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Pharm Exam 1 > Antibiotics I and II > Flashcards

Antibiotics I and II Flashcards

1
Q

Cell Wall Synthesis Inhibitors

A
  • Beta Lactams
  • Vancomycin
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2
Q

Bacteriostatic Abx

A

Erythromycin (macrolides)

Clindamycin

Sulfamethoxazole

Trimethoprim

a

Tetracyclines

i

Chloramphrenicol

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3
Q

Bactericidal Abx

Really Very Fine At Bug Murder

A
  • Rifampin
  • Vancomycin
  • Fluroquinolones
  • Aminoglycosides
  • Beta Lactams
  • Metrondiazole
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4
Q

Beta Lactams

A
  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams (Aztreonam IV)
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5
Q

Three Phases of Cell Wall Synthesis

A
  1. Cytosolic Phase - make the precursuor sugars
  2. Membrane - synthesize disaccharide building blocks
  3. External Phase - synthesize and cross link the strands

C Me, Feel Me, Touch Me, Hear Me……

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6
Q

External Phase and Action of Abx

A
  1. gucosyltransferase (peptidoglycan synthetase) polymerizes disacchardies to make polysaccharide backbone
    * Blocked by Vancomycin
  2. Peptidoglycan transpeptidase (PBP) creates Gly cross-links
  • Blocked by B-lactams - all bind to PBP
  • implication is only active when the cell wall is being syntheized (growing bacteria)
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7
Q

Penicillins

A
  • Penicillin G (IV) and Penicillin VK (PO)
  • Nafcillin (IV)
  • Dicloxacillin (PO)
  • Amoxicillin and Augmentin
  • Ampicillin and (Amp/Sub)
  • Piperacillin (Pip/Tazo)
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8
Q

Cephalosporins

A
  • Cefazolin - IV(1st)
  • Cephalexin - PO (1st)
  • Ceftriaxone - IV (3rd)
  • Ceftazidime - IV (3rd)
  • 5 generations. successive generations have increased Gram -ve activity, and less Gram +ve activity
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9
Q

Carbapenems

A
  • Imipenem
  • Meropenem
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10
Q

Monobactams

A

Aztreonam

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11
Q

Beta Lactam - Mechanism of action

A
  1. Binds PT and it is irreversible covalent bond (looks like D-ala/D-ala of subtrate)
  2. Cell wall is defective. A lytic enzyme attempts to repair it and gets overly activated, causing cell lysis
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12
Q

B-Lactam Resistance Mechanisms

A
  1. Physical Barrier - have an outer cell membrane (gram negative)
  2. Mutant Porin - some B-lactams can go through outer cell membrane through porins, so mutate those
  3. Efflux Pump - pump the b-lactams out of cell
  4. Inactivation - Beta-lactamases bind and inactivate (e.g., penicillinases, B-lactamases)
  5. mutate transpeptidase-PB-2a (MecA gene) does not bind B-lactams (MRSA)
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13
Q

Penicilln G and VK

A
  • susceptible Gram +ves aerobes and anerobes
  • strep., meningococci, enterococci, oral anerobes, syphilis
  • inactivated by gastric acid
  • poor penetration into the CNS
  • renal secretion into the proximal tubule (Vd is small)
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14
Q

Adverse Effects of Penicillin

A
  • direct tox. is low
  • kills good gut bacteria (acidophilus prevents)
  • superinfection (c. diff.)
  • colitis
  • thrombophlebitis
  • CNS - tremors/convulsions (high doses)
  • hypersensitivity
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15
Q

Penicillin Hypersensitivity

A
  • overdiagnosed, prevalence 1%
  • Classification
    • Immediate (0-30 minutes) acute anaphylactic reaction
    • Accelerated (1-72 hrs) - similar to immediate, but milder. hypotension and death are rare
    • Delayed (3-30 days) - usually self-limiting involving skin reactions BUT Stevens-Johnson Syndrome (mild form of TEN)
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16
Q

Penicillinase Resistant Penicillins

A
  • use with penicillinase producing strains of of gram +ve (Strep. and MSSA)
  • Nafcillin (IV) - variable GI absorption, excreted via bile, not kidney
  • Dicloxacillin (PO QID) - skin infections
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17
Q

Extended Spectrum - Aminopenicillins

A
  • Amoxicilln (PO TID or BID) -
    • gram +ve and -ve organims
    • H. influenzae, E. coli, Listeria, Proteus mirabilis, Salmonella, Shigella, enterococci
    • acid-stable, well absorbed
    • Better GI absorption, can give with food
    • rare, non-allergic rash
    • GI distress and diarrhea
  • Ampicillin (PO QID IV) -
    • more GI distress
    • delayed hypersensitivity reactions and non-immune skin reactions
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18
Q

Extended Spectrum Antipseudomonal Penicillins

A

Piperacillin

  • must be IV or IM (bug usually from ventilator anyway)
  • plasma concentrations not proportional to dose
  • sensitive to B-lactamases
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19
Q

Penicillin + B-lactamase inhibitor

A
  • Amoxicillin/Clavulanic Acid (Augmentin)
  • Ampicillin/Sulbactam
  • Piperacillin/Tazobactam
    • clavulanic acid - suicide inhibitor of B-lactamase
    • only inhibits some types of B-lactamases
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20
Q

Cephalosporins - Resistance/Suscep.

A
  • Resistant to penicillinase
  • Gen. 1-2 inactivated by “broad spectrum” B-lactamases
  • Gen 1-3 inactivated by extended spectrum B-lactamases (ESBLs)
  • Gen 1-4 do not bind PB2a (MRSA)
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21
Q

Cephalasporins - Phys Disp.

A
  • Gens 1 & 2 - poor CNS penetration
  • Gen 3 - good CNS penetration
  • well absorbed orally, not affected by food
  • t1/2 of 0.5-2 hours
  • excreted mostly by kidney (probenicid delays renal tubular secretion)
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22
Q

Cephalosporins - Adverse Effects

A
  • Hypersensitivity - cross-reactivity with other cephalosporins and with penicillins (cautious use with those who have a mild/moderate allergy to penicillin)
  • mild nephrotoxicity - enhances nephrotoxicity of aminoglycosides
  • thrombophlebitis with IV
  • diarrhea
  • superinfection
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23
Q

Cephalosporins - Gen I

A
  • primarily for gram +
  • skin, soft tissue infections
  • Cefazolin (IV) - often preferred for surgery prophylaxis. penetrates most tissues, excreted by kidney and has longer 1/2 life
  • Cephalexin (PO) - similar spectrum of activity to cefazolin
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24
Q

Cephalosporin - Gen 3

A
  • Reserved for very serious polymicrobial infections
  • often used with an aminoglycoside
  • susceptible to extended spectrum B-lactamases
  • Ceftriaxone (IV) - good CNS penetration; gonorrhea, Lyme disease (severe) and meningitis
  • Ceftazidime (IV) - t1/2 is 1-2 hours. Penetrates CNS and has good activity against Pseudomonas (turns on a dime)
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25
Q

Carbapenems

A

Imipenem-cilastatin & Meropenem -

  • broadest activity of all antibiotics
  • Most gram + and - rods
  • Pseudomonas
  • reserved for very serious polymicrobial infections
  • resistant to many ESBLs
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26
Q

Imipenem/Cilastatin

A
  • no oral absorption
  • rapidly hyrdolyzed by renal enzyme dihydropeptidase I
  • cilastatin (inhibitor of dihydropep I)
  • renal excretion - modify dose for patients with renal insufficienty
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27
Q

Meropenem

A
  • similar to imipenem
  • not hydrolyzed by dehydropeptidase I
  • cilastatin not required
28
Q

Monobactams

A

Aztreonam (only one we need to know)

  • restistant to beta lactamases
  • gram -ve bacteria (aerobic rods)
  • good activity against entero and Pseudomonas
  • 2nd line to aminoglycosides
  • hypersensitivity rxns, but little cross-reactivity
  • thrombophlebitis at IV site
29
Q

Vancomycin - General

A
  • A glycopeptide
  • Only kills gram +
  • inhibits glucosyltransferase (PS) that adds dissaccharide subunit to growing sugar polymer
  • does this by binding to terminal D-ala-D-ala residues to inhibit GT
  • Resistance: terminal D-Ala mutated to D-lactate
  • reserve for MRSA/C. diff
  • IV unless for C. Diff (then oral)
  • excreted by kidney 90%
  • long t1/2 in anephric patients
30
Q

Vancomycin - Adverse Effects

A
  • irritating to tissues (thrombophlebitis)
  • chills, fever
  • ototoxicity (large doses or other otoxin)
  • flushing (red man syndrome - rapid infusion)
  • nephrotoxicity at highter doses
31
Q

What do we have for Vancomycin resistance?

A

Linezolid - protein synthesis

Daptomycin - membrane depolarizer (pore former)

32
Q

Oxazolidinone - Linezolid

A
  • Gram +
  • very limited indications (2nd/3rd line) when vancomycin is contraindicated
  • unique mechanism of action (no cross-resistance) blocks initiation of protein synthesis
    • binds to 23s RNA of 50s subunit
    • prevents formation of the 70s complex
    • inhibits protein synthesis
33
Q

Linezolid - Resistance

A
  • due to mutation in the 23s RNA
  • reported for enterococci
  • agent of last resort!
34
Q

Linezolid - Phys Disp

A
  • oral and parenteral - can give with food
  • metabolized in liver, excreted in urine

(no need to adjust for renal patients)

35
Q

Linezolid - Adverse Reactions

A
  • nausea, vomiting, diarrhea, headache, rash
  • myelosuprpresion
  • oral contains phenylalanine
  • peripheral and optic neuropathy with prolonged use (reversible)
36
Q

Linezolid - Drug Interactions

A
  • mild inhibitor of MAO - hypertension if taken with foods rich in tyramine
  • watch SSRIs and drugs with pseudophedrine
  • No interactions with Cyp3A4 or others
37
Q

Cyclic Lipopeptide - Daptomycin

A
  • Gram +ves
  • very limited indications (3rd/4th line) - only when vancomycin and linezolid are contraindicated
38
Q

Daptomycin - Mechanism

A
  • needs Ca2+
  • targets cell membrane by oligomerizing with Ca2+ and forms pores in membrane that allow K+ to leave
  • cell death
39
Q

Daptomycin - Clearance and AE

A
  • excreted unchanged in urine (need to adjust for renal pts)
  • IV only
  • muscle weakness (no with statins)
  • fever, headache, insomnia dizziness, rash
40
Q

What are the alternatives to wall agent abx?

A
  • Protein synthesis (translocation) inhibitors
    • Macrolides (gram +/-)​
      • ​​​erythromycin
      • clarithromycin (PO)
      • Azithromycin (PO, IV)
    • lincosaminde (anaerobes)
      • clindamycin (PO, IV)
  • DNA breaker
    • Nitroimidazole (anaerobes)
      • Metronidazole (PO, IV)
41
Q

What are the Macrolides?

A
  • Clarithromycin (PO)
  • Azithromycin (PO, IV)
  • Erythromycin - Don’t use
42
Q

Nitroimidazole-Metrondiazole

A
  • used for anerobes and C. diff bowel surgery
  • flagyl is trade name
  • disrupts DNA by forming covalent bonds that fragment DNA
  • resistance - has reduced levels of nitroreductase
43
Q

Lincosamide - Clindamycin

A
  • PO or IV
  • most +ve aerobes
  • most +ve and -ve anerobes (oral>bowel)
  • Can be used for MRSA
44
Q

Clindamycin - Resistance and Phys. Disp.

A
  • If you are resistant to clindomycin, you are resistant to macrolides. converse not necessarily true
  • oral and parenteral
  • no CNS penetration
  • metabolized by liver (watch in severe hepatic disease)
45
Q

Clindamycin - AE

A
  • diarrhea, nausea
  • Pseudomembranous colitis (usually C. diff. which is resistant to clinda)
  • potentially fatal
  • treated with oral metronidazole or oral vancomycin or fecal transplant
46
Q

Macrolide-Azithromycin

A
  • penetrates tissues well and stays there
  • t1/2 3 days
  • food and antacids decrease bioavailability
  • no CYP-450, so no drug-drug
  • cross-resistance with erythromycin
47
Q

Macrolide-Clarithromycin

A
  • more stable to acid than eryth
  • metabolized by liver (dosage reduced for hepatic pts)
  • eliminated by kidney (dosage reduction for renal pts)

Adverse Effects

  • high doses reversible hearing loss
  • teratogenic - no in pregnancy or kids
  • inhibits CY34A (drug-drug interaction)
48
Q

Macrolides - Mechanism

A
  • Inhibit Protein Synthesis
    • premature release of polypeptides by preventing translocation
  • Gram +ve cocci and bacilli
  • inactive against mot gram -ve bacilli
  • allergy to penicillin alternative
49
Q

What is MLS resistance?

A
  • MLS: Macrolides, Lincosamides and Streptogramins
  • add methyl group to the biding site on the 50s ribosome = resistance to all
50
Q

Protein Synthesis Inhibitors (Class)

A

Tetracyclines

Aminoglycosides

51
Q

Urinary Tract Antiseptics

A

Nitrofurantonin

52
Q

DNA Synthesis Inhibitors (Class)

A

Antifolates

Flruoquinolones

53
Q

Protein Synthesis - Process

A
  • f-met binds to 30s and then 50s binds ftmet in P-site
  • makes a 70s ribosome
54
Q

Translation and the Ribosome - Process

A
  1. aminoacyl-tRNA binds to a vacant A-site and proofreading checks if base pair is correct
  2. a. Peptide bond is formed (PT) b. aminoacyl-tRNA moves to P-site (translocation)
  3. spent tRNA is ejected from E-site. ribosome resets
55
Q

Buy AT 30, CCELL at 50

A

30s inhibitors

A=aminoglycosides

T=tetracyclines

50s

C=clindamycin

C=chloramphenicol

E=erythromycin

L=lincomycin

L=linezolid

56
Q

Tetracyclines (abx you need to know)

A
  • doxycycline
57
Q

Tetracyclines - Mechanism of Action

A
  • usually enter cell due to passive diffusion
  • accumulates in bacteria, eukaryotes don’t
  • binds REVERSIBLY to the 30s
  • blocks binding of the aminoacyl-tRNA to A site
  • prevents addition of aa’s
58
Q

Resistance to Tetracyclines

A

3 mechanisms:

  1. Efflux pumps
  • TET(AE) efflux pump in gram -ve (DoxyR/TigS)
  • TET(K) pump in staph (DoxyS/TigS)
  1. 30s Ribosome protection
    * TET(M) in gram +ve (DoxyR/TigS)
  2. enzymatic inactivation by organism (acetylation)

NB: Tigecycline does not usually share cross-resistance

59
Q

Tetracyclines - Coverage

A
  • bacteriostatic
  • gram +ve and -ve organisms
  • NO to pseudomonas, proteus
  • seldom first line, except Doxy:
    • atypical pneumonia (mycoplasma)
    • NGU (chlamydia)
    • Rocky Mountain spotted fever
    • lyme disease
60
Q

Doxycycline - Properties

A
  • BID oral or IV
  • low renal clearance
  • longer t1/2
  • wider activity
61
Q

Tetracyclines - ADME

A
  • Doxycycline - 95-100% absorbed (can be taken with food) - longer 1/2 h=life
  • Absorption impaired by divalent metals (chelate)
  • distributed widely in bones and teeth, not in CSF (except Mino)
  • Doxy eliminated by non-renal, so safest for renal pts
    *
62
Q

Tetracyclines: Toxicities

A
  • modification of gut microflora
  • superinfection (C. diff, staf, pseudomonas)
  • Doxycycline at higher doeses produces vestibular dysfunction
  • short shelf life - expired drugs cause renal tubular acidosis (Fanconi syndrome)
  • tooth discoloration - no for kids less than 8
  • impair bone growth in developing fetus
63
Q

Aminoglycosides (ones you must know)

A
  • gentamicin
  • tobramycin
64
Q

“mean” GNATS can NOT kill anaerobes

A

NOT - nephrotoxic, ototoxic, teratogen

GNATS - gentamicin, tobramycin (among others)

65
Q

Aminoglycosides - Mechanism

A

binds 30s subunit

  • blocks initiation of synthesis
  • blocks A-site loading
  • causes incorporation of incorrect aa
  • impairs proofreading
  • evidence suggests alteration to increase permeability and leaking of conents
  • likes to stick to membranes
  • needs O2 to get accross membrane and uses H+ pump - low extracellular pH inhibits
66
Q
A

Pharm Exam 1 (3 decks)

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