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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
What are tetracyclines the DOC for
- Rickettsia, bartonella, chlamydia, M. pneumoniae
26
What are tetracyclines adverse effects
- 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
27
What are the drug interactions associated with tetracyclines
- 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
28
What makes glycylcyclines different then tetracycline
It is a synthetic analogue of tetracycline
29
What is the glycycyline
- Tigecycline
30
What is glycylcyclines spectrum of activity
- Very broad spectrum and expensive - Active against many gp and gn including MRSA, also anaerobes - (s. pneumoniae, enterococci, salmonella, shigella, Acinetobacter,
31
What formulations are glycylcyclines in
IV and IM
32
How are glycylcyclines eliminated from the body
The biliary tract (bile system) and feces
33
What are glycylcyclines reserved for
Resistant organisms
34
What is the glycopeptide we use
- Vancomycin - May not penetrate cns - Therapeutic monitoring often used
35
What are glycopeptides MOA (vancomycin)
- inhibits cell wall peptidoglycan synthesis
36
Are glycopeptides bacteriostatic or bactericidal
- Bactericidal
37
What is resistant to glycopeptides
VRE (vancomycin-resistant enterococci), and S. aureus (VISA)
38
What is glycopeptides spectrum
- Gpc, mostly enterococci, PRSP (penicillin resistant streptococci pneumoniae), MRSA, clostridia, clostrioides and some bacilli - DOC for MRSA - No activity against gn
39
When will you use vancomycin's (glycopeptide) different formulations
- IV for serious infections - PO only for C. difficile (not orally absorbed)
40
What are vancomycin (glycopeptide) adverse effects
- Nephrotoxicity (mainly in combo with nephrotoxins) - Ototoxicity (ear toxicity) - Red man syndrome - Granulocytopenia (occurs with long therapY0
41
Why does red man syndrome occur
- 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
What are similar drugs to vancomycin
- Teicoplanin: structurally similar - Daptomycin: lipopeptide; parenteral; once daily, major adverse effect is myopathy
43
What are the fluoroquinolones
Ciprofloxacin, levofloxacin, moxifloxacin
44
What is fluoroquinolones MOA
Inhibits DNA gyrase or topoisomerase II and IV
45
Are fluoroquinolones bacteriostatic/ bactericidal, and concentration dependent/independent killing
- Bactericidal Concentration dependent
46
How are fluoroquinolones resistance
- 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
What are fluoroquinolones spectrum of activity
Highly active against gnb (haemophilus sp., Neisseria, chlamydiae)
48
What are the specific fluoroquinolones most active against
- Ciprofloxacin: most active against P. aeruginosa - Levofloxacin: active against S. pneumoniae (gpc) - Moxifloxacin: active against anaerobes
49
What are the fluroquinolones uses
- Becoming largely resistant to - UTIs, STIs (chlamydia), lower respiratory tract infections, enteritis/ travellers diarrhea, drug resistant mycobacterial infection
50
Formulations of fluoroquinolones
- In both IV or po but parenteral use is not used often as oral bioavailability is so good
51
Adverse effects of fluoroquinolones
- 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
Drug interactions with fluoroquinolones
- 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
General notes with fluoroquinolones
- Many toxicities - Many removed from market - Not used in children < 18 (some exceptions such as cystic fibrosis)
54
When are fluoroquinolones reserved for
- Resistant organisms and when you cant use the DOC
55
What is the sulfonamide
Sulfamethoxazole (SMX)
56
What is the trimethoprim
- trimethoprim (TMP) - Can be used alone especially when there is a sulfa allergy
57
How are sulfonamides and trimethoprim usually given
- Most often given as a combination of TMP/ SMX or co-trimoxazole
58
What is SMX MOA
- Structural analogue of PABA - This competitively inhibits dihydrofolic acid synthesis
59
What is TMP MOA
- Binds to dihydrofolate reductase - This inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid
60
Are SMX and TMP bacteriostatic or bactericidal
Bacteriostatic but together bactericidal
61
Resistance MOA of SMX and TMP
Ability of cell to use preformed folic acid
62
What is the spectrum of activity for SMX and TMP
- 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
What are the uses of SMX and TMP
- Urinary tract infections - Skin and soft tissue infections (MRSA) - PJP (pneumocystic jirovecii) - Many others
64
Adverse effects of sulfonamides and trimethoprim
- Skin rashes (can be severe) - Hypersensitivity - Headache - GI (N,V, D) - Bone marrow suppression (effects blood cell production) - Hyperkalemia and hyponatremia - Photosensitivity
65
What are drug interactions with TMP and SMX
- 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
What are contradictions to TMP/ SMX
- 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
MOA of metronidazole
- Unknown - Possible inhibition of nucleic acid synthesis and disruption of DNA
68
Spectrum of activity for metronidazole
- Anaerobes including C. Difficile - Protozoa: trichomonas, Giardia… - Propionibacterium are resistant
69
What formulations is metronidazole available in
- IV and po (very good bioavailability po)
70
Metronidazole adverse effects
- Gi - Metallic taste - Headache - Peripheral neuropathy - Disulfiram like reaction with alcohol - Insomnia - Stomatitis
71
Drug interactions with metronidazole
- Alcohol: disulfiram reaction - Warfarin: increased INR and bleeding
72
Linezolid MOA
- Inhibits protein synthesis
73
Is Linezolid bacteriostatic or bactericidal
- Usually bacteriostatic - Bactericidal against streptococci
74
Spectrum of activity for Linezolid
- Streptococci, enterococci (VRE also), staphylococci (including MRSA)
75
What is Linezolid reserved for
- Multi drug resistant organisms - Alternative to vancomycin
76
What is Linezolid available in
- IV and oral - Expensive
77
Linezolid adverse effects
- Headache - Nausea, vomiting, diarrhea, - Rash - Increased LFTs - Myelosuppression - Optic/peripheral neuropathy - Lactic acidosis - Decreased seizure threshold
78
Drug interactions with Linezolid
- Increased serotonin syndrome risk with SSRIs and MAOIs Rifampin decreases Linezolid levels

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