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DnD- ID > Pharmacology 1/2 > Flashcards

Pharmacology 1/2 Flashcards

1
Q

MIC

A

lowest concentration of the agent to prevent visble growth

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2
Q

Bactericidal

A
  • kill bacterial cells
  • target biochemical pathways involved in cell wall assembly
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3
Q

Bacteriostatic

A
  • does not kill but slows their growth
  • reversible
    affects protein synthesis
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4
Q

Combo therapy

A
  • polymicrobial infection
  • decrease resistance
  • decrease toxicity
  • enhance inihbition/killing
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5
Q

Synergism

A
  • blockage of steps in metabolic sequence
  • inhibition of enzymatic activity
  • enhancement of antimicrobial agent uptake
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6
Q

Antagonistic

A
  • inhibition of cidal activity by static agents
  • inducing enzymative inactivation
  • competing for target site
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7
Q

Mechanism of Resistance

A
  • reduced entry of abx into pathogen
  • ehanced effluc pump activity (removal)
  • release enzymes that destroy abx
  • altering proteins that transform prodrugs
  • altering target proteins
  • develop alternative pathways to those inhibited by abx
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8
Q

Reduced entry of abx

A
  • gram neg
  • mutation, decrease, absence of porin channels in outer membrane
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9
Q

Destruction of Abx

A
  • B-lactamases inactive B-lactam abx by hydrolysis
  • aminoglycosides altered by acetylation, phosphorylation, adenylation
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10
Q

Incorporation of drug

A
  • not only resistant but using it for growth
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11
Q

Reduced affinity to target site

A
  • point mutations in target activating enzymes
  • mutation of the target
  • target modification
  • acquired resistance form naturally
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12
Q

Altered metabolic pathway

A
  • resistant strain over producing PABA = antagonizes sulfonamide
  • resistant strains produce d-ala-d-lactat instead of D-Ala-D-Ala
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13
Q

Structure of Sulfas and PABA

A

-Sulfonamides are structural analogs of PABA

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14
Q

Sulfonamides

A
  • Inhibit DiHydropteoate synthase
  • synergy with DHFR inhibitors (TMP, pyrimethamine)
  • active against Gram pos, gram neg, and enteric bacteria
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15
Q

Trimethoprim

A
  • inhibit Dihydrofolate reducatase
  • active against, respiratory pathogens, s. aureus (MRSA/MSSA)
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16
Q

Resistance for Sulfas

A
  • Overproduction of PABA
  • produce Dihydropteroate synthase that has low affinity for sulfonamides
  • impair permeability/ active efflux
  • random mutation/ transfer by plasmid
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17
Q

Resistance of TMP

A
  • reduced permeability
  • overproduction of DiHydrofolate reductase
  • produce altered reductase with reduced drug binding
  • mutation, plasmid-encoded TMP- resistant dihydrofolate reductase
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18
Q

Sulfa + TMP

Clinical uses

A
  • decline in use of sulfa due to significant resistance
  • TMP/SMX is the drug of choice for UTI, MRSA
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19
Q

Sulfonamide Drugs

A
  • sulfadiazine
  • Sulfaisoxazole
  • Sulfamethoxazole
  • Mafenide
  • Silver sulfadiazine
  • Sulfactamide sodium
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20
Q

Trimethoprim Drugs

A
  • TMP
  • TMP/SMX
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21
Q

Pyrimethamine Drugs

A
  • Pyrimethamine
  • Pyrimethamine-sulfadoxine
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22
Q

P-Kinetics

TMP

A
  • rapid absoption
  • renal excretion
  • t1/2= 11 hrs
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23
Q

P-Kinetics

Sulfonamides

A
  • absorbed, wide distribution
  • rapid excretion
  • renal excretion
  • t1/2= 5-11 hrs
  • Sulfadoxine T1/2= 4-10 days
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24
Q

Sulfa SE

A
  • Rashes
  • SJS
  • photosensitivity
  • GI distress
  • CNS effects
  • Hemolytic anemia in G6PH deficiency
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25
Q

TMP SE

A
  • Megaloblastic anemia, leukopenia, granulocytopenia
  • TMP/SMX - Sulfa adverse effects
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26
Q

MOA

Quinolones

A
  • Inhibit DNA gyrase (topo 2) and topo 4
  • inhibits the nicking and closing activity of gyrase
  • interferes with seperation of replicated DNA into daughter cells
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27
Q

Quinolone 1st group

A

Norfloxacin

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28
Q

commonly used

Quinolone 2nd group

A

- Ciprofloxacin
-Levofloxacin
- enoxacin
- pefloxacin
- ofloxacin

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29
Q

Quinolone 3rd group

A

- Moxifloxacin
- gatifloxacin
- gemifloxacin

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30
Q

Quinolone 1st Spectrum

A

gram negative aerobic bacteria

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31
Q

Quinolone 2nd Spectrum

A
  • aerobic gram-neg
  • some atypicals
  • cipro: Pseudo
  • Levo: better for S. pneumo
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32
Q

Quinolone 3rd spectrum

A
  • Gram pos
  • same as cipro for gram neg
  • moxi = good for anaerobes
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33
Q

Quinolone resistance

A
  • point mutations in the quinolone bind region of target enzyme, change in permeability
  • Qnr proteins, protect DNA gyrase from fluroquinolones
  • aminoglycoside acetyltransferase that can modify cipro
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34
Q

P-Kinetic

Fluroquinolone

A
  • high bio av, except for Norfloxacin
  • High tissue penetration
  • CYP450 metabolism
  • renal extretion
  • Divalent/trivalent cations impair absorption
  • Moxi = hepatic failure
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35
Q

Fluroquinolone Clinical use

A
  • UTIs
  • P. aeruginosa
  • Bacterial diarrhea
  • Pseudomonas, enterobacter
  • Levo, gati, gemi, moxi = respiratory fluroquinolones
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36
Q

Fluroquinolone SE

A
  • GI effects
  • CNS effects
  • skin effects
  • Phototoxicity
  • Muskuloskeletal (children) avoid during pregnancy
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37
Q

Nitrofurantoin

A
  • urinary antiseptic
  • bactericidal
  • For simple UTIs
  • Super rapid excretion
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38
Q

Nitrofurantoin MOA

A
  • activated in bacteria by reduction via flavoprotein nitrofurantoin reductase
  • unstable metabolites disrupt RNA, DNA
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39
Q

Nitrofurantoin SE

A
  • GI issues
  • neuropathy
  • Pulmonary toxicity
  • Hemolytic anemia in G6PH
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40
Q

B-lactam classes

A
  • penicillins
  • cephalosporins
  • monobactams
  • carbapenems
  • B-lactamase inhibitors
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41
Q

Non B-lactam cell wall inhibitors

A

Glycopeptides
Daptomycin
Fosfomycin
Bacitracin
Polymyxin

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42
Q

Penicillin Drugs

A
  • Methicillin
  • nafcillin
  • oxacillin
  • cloxacillin
  • Penicillin G, V
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43
Q

Penicillin MOA

A
  • B-lactam abx mimic D-ala-D-ala
  • irreversible
  • inhibits the activity of transpeptidase enzyme (PBP) by forming a stable metabolite
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44
Q

Penicillin Spectrum

A
  • Gram pos
  • Gram neg cocci
  • Non B-lactamase anaerobes
  • (anti-staph penicillin) staph and strep
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45
Q

Penicillin resistance

A
  • inactivation of abx by B-lactamase
  • Modification of target PBP
  • impaired penetration of drug to target PBP
  • Antibiotic efflux
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46
Q

Penicillin p-kinetic

A
  • Diclox, amp, amox: acid-stable, well absorbed
  • Binds to plasma proteins (albumins)
  • Poor penetration to the eye, prostate, CNS
  • Excretion : renal, unchanged
  • Naf: only billiary
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47
Q

Clinical use

Penicillin G
B-lactam

A
  • streptococci
  • meningococci
  • enterococci
  • Sus Pneumococci
  • Non B-lactamase staph
  • Gram positive
  • syngeristic with gentamycin and tobramycin
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48
Q

Clinical use

Penicillin V

A
  • minor infections
  • poor bio aval
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49
Q

Clinical use

Benzathine Pen and Procaine Pen

A
  • treatment for b- hemolytic step pharyngitis
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50
Q

Clinical use

Anti-staph Penicillins

A
  • Penicillinase producing staph
  • penicillin sus strains of strep and pneucocci
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51
Q

Clinical use

Nafcillin

A
  • serious systemic staph infection
  • neutropenia
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52
Q

Clinical use

Dicloxacillin

A
  • gram pos
  • sus staph
  • group a strep
  • viridans strep
  • strep pneumo
  • penicillinase producing staph
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53
Q

Extened spectrum Penicillins

A
  • Ampi, amox
  • similar antibacterial spectrum
54
Q

Ampicillin

A
  • not good for nosocomial infections
  • active for gram-positive ans some gram negative
  • Respiratory infection, endocarditis, UTI, GI infection, bacterial meningitis
  • SE: pseudomembranous colitis, vaginal candidiasis
55
Q

Amoxicillin

A
  • gram-positive and some gram-neg
  • UTI, otitis, sinusitis, lower respiratory infection
56
Q

Extended Spectrum Penicillin : carboxy

Ticarcillin

A
  • active: pseudomonas, enterobacter, proteus
  • not used for gram positive cocci and listeria
  • used for serious infections only
57
Q

Extended spec Penicillin: Ureidopenicillins

Piperacillin

A
  • anti-pseudomonas penicillin
  • Pseudomonas, Klebsiella, and other gram-negative
  • can be used with B-lactamase inhibitors to decrease resistance
58
Q

Penicillins SE

A
  • Serious hypersensitivity
  • Anaphylaxis
  • Seizures (renal failure patients)
  • GI discomfort
  • skin rash
  • Meth: interstitial nephritis
  • Oxa: hepatitis
59
Q

Penicillins

Drug interations

A
  • Pen G, V: decrease oral contraceptives effectiveness
    colestipol decreases Pen absorption
    Probenecis increases plasma lvl
  • Amox: increase rash with allopurinol
  • serious toxicity with methotrexate (except amox)
60
Q

MOA

Cephalosporins

A
  • more resistant to B-lactamases
  • Against Gram Positive, increasing Gen decreases gram-ng and B-lactamase
  • Broader spectrum than Penicillins (not against Listeria, enterococci)
  • similar MOA and resistance mechanism as Penicillin
61
Q

Cephalosporin Gen 1

A
  • Cefazolin
  • Cephalexin
  • Cefadroxil
62
Q

Cephalosporin Gen 2

A
  • Cefoxitin
  • Cefuroxime
63
Q

Cephalosporin Gen 3

A
  • Ceftaxime
  • Ceftriaxone
  • Ceftazidime
64
Q

Cephalosporin Gen 4

A
  • Cefepime
65
Q

Cephalosporin Gen 5

A
  • Ceftaroline
  • Ceftolozane
66
Q

Cephalosporin Resistance

A
  • decreased conc. at site of action
  • Alterations in PBP, decreased affinity (1A, 2X)
  • Cephalosporinase hydrolysis by B-lactamase
67
Q

Cephalosporin Gen 1 Activity

A
  • Gram positive cocci ( strep, staph) + MSSA + some gram neg
  • PEK (proteus, E.coli, Klebsiella)
  • No MRSA, Pseudo, etc
  • Renal excretion
  • beware of renal impairment
68
Q

Cephalosporin Gen 2 Activity

A
  • Gram positive Cocci, Klebsiella
  • Cefuroxime: H. influenzae. Moraxella
  • Not used in Meningitis
69
Q

Cephalo Gen 2 P-Kinetics

A
  • renally cleared
  • dosage adjust in renal impairment
  • IM should be avoided
70
Q

Cephalo Gen 3 activity

A
  • H. influ, Neisseria, some enterobacterales, some gram positive cocci
  • Ceftazidime: Pseudomonas
71
Q

Cephalo Gen 3 P-kinetics

A
  • Distributes well in CSF (except oral)
  • Renal excretion
  • Ceftriaxone: billiary excretion
  • IM Ceftriaxone + azithro = gonnorhea
72
Q

Cephalo Gen 3 Clinical use

A
  • Serious infections
  • empiric treatment of sepsis
  • Not for enterobacter infection
  • Ceftriaxone, cefotaxime: meningitis
73
Q

Cefepime

A
  • Against: Pseudo, enterobacter, Staph, strep, Haemophilus, Neisseria
  • IV
  • Penetrates CSF
74
Q

Ceftaroline

A
  • IV
  • Only against MRSA
  • retains binding to PBP2a
  • Not active against AmpC or extended spectrum B-lactamase organisms
75
Q

Cephalo + B-lactamase inhibitor

A
  • Ceftazidime + Avibactam
  • Ceftolozane + tazobactam
76
Q

Cephalo SE

A
  • Allergy (hyper, crossreaction)
  • renal toxicity
  • Methythiotetrazole: bleeding discorder, hypoprothrombinemia , disulfiram reactions
77
Q

Monobactams
(Azetreonam)

A
  • Monocyclic B-lactam ring
  • Binds to PBP-3 and PBP1A
78
Q

Azetreonam

A
  • Aerobic gram-negative bacilli + Pseudo
  • Resistant to B-lactamases
  • Distribute to CSF
  • Used for serious infections
79
Q

Carbapenems Activity

A
  • Broad, gram-negative cocci (Pseudo), Gram-positive, anaerobes
  • Resistant to B-lactamases
  • IV
  • Renal excretion
  • Good distribution, CSF
80
Q

Imipenem + Cilastatin

A
  • given together to prevent breakdown of Imipenem
  • Imipenem is inavtivated by dehydropeptidase in renal = low urinary conc.
81
Q

Carbapenem SE

A
  • NVD
  • rash
  • Infusion site rxn
  • seizures (renal failure)
  • Penicillin cross reactivity allergy
82
Q

B-lactamase inhibitors

A
  • Irreversible potent inhibitors of B-lactamases
  • resemble B-lactam
  • protects penicillins and cephalosporins
  • Mainly for, immunocompromised patients, mixed infections
83
Q

Glycopeptides

A
  • bulky structure = IV
  • gram positive, bactericidal
  • synergistic with gentamicin
84
Q

#glycopeptide

Vancomycin MOA

A
  • inhibits the polymerazation or transglycosylase reactio by binding to D-Ala-D-Ala
85
Q

Glycopeptide Resistance

A
  • D-Ala-D-lactate instead of D-Ala-D-Ala
  • Thickened cell wall with increases D-Ala-D-Ala residues, deadend binding site
86
Q

Glycopeptide P-Kinetics

A
  • orally only for C. diff
  • IV for serious infections
  • renal excretion
  • widely distributed
87
Q

Glycopeptide SE

A
  • ototoxicity, nephrotoxicity
  • Vanco infusion reaction (histamine)
88
Q

Dalbavancin and Oritavancin

A
  • semisynthetic lipoglycopeptide
  • Orita inhibits RNA synthesis and disrupts membrane
89
Q

Daptomycin

A
  • cyclic lipopeptide
  • Against: gram-positive bacteria
  • concentration dependent bactericidal
  • Resistance: genetic changes in mprF gene (membrane charge)
  • Not in CAP
90
Q

Daptomycin p-Kinetics

A
  • Only IV
  • Highly Protein bound
  • renal excretion
91
Q

Daptomycin SE

A
  • damage to musculoskeletal system
  • Rhabdomyolysis
  • nephrotox
  • hepatotox
92
Q

Fosfomycin

A
  • Analog of phosphoenolpyruvate
  • Broad, bactericidal
  • Both gram + and gram -
  • synergy with B-lactam antibiotics, aminoglycosides, fluroquinolones
  • Simple UTIs
  • SE: anaphylaxis, C. diff diarrhea
93
Q

Bacitracin

A
  • cyclic peptide
  • Prevents dephosphorylation in cycling of the lipid carrier that carries peptidoglycan
  • Highly nephrotoxic, topical
  • for lesions of the skin, wounds, membranes
    • neomycin/ polymyxin + hydrocodone
94
Q

Polymyxin

A
  • surfactant active amphipathic agents
  • Gram-negative
  • Interact with phospholipids and disrupt cell membrane
  • Resistance: prevent access of drug to cell membrane
  • given parental, renal excretion
95
Q

Fidaxomicin

A
  • macrolide
  • bactericidal
  • Treats C diff diarrhea
  • inhibits RNA synthesis by RNA polymerases
  • Resistance: Mutation in bacterial RNA polymerase
96
Q

Protein synthesis Inhibitor drugs

A
  • tetracyclines, glyclcyclines
  • macrolides
  • lincosamides
  • streptogramins
  • chloramphenicol
  • oxazolidinones
  • aminoglycosides
97
Q

Protein synthesis inhibitor bactericidal

A
  • streptogramins
  • aminoglycosides
  • sometimes oxasolidinones
98
Q

Protein synthesis Inhibitors

S30

A
  • aminoglycosides
  • tetracyclines + glycylcyclines
99
Q

Protein synthesis Inhibitors

S50

A
  • macrolides
  • lincosamides
  • streptogramins
  • chloramphenicol
  • oxazolidiniones
100
Q

Tetracycline MOA

A
  • broad spectrum, bacteriostatic
  • Passive diffusion
  • binds reversibly to 30S subunit of bacterial ribosome
  • Blocks the binding of aminoacyl-tRNA to the accepter site
101
Q

Tetracycline spectrum

A
  • broad spectrum,
  • active against gram positive and negative, certain anaerobes
  • Tet-resistant strains are susceptible to doxy, mino, tige
  • Resistant: enterobacter, Pseudo, N, gonorrhea
102
Q

Tetracycline Resistance

A
  • decrease abx influx
  • produce ribosomal protection protein that displaces tetracycline from target
  • enzymatic inactivation of tetracyclines
103
Q

Tetracycline P-kinetic

A
  • oral absorption = incomplete
  • only parenteral
  • absorption impaired by divalent and trivalent cations
  • damages growing bone and teeth
104
Q

Tetracycline Clinical use

A
  • drug of choice for rickettsia, borrelia, M. pneumonia, chlamydia
105
Q

Tigecycline

A
  • bacteriostatic
  • gram neg and positive
  • active against vanco resistant bacteria
  • IV, biliary excretion
106
Q

Tetracycline SE

A
  • GI discomfort
  • Photosensitivity
  • hepatotox
  • nephrotox
  • Fanconi syndrome
  • Discoloration of teeth
107
Q

Macrolides Drug names

A
  • Erythromycin
  • Clarithromycin
  • Azithromycin
108
Q

Macrolide Activity

A
  • broad
  • Gram neg and pos
  • bacteriostatic
  • binds to 50S
  • Inhibits the translocation step
109
Q

Macrolide resistance

A
  • reduced permeability of the cell membrane/efflux
  • production of esterases that hydrolyze macrolides
  • MLS type B resistance (modification of ribosome binding site)
110
Q

Macrolide SE

A
  • Cardiac toxicity
  • GI discomfort
  • Hepatotox
111
Q

Clarithromycin

A
  • improved acid stability than Erythro
  • similar spectrum (better against mycobacterium and H Influ)
112
Q

Azithromycin

A
  • Against chlamydia, H. Influ
  • Excellent tissue distribution
  • No DDI as Erythro and clari
  • SE: arrythmia, cardiac death
113
Q

Lincosamide

Clindamycin

A
  • Against strep, staph, pneumo. anaerobes
  • Gram neg and pos
  • Same MOA as macrolides
  • Resistance: mutation, modification by methylase, enzyme inactivation
114
Q

Clindamycin SE

A
  • GI distress
  • Skin rash
  • Pseudomembranous colitis
  • Neuromuscular block
115
Q

Streptogramins
Quinupristin/Dalfopristin

A
  • bactericidal (concentration), gram positive cocci
  • binds to 50S ribosome
  • Quinu bind at same site as macrolides
  • Dalfo binds nearby. synergistic enhancing the binding of quinu
  • Dalfo interferes with polypeptide chaine formation
116
Q

Streptogramins Resistance

A
  • modification of quinu binding site
  • enzymatic inactivation of dalfo
  • increased effluc
117
Q

Chloramphenicol

A
  • reversible, 50S
  • Bacteriostatic
  • aerobic, anaerobic, gram pos and neg
  • Resistance: choramphenicol acetyltransferase
  • decrease entry
118
Q

Chloramphenicol p-kinetic

A
  • prodrug
  • Liver metabolism
  • good distribution, CSF, brain
  • adjust for hepatic failure
119
Q

Chloramphicol SE

A
  • GI discomfort
  • Aplastic anemia
  • gray baby syndrom
  • inhibit CYP
120
Q

Chloramphenicol Clinical use

A
  • serious rickettsia infection
  • bacterial meningitis
  • topical eye infection
121
Q

Oxasolidinones

A

Linezolid

122
Q

Linezolid

A
  • Binds to 23s of 50S
  • prevents formation that initiates protein synthesis
  • bacteriostatic
  • Gram positive
  • Resistance: mutation on 23S binding site
123
Q

Linezolid SE

A
  • GI discomfort
  • skin reaction
  • throbocytopenia
  • optic neuritis, peripheral neuropathy
124
Q

Aminoglycosides drugs

A
  • streptomycin
  • neomycin (very toxic)
  • kanamycin
  • amikacin
  • gentamycin
  • tobramycin
  • sisomicin
  • netilmicin
125
Q

Aminoglycoside MOA

A
  • Blocks initiation of protein synthesis
  • incorporate incorrect amino acid
  • Break polysomes into nonfunctional monosomes
126
Q

Aminoglycosides

A
  • irreversible, bactericidal
  • concentration dependent
  • binds to 30S (16S of ribosome)
127
Q

Aminoglycoside Resistance

A
  • Enzymes inactivate aminoglycoside by AMPylation, acetylation, phosphorylation
  • impaired entry of aminoglycosides into the cell
  • receptor protein on 30S is deleted or altered due to mutation
128
Q

Aminoglycoside spectrum

A
  • tobra, amika, netil, genta – widest spectrum
  • active against aerobic gram negative, MSSA
  • nosocomial infection
  • synergy with B-lactams
129
Q

Aminoglycosides P-Kinetics

A
  • IV or IM
  • highly polar, low distribution in brain and CSF
  • Intrathecal/intraventricular injection to reach high levels in CSF
  • urinary excretion
130
Q

Aminoglycosides SE

A
  • Ototoxicity
  • Nephrotox
  • should not be used during pregnacy
  • potential neuromuscular blockage
131
Q

Mupirocin

A
  • Bactericidal
  • gram pos, some gran neg
  • reversible binding and inhibition of isoleucul tRNA synthase
  • AE: irritation at site, nasal irritation
132
Q

Retapamulin

A
  • semisynthetic pleromutilin deriv
  • tx for uncompliacted superficial skin infection
  • Selective inhibition on 50S

DnD- ID (4 decks)

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