechanism of action of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI)
Incorporated into the DNA strand and cause strand termination
78
adverse effects of abacavir
Associated with mitochondrial toxicity:
- Lactic acidosis
- Hepatic steatosis
- Pancreatitis
- Myopathies
- GI upset
79
Monitoring/ Counseling for NRTI
MUST check if patient has genetic variation *HLA-B5701
80
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Used in combination with NRTIs
81
mechanisms of actions of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Terminates DNA strand formation
82
adverse effects of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)
- Rash
can be life-threatening, counsel patient to seek medical advice immediately if rash occurs
- CNS symptoms
- Hepatotoxicity
83
Protease Inhibitors (PI)
MUST be used in combination with other antiviral medications
84
Mechanism of action: protease inhibitors (PI)
- Inhibits the HIV protease enzyme
- Prevents maturation of the HIV virus
- Immature HIV virus is non-infectious
85
drug-drug interactions of protease inhibitors (PI)
- all protease inhibitors inhibit certain CYP enzymes
| - Some protease inhibitors (PI) can therefore increase serum concentrations of other protease inhibitors
86
Ritonavir
often combined with other drugs for this purpose – RITONAVIR BOOSTING
87
adverse effects of protease inhibitors (PI)
- Hyperglycemia/ diabetes
- Lipodystrophy
- Hyperlipidemia
↑ LFTs (Liver Function Test)
↑ risk of bleeding in patients with hemophilia
88
Integrase Strand Transfer Inhibitors
Used in combination with other antiviral drugs
89
Mechanism of action: Integrase Strand Transfer Inhibitors
Inhibits the enzyme integrase
| Prevents HIV from inserting its viral DNA into the host cell DNA
90
adverse effects for dolutegravir (integrease stand transfer inhibitor)
↑ LFTs
- Insomnia
- Headache
- Diarrhea/nausea
91
monitoring/counseling for dolutegravir (integrease stand transfer inhibitor)
DDI interaction with drugs containing calcium, iron or magnesium
– give dolutegravir 2 hours before these agents
92
what is dolutegravir
an Intergrease Stand Transfer Inhibitor (INSTI)
93
HIV Fusion Inhibitors
Enfuvirtide
94
usage of Enfuvirtide
treatment-resistant HIV-1
95
mechanism of action of enfuvirtide
Blocks entry of HIV into CD4 cells
96
adverse effects of enfuvirtide
- Injection site reactions (98%), especially in first week of treatment
- Pneumonia
- Hypersensitivity reactions
( If this develops, discontinue therapy and never use again)
97
what is maraviroc (CCR5 ANTAGONIST) used for?
treatment-resistant HIV-1 in patients ≥ 16 years old
98
Pathophysiology of maraviroc
Some HIV strains require CCR5 binding to access the host cell = CCR5 tropic
99
mechanism of action of maraviroc
Prevents HIV from binding to the host cell
100
maraviroc requires genetic testing to identify if...
patient’s strain of HIV is CCR5 tropic
101
adverse effects of maraviroc
Upper respiratory tract infections
| ↑ LFTs
102
intial therapy for HIV
always a multi-drug regimen
| INSTI + 2 NRTI
103
Laboratory Tests and Resistance for HIV
- CD4 T cell count - how much immunocompetency is left
| - Viral Load - magnitude of viral replication
104
pre-exposure prohylaxis (PrEP) for hiv is rommended for
patients at high-risk of HIV transmission:
105
Post-exposure Prophylaxis
- Goal to start therapy AS SOON AS POSSIBLE (1 to 2 hours)
| - Therapy can be started up to 72 hours after exposure
106
Non-occupational exposure
| of post- exposure prophylaxis
- Unprotected intercourse, sharing needles, sexual assault
| - 28-day HAART regimen
107
occupational exposure
| of post- exposure prophylaxis
- Accidental needle stick, blood or body fluid splashes
| - 28-day HAART regimen
108
what is selective toxicity
ability of a drug to injure a target organism without injuring other cells or organisms inclose contact with the target
( Kill bacteria, don’t kill host )
109
Narrow spectrum of antimicrobial drugs
active against a few different microbial species
110
Broad spectrum of antimicrobial drugs
= active against wide range of different microbial species
111
Bactericidal effects of antimicrobial drugs
kill bacteria
112
Bacteriostatic effects of antimicrobial drugs
slow bacterial growth
113
How do bacteria develop resistance to antibiotics?
Bacteria may become resistant to antimicrobials over time and with repeat exposure
( Acquired resistance )
114
Resistance to one drug or class may confer
resistance to other drug classes as well
115
Spontaneous mutation method of bacterial resistance to antimicrobial drugs
- random changes in bacterias DNA
| - Spontaneous mutations confer resistance to one drug
116
spontaneous mutations confer
confer resistance to one drug
117
Conjugation method of bacterial resistance to antimicrobial drugs
- Extrachromosomal DNA is transferred from one bacteria to another
- Primarily occurs in gram negative organisms
- Confers resistance to multiple drugs
118
Reduction of Drug Concentration at its Active Site
| mechanisms of bacteria resistance
- Decrease active uptake of the drug
| - Increase active export of the drug
119
Alteration of Drug Target Molecules
| mechanisms of bacteria resistance
If a drug binds to a certain site on the ribosome, the bacteria will change the shape of the ribosome
120
Antagonist Production
| mechanisms of bacteria resistance
-bacteria produce a compound that antagoizes the drugs action
121
Drug Inactivation
| mechanisms of bacteria resistance
Produce enzymes that breakdown the drug
122
The more antimicrobials are used more often,
the faster resistant organisms will emerge. Need to be judicious with use.
123
Broad-spectrum are less likely to cause resistance than narrow spectrum
false. Broad-spectrum are more likely to cause resistance than narrow spectrum since they affect more bacteria
124
Resistant organisms are especially common in
hospitals.
Hospital Acquired Infections (HAI)
Very difficult to treat due to limited antimicrobial options
125
does antimicrobial directly cause changes to bacterial DNA?
Antimicrobials do not directly cause changes to bacterial DNA that make them resistant. They promote resistance via “survival of the fittest”
126
If some bacteria are resistant
antimicrobials create a more favorable environment for them to grow
127
what is a superinfection
New infection that appears during a course of antibiotic treatment for a different infection.
128
Superinfections are more common with what spectrum antimicrobials
broad- spectrum
129
Goal of antimicrobial therapy =
produce maximal antibiotic effects while minimizing harm to the patients
130
Three key principles of selecting antimicrobials
- Identification of the infecting organism
- Organism susceptibility to the drug
- Host factors – site of infection, immunocompetence, etc.
131
what is empiric therapy of antimicrobial
starting the antimicrobial treatment before the infecting organism can be identified =
132
Empiric therapy may use what spectrum antibitics
broad-spectrum antibiotics.
After the organism is identified the therapy can be de-escalated
133
Most infections will have a ‘first-choice’ drug to treat it; however, a patient may not be able to take the ‘first-choice’ drug from a number of reasons such as
allergies or inability for drug to penetrate the site of infection
134
abcess and antibiotics
Abscesses _ must be drained first, antibiotics will not penetrate them
= Foreign bodies _ very difficult to treat
135
Dose of antibiotic must be optimized to:
- Achieve maximum concentrations of antibiotic at site of infection
- Maintain concentrations for longest possible duration
- Goal is typically 4 to 8 times the MIC of the organism
136
Duration of antibiotic therapy depends on the type of infection
- Patients MUST take the full course of antibiotics
| - Patients must be educated not to stop antibiotic early since this leads to increased risk of resistance
137
Why would multiple antibiotics be used at once?
- Empiric therapy for a severe infection
- Mixed infections
- Preventing resistance
- Decreased toxicity
- Enhanced antibacterial action
138
When should antimicrobial prophylaxis be used?
- Surgery
- Bacterial endocarditis
- Neutropenia
- Recurrent urinary tract infections
139
What are ways in which antibiotics are misused
- Treatment of a VIRAL infection
- Treatment of fever with unknown origin
- Improper dosage
- Lack of source control (eg. undrained abscess or no removal of necrotic tissue)
140
What antibiotics are included in the beta-lactam class?
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
141
are beta-lactam antibiotics bacteriostatic or bacteriocidal?
bactericidal,
142
Penicillin Mechanism of Action
Inhibits actions of transpeptidases
Increases actions of autolysins
Weakens the structure of the cell wall → cell lysis
143
penicillin weakens what?
the structure of the cell wall = cell lysis
144
what does penicillin bind to
Penicillins bind to penicillin-binding proteins (PBPs) on the cell membrane
145
penicillin does not penetrate what system?
DOES NOT PENETRATE CNS. eyes or joints well. unless inflammation is present
146
since 90% of penicillin is excreted by kidneys, doses must be.....
doses MUST be reduced in patients with renal impairment
147
common adverse effects of penicillin
- Allergic reaction
- Rash
- Neurotoxicity
148
List the narrow spectrum penicillins and their route of administration.
pencillin G
Sodium IV
Potassium IV
Procaine IM
Benzathine IM
149
Penicillinase-Resistant Penicillins
- Nafcillin
- Oxacillin
- Dicloxacillin
(not effective agaisnt methicillin-resistant MRSA)
NARROW SPECTRUM
150
How does broad spectrum penicillin differ from penicillin G?
increased coverage of gram negative bacteria
151
Are broad spectrum penicillin affected by beta-lactamases?
inactivated by beta-lactamase enzymes
152
what are the broad spectrum penicillins
- Ampicillin IV/PO
| - Amoxicillin PO
153
what are the extended spectrum penicillins
Piperacillin
154
extended spectrum penicillin are...
Highly susceptible to beta-lactamases
155
what bacterias do extended spectrum penicillin cover
1. Gram positive organisms
2. Gram negative organisms
- PSEUDOMONAS aeruginosa
3. Anaerobic organisms
156
WHAT ARE Beta-lactamase inhibitor
drug that inhibits beta-lactamase enzymes.
tazobactam
sulbactam
clavulanate
157
Piperacillin combined with
tazobactam
158
Ampicillin combined with
Sulbactam
159
Amoxicillin combined with
Clavulanate
160
what is anaphylaxis?
an immediate allergic reaction mediated by IgE.
treatment = epinephrine
- often associated with airway swelling, hypotension and cardiovascular collapse
161
If a patient is allergic to penicillin, they are considered allergic to...
ALL penicillins
162
Most patients will be able to take cephalosporins since there is only a ~1% risk of cross-reactivity BUT
- If reaction is mild = give cephalosporins
| - If reaction is severe (anaphylaxis) = do NOT give cephalosporins, select alternative agent
163
are cephalosporins bactericidal or bacteriostatic
bactiricidal
164
cephalosporins are more resistance to
beta-lactamase enzymes
165
How are cephalosporin antibiotics categorized?
Note that not all cephalosporins are equally susceptible to beta-lactamase enzymes.
- 1st generation tend to be the most susceptible to beta-lactamase enzymes
- the fifth generation are the most resistant.
Beta-lactam antibiotics;
- chemical structure composed of a beta-lactam ring with varying side chains
166
what generation of cephalosporins are more resistant
5th generation are more resistant.
1st generations are most susceptible
167
Which generations of cephalosporins can be used to treat CNS infections?
3-5
168
Which generations have the most gram negative coverage?
2-5
169
Which generations have the leastgram negative coverage?
1
170
Describe the pharmacokinetics of cephalosporins?
Poor oral absorption; most agents are given IV
171
What is the drug-drug interaction between ceftriaxone and calcium?
- Precipitates can form
- Do NOT reconstitute or mix ceftriaxone with calcium-containing solutions
- Do NOT administer through the same line at the same time
172
List the carbapenem antibiotics.
- Imipenem/ cilastin
- Meropenem
- Doripenem
- Ertapenem
173
What bacteria do carbapenem antibiotics cover?
Broad-spectrum of antimicrobial activity
- gram positive (no MRSA)
- Gram negative
Anaerobes
174
carbapenem MRSA or no MSRA
no MSRA
175
carbapenems relation with beta-lactase enzymes
Very resistant to beta-lactamase enzymes
176
What serious adverse effect is associated with meropenem and Imipenem/cilastin?
seizure
177
What are monitoring/counseling points for beta-lactam antibiotics?
Monitor for
- Clinical signs of improvement
- Allergic reactions
- Signs of worsening or new infections
- Adverse effects including seizure
- Ensure patient completes and appropriate course of therapy
Dose adjustments for renal impairment
178
Imipenem has DDI with............. and can......... of valproic acid
valproic acid, decrease levels
179
What type of antibiotic is aztreonam?
Unique type of beta-lactam called a monobactam
180
When is aztreonam the drug of choice?
Drug of choice for gram negative coverage in a patient with a penicillin allergy
181
What types of bacteria does aztreonam cover?
ONLY gram negative organisms, including Pseudomonas
182
mechanism of actions of macrolides
inhibits growth of the peptide chain and production of vital proteins
