Pneumonia Pharm Flashcards
list the 6 azaleas
Triazoles
- Fluconazole (Diflucan)
- Itraconazole (Sporanox)
- Voriconazole (Vfend)
- Posaconazole (Noxafil)
- Isavuconazole (Cresemba)
Imidazole
- Ketoconazole (often 2nd line)
mechanism of action for the triazoles
- 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
which two azoles have the broadest spectrum?
posaconazole
isavuconazole
Which two azoles must be given on an empty stomach
Itraconazole
voriconazole
which azole’s absorption can be saturated? what does this mean?
Posaconazole
- limited amt can be given in a day
which azole is a prodrug
isavuconazole
which azole has nonlinear kinetics? implication?
voriconazole
- small increase in dose can result in greater serum concentration change
which azole has an active metabolite?
Itraconazole
why do azoles have potential for significant drug interactions?
- they are either metabolized by the P450 system
- they inhibit enzymes that metabolize other drugs
What are two common ADRs of all azoles
GI distress
hepatotoxicity
What are the 2 unique ADR for Itraconazole
HTN
Heart failure
What are the 3 unique ADR for Isavuconazole
N/v/d
HA
Shorten QT interval
What is the unique ADR for voriconazole
neurologic
- confusion
- agitation
- myoclonic movements
- auditory hallucinations
What three azoles require loading doses
Voriconazole
Posaconazole
isavuconazole
what are the common monitoring parameters for all azoles
- serum level of drug
- liver enzymes (all)
- drug interactions
What drug interaction can reduce azole effect? what does this cause?
- Drugs that INDUCE CYP (rifampin, rifabutin, anticonvulsants)
- leads to treatment failure
What happens if azoles inhibit CYP? what should you do?
- affect other drugs metab by that route
- always look drug interactions up when use azole, ask a pharmacist if needed!
What are two additional monitoring parameters for itraconazole and isavuconazole
potassium
edema
what is an additional monitoring parameter for voriconazole
neuro changes
MoA amphotericin B
- Binds ergosterol in fungal cell membranes,
- Forms pores in the membrane that allow leakage of cellular components
- Fungicidal
List the three formulations of amphotericin B
- Amphotericin B deoxycholate “conventional”
- Amphotericin B lipid complex (Abelcet)
- Liposomal amphotericin B (AmBisome)
What is the daily dose for Amphotericin B deoxycholate “conventional”
0.5 to 1.5 mg/kg per day (IV)
What is the daily dose for Amphotericin B lipid complex (Abelcet)
Around 3-6 mg/kg/day (IV)
What is the daily dose for Liposomal amphotericin B (AmBisome)
Around 3-6 mg/kg/day (IV)
What is important about formulations and dosing of the three formulations of amphotericin B
- Formulations are NOT interchangeable
- diff dosing recommendations
- *Do not mix them up!!
What are the sx of infusion related reaction to amphotericin B?
- Nausea
- Vomiting
- Chills
- Rigors
*Usually during or immediately following infusion
how to pretreat pt who is going to take amphotericin B to help reduce occurrence of infusion related reaction sx?
Reduce incidence:
- acetaminophen
- hydrocortisone
- diphenhydramine
Treat nausea
- promethazine
- prochlorperazine
- ondansetron
4 ways to prevent phlebitis due to amphotericin B
- 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
5 monitoring parameters of patient on amphotericin B
- 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
Pathogenesis of amphotericin B
- 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
3 electrolyte changes with amphotericin B nephrotoxicity
Hypokalemia
Hypomagnesemia
Hyperchloremic acidosis
risk factors for development of amphotericin B nephrotoxicity
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
what is done to prevent or reduce occurrence of amphotericin B nephrotoxicity?
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
Which formulations of amphotericin B is most and which is least nephrotoxic
- 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
What is acronym for pnuemocystis jirovecii pneumonia
PCP
First line abx for mild, moderate, and severe PCP
Trimethoprim-sulfamethoxazole (Bactrim)
Mild and moderate: ORAL
Severe: IV
which severities of PCP require use of corticosteroids
moderate and severe
why most often need an alternative abx therapy in PCP?
sulfa allergy to Bactrim
What should be tested for if need alternative abx for PCP?
G6PD deficiency
- if deficient, have risk of developing hemolytic anemia when exposed to dapsone or primaquine
What are the alternative abx therapies for mild PCP
- Trimethroprim-dapsone
- Clindamycin-primaquine
- Atovaquone (only in mild disease)
What are the alternative abx therapies for moderate PCP
- Trimethroprim-dapsone
2. Clindamycin-primaquine
What are the alternative abx therapies for severe PCP
- Trimethroprim-dapsone
- Clindamycin-primaquine
- IV Pentamidine
What is alternative therapy for MILD PCP if pt also has G6PD deficiency
Atovaquone
What is alternative therapy for MOD/SEVERE PCP if pt also has G6PD deficiency
- Atovaquone
- Desensitize to TMP-SMX
- IV pentamidine
8 Common ADR to Bactrim
- GI intolerance
- Photosensitivity
- Rash
- Fever
- Leukopenia
- Hyperkalemia
- Acute kidney injury
- Hepatotoxicity
8 common ADR to TMP-Dapsone
- GI upset
- Rash
- Fever
- Hemolytic anemia
- Methemoglobinemia
- Neutropenia
- Hyperkalemia
- Transaminase elevations
6 common ADR to clindamycin-primaquine
- Rash
- Fever
- Diarrhea (including C. diff)
- Hemolytic anemia
- Neutropenia
- Methemoglobinemia
3 common ADR to Atovaquone
- GI distress
- Fever
- Transaminase elvations
**Generally well tolerated
13 common ADR to Pentamidine
- Nephrotoxicity - cumulative effect
- Pancreatitis
- Permanent insulin dependent diabetes mellitus
- Nausea
- Taste disturbance
- Cardiac arrhythmias
- Hyperkalemia
- Nephrotoxicity
- Pancreatitis
- Hypokalemia
- Hypocalcemia
- Hypoglycemia
- Hyperglycemia
If a pt is not on ART and has PCP, when should ART be started?
Why?
Within two weeks of PCP tx because it can reduce risk of AIDS progression and death
**Dr. Letassy emphasized to KNOW this
What is needed to help prevent recurrence of PCP?
secondary prophylaxis abx therapy
**Dr. Letassy emphasized to KNOW this
What is dosing of secondary prophylaxis abx therapy for PCP
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
What is criteria for stopping secondary prophylaxis abx therapy?
- undetectable viral load
and - rise in CD4 ≥ 200 for at least three months
**Dr. Letassy emphasized to KNOW this
MoA Dapsone
Competitive antagonist of PABA, prevents normal bacterial utilization of PABA to synthesize folic acid
MoA Atovaquone
Inhibits electron transport in mitochondria = inhibition of metabolic enzymes responsible for synthesis of nucleic acids and ATP
MoA Trimethoprim
- Dihydrofolate reductase inhibitor
- Inhibits folic acid reduction to tetrahydrofolate
- Inhibition of bacterial synthesis of nucleic acids and proteins
Risk for drug resistant strep pneumonia in CAP
- 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
Define uncomplicated pneumonia
- do not require hospitalization
- no comorbidities
- no recent antibiotic use - low rate of resistance
Uncomplicated CAP - appropriate outpatient treatment
Macrolides
- Azithromycin
- clarithromycin
- clarithromycin XL
Tetracycline
- doxyclycline
What class are erythromycin, azithromycin, and clarithryomycin
macrolide
what class is doxycycline
tetracycline
Define complicated pneumonia
- comorbidities
- recent antibiotic use
- high rate of resistance
Appropriate outpatient tx for patient with complicated CAP
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
beta-lactam effective against s. pneumoniae
- high dose amox
- amox-clavulonic acid
- cefpodoxime
- cefuroxime
Appropriate abx for hospitalized CAP
Fluoroquinolone
- levofloxacin
- moxifloxacin
- gemifloxacin
OR
anti-pneumococcal beta-lactam (cefotaxime, ceftriaxone, ampicillin-sulbactam, ertapnem) PLUS a macrolide (azith, clarith, eryth)
Respiratory fluoroquinolones
- levofloxacin
- moxifloxacin
- gemifloxacin
anti-pneumococcal beta-lactam
- cefotaxime
- ceftriaxone
- ampicillin-sulbactam
- ertapnem
Appropriate combo for patient admitted to ICU with CAP
- Antipneumococcal beta-lactam + azithromycin
- antipneumococcal beta-lactam + respiratory fluoroquinolone
- if penicillin allergic - respiratory fluoroquinolone + aztreonam
What are the three vaccinations that protect against pneumonia
- influenza
- Prevnar 13
- Pneumovax
ID risk factors for QT prolongation
- 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
which two common classes of drugs can cause QT prolongation
macrolide and fluoroquinolones
what is the risk of QT prolongation
can result in torsades de pointes - a type of ventricular tachycardia that can lead to sudden cardiac death
What is an alt tx for pts with high risk for QT prolongation
doxycycline
Gemfloxacin rash
- 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
most frequent cause of “typical” bacterial pneumonia in children
streptococcus pneumoniae
child <5 with suspected s. pneumoniae CAP, what is appropriate abx
high dose amoxicillin
Child with type 1 hypersensitivity to penicillin - abx treatment for s. pneumoniae CAP
clindamycin or macrolide
Child with non-type 1 hypersensitivity to penicillin - abx treatment for s. pneumoniae CAP
2nd or 3rd gen cephalosporin (Cefdinir)
What are 2 most common pathogens to cause CAP in children 5+ yo who are not ill enough to be hospitalized?
Atypical pathogens:
- m. pneumoniae
- c. pneumoniae
*why treat a little diff than high dose amox which is for s. pneumoniae
Child 5+ with CAP with suspected atypical bacterial etiology what is appropriate abx class
Macrolide
clarithromycin
azithromycin
If 5+ child with CAP fails to respond to macrolide therapy, what do you suspect? How treat?
- macrolide resistant pathogen
- fluroquinolone
Early onset-HAP
- definition
- tx guidelines
Hospital onset pnuemonia
- Occurs within the first 4 days of hospitalization
- No need for broad-spectrum coverage because risk for MDR organisms is low
Late onset-HAP
- def
- tx guidelines
Hospital onset pnuemonia
- Occurs 5 or more days following hospital admission
- Broad-spectrum coverage required for increased risk of MDR (multidrug resistant) organism
VAP
define
Ventilator assisted pneumonia
- develops 48-72 hours after et intubation
Risk factors for MDR orgs
- 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
Pt has early onset disease, no known risk factors for MDR pathogens, select appropriate abx tx
- Ceftriaxone
- Levofloxacin
- Moxifloxacin
- Ampicillin-sulbactam
- Ertapenem
- early onset first 4 days
- know risk factors too!
Pt has late onset disease OR known risk factors for MDR pathogens, select appropriate abx classes tx
- Antispseudomonal cephalosporin
- Antipseudomonal carbapenem
- beta-lactam/beta-lactamase inhibitor
PLUS - antipseudomonal fluoroquinolone
- aminoglycoside
PLUS/MINUS - Linezolid
