Antimicrobial Adverse Effects (Pre-Study) Flashcards

1
Q

What is the Drug of Choice for Syphilis?

A

Penicillin G

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2
Q

What do you give Penicillin V for?

A

Oropharyngeal Infections

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3
Q

What are the most narrow spectrum Penicillins?

- what advantage do they have?

A

Oxacillin, Nafcillin

*These are Penicillinase Resistant

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4
Q

What limits the oral bioavailability of Penicillins?

A

Gastric Acid may hydrolize

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5
Q

Which penicillins can be given parenterally?

A

Ampicillin
Piperacillin
Ticaracillin

(Parent’s AParTment)

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6
Q

How are penicillins excreted?

A

Unchanged in the Urine

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7
Q

What two penicillins undergo hepatic elimination?

A

Nafcillin and Ampicillin

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8
Q

A patient with what complications is most likely to experience adverse effects of penicillin?

A

Renal Failure or anything reducing kidney filtration will increase the blood concentration of Penicllins

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9
Q

What group of Penicillins is most likely to cause Hepatic Damage?
- what are some other WEIRD symptoms to know?

A

Semisynthetic Penicllins (AOA - Amoxicillin, Oxacillin, Amoxicillin)

SYMPTOMS TO KNOW:
• Granulocytopenia or Agranulosis
• Muscle Irritability
• SIEZURES

**Remember all these are way more likely to occur in renally impaired patients

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10
Q

Should you rely on your oral contraceptive when taking Penicilllins?
- why not?

A

NO

Oral Contraceptives get Glucuronated and Sulfonated by Phase II metabolism, Microflora in the Intestines convert Phase II products of OCs back to the original OC that can be absorbed. This type of Enterohepatic cyclining is relied upon to prolong the effects of OCs.

**Penicllins and other drugs that hurt your microflora will render OCs less effective

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11
Q

Besides penicillins, what other drugs reduce the efficacy of oral contraceptives?

A
  • RIFAMPIN (MOST Problematic)
  • Penicillin
  • SMX-TMX
  • Tetracyclines
  • Minocycline
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12
Q

How are most cephalosporins administered?

- how good is their penetration into body fluids and ECF?

A

IV/IM

*Good penetration, especially with concurrent inflammation

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13
Q

How are most Cephalosporins Excreted?

- what is the main exception?

A
  • Renally (this is no surprise as a penicillin off-shoot)

EXCEPTION:
Ceftriaxone

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14
Q

Which of the Cephalosporins reach high enough concentrations in the CSF to treat meningitis?

A
  • Ceftriaxone
  • Cefotaxime
  • Ceftazidime
  • Cefepime
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15
Q

What instructions should you give to patients taking oral forms of:

  • Penicillins
  • Cephalosporins
A

Penicillins - take with H2O

Cephalosporins - take with Milk or Food

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16
Q

What is imipenem often co-formulated with and why?

A

Cilastin - this reduces renal toxicity

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17
Q

What is special about Aztreonam?

A

Its ß-lactamase Resistant

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18
Q

How is aztreonam administered?

A

IV or IM

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19
Q

How do you administer Imipenem and Meropenem?

  • Toxicity?
  • Distribution?
A

Given IV or IM (imipenem only)

  • Renal Toxicity
  • Readily Distributed
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20
Q

What are some side effects common to all of the ß-lactams?

A
  • Possibilities of Allergic Reactions

- Serum Sickness (type III hypersensitivies)

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21
Q

What are some Weird Effects of Imipenem/Cilastin?

- Meropenem?

A

Imipenem/Cilastin:
• C. Diff.
• Seizure

*Meropenem is must less likely to produce seizures

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22
Q

Why would you give Vancomycin orally?

A

Treatment of C. Diff. infections

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23
Q

How is Fosfomycin excreted?

- how is this important for what it is often used to treat?

A

Fosfomycin:

  • excreted Renally where it is concentrated in the Urine
  • often used to treat UTIs
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24
Q

What rare and very adverse symptom to some people taking Daptomycin experience?
- patients taking what other medicine concurrently can make this more likely to happen?

A
  • Daptomycin
  • Statins (HMG-CoA reductase inhibitors) can increase the chances of the symptoms occurring (these people should be monitored)
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25
Q

What are the Broad Spectrum Protein Synthesis Inhibitors?

A

TETRACYCLINS
• Doxycycline
• Minocycline
• Tigecycline

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26
Q

What are the Moderate Spectrum Protein Synthesis Inhibitors?

A
MACROLIDES
• Azithromycin
• Clarithromycin
• Erythromycin
• Telithromycin
• Fidaxomicin

KETOLIDES
• Telithromycin

27
Q

What are the Narrow Spectrum Protein Synthesis Inhibitors?

A

STREPTOGRAMINS
- Quinupristin-Dalfopristin

LINCOSAMIDES
- Clindamycin

LINEZOLID

28
Q

Which Tetracyclin is only given IV, which is only given PO?

- others?

A

Tetracyclin - PO only
Tigecyline - IV only

Others: all others are IV or PO

29
Q

How are Tetracylines Eliminated?

  • any unique ones?
  • Distribution?
A

Renal and Hepatic

DOXYCYCLINE:

  • Predominantly Hepatic Elimination
    (note: causes less stomach upset than others)

Distribution:
- Good penetration into all tissues including CSF

30
Q

Are Tetracyclines more likely to cause liver damage when given IV or PO?

A

IV

31
Q

What is a super unique effect of tetracyclines?

A

Hairy Tongue seen in people that use tobacco or have poor hygiene

32
Q

What Protein Synthesis inhibitors are Really bad about causing CYP interations?
- Exceptions

A

Macrolides and Ketolides
• Specifically - Erythromycin and Telithromycin
(Medium Spectrum Prot. Synth. Inhib.)

Exceptions:
- Azithromycin

33
Q

What drugs should you really monitor the levels of when given to a patient taking Macrolides or Ketolides?
- how should dosing be adjusted?

A

Midazolam (REDUCE DOSE BY 75%)
Clozapine (avoid or REDUCE DOSE BY 50%)
Theophylline
Warfarin (monitor INR (clotting rate))

34
Q

Why do experts from the Medical Letter advise against ever using Telithromycin?

A

it can cause:
• Fatal Hepatotoxicity
• Exacerbate MYASTHENIA GRAVIS
• Visual Disturbances

35
Q

Why might you not want to drink while taking macrolides?

A

Heavily CYP metabolized and so it EtOH

36
Q

When would you give Quinpristin-dalfoprisitin?

  • what is the method of elimination?
  • Frequent side effects?
A

Infections that are Vanc. resistant

Elimination:
- HEPATIC w/ very little renal

Frequent:

  • Thrombophlebitis
  • Arthralgia
  • Myalgia
37
Q

WHAT IS THE BLACKBOX WARNING OR CHLORAMPHENICAL?

A
  • Serious and Fatal Blood Dyscrasias

* Aplastic Anemia ending in Leukemia

38
Q

What precautions should you take if you were to ever give Chloramphenicol?

  • how is it administered?
  • Penetration?
A
  • Hostpitalize these People and only use a last resort
  • DO NOT give to babies - Grey Baby Syndrome (hypotension, cyanosis, and often death)
  • Given IV
  • Widely distributed, but poorest distribution to the CSF
39
Q

Linezolid:

  • Dosing
  • Elimination
  • Distribution
A

Dosing: IV or PO
Elimination: Extensive Renal and Hepatic
Distribution: Widespread, Excellent to CSF, Good into the brain

40
Q

Adverse effects of Linezolid?

A
  • Peripheral and Optic Nerve Neuropathy
  • Reversible Thrombocytopenia (long term use)
  • Serotonin Syndrome with patients taking SSRIs
41
Q

What group of drugs works synergistically with cell was synthesis inhibitors?

A

Aminoglycosides

42
Q

What are the 3 most widely used Aminoglycosides?

- which is reserved for use if treatment fails with the other two?

A

Amikacin - Typically Put on Reserve
Gentamicin
Tobramycin

43
Q

WHAT IS THE BLACK BOX WARNING FOR AMINOGLYCOSIDES?

A

Neuro- and Ototoxicity
Nephrotoxicity
Neuromusclular Blockade (respiratory Paralysis possible)

44
Q

Aminoglycoside:

  • Dosing
  • Elimination
  • Monitoring
A

Dosing: Parenteral
Elimination: 100% renal
Monitor: BUN/Creatinin, Serum Drug Level, Audiometry

45
Q

What is the drug classification of SMX-TMX?

- elimination

A

Antimetabolites

Elmination:
- Equal pts. Hepatic and Renal

46
Q

Which of the Fluoroquinolones has the highest risk of causing Drug-Drug interactions, or problems with EtOH interactions?

A

Ciprofloxacin

- CYP1A2 and 3A4

47
Q

Which of the Fluoroquinolones do you not have to worry about renal dysfunction with?

A

Moxifloxacin

48
Q

WHAT IS THE BLACK BOX WARNING FOR FLUROQUINOLONES*

A

TENDONITIS AND TENDON RUPTURE

MUSCLE WEAKNESS IN PTS WITH MYASTHENIA GRAVIS

49
Q

Why might the Central Compartment be more accessible during infection?

A

During Infection:

  • Inflamed meninges get Leaky and can permit easier penetration
  • Inflammation inhibits P-gp activity
  • CSF production is diminished and less outward bulk flow
50
Q

What drug should you hesitate to administer intrathecally for fear of inducing siezure?
- what should you use instead?

A

ß-lactams
(Cefazolin, Imipenem, Aztreonam)

Use Meropenem Instead

51
Q

What drug would you never administer intrathecally because its not necessary?

A

Fluroquinolones - these have really high BBB penetration already

52
Q

Should you use aminoglycosides to treat a CSF infection?

- why?

A

NO, because these have such a narrow therapeutic window there

53
Q

Drug Binding to Plasma Proteins

  • What proteins specifically?
  • Why more of issue during severe acute illness?
  • How does this affect drug concentration?
A

Proteins:
• Albumin or Alpha-1-Acid Glycoprotein

Issue with illness:
• 40% reduction in serum albumin in critically ill pts.

Effect on Drug Concentration:
• More Free Drug in Serum - FREE FRACTION gets eliminated
• Increased Vd and CL for highly protein-bound agents
• Result = SUB-OPTIMAL Treatment

54
Q

What drugs should you under no circumstance use during pregnancy?

A

Clarithromycin
Tetracyclines
Sulfonamides (at term)

55
Q

What drugs are probably safe to use during pregnancy?

A
  • Amoxicillin/Ampicillin
  • Azithromycin
  • Cephalosporins
  • Clindamycin
  • Daptomycin
  • Dicloxacillin
56
Q
  • *What drugs operate on the basis of Concentration Dependent Killing?
  • how does this affect dosing?
A

Aminoglycoside and Fluoroquinolones

  • Once Daily Dosing
57
Q
  • *What drugs operate on the basis of Time-dependent killing?
  • how does this affect dosing?
A

ß lactams and Vancomycin

  • all you need to do is keep serum concentrations above the MBC
58
Q
  • *What is the Post-Antibiotic effect?

- Possible Explanations?

A

Continued Inhibition of Microbial expansion/activity after Serum Drug concentration falls

(1) Slow Recover after reversible nonlethal damage to cell structures
(2) Persistence of Drug at Binding Site or Within the Periplasmic Space
(3) Need to Synthesize new enzymes before growth can resume
(4) Postantibiotic Leukocyte Enhancement (PALE)

59
Q

How do we make choices on what drug to use?

A

Base it on the likely infective organism, antatomical location, and patient environment

60
Q

What is the biggest advantage of giving drugs IV or IM?

A
  • Increases Adherance

- Speeds onset of Treatment

61
Q

What type of elimination predominates across most antimicrobials?

A

Renal - so you may need to do some dose adjustment

62
Q

Among the macrolides, which have the most CYP interactions?

- the least?

A

Erythromycin and Telithromycin > Clarithromycin

63
Q

What are some common side effects of using antimicrobials?

- rare, but not unheard of side effects?

A
  • GI upset
  • Injection site reactions

More Rare:
- Blood Dyscrasia