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Pulmonology > Pneumonia Pharm > Flashcards

Pneumonia Pharm Flashcards

1
Q

list the 6 azaleas

A

Triazoles

  • Fluconazole (Diflucan)
  • Itraconazole (Sporanox)
  • Voriconazole (Vfend)
  • Posaconazole (Noxafil)
  • Isavuconazole (Cresemba)

Imidazole
- Ketoconazole (often 2nd line)

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2
Q

mechanism of action for the triazoles

A
  • Inhibit cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase
  • This enzyme converts lanosterol to ergosterol, a vital component of fungal cellular membrane
  • Causes significant damage to cell membrane by increasing permeability = cell lysis and death
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3
Q

which two azoles have the broadest spectrum?

A

posaconazole

isavuconazole

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4
Q

Which two azoles must be given on an empty stomach

A

Itraconazole

voriconazole

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5
Q

which azole’s absorption can be saturated? what does this mean?

A

Posaconazole

- limited amt can be given in a day

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6
Q

which azole is a prodrug

A

isavuconazole

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7
Q

which azole has nonlinear kinetics? implication?

A

voriconazole

- small increase in dose can result in greater serum concentration change

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8
Q

which azole has an active metabolite?

A

Itraconazole

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9
Q

why do azoles have potential for significant drug interactions?

A
  • they are either metabolized by the P450 system

- they inhibit enzymes that metabolize other drugs

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10
Q

What are two common ADRs of all azoles

A

GI distress

hepatotoxicity

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11
Q

What are the 2 unique ADR for Itraconazole

A

HTN

Heart failure

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12
Q

What are the 3 unique ADR for Isavuconazole

A

N/v/d
HA
Shorten QT interval

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13
Q

What is the unique ADR for voriconazole

A

neurologic

  • confusion
  • agitation
  • myoclonic movements
  • auditory hallucinations
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14
Q

What three azoles require loading doses

A

Voriconazole
Posaconazole
isavuconazole

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15
Q

what are the common monitoring parameters for all azoles

A
  • serum level of drug
  • liver enzymes (all)
  • drug interactions
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16
Q

What drug interaction can reduce azole effect? what does this cause?

A
  • Drugs that INDUCE CYP (rifampin, rifabutin, anticonvulsants)
  • leads to treatment failure
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17
Q

What happens if azoles inhibit CYP? what should you do?

A
  • affect other drugs metab by that route

- always look drug interactions up when use azole, ask a pharmacist if needed!

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18
Q

What are two additional monitoring parameters for itraconazole and isavuconazole

A

potassium

edema

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19
Q

what is an additional monitoring parameter for voriconazole

A

neuro changes

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20
Q

MoA amphotericin B

A
  • Binds ergosterol in fungal cell membranes,
  • Forms pores in the membrane that allow leakage of cellular components
  • Fungicidal
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21
Q

List the three formulations of amphotericin B

A
  1. Amphotericin B deoxycholate “conventional”
  2. Amphotericin B lipid complex (Abelcet)
  3. Liposomal amphotericin B (AmBisome)
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22
Q

What is the daily dose for Amphotericin B deoxycholate “conventional”

A

0.5 to 1.5 mg/kg per day (IV)

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23
Q

What is the daily dose for Amphotericin B lipid complex (Abelcet)

A

Around 3-6 mg/kg/day (IV)

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24
Q

What is the daily dose for Liposomal amphotericin B (AmBisome)

A

Around 3-6 mg/kg/day (IV)

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25
Q

What is important about formulations and dosing of the three formulations of amphotericin B

A
  • Formulations are NOT interchangeable
  • diff dosing recommendations
  • *Do not mix them up!!
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26
Q

What are the sx of infusion related reaction to amphotericin B?

A
  • Nausea
  • Vomiting
  • Chills
  • Rigors

*Usually during or immediately following infusion

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27
Q

how to pretreat pt who is going to take amphotericin B to help reduce occurrence of infusion related reaction sx?

A

Reduce incidence:

  • acetaminophen
  • hydrocortisone
  • diphenhydramine

Treat nausea

  • promethazine
  • prochlorperazine
  • ondansetron
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28
Q

4 ways to prevent phlebitis due to amphotericin B

A
  • Infusion via a central line (bigger site less irritation)
  • Use of alternating infusion sites
  • Avoidance of final amphotericin B infusion concentrations exceeding 0.1 mg/mL
  • Avoidance of infusion times of less than an hour
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29
Q

5 monitoring parameters of patient on amphotericin B

A
  • Monitor for infusion- related reactions during and following administration
  • Measurements of renal function daily during initiation of therapy (up to two weeks) and at least weekly after if pt is stable
  • Some recommend not to use or to instead use lipid-based formulation if creatinine > 2.5 mg/dL
  • Assess serum electrolytes (k and mg especially) at baseline and at least twice weekly during therapy, more if have hypokalemia or hypomagnesemia
  • CBC weekly to watch for anemia and leukopenia
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30
Q

Pathogenesis of amphotericin B

A
  • Nephrotoxicity is very common
  • Reversible and often transient decline in GFR
  • Presentation: elevation in serum creatinine concentration
  • Severe renal failure to drug alone is less common

Actual pathogenesis:

  • Renal vasoconstriction of afferent arteriole
  • Distal tubular injury
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31
Q

3 electrolyte changes with amphotericin B nephrotoxicity

A

Hypokalemia
Hypomagnesemia
Hyperchloremic acidosis

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32
Q

risk factors for development of amphotericin B nephrotoxicity

A

Nephrotoxins

  • Concurrent administration of another nephrotoxin such as aminoglycoside, cyclosporine, chemo, foscarnet
  • Chronic kidney disease at baseline
  • Dose dependent – risk of renal dysfunction low at doses of less than 0.5 mg/kg and cumulative dose less than 600 mg
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33
Q

what is done to prevent or reduce occurrence of amphotericin B nephrotoxicity?

A

salt loading
- IV normal saline infusion before and after administration can protect against or ameliorate amphotericin B-induced decline in GFR but not signs of tubular dysfunction

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34
Q

Which formulations of amphotericin B is most and which is least nephrotoxic

A
  • Amphotericin B deoxycholate is worst for nephrotoxicity 32.5%
  • Amphotericin B (AmBisome) is the best for nephrotoxicity 14.5%

**Lipid based formulations reduce but don’t eliminate risk

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35
Q

What is acronym for pnuemocystis jirovecii pneumonia

A

PCP

36
Q

First line abx for mild, moderate, and severe PCP

A

Trimethoprim-sulfamethoxazole (Bactrim)
Mild and moderate: ORAL
Severe: IV

37
Q

which severities of PCP require use of corticosteroids

A

moderate and severe

38
Q

why most often need an alternative abx therapy in PCP?

A

sulfa allergy to Bactrim

39
Q

What should be tested for if need alternative abx for PCP?

A

G6PD deficiency

- if deficient, have risk of developing hemolytic anemia when exposed to dapsone or primaquine

40
Q

What are the alternative abx therapies for mild PCP

A
  1. Trimethroprim-dapsone
  2. Clindamycin-primaquine
  3. Atovaquone (only in mild disease)
41
Q

What are the alternative abx therapies for moderate PCP

A
  1. Trimethroprim-dapsone

2. Clindamycin-primaquine

42
Q

What are the alternative abx therapies for severe PCP

A
  1. Trimethroprim-dapsone
  2. Clindamycin-primaquine
  3. IV Pentamidine
43
Q

What is alternative therapy for MILD PCP if pt also has G6PD deficiency

A

Atovaquone

44
Q

What is alternative therapy for MOD/SEVERE PCP if pt also has G6PD deficiency

A
  1. Atovaquone
  2. Desensitize to TMP-SMX
  3. IV pentamidine
45
Q

8 Common ADR to Bactrim

A
  • GI intolerance
  • Photosensitivity
  • Rash
  • Fever
  • Leukopenia
  • Hyperkalemia
  • Acute kidney injury
  • Hepatotoxicity
46
Q

8 common ADR to TMP-Dapsone

A
  • GI upset
  • Rash
  • Fever
  • Hemolytic anemia
  • Methemoglobinemia
  • Neutropenia
  • Hyperkalemia
  • Transaminase elevations
47
Q

6 common ADR to clindamycin-primaquine

A
  • Rash
  • Fever
  • Diarrhea (including C. diff)
  • Hemolytic anemia
  • Neutropenia
  • Methemoglobinemia
48
Q

3 common ADR to Atovaquone

A
  • GI distress
  • Fever
  • Transaminase elvations

**Generally well tolerated

49
Q

13 common ADR to Pentamidine

A
  • Nephrotoxicity - cumulative effect
  • Pancreatitis
  • Permanent insulin dependent diabetes mellitus
  • Nausea
  • Taste disturbance
  • Cardiac arrhythmias
  • Hyperkalemia
  • Nephrotoxicity
  • Pancreatitis
  • Hypokalemia
  • Hypocalcemia
  • Hypoglycemia
  • Hyperglycemia
50
Q

If a pt is not on ART and has PCP, when should ART be started?
Why?

A

Within two weeks of PCP tx because it can reduce risk of AIDS progression and death

**Dr. Letassy emphasized to KNOW this

51
Q

What is needed to help prevent recurrence of PCP?

A

secondary prophylaxis abx therapy

**Dr. Letassy emphasized to KNOW this

52
Q

What is dosing of secondary prophylaxis abx therapy for PCP

A

After completed 21 day course of tx, should continue to receive antimicrobial therapy at a reduced dose to prevent recurrence.

**Dr. Letassy emphasized to KNOW this

53
Q

What is criteria for stopping secondary prophylaxis abx therapy?

A
  • undetectable viral load
    and
  • rise in CD4 ≥ 200 for at least three months

**Dr. Letassy emphasized to KNOW this

54
Q

MoA Dapsone

A

Competitive antagonist of PABA, prevents normal bacterial utilization of PABA to synthesize folic acid

55
Q

MoA Atovaquone

A

Inhibits electron transport in mitochondria = inhibition of metabolic enzymes responsible for synthesis of nucleic acids and ATP

56
Q

MoA Trimethoprim

A
  • Dihydrofolate reductase inhibitor
  • Inhibits folic acid reduction to tetrahydrofolate
  • Inhibition of bacterial synthesis of nucleic acids and proteins
57
Q

Risk for drug resistant strep pneumonia in CAP

A
  • Age >65 years
  • Beta-lactam, macrolide, or fluoroquinolone therapy within the past three to six months
  • Alcoholism
  • Medical comorbidities
  • Immunosuppressive illness or therapy
  • Exposure to a child in a daycare center
58
Q

Define uncomplicated pneumonia

A
  • do not require hospitalization
  • no comorbidities
  • no recent antibiotic use - low rate of resistance
59
Q

Uncomplicated CAP - appropriate outpatient treatment

A

Macrolides

  • Azithromycin
  • clarithromycin
  • clarithromycin XL

Tetracycline
- doxyclycline

60
Q

What class are erythromycin, azithromycin, and clarithryomycin

A

macrolide

61
Q

what class is doxycycline

A

tetracycline

62
Q

Define complicated pneumonia

A
  • comorbidities
  • recent antibiotic use
  • high rate of resistance
63
Q

Appropriate outpatient tx for patient with complicated CAP

A

Fluoroquinolone

  • levofloxacin
  • moxifloxacin
  • gemifloxacin

OR

combo of:

  • beta-lactam (high-dose amox, amox-clavulonic acid, cefpodoxime, cefuroxime)
  • macrolide (azithromycin, clarithromycin, clarithromycin XL) OR doxycycline

5 day tx

64
Q

beta-lactam effective against s. pneumoniae

A
  • high dose amox
  • amox-clavulonic acid
  • cefpodoxime
  • cefuroxime
65
Q

Appropriate abx for hospitalized CAP

A

Fluoroquinolone

  • levofloxacin
  • moxifloxacin
  • gemifloxacin

OR

anti-pneumococcal beta-lactam (cefotaxime, ceftriaxone, ampicillin-sulbactam, ertapnem) PLUS a macrolide (azith, clarith, eryth)

66
Q

Respiratory fluoroquinolones

A
  • levofloxacin
  • moxifloxacin
  • gemifloxacin
67
Q

anti-pneumococcal beta-lactam

A
  • cefotaxime
  • ceftriaxone
  • ampicillin-sulbactam
  • ertapnem
68
Q

Appropriate combo for patient admitted to ICU with CAP

A
  1. Antipneumococcal beta-lactam + azithromycin
  2. antipneumococcal beta-lactam + respiratory fluoroquinolone
  3. if penicillin allergic - respiratory fluoroquinolone + aztreonam
69
Q

What are the three vaccinations that protect against pneumonia

A
  1. influenza
  2. Prevnar 13
  3. Pneumovax
70
Q

ID risk factors for QT prolongation

A
  • Advanced age
  • Hypokalemia
  • Hypomagnesemia
  • Clinically significant bradycardia and the use of other agents that prolong the QT interval, including class IA and class III antiarrhythmic agents and certain azoles
71
Q

which two common classes of drugs can cause QT prolongation

A

macrolide and fluoroquinolones

72
Q

what is the risk of QT prolongation

A

can result in torsades de pointes - a type of ventricular tachycardia that can lead to sudden cardiac death

73
Q

What is an alt tx for pts with high risk for QT prolongation

A

doxycycline

74
Q

Gemfloxacin rash

A
  • 2.8% of patients overall
  • 14% in women under 40 years of age who received the drug for seven or more days
  • incidence is much lower when used for the recommended five-day duration.
  • generally mild, occurs after the fifth day of therapy
  • resolves with discontinuation of the agent.
  • not associated with phototoxicity or hypersensitivity
  • does not preclude the use of other fluoroquinolones in the future, but repeated courses of gemifloxacin should be avoided
75
Q

most frequent cause of “typical” bacterial pneumonia in children

A

streptococcus pneumoniae

76
Q

child <5 with suspected s. pneumoniae CAP, what is appropriate abx

A

high dose amoxicillin

77
Q

Child with type 1 hypersensitivity to penicillin - abx treatment for s. pneumoniae CAP

A

clindamycin or macrolide

78
Q

Child with non-type 1 hypersensitivity to penicillin - abx treatment for s. pneumoniae CAP

A

2nd or 3rd gen cephalosporin (Cefdinir)

79
Q

What are 2 most common pathogens to cause CAP in children 5+ yo who are not ill enough to be hospitalized?

A

Atypical pathogens:

  1. m. pneumoniae
  2. c. pneumoniae

*why treat a little diff than high dose amox which is for s. pneumoniae

80
Q

Child 5+ with CAP with suspected atypical bacterial etiology what is appropriate abx class

A

Macrolide
clarithromycin
azithromycin

81
Q

If 5+ child with CAP fails to respond to macrolide therapy, what do you suspect? How treat?

A
  • macrolide resistant pathogen

- fluroquinolone

82
Q

Early onset-HAP

  • definition
  • tx guidelines
A

Hospital onset pnuemonia

  • Occurs within the first 4 days of hospitalization
  • No need for broad-spectrum coverage because risk for MDR organisms is low
83
Q

Late onset-HAP

  • def
  • tx guidelines
A

Hospital onset pnuemonia

  • Occurs 5 or more days following hospital admission
  • Broad-spectrum coverage required for increased risk of MDR (multidrug resistant) organism
84
Q

VAP

define

A

Ventilator assisted pneumonia

- develops 48-72 hours after et intubation

85
Q

Risk factors for MDR orgs

A
  • antimicrobial therapy in past 90 days
  • current hospitalization =>5 days
  • high frequency of resistance in community/hospital unit
  • immunosuppressed
  • HCAP risk factors:
  • hosp => 2 days in last 90 days
  • nursing home/extended care
  • home infusion therapy
  • chronic dialysis w/in 30 days
  • home wound care
  • fam member with path-resistant pathogen
86
Q

Pt has early onset disease, no known risk factors for MDR pathogens, select appropriate abx tx

A
  • Ceftriaxone
  • Levofloxacin
  • Moxifloxacin
  • Ampicillin-sulbactam
  • Ertapenem
  • early onset first 4 days
  • know risk factors too!
87
Q

Pt has late onset disease OR known risk factors for MDR pathogens, select appropriate abx classes tx

A
  • Antispseudomonal cephalosporin
  • Antipseudomonal carbapenem
  • beta-lactam/beta-lactamase inhibitor
    PLUS
  • antipseudomonal fluoroquinolone
  • aminoglycoside
    PLUS/MINUS
  • Linezolid

Pulmonology (11 decks)

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