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Pharmacology Mod 3 > Introduction to antimicrobial drugs and cell wall synthesis inhibitors (INCOMPLETE) > Flashcards

Introduction to antimicrobial drugs and cell wall synthesis inhibitors (INCOMPLETE) Flashcards

1
Q

What factors play in to determining appropriate antibiotic therapy

A

most likely organism causing infection
likely susceptibility of the organism to antibiotic
site of infection
patient factors - i.e comorbiditites
also cost

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2
Q

What “host factors” must be taken into account prior to prescribing an antibiotics

A

Immunosuppression, kidney or liver disease

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3
Q

What is Empiric therapy

A

broad-spectrum treatment prior to identification of organism

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4
Q

What is the prescription of a broad-spectrum antibiotic prior to the organism identification called

A

Empiric therapy

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5
Q

Critically ill patients require what type of therapy for what is presumed an bacterial infection

A

empirical therapy

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6
Q

when is emperic therapy indicated

A

critically ill patients

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7
Q

If a critically ill patient present with a history of a prior MRSA infection, with a new skin infection - what type of therapy is necessary for this patient

A

a empiric MRSA coverage antibiotic

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8
Q

what does the choice of broad-spectrum antibiotics for empirical treatment depend on

A

the patient clinical condition, potential site of infection and knowledge of microbes that may be causing infection

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9
Q

What are antibiotic susceptibility considerations based on

A

patterns of antibiotic sensitivity (based on local antibiogram and historical data)
lab testing - MIC and MBC

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10
Q

What is MIC and what does it stand for

A

Minimal inhibitory concentration - lowest concentration of drug that inhibits bacterial growth

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11
Q

what is MBC and what does it stand for

A

Minimal bactericidal concentrations - the lowest concentration of drug that kills bacteria

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12
Q

What is the MOA for bactericidal medications

A

antibiotic kills the bacteria
host defenses NOT required

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13
Q

if an antibiotic kills the bacteria - what type of antibiotic is it

A

bactericidal antibiotic

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14
Q

What type of antibiotic inhibits the bacterias replication and requires host defense

A

bacteriostatic antibiotic

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15
Q

What is the MOA for bactericidal medications

A

antibiotic kills the bacteria
host defenses NOT required

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16
Q

what is MOA for bacteriostatic medications

A

antibiotic inhibits bacterial replication; does not kill bacteria
host defense REQUIRED

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17
Q

what are the two antibiotic mechanism of actions

A

Bactericidal and bacteriostatic

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18
Q

other considerations for choosing antibiotic therapy

A

route of administration (oral, IV, IM)
tissue distribution (CNS penetration)
side effects and toxicities (allergies, kidney toxicity in context of other nephrotoxic drugs or renal insufficiencies)
routes of metabolism/elimination

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19
Q

in choosing antibiotic therapy what considerations do we have to make for immune status

A

neutropenia, cell-mediated defects, etc.
bactericidal drugs for compromised hosts

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20
Q

in choosing antibiotic therapy what anatomical considerations do we have to make

A

abscesses, necrotic tissues, foreign material
match drug bioavailability to site of infection
bactericidal drugs for “immune-protected” sites (CNS, eye, bacterial endocarditis)

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21
Q

What is it called when a percentage of the total drug administered reaches the systemic circulation

A

bioavailability

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22
Q

Define Bioavailability

A

percentage of drug that reaches the systemic circulation of the total amount administered

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23
Q

Renal function consideration in choosing antibiotic therapy

A

dose adjustment required for some drugs that are renally excreted

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24
Q

what drug-drug interactions with antibiotics need to be considered

A

antibiotic effects on INR for patients on warfarin

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25
Q

what age groups do we avoid using chloramphenicol and sulfonamides

A

neonates

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26
Q

what age groups do we avoid tetracyclines with

A

young children - discolors teeth

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27
Q

who should avoid amino-glycosides

A

pregnancy - ototoxic effects on fetus

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28
Q

What is it called when the combined effect of two antibiotics is greater than the sum of their independent activities?

A

Synergy

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29
Q

What is synergy

A

when the combined effect of two antibiotics is greater than the sum of their independent activities

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30
Q

what is it called when the combination of two antibiotics is less than the sum of their independent activities?

A

Antagonism

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31
Q

what is antagonism

A

when the combined effect of two antibiotics is less than the sum of their independent activities

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32
Q

What is it called when the effect of two antibiotics equals the sum of their independent activities?

A

Indifference

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33
Q

what is indifference

A

when the effect of two antibiotics equal the sum of their independent activities

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34
Q

When is it warranted to use antibiotic combinations

A
  • prevention of bacterial resistance
  • treatment of polymicrobial infections
  • initial therapy for critically ill patients with unknown source of infection
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35
Q

what increases with combination therapy without good rationale

A

toxicity and cost with little to no benefit

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36
Q

why is tuberculosis treated with combination therapy

A

to decrease the resistance to monoantibiotics

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37
Q

What is chemoprophylaxis

A

the use of drugs to prevent disease
example: prophylactic antibiotic for post joint replacement dental appointment

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38
Q

what are examples of times antibiotic prophylaxis is necessary

A

prior to surgery
pts undergoing dental extractions who have prosthetic heart valves or joints
prevention of TB or meningitis in pts who are in close contact to infected individuals
PJP in HIV-infected pts
and chronic recurrent UTIs

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39
Q

What are cell wall synthesis inhibitors

A

penicillin - sensitive and resistant
cephalosporins
monobactam
carbapenems
glycopeptides

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40
Q

What are gram positive organisms (5)

A

Steph and strep
bacillus anthracis
enterococcus species
clostridium species

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41
Q

What are common gram negative organisms (8)

A

enterobacter colacae
helicobacter pylori
salmonella
hemophilus influenze
pseudomonas
klebsiella
legionella
escherichia coli

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42
Q

what is selective toxicity

A

the basis for effective antibacterial treatment

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43
Q

What is the basis for effective antibacterial treatment

A

selective toxicity

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44
Q

What drug is a lipopeptide antibiotic that targets resistant gram positive bacteria?

A

Daptomycin - it is newly developed

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45
Q

What is Daptoymycin

A

a newly developed lipopeptide antibiotic that targets resistant gram positive bacteria

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46
Q

What are the ribosomal subunits of bacteria and what do they make

A

50S and 30S and they combine to make 70S ribosomal mRNA complex that has significant differences from the 80S ribosomal RNA of mammalian cells

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47
Q

What is the term for antibiotics that target the ribosome

A

protein synthesis inhibitors

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48
Q

what are protein synthesis inhibitors

A

antibiotics that target the ribosome and are typically bacteriostatic

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49
Q

Types of Cell wall inhibitor antibiotics are

A

Penicillins, cephalosporins, aztreonam and carbapenems

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50
Q

if a autolytic enzyme is activated what is the response

A

it causes breaks in the bacterial cell wall

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51
Q

what is the MOA of beta-lactam antibiotics

A

interfere with cell wall synthesis by binding to PBP and compromise the cell wall integrity - osmotic lysis
enhances cell wall breakdown my activating autolytic enzymes (autolysins)

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52
Q

what does PBP stand for

A

penicillin binding proteins

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53
Q

What do penicillins consist of

A

thiazolidine ring
beta-lactam ring
side chain (R)

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54
Q

what is the beta-lactam ring needed for

A

essential for antibacterial activity

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55
Q

what determines the antibacterial spectrum and pharmacologic properties of a particular penicillin?

A

The side change (R)

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56
Q

what organisms express beta-lactamase enzymes and are resistant to Penicillin G?

A

S. aureus and anaerobic bacterium Bacteroides fragilis

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57
Q

what is penicillin G susceptible to?

A

hydrolysis by Beta-lactamase enzymes

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58
Q

What do the Side Chain (R) determine

A

the antibacterial spectrum and pharmacologic properties of a particular penicillin

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59
Q

What are the different classifications of penicillins

A

Natrual penicillins (penicillinase-senstive)
aminopenicillins(penicillinase- senstivie)
semi-synthetic (penicillinase- resistant)
ureidopenicilin
beta-lactamase inhibitors

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60
Q

what are the natural penicillins types

A

penicillinase-senstive
penicillin G
penicillin V

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61
Q

what are the aminopenicillins types

A

penicillinase-senstive
ampicillin
amoxicillin

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62
Q

What are the semi-synthetic penicillin types

A

penicillinase-resistant
nafcillin
oxacillin
dicloxacillin

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63
Q

what is the ureidopenicillin types

A

piperacillin - antipseudomonal

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64
Q

what are the beta-lactamase inhibitors types

A

ampicillin/sulbactam(unasyn)
amoxicillin.clavulonate(augmentin)
pipieracillin/tazobactam (zosyn)

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65
Q

How is Penicillin V administered

A

Oral formulation

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66
Q

How is penicillin G administered

A

IV or IM formulation

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67
Q

what type of microbial does penicillin G, V attack

A
  • gram positive cocci: STREP
  • gram Negative cocci : Neisseria meningitidis
  • Anaerobes (oral)
  • spirochetes
  • other organisms such as pasteurella multocidal (cat bites)

NO STAPH coverage

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68
Q

What are the gram positive cocci that penicillin G and V treat

A

STREP
S. pneumoniae
Group A Strep (s. pyogenes)
Group B strep (s. agalactiae)
Group C, G streptococcus
Viridans streptococci

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69
Q

What gram negative cocci does penicillin G and V treat

A

Neisseria meningitisis: meningitis and bacteremia

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70
Q

What anaeobes are penicillin G and V not useful for

A

bacteroides fragilis and other bacteroide species due to the presence of beta-lactamase

therefore, not useful for intra-abdominal infections

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71
Q

What cat bite related organism is affected by penicillin G and V?

A

Pasteurella multocida

72
Q

What spirochetes do penicillin G and V treat

A

Treponema pallidum (syphilis) and Borrelia burgdorfi (lyme disease) - although rarely used

73
Q

What anaerobes do penicillin G and V treat

A

they are good against oral anaerobees: Peptostreptococcus, prevatella, fusobacterium, clostridium species

74
Q

what type of microbial does penicillin G and V not affect

A

Staph

75
Q

What is the most common use for penicillin V

A

group A strep - S. PYOGENES

76
Q

What patients require dose adjustments when using Penicillin G

A

patient with Renal insufficiency

77
Q

How is penicillin G administered

A

usually 1-4million units IV Q4 hours due to short half-life (.5hrs) requires frequent dosing and has poor oral bioavailability and acid labile

78
Q

What are the IM formulations of Penicillin G

A

Procaine penicillin and Benzathine penicillin
requires mixing with another med for better absorption IM

79
Q

Side effects of Penicillin G

A

rash, anaphylaxis and seizures

80
Q

when is penicillin contraindicated

A

with a history of hypersensitivity to beta-lactams antibiotics, and use in caution with patients with asthma or hx of multiple allergens

81
Q

what is resistant to Penicillins

A

98% of S. Aureus contain a penicillinase which hydrolyzes the beta-lactam ring

82
Q

what medication should be avoided if S.aureus is suspected

A

Penicillin G

83
Q

What does methicillin work against

A

Gram positive cocci (STREP)
S. aureus, S. epidermidis (if susceptible)

NO GRAM NEGATIVE activity

84
Q

what type of penicillin is methicllin

A

semi-synthetic penicillin - first penicillin developed to resist hydrolysis by staphylococcal beta - lactamase

85
Q

What is methicillin to cause as an adverse side effect

A

interstitial nephritis

86
Q

what is Nafcillin and oxacillin

A

IV/IM formation(acid labile) - more common than methicillin

87
Q

what is dicloxacillin

A

PO formulation - more common than methicillin

88
Q

what semi-syntheitc penicillins have no renal or hepatic impairment dose adjustments

A

dicloxacillin and oxacillin

89
Q

What patients require caution when planning to use a nafcillin antibiotic

A

patients with renal and hepatic impairment

90
Q

What semi-synthetic penicillin do you need to use caution for renal and hepatic impairment

A

nafcillin

91
Q

What are oxacillin and nafcillin side effects

A

rash
GI upset
Elevated AST/ALT
neutropenia
allergic interstitial nephritis

92
Q

What do aminopenicillins act against?

A

Gram positive Strep (penicllin-susceptible S. Aureus) (they are less active against Group B strep, S. penumonia and group B strep)
Gram negative (H. influenzea and E. coli)

93
Q

what is ampicillin/amoxicillin highly active for

A

enterococci and listeria monocytogenese

94
Q

What are the common side effects of ampicillin/amoxicillin

A

Rash
Diarrhea

95
Q

what are the contraindications for the use of ampicillin/amoxicillin

A

hypersensitivity reactions to beta-lactam antibiotics

96
Q

What is Beta-lactamase

A

it is produced by the bacteria and results in a resistance to beta-lactam antibiotics

97
Q

what are examples of beta-lactamase inhibitor antibiotics

A

Ampicillin-sulbactam (Unasyn)(IV) and Amoxicillin-Clavulante (Augmentin) (PO)

98
Q

What is the benefit of using a beta-lactamase inhibitor

A

it increases the spectrum of activity

99
Q

what do beta-lactamase inhibitors act on

A

Gram positive (S. aureus susceptible ot MSSA)
Gram negative (H. influenza, E. coli, K.pneumoniae, K. oxytoca)
Anaerobes (bacteroides fragilis)

100
Q

What type of penicillin is Piperacillin-Tazobactam (Zosyn)

A

Ureidopenicillin

101
Q

what is piperacillin-tazobactam (zosyn) active toward

A

gram positive (No MRSA coverage)- strep
and has expanded gram negative coverage of P. aeruginosa, S. marcescens, E.coli and klebsiella)
Also excellent anaerobic activity for B. fragilis

102
Q

what patients need to have the dose of piperacillin-tazobactam adjusted?

A

patients with renal insufficiency

103
Q

What penicillins is considered the prototype

A

penicillin G (IV and IM)

104
Q

What penicillin is considered acid-resistance

A

Penicillin VK (PO)

105
Q

What penicillins are considered Beta-lactamase-resistant

A

methicillin
nafcillin
oxacillin
dicloxacillin (PO)

(Staph PCNs)

106
Q

What penicillins are available for combo treatment

A

amoxicillin and ampicillin

107
Q

What penicillin is considered “anti-pseudomonas”

A

piperacillin

108
Q

what penicillins are combination treatments with beta lactamase inhibitors

A

augmentin (PO)
Unasyn (IV)
Zosyn (IV)

109
Q

What are the three beta-lactamase inhibitor combination therapies

A

Amoxicillin/clavulanate (PO)
ampicillin/sulbactam(IV)
Piperacillin/Tazobactam(IV)

110
Q

How are cephalosporins like penicillins

A

they contain beta-lactam ring and inhibit cell wall synthesis and are bacteriecidal

111
Q

how are cephalosporins UNlike penicillins?

A

they are resistant to hydrolysis by many beta-lactamases
‘R1’ and ‘R2’ side chain substitutions alter the antibacterial spectrum and pharmacokinetics

112
Q

What are cephalosporins

A

beta-lactam antibiotics derived from 7-aminocephalosporanic acid

113
Q

What cephalosporins are LAME

A

organisms not covered by cephalosporins
Listeria
Atypicals (chlamydia, Mycoplasma)
MRSA and
Enterococci

(*except ceftaroline covers MRSA)

114
Q

What are the first generation cephalosporins

A

cefazolin and cephalexin

115
Q

what generation of cephalosporins are cefazolin and cephalexin

A

first generation

116
Q

what are second generation cephalosporins

A

cefuroxime

117
Q

what generation of cephalosporin is ceuroxime

A

second generation

118
Q

what are third generation cephalosporins

A

ceftriaxone and ceftazidime

119
Q

what generation cephalosporin are ceftraixone and ceftazidime

A

third generation

120
Q

what are fourth generation cephalosporins

A

cefepime

121
Q

what generation cephalosporin is cefepime

A

fourth generation

122
Q

what are 5th generation cephalosporins

A

ceftaroline

123
Q

what generation cephalosporin is ceftaroline

A

fifth generation

124
Q

as the generations increase what happens to the gram negative and gram positive activity

A

as the generations increase, the gram negative activity increases and the gram positive activity decreases

125
Q

What are the common adverse reactions to beta-lactam antibiotics

A

hypersensitivity
superinfections and
renal dose adjustments

126
Q

What generations of cephalosporins do NOT enter the CSF

A

first and second generations
Cefazolin, cephalexin and cefuroxime (IV and PO)

127
Q

What generations of cephalosporins penetrate the blood-brain barrier well, therefore being the drug of choice for treating CNS infections?

A

Third and fourth generation cephalosporins
ceftriaxone and ceftazidime

128
Q

What are first generation cephalosporins used to treat?

A

Streptococci, S. aureus(MSSA), proteus mirabilis, senstive E. coli and Klebsiella species

(Skin and bone infection and surgical prophylaxis)

129
Q

What are second generation cephalosporins used to treat?

A

they have improved gram negative coverage including beta-lactamase positive H. influenzae and Neisseria species and have slightly reduced gram positive activity

(inner ear infections/sinusitis)

130
Q

What are third generation cephalosporins used to treat?

A

improved gram negative activity; they retain gram positive activity of the first generation drugs

(community-acquired pneumonia and CNS infections)

131
Q

What are third generation cephalosporins used to treat?

A

gram negative rods including pseudomonas; loses gram positive activity

(nosocomial infections)

132
Q

What are fourth generation cephalosporins used to treat?

A

excellent gram positive and gram negative activity including pseudomonas

Nosocomial infections

133
Q

What are fourth generation cephalosporins used to treat?

A

efficacy against MRSA

No pseudomonas coverage

134
Q

What generation of cephalosporins is indicated for skin, surgical prophyaxis (strep, MSSA, PEcK)

A

first generation
cephalexin and cefazolin

135
Q

what generation of cephalosporins are indicated for ear infections, sinusitis and some GYN infections (PID)?

A

second generation
cefuroxime

136
Q

What generation of cephalosporins are indicated for CNS penetration

A

third generation:
DOC is ceftriaxone(IV) but ceftazidime(IV) is also good

137
Q

What generation of cephalosporins are indicated for gram positive and gram negative as well as pseudomonas

A

fourth generation
Cefepime (IV)

138
Q

what generation of cephalosporins are indicated for the treatment of MRSA?

A

5th generation
Ceftaroline (IV)

139
Q

What do monobactams inhibit

A

cell wall synthesis

140
Q

What is the primary monobactam drug?

A

Aztreonam which is administered IV or IM

141
Q

What is the benefit to Aztreonam?

A

there is no cross-allergenicity with the betra-lactams and those who are allergic to penicillins or cephalosporins may use these without concern

142
Q

what is aztreonam used to treat?

A

broad gram negative activity including pseudomonas aeruginosa

They have no Gram positive or anaerobic activity

143
Q

What are the adverse effects of Aztreonam?

A

generally well tolerated but occasionally cause GI upset

144
Q

What type of drug class is vancomycin a part of

A

it is a glycopeptide and inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminal and prevents cross-linking

Bactericidal

145
Q

what is vancomycin used to treat?

A

drug-resistant gram positive infections including MRSA and C. diff

No gram negative activity

146
Q

What are possible side effects of Vancomycin

A

“red man syndrome” - infusion related flushing
dose-dependent ototoxicity and nephrotoxicity

147
Q

what is the DOC for MRSA

A

Vancymyocin because it is narrow spectrum

148
Q

what is the cell membrane inhibitor?

A

daptomycin (IV Only)

149
Q

what does daptomycin inhibit

A

it is a lipopeptide that inhibits the cell membrane

150
Q

what is the administration of Daptomycin?

A

IV only

151
Q

is daptomycin bactericidal or bacterostatic

A

bactericidal

152
Q

What patients require dose adjustments for the use of Daptomycin

A

renal impairment

153
Q

what spectrum drug is daptomycin

A

narrow spectrum for gram positive bacteria only such as MRSA and VRE

154
Q

when is daptomycin used?

A

last line treatment to avoid overuse

155
Q

What does carbapenems inhibit?

A

cell wall synthesis

156
Q

what spectrum drug is carbapenems

A

one of the most broad spectrum antibiotics

157
Q

what does carbapenems treat

A

gram positive cocci, gram negative rods and resistant gram negative rods (pseudomonas aeruginosa and enterobacter species as well as anaerobes

158
Q

when is carbapenems implemented

A

last resort medication

159
Q

what is beta-lactamase

A

it is produced by the bacteria resulting in resistance to beta-lactam antibiotics

160
Q

what is the purpose of beta-lactamase inhibitors

A

they inactivate the beta-lactamases but not all beta-lactamases are able to be inhibited

161
Q

what are the two beta-lactamases that are not able to be inhibited

A

chromosomal (Amp C) beta-lactamases
extended spectrum beta-lactamases (ESBL)

162
Q

What are SPACE organisms

A

chromosomally mediated beta-lactamases
they have low level of constitutive production of AmpC Beta-lactamase

163
Q

What does SPACE stand for

A

S- serratia marcescens
P - proteus (indole+) species and Providencia species
A - Acinetobacter baumannii
C - citrobacter freundii
E - enterobacter species

Others: Hafnia alvei, Morganella morganii

164
Q

What are ESBLs

A

Extended Spectrum beta-lactamases

165
Q

what are needed when treating SPACE organisms

A

they have beta-lactamases and need coverage with beta-lactamase inhibitors

166
Q

Where are ESBLs found

A

mainly in E.coli and Klebsiella species and Carbapenems are used to treat

167
Q

What are the three main Carbapenems

A

Imipenem (IV)
Meropenem (IV)
Ertapenem (IV)

168
Q

why is imipenem used with cilastatin??

A

imipenem is inactivated by renal DHP and cilastatin inhibits DHPs

169
Q

what are the adverse effects of impenem?

A

encephalopathy and seizures

170
Q

what spectrum of activity do carbapenems have

A

gram positive organisms (NOT MRSA)
gram negative organisms

171
Q

What gram positive organisms are carbapenems used for

A

MSSA, MSSE, S. pneumoniae and it has marginal activity against E. faecalis

172
Q

What gram negative organisms are carbapenems used for

A

they are very active against enterobacteriaceae and pseudomonas and ESBL (space organisms)

Not MRSA

173
Q

What is Fosfomycin

A

bactericidal - cell wall synthesis inhibitor that inhibits the enzyme pyruvyl transferase

174
Q

what is fosfomycin commonly used to treat

A

UTI particularly those caused by E.coli and Entercoccus faecalis

also trains activity against some MDR organisms including ESBL-producing E.coli

175
Q

what are side effects of fosfomycin

A

diarrhea and vaginitis

Pharmacology Mod 3 (2 decks)

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