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Antibiotics (rest) Flashcards

1
Q

What are the macrolide antibiotics

A
  • Erythromycin
    • Clarithromycin
    • Azithromycin
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2
Q

What is the MOA of macrolides

A
  • Attach to the 23S rRNA on the 50S subunit of bacterial ribosome-> results in inhibition of protein synthesis
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3
Q

Are macrolides bactericidal

A
  • Generally bacteriostatic; time dependent killing
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4
Q

Are macrolides concentration dependent or independent

A
  • Independent
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5
Q

What causes resistance in macrolides

A
  • Methylation of the rRNA receptor
    • Inactivating enzymes
    • Active efflux
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6
Q

What is the spectrum of activity for macrolides

A
  • Good gram positive: pneumococci, streptococci and corynebacteria
    • Good against organisms where peptidoglycan is not important: M pneumoniae, chlamydia trachomatis, C. pneumophilia, bordatella pertussis (whooping cough), campylobacter jejuni (gut infection), helicobacter pylori (gut infection)
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7
Q

What are the uses of macrolides

A
  • Upper respiratory tract infections
    • Sexually transmitted infections
    • Acne
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8
Q

What are drug interactions with macrolides

A
  • Many DI mainly with erythromycin and clarithromycin
    • Erythromycin/ clarithromycin are substrates and inhibitors of CYP 3A4 (drugs that are metabolized by this include antiarrhythmics, antidepressants, benzodiazepines, anticonvulsants, statins..//// this DI may increase toxicity)
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9
Q

What is erythromycin available as

A
  • Base, stearate (succinate: not covered in sask) or estolate
    • Need to know which formulation is intended to dispense
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10
Q

What formulations is erythromycin available as

A
  • IV or oral
    • IV causes severe phlebitis (burns veins so have to change IV site often)
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11
Q

Adverse effects of erythromycin

A
  • Gi
    • Increased liver function tests (LFTs)
    • Cholestatic hepatitis: increased with estolate and pregnancy
    • QT prolongation/ cardiac arrhythmias particularly when combined with CYP 3A inhibitors
    • More drug interactions in comparison to beta lactams
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12
Q

What is clarithromycin and azithromycin’s spectrum of activity

A
  • Active against staph and strep
    • Enhanced activity against many organisms including L. pneumophilia, chlamydia trachomatis, chlaydiophia pneumoniae, moraxella catarrhalis, H. influenzae (azithromycin), mycobacterium avium and other mycobacteria
    • Useful for some MRSA
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13
Q

If an organism is R to erythromycin then what does that mean for clarithromycin and azithromycin

A

Also R to these drugs

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14
Q

What is the benefit of clarithromycin/ azithromycin in comparison to erythromycin

A
  • Less frequent dosing (Erythro is 4 times, clarithro is 2 times and azithro is once daily)
    • Lower rate of gi adverse effects
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15
Q

What is special about azithromycin

A
  • Gorillamycin
    • Long half life leads to long intracellular concentration (this means that 5 days of azithromycin is equal to 10 days of therapy)
    • This also means that longer periods of dosing could lead to more resistance
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16
Q

What is the MOA of clindamycin

A
  • Same as macrolides
    • Attach to the 23S rRNA on the 50S subunit of bacterial ribosome-> results in inhibition of protein synthesis
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17
Q

What is the spectrum of activity of clindamycin

A
  • Anaerobes, S. aureus including some MRSA as well as streptococci
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18
Q

When is clindamycin used in patients

A
  • Patients with a penicillin allergy or with resistant organics
    • Not DOC for anything
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19
Q

What formulations is clindamycin in

A
  • Oral or parenteral
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20
Q

What are clindamycin’s adverse effects

A
  • Nausea, vomiting, diarrhea
    • Rash
    • High LFTs
    • Esophageal irritation
    • Associated with C. difficile diarrhea
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21
Q

What are the tetracyclines

A

Tetracycline, minocycline, doxycycline

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22
Q

What is the MOA of tetracyclines

A

Inhibits the binding of aminoacyl-tRNA to the 30S unit of the ribosome-> this inhibits protein synthesis

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23
Q

Are tetracyclines bacteriostatic or bactericidal

A

Bacteriostatic

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24
Q

What is tetracyclines spectrum of activity

A
  • active against many gp and gn organisms
    • Has high rates of resistance ( E.coli and S. pneumoniae)
      Also used in Nocardia, P.Acne
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25
Q

What are tetracyclines the DOC for

A
  • Rickettsia, bartonella, chlamydia, M. pneumoniae
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26
Q

What are tetracyclines adverse effects

A
  • Gi upset (nausea, vomiting, diarrhea///N,V,D)
    • Skin rashes
    • Photosensitivity
    • Yeast overgrowth
    • Deposited in bones and teeth so don’t use in children under 8
    • Hepatitis
    • Hepatitis
    • Vestibular toxicity (dizziness, vertigo, ataxia)- minocycline
    • Minocycline is also associated with more hypersensitivity reactions
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27
Q

What are the drug interactions associated with tetracyclines

A
  • Some anticonvulsants can reduce tetracycline levels
    • Divalent/ trivalent cations reduce absorption (don’t take with a multi vitamin
    • Avoid with milk/ dairy products as binds with calcium and can affect bones/ teeth (doxycycline binds to calcium less)
    • Increase INR and bleeding with warfarin
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28
Q

What makes glycylcyclines different then tetracycline

A

It is a synthetic analogue of tetracycline

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29
Q

What is the glycycyline

A
  • Tigecycline
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30
Q

What is glycylcyclines spectrum of activity

A
  • Very broad spectrum and expensive
    • Active against many gp and gn including MRSA, also anaerobes
    • (s. pneumoniae, enterococci, salmonella, shigella, Acinetobacter,
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31
Q

What formulations are glycylcyclines in

A

IV and IM

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32
Q

How are glycylcyclines eliminated from the body

A

The biliary tract (bile system) and feces

33
Q

What are glycylcyclines reserved for

A

Resistant organisms

34
Q

What is the glycopeptide we use

A
  • Vancomycin
    • May not penetrate cns
    • Therapeutic monitoring often used
35
Q

What are glycopeptides MOA (vancomycin)

A
  • inhibits cell wall peptidoglycan synthesis
36
Q

Are glycopeptides bacteriostatic or bactericidal

A
  • Bactericidal
37
Q

What is resistant to glycopeptides

A

VRE (vancomycin-resistant enterococci), and S. aureus (VISA)

38
Q

What is glycopeptides spectrum

A
  • Gpc, mostly enterococci, PRSP (penicillin resistant streptococci pneumoniae), MRSA, clostridia, clostrioides and some bacilli
    • DOC for MRSA
    • No activity against gn
39
Q

When will you use vancomycin’s (glycopeptide) different formulations

A
  • IV for serious infections
    • PO only for C. difficile (not orally absorbed)
40
Q

What are vancomycin (glycopeptide) adverse effects

A
  • Nephrotoxicity (mainly in combo with nephrotoxins)
    • Ototoxicity (ear toxicity)
    • Red man syndrome
    • Granulocytopenia (occurs with long therapY0
41
Q

Why does red man syndrome occur

A
  • Have to infuse a lot of vancomycin and if you do it to fast then will commonly occur chest and up
    • Ex. You would have to infuse 500mg over an hour
42
Q

What are similar drugs to vancomycin

A
  • Teicoplanin: structurally similar
    • Daptomycin: lipopeptide; parenteral; once daily, major adverse effect is myopathy
43
Q

What are the fluoroquinolones

A

Ciprofloxacin, levofloxacin, moxifloxacin

44
Q

What is fluoroquinolones MOA

A

Inhibits DNA gyrase or topoisomerase II and IV

45
Q

Are fluoroquinolones bacteriostatic/ bactericidal, and concentration dependent/independent killing

A
  • Bactericidal
    Concentration dependent
46
Q

How are fluoroquinolones resistance

A
  • Alteration of the A or B subunit of DNA gyrase
    • Mutation in ParC or ParE of topoisomerase IV
    • Change in outer membrane permeability
      Efflux pumps
47
Q

What are fluoroquinolones spectrum of activity

A

Highly active against gnb (haemophilus sp., Neisseria, chlamydiae)

48
Q

What are the specific fluoroquinolones most active against

A
  • Ciprofloxacin: most active against P. aeruginosa
    • Levofloxacin: active against S. pneumoniae (gpc)
    • Moxifloxacin: active against anaerobes
49
Q

What are the fluroquinolones uses

A
  • Becoming largely resistant to
    • UTIs, STIs (chlamydia), lower respiratory tract infections, enteritis/ travellers diarrhea, drug resistant mycobacterial infection
50
Q

Formulations of fluoroquinolones

A
  • In both IV or po but parenteral use is not used often as oral bioavailability is so good
51
Q

Adverse effects of fluoroquinolones

A
  • Nausea, vomiting, diarrhea (most common)
    • Insomnia, headache, dizziness
    • Other CNS effects (seizures)
    • Skin rashes
    • Impaired liver function
    • Tendinitis or tendon rupture (over 60 usually)
    • Prolongation of QTc interval
    • Hypo/hyperglycemia (link to seizures)
    • C. Difficile
    • Peripheral neuropathy (nerve pain like hitting funny bone)
52
Q

Drug interactions with fluoroquinolones

A
  • Bind to di/ tri- valent vations
    • QTc prolongation
    • CYP 1A2 inhibition can result in increased concentration of drugs that are metabolized by this
    • Increased INR with warfarin
53
Q

General notes with fluoroquinolones

A
  • Many toxicities
    • Many removed from market
    • Not used in children < 18 (some exceptions such as cystic fibrosis)
54
Q

When are fluoroquinolones reserved for

A
  • Resistant organisms and when you cant use the DOC
55
Q

What is the sulfonamide

A

Sulfamethoxazole (SMX)

56
Q

What is the trimethoprim

A
  • trimethoprim (TMP)
    • Can be used alone especially when there is a sulfa allergy
57
Q

How are sulfonamides and trimethoprim usually given

A
  • Most often given as a combination of TMP/ SMX or co-trimoxazole
58
Q

What is SMX MOA

A
  • Structural analogue of PABA
    • This competitively inhibits dihydrofolic acid synthesis
59
Q

What is TMP MOA

A
  • Binds to dihydrofolate reductase
    • This inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid
60
Q

Are SMX and TMP bacteriostatic or bactericidal

A

Bacteriostatic but together bactericidal

61
Q

Resistance MOA of SMX and TMP

A

Ability of cell to use preformed folic acid

62
Q

What is the spectrum of activity for SMX and TMP

A
  • wide spectrum of gp, gn, chlamydiae, nocardiae and protozoa
    • Staphylococci (including MRSA)
    • Streptococcus pneumonia *not group A strep
    • S. Maltophilia
    • Moraxella
    • H. influenza
    • Enterobacteriaciae
    • Brucella
    • Pneumocystis jirovecii
63
Q

What are the uses of SMX and TMP

A
  • Urinary tract infections
    • Skin and soft tissue infections (MRSA)
    • PJP (pneumocystic jirovecii)
    • Many others
64
Q

Adverse effects of sulfonamides and trimethoprim

A
  • Skin rashes (can be severe)
    • Hypersensitivity
    • Headache
    • GI (N,V, D)
    • Bone marrow suppression (effects blood cell production)
    • Hyperkalemia and hyponatremia
    • Photosensitivity
65
Q

What are drug interactions with TMP and SMX

A
  • 2C9 inhibitor; 3A4 substrate- increased levels of carvedilol, digoxin, phenytoin
    • Increased INR and bleeding with warfarin
    • Hypoglycemic agents; increased risk of hypoglycemia
    • Drugs which increase potassium levels
66
Q

What are contradictions to TMP/ SMX

A
  • CI in first and 3rd trimester of pregnancy
    • Caution in renal dysfunction (exacerbates hyperglycemia)
    • Kernicterus: brain damage from high levels of bilirubin in the babys blood
      Sulfa displaces bilirubin and can get into the infants blood
67
Q

MOA of metronidazole

A
  • Unknown
    • Possible inhibition of nucleic acid synthesis and disruption of DNA
68
Q

Spectrum of activity for metronidazole

A
  • Anaerobes including C. Difficile
    • Protozoa: trichomonas, Giardia…
    • Propionibacterium are resistant
69
Q

What formulations is metronidazole available in

A
  • IV and po (very good bioavailability po)
70
Q

Metronidazole adverse effects

A
  • Gi
    • Metallic taste
    • Headache
    • Peripheral neuropathy
    • Disulfiram like reaction with alcohol
    • Insomnia
    • Stomatitis
71
Q

Drug interactions with metronidazole

A
  • Alcohol: disulfiram reaction
    • Warfarin: increased INR and bleeding
72
Q

Linezolid MOA

A
  • Inhibits protein synthesis
73
Q

Is Linezolid bacteriostatic or bactericidal

A
  • Usually bacteriostatic
    • Bactericidal against streptococci
74
Q

Spectrum of activity for Linezolid

A
  • Streptococci, enterococci (VRE also), staphylococci (including MRSA)
75
Q

What is Linezolid reserved for

A
  • Multi drug resistant organisms
    • Alternative to vancomycin
76
Q

What is Linezolid available in

A
  • IV and oral
    • Expensive
77
Q

Linezolid adverse effects

A
  • Headache
    • Nausea, vomiting, diarrhea,
    • Rash
    • Increased LFTs
    • Myelosuppression
    • Optic/peripheral neuropathy
    • Lactic acidosis
    • Decreased seizure threshold
78
Q

Drug interactions with Linezolid

A
  • Increased serotonin syndrome risk with SSRIs and MAOIs
    Rifampin decreases Linezolid levels

152 (8 decks)

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