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Step 1 > Sketchy Pharma Antimicrobials > Flashcards

Sketchy Pharma Antimicrobials Flashcards

1
Q

Mechanism of Beta-lactam abx

A

Beta-lactams bind to penicillin binding proteins (PBPs) on bacterial cell walls to interfere w/ transpeptidation of peptidoglycan synthesis
-PBP required to cross-link peptidoglycan, so penicillins binds to PBPs to prevent this
Prevent cell wall synthesis => bacteriocidal

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2
Q

Main indication for Penicillin

A

Penicillin mainly for Gram positive cocci, mainly strep

Oral Penicillin (PenG) uses: GAS pharyngitis, rheumatic fever

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3
Q

Other indications for Penicillin

(a) Against what gram negative
(b) What infxn from dog bites
(c) Against what filamentous rod
(d) Against what cause of food poisoning

A

Penicillin indications in addition to strep throat

(a) Penicillin works against neisseria meningitis! (gram negative)
(b) Pasteurella from dog bites
(c) Actinomyces israelii (skin infxn after jaw trauma)
(d) C. perfinges- so can use IV PenG for gas gangrene

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4
Q

MC cause of resistance to penicillin

A

Beta-lactamases, expressed by plasmid genes, that cleave the beta-lactam ring

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5
Q

Shared side effects of penicillin-class of abxs

A

Beta-lactams (Penicillins, Cephalosporins)

  1. Hypersensitivity reactions
  2. Interstitial nephritis
  3. Autoimmune hemolytic anemia
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6
Q

Explain how the structure of Nafcillin changes its coverage

A

Nafcillin has a large R-group side chain on its beta-lactam ring that doesn’t allow beta-lactamase to cleave it => nafcillin is effective against beta-lactamase producing staph species (MSSA)

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7
Q

Mechanism of resistance of MRSA to Nafcillin

A

MRSA: staph species that contain altered PBPs (penicillin binding proteins) that have low affinity for Nafcillin => Nafcillin can’t bind and kill the bacteria

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8
Q

First line indications for Naficillin

A

MSSA- think Staph aureus (‘Naf for staph’) endocarditis/osteomyelitis/folliculitis/abscess

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9
Q

Differentiate ampicillin and amoxicillin

A

Ampicillin- IV administration
-combined w/ sulbactam (Unasyn) to cleave beta-lactamase

Amoxicillin- PO
-combined w/ clavulnate (augmentin)

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10
Q

Indications of amoxicillin

(a) Main indications
(b) Why useful for ppx in aspenic pts

A

Amoxicillin = extended-spectrum penicillin

(a) Strep throat, otitis media, sinusitis
(b) Covers encapsulated bacteria H. influenza and S. pneumo

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11
Q

First line abx for

(a) Ppx in asplenic pts
(b) Staph endocarditis
(c) Syphilis

A

First line abx for

(a) Ppx in aspenia = Amoxicillin = extended-spectrum penicillin
(b) Staph endocarditis = Nafcillin
(c) Syphilis = single dose IV penicillin

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12
Q

First line abx for

(a) Intrapartum GBS ppx
(b) Ppx before dental procedure in pts at high risk for endocarditis
(c) Listeria meningitis
(d) Gonorrhea

A

First line abx for

(a) Intrapartum GBS ppx = PenG
(b) Ppx for dental procedure in pts w/ artificial heart valves = Amoxicillin b/c covers S. pneumo
(c) Listeria meningitis = Ampicillin (IV extended coverage penicillin)
(d) Gonorrhea tx w/ single dose of IV ceftriaxone

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13
Q

Beta-lactam abx associated w/

(a) Rash in pt w/ infectious mononucleosis
(b) Drug induced liver injury

A

(a) Amoxicillin and ampicillin are associated w/ rash in pts w/ EBV
- also associated w/ SJS
(b) Amoxicillin has high association w/ DILI

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14
Q

Key indications for Piperacillin and Ticarcillin

A

Piperacillin (combined w/ tazobactam = Zosyn) and Ticarcillin are extended-spectrum penicillins w/ coverage of pseudomonas and anaerobes

-so used as empiric tx for HCAP and sepsis

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15
Q

Name the three combo drugs of penicillin and beta-lactamase inhibitor

A

Combo drugs

  1. Amoxicillin w/ clavulate = Augmentin (PO)
  2. Ampicillin w/ tazobactam = Unasyn
  3. Piperacillin w/ tazobactam = Zosyn
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16
Q

Mechanism of action of cephalosporins

A

Cephalosporins are beta-lactams, so still same mechanism as Penicillin, Nafcillin, Ampicillin etc

Bacteriocidal- halt peptidoglycan synthesis by binding PBP (penicillin binding proteins)

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17
Q

1st gen cephalosporins

(a) Main indication
(b) Extent of G- coverage

A

1st gen cephalosporins = Cephalexin and Cefazolin (Keflex): mainly gram positive coverage w/ tiny bit of gram negative

(a) Surigcal infection ppx, cellulitis and abscess from Strep/Staph
(b) Covers PEK organisms that cause UTI: Proteus, E. Coli, Klebsiella

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18
Q

Name the 2nd gen cephalosporins

A

2nd gen cephalosporins = Cefuroxime, Cefotetan, Cefoxitin

Covers same as first gen (staph/strep w/ Klebsiella Proteus E. coli) plus HENS: H. flu, neisseria, and serratia

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19
Q

3rd gen cephalosporins

A

3rd gen cephalosporins = Ceftraixone, Cefotaxime, Ceftazidime

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20
Q

Name the 3 components of empiric meningitis tx in 68 yo M

A

Empiric tx of meningitis

  1. Ceftriaxone for broad gram negative coverage w/ good CNS penetration
  2. Vanc for MRSA coverage
  3. Ampicillin for Listeria coverage since over 65
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21
Q

Distinguish the two types of 3rd gen cephalosporins

A

3rd gen cephalosporins: Ceftraixone and Cefotaxime great for meningitis, cross BBB

But then Ceftazidime is special b/c it covers pseudomonas! So use Ceftrazidime for HCAP and ventilator-associated pneumonia

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22
Q

Differentiate 4th and 5th generation cephalosporins

A

4th gen cephalosporin = Cefepime- broad spectrum w/ good CNS penetration (tx meningitis) and covers pseudomonas
-but still no MRSA coverage

5th gen cephalosporin = Ceftaroline- Cefepime plus MRSA coverage!!!!! Can bind to the altered PBPs of MRSA

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23
Q

Main side effects of cephalosporins

A

Cephalosporins are beta-lactams (like penicillin, ampicillin, nafcillin, aztreonam, imipenem) so have the same major side effects

  1. Hypersensitivity- cross reactive w/ penicillin allergy
    - so if pts have IgE against Penicillin, more likely they’ll also have type I hypersensitivity against cephalosporins
  2. interstitial nephritis
  3. autoimmune hemolytic anemia
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24
Q

Explain the progression as you get to higher generations of cephalosporins

A

Start w/ mainly G+ coverage, get increasingly more G- up to 3rd gen which has big G- coverage

Then 4th gen has broad G+ and G- coverage (broad spectrum), while 5th gen is everything + MRSA

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25
Q

Mechanism of

(a) Aztreonam
(b) Vancomycin

A

Mechanisms

(a) Aztreonam = monobactam, beta lactam abx => bacteriocidal by binding PBPs to half peptidoglycan wall synthesis

(b) Vancomycin directly binds D-ALA-D-ALA oligopeptide of the cell wall (not indirectly by binding PBPs)
- this is why Vanc is effective against MRSA, which has altered PBPs

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26
Q

Mechanism of

(a) Imipenem, Meropenem
(b) Daptomycin

A

Mechanisms

(a) Carbapenems are beta-lactams => bacteriocidal by binding PBPs to half peptidoglycan wall synthesis
(b) Daptomycin works against gram positives by inserting its lipid tail into the membrane and causing depolarization => bacteriocidal

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27
Q

Which abx requires co-administration w/ Cilastatin

A

Cilastatin = dehydropeptidase enzyme inhibitor

Co-administer cilastatin w/ Imipenem b/c otherwise Imipenem gets inactivated by dehydropeptidase in the renal tubules

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28
Q

Explain the mechanism by which certain enterococci strains are resistant to vancomycin

A

VRE gain resistant b/c of altered peptidoglycan (cell wall) structure

Normally peptidoglycan is D-ALA-D-ALA chains, while VRE have D-ALA-D-LAC chains instead => Vanc can’t bind :-(

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29
Q

Why are vanc troughs monitored?

A

Vanc levels are measured b/c the drug is 90% excreted by glomerular filtration, which can greatly vary from person to person and w/ certain concomitant medications etc

So want high enough levels to penetrate tissues but don’t want to cause toxicitiy (thrombophlebitis, nephrotoxicity, ototoxicity) => monitor levels

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30
Q

Vancomycin side effects

A

Vancomycin side effects

  • Red man infusion syndrome
  • thrombophlebitis
  • rare: ototoxicity and nephrotoxicity
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31
Q

Buzzword w/ abx

a) Red man syndrome
(b

A

Buzzword

(a) Red man syndrome = infusion syndrome from histamine release 2/2 vancomycin

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32
Q

Side effect of daptomycin that requires monitoring

A

Daptomycin is associated w/ myopathy, requiring monitoring of CPK levels in pts on chronic daptomycin tx

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33
Q

Indications for Daptomycin

A

Daptomycin (depolarizes cell membranes of G+) for VRE, vanc resistant strep, MRSA bacteremia, MRSA endocarditis

NOT for MRSA pneumonia!!! inactivated by pulmonary surfactant

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34
Q

Which MRSA infection is Daptomycin contraindicated in?

A

Well not contraindicated in by Daptomycin is ineffective against MRSA pneumonia b/c Daptomycin is inactivated by pulmonary surfactant

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35
Q

Which MRSA infection is Daptomycin contraindicated in?

A

Well not contraindicated in by Daptomycin is ineffective against MRSA pneumonia b/c Daptomycin is inactivated by pulmonary surfactant

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36
Q

Name the beta-lactam abx classes

A

Tons of beta-lactams: all w/ the same mechanism = bind to PBPs (penicillin binding proteins) to inhibit peptidoglycan wall synthesis = bacteriocidal

Penicillin
Nafcillin, Oxacillin
Amoxicillin, Ampicillin, Piperacillin, Ticarcillin
Cephalosporins (all 5 generations)
Monobactams (aztreonam) 
Carbapenems
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37
Q

Name abx that target the cell wall but are not beta-lactams

A

Vancomycin- binds directly to D-ALA-D-ALA instead of PBPs (penicillin binding proteins)

Daptomycin- depolarizes the cell membrane by inserting its lipid tail

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38
Q

Name abx that target the cell wall but are not beta-lactams

A

Vancomycin- binds directly to D-ALA-D-ALA instead of PBPs (penicillin binding proteins)

Daptomycin- depolarizes the cell membrane by inserting its lipid tail

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39
Q

Mechanism of tetracyclines

(a) What else has a similar mechanism?

A

Tetracycliines (Doxycycline, Mincecycline) enter the bacteria and reversibly bind to the 30S subunit to inhibit translocation, bacteriostatic

(a) Aminoglycosides also bind to 30S ribosomal subunit, but they’re bacteriocidal

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40
Q

2 abx used for moderate to severe acne

A

Tetracyclines (doxycycline)- skin anaerobes, bacteriostatic, inhibits bacterial protein synthesis by binding to 30S subunit

Clindamycin, kills off the cutaneous anaerobic flora, bacteriostatic, inhibits bacterial protein synthesis by binding to 50S subunit

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41
Q

What two populations are tetracyclines contraindicated in?

A

Tetracyclines are contraindicated in children under 8 and pregnant women

Children b/c tetracyclines bind to newly formed bone and teeth => classically causes teeth discoloration

Teratogenic b/c binds Ca2+ in fetal teeth and bone => malformations

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42
Q

What abx can you not take with milk or ferrous sulfate?

A

Avoid milk, ferrous sulfate, and antacids w/ tetracycline b/c tetracyclines are absorbed by divalent cations (Ca2+, Fe2+, Mg2+) in the gut which decreases absorption

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43
Q

What abx is associated w/ Fanconi syndrome

A

Fanconi syndrome- causes a type 2 renal tubular acidosis- is associated w/ use of expired tetracyclines

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44
Q

Explain the mechanism of bacterial resistance to tetracyclines

A

Tetracyclines work by binding bacterial ribosomal 30S subunit, which requires them to be inside the cell

Resistance develops by efflux pumps that literally pump the abx out of the bacteria, or by alteration of the ribosomal subunit

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45
Q

Main indications for Doxycycline

A

Doxycycline first line for

  • Rickettsia (rocky mtn spotted fever), also covers other tick borne illness (Ehrlichia, francisella, Borrelia bergdorferi- use in early Lyme’s disease)
  • community acquired pneumonia from atypical bugs (mycoplasma and chlamydia)
  • zoonotics: Brucella, Coxiella (Q-fever), Yersinia (black plague)

Does cover MRSA (but not first line)

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46
Q

Which antibiotic that inhibits bacterial protein synthesis is bacteriocidal

A

Only abx w/ mechanism of inhibiting protein synthesis that is bacteriocidal = aminoglycosides (streptomycin, gentamycin, tobramicin, amikacin)

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47
Q

Side effects of doxycycline

A

Photosensitivity and GI (N, V, D)

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48
Q

Drugs for tx of atypical (walking) pneumonia

A

Tetracyclines (doxycycline, inhibit bacterial protein synthesis by binding to 30S) covers mycoplasma and chlamydia atypical pneumonia

Macrolides (Azithromycin, inhibit bacterial protein synthesis by binding to 50S) covers mycoplasma, legionella, and chlamydia pneumonia

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49
Q

Mechanism of macrolides

A

Macrolides = Azithromycin, Clarythromycin, Erythromycin

Bacteriostatic, inhibit 50S subunit

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50
Q

Tx of community acquired pneumonia in pts w/ penicillin allergy

A

Macrolides (Azithromycin): good coverage of S. pneumo, H. influenza, and Moraxella catarrhalis

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51
Q

Mechanism of the triple therapy used for H. pylori eradication

A

H. pylori triple therapy

  1. PPI to reduce acid production which is elevated due to the infection
  2. Clarythromycin = macrolide abx, bacteriostatic, inhibits bacterial protein synthesis by binding 50S
  3. Amoxicillin = extended-coverage beta-lactam, bacteriostatic, inhibits cell wall synthesis
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52
Q

Abx of choice for

(a) Cat scratch fever
(b) Congenital conjunctivitis

A

Abx of choice for

(a) Cat scratch fever 2/2 bartonella henselae = Azithromycin (macrolide)
(b) Congenital conjunctivitis- think gonorrohea and chlamydia, tx w/ erythromycin (macrolide)

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53
Q

Abx of choice for

(a) Diptheria
(b) Aspiration pneumonia c/b abscess formation

A

Abx of choice for

(a) ‘Bull’s neck’ from C. diptheria = erythromycin (macrolide)
(b) Really good oral anaerobic coverage w/ great abscess penetration = clindamycin (own class, bacteriostatic, inhibits 50S)

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54
Q

Abx of choice for polymicrobial infections of the female genital tract such as endometriosis or infected retained products of conception

A

Want broad coverage: gentamycin plus clindamycin

  • Gentamycin
  • clindamycin = inhibits bacterial protein synthesis by binding 50S
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55
Q

Two txs for gas gangrene/myonecrosis

A

Clostridium perfinges (G+ bacilli) can cause gas gangrene/myonecrosis

Tx w/ IV PenG (beta lactam, inhibits cell wall synthesis, bacteriocidal) or clindamycin (inhibits protein synthesis by binding 50S, bacteriostatic)

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56
Q

Tx for bordetella pertussis

A

Azithromycin = Macrolide abx, inhibits bacterial protein synthesis by binding to 50S

Use Azithromycin over Erythro or Clarythromycin in infants under 1 mo

-can also give Azithromycin for pertussis ppx to close contacts

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57
Q

In addition to metronidazole, what abx covers gardenerella vaginosis?

A

Gardenerella vaginosis = anaerobe, can also be covered by clindamycin which has great anaerobe coverage

‘clindamycin for anaerobes above the diaphragm (oral anaerobes that cause aspiration pneumonia), metronidazole for anaerobes below the diaphragm

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58
Q

Abx w/ highest risk of C. Dif

A

Clindamycin = MC implicated in pseudomembranous colitis 2/2 C. Dif

Mechanism of clindamycin = inhibits bacterial protein synthesis by binding 50S

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59
Q

Name the abx not used in the US, but often used in third world countries to combat meningitis outbreaks

A

Chloramphenicol
-bacteriostatic inhibitor of microbial protein synthesis

Super duper cheap, but not used here b/c of side effects: hematologic (aplastic anemia), gray-baby syndrome

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60
Q

Mechanism of

(a) Linzeolid
(b) Streptomycin
(c) Isoniazid

A

Mechanisms

(a) Linezolid = bacteriostatic, binds 50S to prevent formation of initiation complex => inhibiting bacterial protein synthesis
(b) Streptomycin = type of aminoglycoside => bacteriocidal protein synthesis inhibitor
(c) Isoniazid = inhibits synthesis of mycolic acid (necessary component of mycobacterium cell wall, what makes it stain acid fast positive)

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61
Q

Mechanism of

(a) Gentamycin/Tobramycin
(b) Rifampin

A

Mechanisms

(a) Gentamycin/Tobramycin are aminoglycosdies that are bacteriocidal inhibitors of bacterial protein synthesis
(b) Rifampin binds to bacterial-dependent RNA polymerase to prevent RNA production

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62
Q

When are the following used a single agents

(a) Isoniazid
(b) Rifampin

A

Often used in combo to prevent resistance, but can be used alone in certain circumstances

(a) Isoniazid tx alone for tx of latent Tb to prevent reactivation
(b) Rifampin can be used as monotherapy to prevent meningitis (2/2 H. influenza and N. meningitis) in close contacts

63
Q

Abx to use w/ caution in pts w/ depression

A

Linezolid, is a partial inhibitor of MAO, so can precipitate serotonin syndrome if used w/ other 5-HT agents

64
Q

2 agents effective against VRE

A
  1. Daptomycin: cell wall inhibitor by depolarizing cell membrane, bacteriocidal
  2. Linezolid- bacteriostatic, inhibits protein synthesis by binding to 50S to prevent formation of initiation complex
65
Q

Toxicities of Linezolid

A

Linezolid toxicities

  1. Hematologic
    - MC thrombocytopenia, also anemia and neutropenia
  2. Neuropathy: optic neuropathy and peripheral neuropathy
66
Q

Main indications for Linezolid

A

Linezolid (bacteriostatic inhibitor of bacterial protein synthesis)

For serious/nosocomal G+ infections

  • nosocomial pneumonia
  • complicated cellulitis from MRSA or VRE
67
Q

Mechanism of

(a) Aminoglycosides
(b) Ethambutol

A

Mechanism

(a) Aminoglycosides = bactericidal inhibitors of bacterial protein synthesis
(b) Ethambutol blocks arabinosyl transferase to inhibit carbohydrate formation at the cell wall

68
Q

Mechanism of all RI and E RIPE agents

A

Mechanisms:

  • Rifampin works by inhibit RNA polymerase
  • Isoniazid inhibits mycolid acid (cell wall component) synthesis
  • Pyrazinamide: mechanism unknown
  • Ethambutol blocks arabinosyl transferase, inhibiting carb formation at the cell wall
69
Q

Which class of abx are often coupled w/ cell wall active drugs

A

Aminoglycosides are actively transported across cell membrane by an O2 dependent process (hence efficacy against aerobic bacteria), but need to get past cell wall first => pair w/ beta-lactam or Vancomycin

70
Q

2 indications of streptomycin

A

Streptomycin (aminoglycoside- bacteriocidal bacterial protein synthesis inhibitor)

  1. tularemia by Francisella tularensis (rabbits)
  2. black plague by yersinia pestis
71
Q

Benefit of Amikacin over Gentamycin and Tobramycin

A

All 3 are aminoglycosides (bacteriocidal bacterial protein synthesis inhibitors)

But Gentamycin and Tobramycin are inactivated by certain acetylation enzymes found in enterococci species => require high doses, while Amikacin is resistant to that enzyme

72
Q

Main toxicities of Amikacin

A

Amikacin (big gun aminoglycoside) toxicities:

  • ototoxicity that often presents as vistibular disturbance: dizziness, ataxia
  • nephropathy: ATN- brown muddy fasts
73
Q

2 contraindications to aminoglycoside therapy

A
  1. Pregnancy- can cause ototoxicity (deafness) in newborn

2. Myasthenia Gravis b/c aminoglycosides have rare side effect of neuromuscular blockade

74
Q

Main side effects of isoniazid

A

Isoniazid = INH ‘injury to nerves and hepatocytes’

  • Peripheral neuropathy (2/2 B6 deficiency), ataxia, paresthesias
  • expect asympatomatic rise is aminotransferases
75
Q

Mechanism by which bacteria develop resistance to

(a) Isoniazid
(b) Rifampin

A

(a) Isoniazid is activated by KatG (catalase peroxidase) made by bacteria, so mutations that downregulate KatG expression confer resistance to isoniazid
(b) Bacteria can mutate their RNA polymerase => Rifampin can’t bind

76
Q

What to co-administer w/ isoniazid

A

Coadminister pyridioxine (vit B6) w/ isoniazid to prevent side effect of periphery neuropathy

77
Q

Describe the effect of RIPE drugs on cyt p450

A

Isoniazid inhibits cyt p450 => can increase levels of drugs metabolized by cyt p450 (ex: wafarin, AEDs)

While Rifampin is a potent cyt p450 inducer/activator

78
Q

Less common side effects of isoniazid

(a) Autoimmune
(b) pH abnormality
(c) CNS

A

Isoniazid (inhibit mycolic acid synthesis) less common side effects (aside from peripheral neuropathy and elevated LFTs)

(a) Drug-induced lupus
(b) Metabolic acidosis (MUD PILES)
(c) Seizures

79
Q

What makes isoniazid metabolism clinical relevant?

A

Isoniazid is metabolized by liver enzyme N-acetyltransferase

-certain ppl are slow acetylators => have increased risk of side effects such as vit B6 deficiency peripheral neuropathy

80
Q

Main side effect of

(a) Rifampin
(b) Ethambutol

A

Main side effect of

(a) Rifampin therapy = benign orange-red discoloration of body fluids
- urine, sweat, saliva
(b) Ethambutol = optic neuritis => reduced visual acuity and red/green color blindness

81
Q

Side effects of pyrazinamide

A

Pyrazinamide

  • severe hepatotoxicity, can even cause hepatic necrosis
  • hyperuricemia, can precipitate acute gouty attacks
82
Q

Main side effect of RIPE therapy

A

Hepatotoxicity

83
Q

Abx that is associated w/

(a) Red/green color blindness
(b) Red/orange discoloration of body fluids
(c) Increased side effects in slow acetylators

A

(a) Red/green color blindness 2/2 optic neuritis seen w/ Ethambutol therapy
(b) Red/orange discoloration of urine, saliva, sweat from Rifampin
(c) Isoniazid metabolized by N-acetyltransferase in the liver, so slow acetylators have increased risk of side effects of isoniazid therapy (peripheral neuropathy)

84
Q

Bactrum mechanism

A

Bactrum = combo drug w/ synergistic activity (bacteriostatic alone, bacteriocidal togther), blocks folate synthesis at two sequential steps

  • SMX (sulfa drug) = PABA analog that blocks PABA –> DHF
  • TMP blocks dihydrofolate reductase to block DHF –> THF
85
Q

HIV ppx

(a) CD4 200
(b) CD4 100
(c) CD 50

A

Once CD4 count reaches under

(a) 200- ppx w/ Bactrum against PJP (pneumocystis jirovecii pneumonia)
(b) 100- ppx w/ Bactrum against toxoplasmosis
(c) 50- ppx w/ Azithromycin against MAC

86
Q

Bactrum coverage

(a) First line for what?
(b) Important G pos coverage
(c) Filamentous rod

A

Bactrum coverage

(a) First line for UTIs (good gram neg coverage), also tx acute prostatitis
(b) Covers MRSA!
(c) Covers nocardia (partially acid fast filamentous rod)

87
Q

Which abx to really avoid alcohol on

A

Metronidazole 2/2 disulfiram-like reaction: flushing, tachycardia, palpitations, N/V in response to EtOH

88
Q

Teratogenic effects of

(a) TMP-SMX
(b) Fluoroquinolones

A

(a) Bactrum teratogenic during first trimester due to folate inhibition => increased risk neural tube defects
(b) Fluoroquinolones contraindicated in pregnancy and children under 10 2/2 cartilage damage/arthropathy

89
Q

Use of bactrum in HIV pts

A

Bactrum used to tx and ppx for PJP (pneumocystis jirovecii pneumonia)

Also bactrum for CD4 under 100 for toxo ppx

90
Q

Main adverse effect of bactrum therapy

A

Pancytopenia 2/2 folate inhibition

-can cause megalobalstic anemia

91
Q

General side effects common to all sulfa drugs

A
  • hypersensitivity rxn (2nd MC abx to cause hypersensitivity rxn behind penicillins)
  • SJS/TEN risk
  • hemolytic anemia in G6PD deficiency
  • type IV renal tubular acidosis => hyperkalemia
  • interstitial nephritis
  • photosensitivity
92
Q

Explain why sulfa drugs have a ton ton of drug interactions

A

Sulfa drugs do 2 things: (1) inhibit cyt p450 (20 displace drugs from albumin

=> increase in concentration of many drugs (ex: warfarin)

93
Q

Why are sulfonamides contraindicated in

(a) First trimester
(b) Third trimester

A

Sulfa drugs

(a) Increase risk neural tube defects 2/2 inhibition of folate synthesis
(b) Third trimester- displaces unconjugated bili from albumin => increased risk of kernicterus in neonates

94
Q

Mechanism of fluoroquinolones

A

Fluoroquinolones are bacteriocidal, inhibit bacterial topoisomerase DNA gyrase => inhibits bacterial replication

DNA gyrase needed to relieve strain during unwinding and replication

95
Q

Tx of complicated vs. uncomplicated UTI

A

Uncomplicated UTI- tx w/ Batrum (good G- coverage)

Complicated UTI first line is fluoroquinolones (ciprofloxacin)- complicated meaning in diabetic pt or pt w/ h/o urinary obstruction b/c want to cover for pseudomonas

96
Q

Empiric tx for pyelonephritis

A

Pyelonephritis empiric tx = ciprofloxacin (fluoroquinolone, inhibits DNA gyrase to inhibit bacterial DNA replication)

97
Q

Main indication for fluoroquinolones

A

Fluoroquinolones have great gram negative coverage

  • GI gram neg bacilli: Shigella, Salmonella, E. Coli, campylobacter
  • complicated UTI and pyelonephritis b/c pseudomonal coverage
  • Gram neg osteomyelitis b/c good bone penetration: specifically salmonella osteo in SCD
98
Q

Gram positive coverage of fluoroquinolones

A

Fluoroquinolones (ciprofloxacin) covers bacillus anthracis (necrotizing, hemorrhagic pneumonia)

99
Q

Name the respiratory fluoroquinolones

(a) Indications

A

Respiratory fluoroquinolones = Levofloxacin and Moxifloxacin

(a) community acquired pneumonia (S. pneumonia) and atypical pneumonia (mycoplasma and legionella)

100
Q

Two classes of abx that shouldn’t be taken with milk

A

Both fluoroquinolones (Cipro, levofloxacin, moxifloxacin) and tetracycline absorption are inhibited by divalent cations (Mg, Ca, Fe) => leave a few hours btwn drug and drinking milk

101
Q

Two classes of abx that can prolong QT interval

A

Both fluoroquinolones (Cipro, levofloxacin) and macrolides (Azithromycin, Clarithrymycin) can prolong QT => increase risk of Torsades

102
Q

Rare but specific side effect of fluoroquinolones

A

Fluoroquinolones (cipro, levofloxacin, moxifloxain) carry risk of tendon damage/rupture and cartilage damage/arthropathy
-esp in elderly and pts on chronic steroids

103
Q

Metronidazole

(a) Main indication
(b) 2 protozoa

A

Metronidazole

(a) Polymycrobial anaerobic infxns (ex: intraabdominal), vaginitis from Trich, BV by gradnerella
- “clindamycin for anaerobes above the diaphragm, metronidazole for anaerobes below the diaphragm”

(b) 2 protozoa: entamoeba histolytica and Giardia

104
Q

2 female GU indications of Metronidazole

A

Metronidazole for tx of

  1. vaginitis/cervicitis from Trichomonas
  2. bacterial vaginosis from gardnerella
105
Q

Triple therapy H. pylori regimen for pt w/ Penicillin allergy

A

H. pylori regular triple therapy: PPI, Amoxillin, Clarithrymycin

Amox allergy => can replace amox w/ metronidazole

106
Q

Mechanism of

(a) Zidovudine
(b) Ritonavir
(c) Efaverenz

A

Mechanism

(a) Zidovudine = prototype NRTI
(b) Ritonavir = protease inhibitor ‘navir’
(c) Efaverenz = NNRTI (non-nucleoside reverse transcriptase inhibitor)

107
Q

Mechanism of

(a) Lamivudine
(b) Navirapine
(c) Maraviroc

A

Mechanism

(a) Lamivudine = NRTI (like Emtrictiabine, Zidovudine, stavidine, didanosine)
(b) Navirapine = NNRTI
(c) Maraviroc = entry inhibitor by binding CCR5

108
Q

Mechanism of

(a) Enfuvirtide
(b) Raltegravir
(c) Indinavir

A

Mechanism

(a) Enfuvirtide = fusion inhibitor, binds pg41
(b) Raltegravir = integrase inhibitor

109
Q

3 groups of cells invaded by HIV

A

HIV infects

  1. CD4 T cells
  2. Macrophages
  3. Dendritic cells
110
Q

Relevance of HIV env gene

(a) Env mutations infer mutations against what?

A

HIV env gene codes for gp41 and gp120 surface glycoproteins
-first gp120 binds CCR5 and CXCR4 for viral entry, then gp41 facilitates HIV fusion

(a) So env mutations => resistance against entry inhibitors (Maraviroc- bind CCR5 to prevent gp120 binding) and fusion inhibitors (Enfuvirtide- binds gp41)

111
Q

HIV proteins (and the genes that encode them) responsible for

(A) Entry

(b) Fusion
(c) Integration

A

HIV proteins

(a) Entry by gp120 coded for by HIV env gene
(b) Fusion by gp41 also coded for by HIV env gene
(c) Integration by integrase coded by HIV pol gene

112
Q

Relevance of HIV pol gene

(a) Pol mutations infer mutations against what?

A

HIV pol gene codes for: reverse transcriptase, integrase, protease

(a) Pol mutation can confer resistance to NRTI (Zidovudine), NNRTI (Nevirapine), integrase inhibitor (Raltegravir) and protease inhibitors (Indinavir, Ritonovir)

113
Q

Which HIV drug most directly prevents the transcription of HIV mRA?

A

HIV mRNA only made once cDNA has been incorporated into the host genome, so integrase inhibitors most directly inhibit mRNA transcription

Integrase inhibitor = Raltegravir

114
Q

3 key enzymes coded for by HIV pol gene

A

HIV pol gene codes for

  1. reverse transcriptase
  2. integrase
  3. protease
115
Q

Mechanism of NRTIs

A

NRTI = nucleoside reverse transcriptase inhibitors work as competitive inhibitors of RT
-these nucleoside/tide analogues lack 3’ OH end needed for 3’ to 5’ phosphodiester bond => causes premature chain termination halting DNA synthesis

Nucleoside analogues require intracellular phosphorylation for activation

116
Q

Mechanism of NNRTIs

A

NNRTI = non-nucleside reverse transcriptase inhibitors

Bind directly to HIV reverse transcriptase => allosterically inhibiting RT to half DNA polymerase

117
Q

Contrast activation of NRTI and NNRTI

A

NRTI = nucleoside analogues that cause premature chain termination
-nucleosides require intracellular phosphorylation for activation

NNRTI = allosteric inhibition directly of DNA polymerase
-no intracellular activation required

118
Q

NRTI SEs

(a) pH disturbance
(b) Neuro finding

A

NRTI SEs

(a) Lactic acidosis
(b) Peripheral neuropathy: esp Lamivudine, Stavudine, Didanosine

119
Q

Differentiate both NRTIs: Lamivudine and Tenofovir

A

Lamivudine is a nucleoside => requires intracellular phosphorylation for activation

While Tenofovir is a nucleotide => doesn’t require any activation

Both Lamivudine and Tenofovir (NRTIs) are used in to tx Hep B
-recall Hep B has reverse transcriptase but isn’t a retrovirus b/c doesn’t integrate into host genome

120
Q

Which NRTI is first line during pregnancy to reduce risk of HIV vertical transmission?

A

Zidovudine = NRTI given to pregnant F to reduce risk of vertical transmission
-can be taken regardless of viral load/CD4 count

121
Q

Risk to mother of ZIdovudine therapy

A

Zidovudine = NRTI given to pregnant F to reduce risk of vertical transmission
-can be taken regardless of viral load/CD4 count

But carries real risk of myeosuppresion => granulocytopenia, anemia

122
Q

Which NRTI is known for causing

(a) Dose dependent pancreatitis
(b) Delayed hypersensitivity rash
(c) Hyperpigmentation of hands and soles

A

NRTI associated w/

(a) Dose dependent pancreatitis = Didanosine
(b) Delayed type IV hypersensitivity rash = Abacavir
(c) Hyperpigmentation of hands and soles = Entricitabine

123
Q

Main AE of NNRTI therapy

A

NNRTI therapy main SE = liver failure

  • can occur w/in 6 weeks of starting therapy
  • can be pretty severe, even fatal
124
Q

Which class of antiretrovirals requires intracellular activation?

A

Only NRTIs that are nucleosides require intracellular activation by phosphorylation

So NRTIs that are nucleotides (tenofovir), NNRTI, protease inhibitors etc don’t require activation

125
Q

Mechanism of protease inhibitors

A

Protease inhibitors inhibit proteases encoded for by DNA pol gene taht are required for cleavage of precursor polypeptide molecule needed to form a mature virion

So protease inhibitor causes virion to remain immature

126
Q

MC SE of protease inhibitors

A

SE of protease inhibitors = metabolic

  • hyperglycemia 2/2 insulin resistance
  • dyslipidemia
127
Q

How to avoid interaction btwn Rifampin and protease inhibitors?

A

Rifampin is a potent cyt p450 activator, while protease inhibitors are metabolized by cyt p450 and also activate cyt p450

So Rifampin reduces the concentration of protease inhibitors so use together is contraindicated
-use Rifabutin instead = same mechanism of Rifampin w/ less cyt p450 induction

128
Q

Backbone of ART

A

NRTIs

Usual initial therapy is 2 NRTIs w/ one additional drug

129
Q

What stimulates endogenous interferon release?

(a) From what cells?

A

Interleukin signals from infected cells cause release of interferon (a) from virally infected cells

130
Q

Indications for tx w/

(a) IFN-beta
(b) IFN-gamma

A

(a) IFN-beta used in tx of relapsing-type MS
(b) IFN-gamma to reduce recurrent infxns in chronic granulomatous disease (NADPH oxidase deficiency => defective oxygen-dependent killing)

131
Q

Indications for IFN alpha therapy

(a) Main
(b) 3 malignancies

A

IFN alpha

(a) Used in tx of hep B and hep C
(b) 3 malignancies
1. malignant melanoma
2. Hairy cell leukemia
3. renal cell carcinoma

132
Q

How to define success in tx of Hep C

A

No detectable HCV RNA for 6 months after stopping therapy = sustained virologic response

So SVR = goal of HCV therapy

133
Q

Ribavirin mechanism of action

A

Ribavirin (used int traditional HCV tx) is a guanosine nucleoside analog
-requires intracellular phosphorylation before active

134
Q

Ribavirin main indication

(a) Old indication
(b) Main side effect

A

Ribavirin = guanosine nucleoside analogue requiring intracellular phosphorylation

(a) Used in traditional tx regimen for Hep C (w/ interferon alpha)
(b) Main side effect = dose dependent hemolytic anemia

135
Q

Mechanism of Hep C drugs

(a) Sofosbuvir
(b) Simeprevir

A

Hep C drugs: traditional regimen of weekly pegylated interferon-alpha w/ daily ribavirin (guanosine nucleoside analogue)

Newer drugs

(a) Sofosbuvir = nucleoside analog that directly inhibits RNA production (directly inhibits RNA polymerase)
(b) Simeprevir = NS 3/4A protease inhibitor

136
Q

Mechanism of acyclvoir

(a) How do they specifically target virally infected cells

A

Acyclovir = guanosine nucleoside analogue that halts viral DNA polymerase

(a) Only infects HSV infected cells b/c only hepatitis virus codes for the viral thymidine kinase needed for first phosphorylation (activation) step of acyclovir
- hence why acyclvoir isn’t effective against CMV (CMV doesn’t code for the necessary thymidine kinase)

137
Q

Mechanism by which herpes strains can become resistant to acyclovir

A

If herpes virus mutates its thymidine kinase then it won’t phosphorylate acyclovir => resistant

138
Q

Drug of choice for

(a) Daily suppressive therapy for HSV
(b) HSV encephalitis

A

Drug of choice

(a) Valacyclvoir for HSV suppressive therapy in ppl w/ multiple yearly recurrence
- use val b/c better oral bioavailability
(b) HSV encephalitis- use IV acyclovir

139
Q

2 drugs that can tx acyclovir-resistant strains of HSV

A

HSV can become resistant to acyclvoir by mutating its thymidine kinase => acyclovir can’t get activated

So instead use Cidofovir or Foscarnet- which don’t require phosphorylation by viral kinase => are active against both acyclovir and ganciclovir resistant strains of HSV, CMV, VZV

140
Q

Mechanism of valacyclovir

A

Valacyclovir = pro-drug of acyclovir w/ better oral bioavailability

So same mechanism of acyclovir = guanosine nucleoside analogue requiring phosphorylation by HSV thymidine kinase first then two more phosphorylations by cellular kinases

Just better oral bioavailability than acyclvoir (b/c prodrug) but same mechanism

141
Q

Interstitial nephritis

(a) Which anti-viral
(b) Which anti-bactierial

A

Interstitial nephritis = inflammation of the renal interstitium characteristic side effect of

(a) IV acyclovir
(b) Penicillins

142
Q

Traditional tx regimen for Hep C

(a) Now what?

A

Traditional regimen = weekly pegylated interferon alpha w/ daily ribavirin

(a) But now we have protease inhibitors (SImeprevir) and polymerase inhibitors (Sofosbuvir) so trying to move towards interferon/ribavirin-free regimens

143
Q

2 things to do before choosing treatment regimen for Hep C

A
  1. Genotype the strain of Hep C

2. Indirectly (aka clinically, not w/ liver biopsy) degree of liver fibrosis

144
Q

HIV pt noncompliant w/ meds p/w retinal infiltrates and retinal hemorrhage- most likely dx?

(a) Drug of choice

A

Dx = CMV retinitis, esp if CD4 under 50

a) Tx w/ either IV ganciclovir or valganciclovir (better oral bioavailability w/ same efficacy

145
Q

Mechanism of ganciclovir

A

Ganciclovir (like acyclovir) is a guanosine nucleoside analog

  • first step of activation (first phosphorylation) is catalyzed by CMV-encoded viral kinase
  • next two phosphorylations by host cellular kinases

So only active in CMV-infected cells b/c requires CMV-encoded viral kinase for first activation step

146
Q

What differentiates acyclovir and ganciclovir?

A

Acyclvoir and ganciclovir are both guanosine nucleoside analogs that require 3 phosphorylations before are active to be incorporated into DNA synthesis (and therefore able to inhibit DNA polymerase)

Acyclovir requires activation by thymidine kinase encoded by HSV, while ganciclovir requires activation by viral kinase encoded by CMV (so they both only are active in cells infected by HSV and CMV respectively)

147
Q

Who should get HSV ppx?

(a) Drug of choice

A

HSV ppx for mothers w/ active genital lesions to prevent vertical transmission, also in in high-risk immunocompromised or organ transplant pts

(a) Oral valayclovir daily

148
Q

Who should get CMV ppx?

(a) Drug of choice

A

CMV ppx for solid-organ and bone marrow transplant pts, also some HIV pts w/ CD4 under 50 (risk of CMV retinitis, colitis, esophagitis)

(a) Valganciclovir b/c better oral bioavailability than ganciclovir

149
Q

Main side effects of acyclovir and ganciclovir

A

Acyclovir- interstitial nephritis or crystalline nephropathy

Ganciclovir- bone marrow suppression

150
Q

Danger of giving HIV pt on Zidovudine ganciclovir tx for CMV retinitis

A

Both Zidovudine (NRTI) and ganciclovir cause bone marrow suppression- additive bone marrow suppression when given together

151
Q

Mechanism of Foscarnet vs. Cidofovir

(a) Main indication

A

Foscarnet and Cidofovir both directly inhibit viral DNA polymerase (don’t require any phosphorylation/intracellular activation like acyclovir/ganciclovir)

(a) Use to tx acyclovir-resistant HSV strains and ganciclovir- resistant CMV striains

152
Q

Which antiviral should be coadministered w/ Probenecid

A

Probenecid blocks tubular secretion of Cidofovir (direct viral DNA polymerase inhibitor) to reduce nephrotoxic effects

Probenecid also prevents excretion (and therefore increases plasma concentration) of tons of drugs: MTX, PCN, NSAIDs

153
Q

Main side effects of the two drugs that are effective against acyclovir resistant HSV

A

Foscarnet and Cidofovir directly inhibit viral DNA polymerase => are active against acyclovir-resistant RSV and ganciclovir-resistant CMV

Main SE:

  • Foscarnet: renal insufficiency and electrolyte disturbances that can lead to seizure
  • Cidofovir: nephrotoxicity, reduce by coadministering w/ Probenecid

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