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Block 2 > Antimicrobials > Flashcards

Antimicrobials Flashcards

1
Q

Antibiotic MOAs and classes

A

Cell wall synthesis inhibitors:
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams

Peptidoglycan formation inhibitor (D-ala-D-ala binding):
- Glycopeptides/Vancomycin

Inhibit topoisomerase II and IV:
- Fluoroquinolones

30S ribosomal subunit:
- Aminoglycosides
- Tetracyclines

50S ribosomal subunit:
- Clindamycin
- Chloramphenicol
- Macrolides (Erythromycin)
- Linezolid

Folic acid synthesis inhibitors:
- Trimethoprim-sulfamethoxazole

Other:
- Metronidazole
- Lincosamides
- Anti-TB agents

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2
Q

Beta-lactam MOA

A

Beta-lactams bind to penicillin-binding-proteins (PBPs, aka transpeptidases) and block transpeptidase cross-linking of peptidoglycan in cell wall

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3
Q

Beta-lactam: bacterial mechanisms of resistance

A
  • cleavage of beta-lactam ring via beta-lactamases
  • alteration of binding site (PBP), seen in Staph aureus and Strep pneumoniae
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4
Q

General beta-lactam side effects

A
  • rash
  • GI upset
  • hypersensitivity reactions (types I-IV)
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5
Q

Beta-lactam drugs

A
  • Penicillins (penicillin G, ampicillin, amoxicillin, methicillin)
  • Cephalosporins (cephalexin, cefuroxime, ceftriaxone, cefepime)
  • Carbapenems (imipenem-cilastatin*, meropenem, doripenem)
  • Monobactams (atreonam)

*imipenem is combined with cilastatin, a dehydropeptidase inhibitor, which prevents breakdown of imipenem in kidneys

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6
Q

Carbapenem

A
  • resistant to β-lactamase
  • used to treat extended-spectrum beta-lactamase-producing bacteria (ESBL)
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7
Q

beta-lactam + beta-lactamase inhibitor combinations

A
  • Amoxicillin-Clavulanic acid
  • Ampicillin-Sulbactam
  • Piperacillin-Tazobactam

“-bactam”

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8
Q

Glycopeptides (Vancomycin) MOA

A

Inhibits peptidoglycan formation by binding to the D-ala-D-ala of the peptide terminus, inhibiting transglycosylation

Gold standard for treating MRSA and coagulase-negative Staph

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9
Q

Vancomycin: bacterial mechanisms of resistance

A

the last D-ala residue is replaced by D-lactate, so vancomycin cannot bind

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10
Q

Vancomycin side effects

A
  • nephrotoxicity
  • ototoxicity
  • Vancomycin flushing reaction / infusion reaction (mast cell degranulation with release of histamine, not a true allergy)
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11
Q

Ribosomal protein synthesis inhibitors

Buy “AT” 30, “CCEL” at 50

A

30S ribosomal subunit inhibitors:
A - Aminoglycosides (amikacin, gentamicin, streptomycin)
T - Tetracyclines (doxycycline, tetracycline)

50S ribosomal subunit inhibitors:
C - Clindamycin
C - Chloramphenicol
E - Erythromycin (Macrolide class)
L - Linezolid

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12
Q

Aminoglycoside MOA

A

binds to 30S ribosomal subunit, inhibiting initiation complex and leading to misreading of mRNA ==> mistranslation

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13
Q

Aminoglycoside bacterial method of resistance

A

bacterial transferases inactivate drug by acetylation, phosphorylation, adenylation

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14
Q

Aminoglycoside side effects

A
  • nephrotoxicity
  • ototoxicity
  • teratogenicity
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15
Q

Tetracycline MOA

A

binds to 30S ribosomal subunit and prevents attachment of aminoacyl-tRNA

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16
Q

Tetracycline side effects

(Doxycycline)

A
  • photosensitivity
  • drug deposits in bones/teeth ==> inhibition of bone growth and teeth discoloration in children
  • drug-drug interaction: divalent cations can bind to tetracycline and inhibit drug absorption

great for treating organisms that don’t gram-stain well
- gram-negative bacteria
- spirochetes & zoonotics

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17
Q

Tigecycline

A

tetracycline-derivative, binds to 30S ribosomal subunit

used for MRSA and VRE

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18
Q

Clindamycin MOA

A

blocks translocation at 50S subunit, preventing peptide chain elongation

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19
Q

Clindamycin side effects

A
  • C. diff overgrowth, causing Pseudomembranous Colitis
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20
Q

Chloramphenicol MOA

A

blocks peptidyltransferase at 50S subunit

not really used clinically anymore

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21
Q

Chloramphenicol side effects

A
  • anemia
  • gray baby syndrome: permature infants lack liver UDP-glucuronyltransferase
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22
Q

Macrolide (Erythromycin) MOA

A

blocks translocation by binding to 23s rRNA component of 50S subunit, preventing peptide chain elongation

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23
Q

Macrolide side effects

A
  • GI motility ==> vomiting
  • prolongation of QT interval ==> cardiac arrythmias
  • drug-drug interactions with erythromycin
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24
Q

Linezolid MOA

A

prevents formation of the initiation complex by binding to 23S rRNA of the 50S subunit

used to treat MRSA and vancomycin-resistant Enterococcus (VRE)

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25
Q

Linezolid side effects

A
  • bone marrow suppression ==> pancytopenia (decrease in RBCs, WBCs, platelets)
  • serotonin syndrome
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26
Q

Fluoroquinolone MOA

A

inhibits prokaryotic topoisomerase II (DNA gyrase) and topoisomerase IV ==> inhibition of DNA synthesis

ex: levofloxacin

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27
Q

Fluoroquinolone side effects

A
  • tendonitis/tendon rupture
  • QT prolongation
  • drug-drug interactions with divalent cations
  • teratogenicity
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28
Q

Folic acid synthesis inhibitors MOA

A
  • Trimethoprim:
    inhibits bacterial dihydrofolate reductase
  • Sulfonamides (Sulfamethoxazole):
    inhibits dihydropteroate synthase

when used in combination, they act synergistically and are bactericidal, and also decrease the likelihood of bacteria developing resistance to either of the drugs

  • Dapsone
    inhibition of dihydrofolic acid synthesis via competitive inhibition of para-aminobenzoic acid (PABA) for dihydropteroate synthetase
    –> different structure from Sulfonamides, but similar MOA
29
Q

Folic acid synthesis inhibitor side effects

A

Trimethoprim:
- hyperkalemia (increased K+ levels)
- bone marrow suppression

Sulfonamides:
- hypersensitivity reactions
- hemolysis if G-6-PD deficient
- Steven-Johnson syndrome (bad skin disorder)
- photosensitivity

30
Q

Daptomycin MOA

A

binds to cytoplasmic membrane ==> creates transmembrane channels ==> depolarizes cell

used for MRSA, vancomycin-resistant Enterococcus (VRE)

31
Q

Daptomycin side effects

A
  • myopathy
  • rhabdomyolysis
  • inactivated by pulmonary surfactant (cannot be used in pneumonia cases)
32
Q

Polymyxin MOA

A

cationic polypeptides bind to cell membrane (detergent-like) ==> disrupt cell membrane ==> bacterial cell death

used for very drug-resistant gram-negative rod infections

“Polymyxins nix your nephrons and neurons”

33
Q

Polymyxin side effects

A
  • nephrotoxic
  • neurotoxic
34
Q

Treatments for MRSA

A

Very Deadly Like Children Die Too

  • Vancomycin
  • Daptomycin
  • Linezolid
  • Clindamycin
  • Doxycycline
  • TMP-SMX
35
Q

Treatments for VRE

A
  • Linezolid
  • Daptomycin
36
Q

Treatments for ESBL bacteria

A

Extended-spectrum beta-lactamase bacteria: E. coli, Klebsiella

Tx: carbapenems (imipenem-cilastatin)

37
Q

Anti-tubercular drugs
(anti-TB drugs)

A

RIPE:
- Rifampin
- Isoniazid
- Pyrazinamide
- Ethambutol

General treatment: 4 drugs for 2mo, then just Rifampin and Isoniazid for 4mo = 6mo total

Latent treatment: Rifampin for 4mo, Isoniazid (with Vit B6) for 9mo

38
Q

Isoniazid MOA

A

inhibits mycolic acid synthesis

39
Q

Isoniazid side effects

A
  • hepatotoxicity
  • peripheral neuropathy due to vitamin B6 deficiency <- supplement pts with vit B6 to prevent neurotoxicity

“INH: Injures Neurons and Hepatocytes”

40
Q

Rifampin MOA

A

inhibits bacterial DNA-dependent RNA polymerase ==> Ramps up cyt P450 ==> prevents mRNA synthesis

Rapid resistance if used alone

41
Q

Rifampin side effects

A
  • many drug interactions because Rifampin is a potent inducer of CYP450 system (drug metabolism pathway)
  • Rifampin causes Red-orange discoloration of all body fluids
42
Q

Pyrazinamide side effects

A
  • hepatotoxicity
  • hyperuricemia
43
Q

Ethambutol MOA

A

inhibits arabinosyltransferase ==> inhibits cell wall synthesis

44
Q

Ethambutol side effects

A
  • optic neuropathy
  • can cause red-green colorblindness and decreased visual acuity

“EYEthambutol”

45
Q

Dapsone

A

used for leprosy, non-TB mycobacteria, some parasitic infections

MOA:
- inhibits dihydropteroate synthase

Side effects:
- hemolysis in patients with G-6-PD deficiency
- methemoglobinemia

46
Q

Treatable viruses

A
  • Herpesviruses: HSV, CMV, VZV
  • Influenza A and B
  • RSV
  • Papillomavirus
  • HIV
  • Hepatitis B and C

Goal: minimize spread

47
Q

Antivirals for HSV and VZV

A
  • Acyclovir
  • Valacyclovir
  • Famciclovir
48
Q

Acyclovir MOA

A
  • guanosine analog
  • acyclovir ==> acyclovir monophosphate ==> acyclovir diphosphate ==> acyclovir triphosphate (active product)
  • competitive inhibitor of Herpesvirus DNA polymerase, stops lengthening of DNA strand
49
Q

Acyclovir side effects

A
  • wide range of uses
  • IV formulation side effects: crystalline nephropathy, acute renal failure
  • MOR: mutation of thymidine kinase
50
Q

Valacyclovir and Famciclovir

A
  • oral prodrugs (need to be converted to active form)
  • Valacyclovir ==> Acyclovir
  • Famciclovir ==> Penciclovir
  • better bioavailability than Acyclovir
51
Q

Antivirals for CMV

A
  • Ganciclovir
  • Valganciclovir
  • Cidofovir
  • Foscarnet
  • Letermovir

these drugs also work to treat HSV and VZV, but are only used if pt is resistant to Acyclovir

52
Q

Ganciclovir and Valganciclovir

A

Ganciclovir:
- IV formulation only
- side effects: bone marrow toxicity (neutropenia) <- due to DNA polymerase being targeted, dividing cells are affected
- MOR: mutated viral protein kinase

Valganciclovir:
- prodrug of Ganciclovir
- oral drug only

53
Q

Cidofovir

A
  • used for CMV, acyclovir-resistant HSV
  • nucleotide analog
  • direct inhibitor of DNA polymerase
  • already has phosphate on it, so does not require viral kinase phosphorylation; can be used when there is a mutation in the viral thymidine kinase
  • MOR: mutated cellular kinase
  • side effects: nephrotoxicity
54
Q

Foscarnet

A
  • used for ganciclovir-resistant CMV or acyclovir-resistant HSV
  • pyrophophate analog
  • inhibition of DNA polymerase via binding to pyrophosphate binding-site
  • does not require any kinase activation
  • side effects: nephrotoxicity
  • MOR: mutated viral DNA polymerase

“Foscarnet = pyro”fos”phate analog”

55
Q

Antivirals for Influenza A & B

A

inhibition of influenza neuramindase (“N”):
- Zanamavir: inhaled, contraindicated in asthma
- Oseltamivir: oral
- Baloxavir: new drug

56
Q

Antiviral for RSV

A

Ribavirin:
- inhibits RNA-dependent RNA polymerase
- side effects: dose-related hemolytic anemia, teratogenic

Palivizumab:
- targets F glycoprotein on RSV surface
- used for prevention of RSV in high-risk infants and children

57
Q

Antifungals

A
  • Polyenes (Amphotericin B, Nystatin)
  • Azoles (“-azole”)
  • Echinocandins (“-fungin”)
  • 5-Fluorocytosine
  • Allylamines (Terbinafine)
  • Griseofulvin
58
Q

Amphotericin B

A
  • binds to ergosterol
  • used for serious, systemic mycoses: Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
  • side effects: fever/chills (“shake and bake”), hypotension, kidney dysfunction
  • side effects due to drug binding to cholesterol

“Amphotericin ‘tears’ holes in the fungal membrane by forming pores.”

amphibians have fungi? amphotericin B

59
Q

Nystatin

A
  • same mechanism as Amphotericin B: binds to ergosterol, forming pores in membrane
  • topical use only
60
Q

5-Fluorocytosine (Flucytosine)

A
  • inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil
  • used for systemic fungal infections in combination with Amphotericin B: Cryptococcus meningitis
  • side effects: bone marrow suppression
61
Q

Azoles

A
  • inhibits fungal sterol (ergosterol) synthesis by inhibiting cyt P-450 enzyme
  • used for local/less serious systemic mycoses
  • relatively friendly drug
62
Q

Allylamines (Terbinafine)

A
  • inhibits squalene epoxidase (early ergosterol synthesis)
  • used for dermatophytoses (onychomycosis, nail infections)
  • side effects: GI upset
63
Q

Echinocandins

A
  • “-fungin”: Anidulafungin, caspofungin, micafungin
  • inhibits cell wall synthesis (beta-glucan)
  • used for Candida
  • side effects: GI upset

“Echinocandins work against Candida”

64
Q

Griseofulvin

A
  • disrupts mitosis by interfering with microtubule function
  • used for dermatophytes (tinea, ringworm)
  • side effects: teratogenic, carcinogenic
65
Q

Antiprotozoa

A

Metronidazole:
- G - Giardia
- E - Entamoeba
- T - Trichomonas

“The METRO: GET out of his way!”

66
Q

Metronidazole side effects

A
  • disulfiram-like reaction when taken with alcohol: flushing, tachycardia, hypotension, abdominal pain, vomiting
  • metallic taste
67
Q

Antiparasitics

A

Albendazole/Mebendazole:
- pinworm (“worms are bendy”)
- MOA: microtubule inhibitors

Ivermectin:
- Strongyloides
- MOA: paralyzes parasite by enhancing GABA transmission and cell hyperpolarization

Primaquine:
- liver hypnozoite stage of Plasmodium vivax/ovale
- side effects: hemolytic crisis in those with G-6-PD deficiency

Chloroquine:
- sensitive malaria

68
Q

Antimalarials

A

Chloroquine:
- sensitive spp
- blood stage (schizont)

Mefloquine:
- resistant spp
- blood stage (schizont)

Atovaquone/Proguanil:
- resistant spp
- liver schizont

Quinidine or Artestunate:
- life-threatening infection
- blood stage (schizont)
- side effects: cinchonism, long QT syndrome

Primaquine:
- P vivax and P ovale
- liver hypnozoite stage
- hemolytic anemia in patients with G-6-PD deficiency

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