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Antibiotics Flashcards

1
Q

what are the different types of penicillins?

A

natural penicillins (PCN G, PCN B, PCN G Procaine); aminopenicillins (amoxicillin, amp); penicillinase-resistance penicillins (oxacillin, cloxacillin, methacillin, nathacillin); extended spectrum penicillins (tigeracillin, piperacillin and azocillin)

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2
Q

what do all penicillins contain?

A

a nucleus which is composed of a b-lactam ring

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3
Q

what is the mechanism of action for natural penicillins?

A

exert bactericidal action against penicillin suscpetible microorganisms during the stage of active replication; interfere with bacterial cell wall synthesis by reacting to one or more PCN binding proteins

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4
Q

how many different types of binding proteins do bacteria produce?

A

4

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5
Q

what is the mechanism by which resistance is formed against natural PCNs by bacteria?

A

mediated mainly through production of B-lactamase, which covalently binds to the B-lactam bond to form an acyl enzyme intermediate, which destroys the activity of the drug

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6
Q

what is the method of metabolism and disposition of natural PCNs?

A

metabolism and disposition vary significantly among the various PCNs, also vary with the age of the patient

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7
Q

Most natural PCNs are not well absorbed by the GIT, with what exception?

A

PCN V

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8
Q

Which natural PCN is generally used parenterally?

A

PCN G

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9
Q

To what do natural PCNs bind?

A

serum proteins, mainly albumin

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10
Q

do natural PCNs penetrate the CSF?

A

No

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11
Q

what is the spectrum of activity of natural PCNs on gram positive cocci?

A

effective against most strains of streptococci and susceptible strains of staphococi, enterococci and pneumoncocci; tolerance to PCN from group B streptococci isolates have been reported; PCN acts synergistically with gent or tobramycin against many strains of enterococci

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12
Q

what is the spectrum of activity of natural PCNs on gram positive bacilli?

A

listerium

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13
Q

what is the spectrum of activity of natural PCNs on gram negative bacteriai?

A

H influenza, gonhorrhea, streptobacillis monolith forms

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14
Q

what is the spectrum of activity of natural PCNs on anaerobic bacteria and spirochetes?

A

covers spirochetes; anaerobic: clostrius species

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15
Q

what are the clinical uses of natural PCNs?

A

effective in the treatment of: group A step, group B strep, meningococci, actinomyces, T.pallidum, also susceptible streptococcus pneumoniae, enterococci and gonococci

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16
Q

what should be done in patients with poor compliance?

A

option of IM benzothulium PCN can be given Q3-4 wk

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17
Q

natural PCNs are the drug of choice in the treatment of what STI?

A

primary, secondary, tertiary syphilis (not neuro)

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18
Q

what treatment is recommended for patients with congenital syphilis?

A

PCN G or procaine PCN

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19
Q

what adverse reactions have been a/w administration of natural PCNs?

A

allergic reactions, hematologic toxicity (coombs positive hemolytic anemia, leukopenia and thromobocytopenia), Na overload, hyperkalemia and neurologic toxicity (sz reported following massive dose); severe even fatal anaphylaxis has occured

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20
Q

how frequently do anaphylaxis reactions occur in pts receiving natural PCNs?

A

estimated to occur in 0.01-0.05% of persons

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21
Q

what can occur in patients receiving cont IV tx with PCN G?

A

in high doseage may suffer severe and even fatal K poisoning, particularly if they have some degree of renal insufficiency

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22
Q

what is the interaction with natural PCNs and concurrent administration of bacteriostatic antibiotics?

A

may diminish the bactericidal effects of PCNs by slowing the rate of bacterial growth

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23
Q

What can prolong PCN blood levels?

A

concurrent administration of probenecid, which blocks the renal tubular secretions of PCNs

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24
Q

what is the composition of aminoPCNs?

A

contain a free amino group at the alpha position on the b-lactam ring of the PCN nucleus, increasing their ability to penetrate the outer membranes of the gram negative organisms

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25
what is the mechanism of action of aminoPCNs?
exert bactericidal action against PCN-susceptible microorganisms during the stage of active replication
26
what is the mechanism by which resistance is formed against aminoPCNs by bacteria?
aminoPCNs are inactivated by the B-lactamases produced by either gram positive or gram negative bacteria
27
what is the preferred oral aminoPCN?
amoxicillin has the best absoprtion and bioavailability, absorption is impaired by food
28
where do aminoPCNs achieve therapeutic levels?
in most bodily fluids- CSF, peritoneal, joint and pleural
29
how are aminoPCNs cleared by the body?
kidneys
30
what is the spectrum of activity of aminoPCNs?
increased efficacy against most strains of enterococc, listeria, L. monocytogenes, H influenza, N gonorrhea; [some strains of E coli, shigella and salmonella are resistant]
31
what is the clinical use of amoxicillin?
drug of choice for acute otitis media, some clinical manifestations of Lyme dz
32
what is the clinical use of ampicillin?
widely ised in septic neonates partly because of its coverage against listeria
33
what are the adverse events a/w aminoPCNs?
hypersensitivity reactions
34
what are penicillinase-resistant PCNs?
semisynthetic PCN derivatives
35
what is the mechanism of action of penicillinase-resistant PCNs?
act by binding to PBPs and preventing cell wall synthesis; resistant to the action of bacterial penicillinases by steric hinderance of the acyl chain, thereby preventing opening of the b-lactam ring
36
what is the spectrum of activity of penicillinase-resistant PCNs?
effective against b-lactamase producing isolates of staphylococcus aureus and coagulase-negative staphylococci
37
what is the pharmacokinetics of penicillinase-resistant PCNs?
absorbed after oral administration, adversely affected by food; urinary/biliary excretion
38
what are the clinical indications of penicillinase-resistant PCNs?
semi-synthetic PCNs are commonly used for the empiric tx of skin and skin structure infections and bone and joint infections when staphylococcus aureua is a likely pathogen
39
how does interstitial nephritis manifest clinically?
fever, rash, eosinophilia, proteinurea and hematuria
40
what are the adverse effects a/w methicillin use?
interstitial nephritis
41
what are the adverse effects a/w oxacillin use?
cholestasis without jaundice; liver enzymes return WNL s/p tx cessation
42
what is the spectrum of activity of extended-spectrum PCNs?
broader spectrum of activity than natural PCNs and aminoPCNs
43
what is the pharmacokinetics of extended-spectrum PCNs?
serum and tissue levels are not adequate for the treatment of systemic infections, better suited for uncomplicated UTIs; minimal CSF penetration; primary elimination if renal
44
what are the clinical indications of extended-spectrum PCNs?
effective against a variety of gram negative organisms; prescribed in combination with gentamicin to combat gram negative bacilli; generally used clinically in combination with a b-lactamase inhibitor
45
what are the adverse effects of extended-spectrum PCNs?
hypersensitivity reactions, similar to the other types of PCNs, inhibition of platelet aggregation- platelet dysfx and prolonged bleeding times
46
what is the interaction of extended-spectrum PCNs with warfarin?
decreased anticoagulation effect
47
what is the interaction of extended-spectrum PCNs with piperacillin?
potentiate the action of non depolarizing blocking agents
48
what is the interaction of extended-spectrum PCNs with aminoglycosides?
has been shown to degrade the aminoglycoside
49
because of varied drug interactions with extended-spectrum PCNs, what is the recommendation for their parenteral administration?
this class of drugs should not be mixed in solutions and their administration be separated by 30-60 min
50
what is the mechanism of action of cephalosporins?
possess a b-lactam ring; interfere with synthesis of peptidoglycan in the bacterial cell wall and binds to and inactivates PBPs, which are enzymes responsible for the synthesis of the bacterial cell wall
51
how are cephalosporins classified?
classified into generations on the basis of their spectrum of microbiologic activity. this classification reflects increase in stability of higher generations to various bacterial b-lactamases,
52
Given alone, none of the cephalosporins are effective against what organisms?
MRSA, listeria or clostridium species
53
what is the spectrum of activity of first gen cephalosporins?
good activity against G+ cocci and relatively modest activity against many G-. most G+ cocci are susceptible (except MRSA, staph epidermis and entercocci).
54
what is the spectrum of activity of second gen cephalosporins?
more active against G- although less than third gen; variable activity against G+ cocci, improved activity against H influenza, gonohrrea and Nisseria meningitis
55
what is the spectrum of activity of third gen cephalosporins?
more active against enterbactors including b-lactamase producing strain, also against staph pneumonia.
56
what is the spectrum of activity of fourth gen cephalosporins?
have a greater spectrum of activity than the third gen; effective against H influenza, nisseria species and pseudonomas. Also effective against G+ cocci: staph aureus, staph pneumonia and other streptococci
57
what are the pharmacokinetics of cephalosporins?
good penetration into tissues and fluid compartments, including CSF
58
what is the mechanism by which bacterial builds resistance to cephalosporins?
three mechanisms of resistance: 1) inactivation by bacterial B-lactamase, 2) alterations of PBPs, 3) alteration of bacterial permeability
59
what is the clinical use of first and second gen cephalosporins?
skin and respiratory tract infections
60
what is the clinical use of third gen cephalosporins?
empiric treatment
61
what is the clinical use of fourth gen cephalosporins?
febrile neutropenia dn nosocomial infections
62
what are the adverse reactions a/w cephalosporin administration?
maculopapular skin eruptions, drug fever and a positive Coombs test; frequency of anaphylactic reaction varies from 0.0001-0.1%; renal insufficiency may require doseage adjustments
63
what are the advantages of aminoglycosides?
effective against G- organisms, synergism with b-lactam antibiotics, limited bacterial resistance and low cost
64
what has compromised the successful use of aminoglycosides?
nephrotoxicity and ototoxicity in significant number
65
what is the mechanism of action of aminoglycosides?
alter the integrity of the bacterial cell wall membrane in growing bacteria by way of disturbing protein synthesis; binding of the aminoglycosides to the bacterial cell membrane itself may play a role int he rapid bacterial cell death
66
what are the clinical uses for aminoglycoside prescription?
mainly used for treating serious G- infections caused by enteric bacilli; act synergistically with cephalosporins and PCNs; used in combination with vanc for S. aureus, both methicillin- sensitive and methicillin-resistant
67
what are the indications for aminoglycoside administration?
NEONATAL SEPSIS; G- bacteria (E coli, klebsiella species, enterobacter species and pseudomonas species); synergistic with b-lactam antibiotics in treating group B strep and coag neg staph infx; important role in the initial empiric treatment of neonatal septicemia; UTI
68
how to aminoglycosides treat UTIs?
excreted by way of glomerular filtration and are partly actively reabsorbed, leading to high tissue and urine concentrations
69
renal toxicity may be r/t what with aminoglycoside administration?
toxicity seems to be r/t high trough concentration, indicating that these concentrations are not low long enough to prevent renal accumulation
70
what due most experts attribute ototoxicity to with aminoglycoside administration?
r/t total dose and duration of tx rather than to serum aminoglycoside concentration
71
what are risk factors for neonatal hearing loss?
perinatal infection, meningitis, preterm birth, hyperbili, BW <1500g, RDS, asphyxia, mechanical ventilation, bx and diuretics
72
how does nephrotoxicity occur with aminoglycoside administration?
proximal tubular injury leading to cell necrosis; occurs less frequently than in adults
73
how does ototoxicity occur with aminoglycoside administration?
potentially cochleo- and vestibulotoxic; hearing loss if usually BL, symmetrical and permanent; can have a delayed onset of months
74
what special circumstances would require adjustments made to how aminoglycosides are ordered?
renal compromise, s/p asphyxia, low apgar scores or is receiving other nephro/ototoxic drug (indomethacin or diuretics); doseges and intervals are dependent on GA and PNA
75
how has recommendations concerning monitoring and doseage changed with aminioglycosides?
has been revised toward larger doses in extended intervals
76
what is the frequency of complications with aminoglycosides in courses <7 days?
very rare
77
when is TDM mandated in aminoglycoside administration?
3rd or 4th dose
78
what is the most widely used glycopeptide antibiotic?
vanc; frequently used for G+ infections
79
When is vanc at risk of being inactivated?
when administered simultaneously with heparin in high concentrations
80
what is the mechanism of action of glycopeptides?
bacterialcidal activity of vanc is based on the inhibition of bacterial cell wall synthesis
81
what is VIRSA?
vancyomycin intermediate resistant staph aureus; resistance is r/t aggregated and thickened cell walls. infx with VIRSA is a/w failure to tx with vanc
82
how has resistance to vanc come about?
a mechanical factor in the clinical resistance of staph aureus infx to van is r/t a production of a bile film on the bacteria, which shields it from the abx
83
where is clinically important resistance to glycopeptides seen?
in enterococci, s aureus and s epidermis
84
what are the indications for glycopeptide use?
drugs of choice for methicillin-resistant strains of staphylococcal infections; widely used empirically for the treatment of CLABSI; late onset septicemia
85
what are the pharmacokinetics r/t glycopeptides?
eliminated primarily by glomerular filtration; VANC CANNOT BE RELIED UPON TO ADEQUATELY TX G + MENINGITIS WHEN GIVEN ALONE; GA and PNA and post conceptual age all have the ability fo alter the pharmacokinetics of this drug, more so PCA
86
what are the drug related adverse effects of glycopeptides?
thrombocytopenia, neutropenia, eosinopilia, chills, fever, rash, nephrotoxicity and ototoxicity
87
what are infusion related adverse effects r/t vanc administration?
"red man" syndrome- a histamine mediated rash of the face, neck, upper trunk, back and arms; a/w puritius, tingling, flushing, tachycardia and shock; CAUSED BY THE RATE OF INFUSION

Pharmacology Final (5 decks)

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