Common resistant pathogens
Klebsiella pneumoniae (ESBL, CRE)
Escherichia coli (ESBL, CRE)
Acinetobacter baumanii
Enterococcus faecalis, Enterococcus faecium (VRE)
Staphylococcus aureas (MRSA)
Pseudomonas aeruginosa
CYP inducers
PS PORCS: phenytoin, smoking, phenobarbital, oxcarbazepine, rifampin, carbamazepine, St. John's wort
CYP inhibitors
G PACMAN: grapefruit, protease inhibitors, azole antifungals, cyclosporine (also cimetidine, cobicistat), macrolides (clarithro, erythro), amiodarone, non-DHP CCBs (diltiazem and verapamil)
List of approved drugs that can be interchanged with generics based on therapeutic equivalence
Orange Book (FDA)
Information on epidemiology and vaccine-preventable diseases
Pink Book (CDC)
News reports on regulatory, legislative, legal and business developments
Pink Sheet (Pharma Intelligence)
List of biological drug products, including biosimilars
Purple Book (FDA)
Drug pricing information
Red Book, Pharmacy
Summaries of pediatric infectious diseases, antimicrobial treatment and vaccinations
Red Book, Pediatrics (AAP)
Information of the health risks of international travel, required vaccines and prophylaxis medications
Yellow Book (CDC)
Information on approved animal drug products
Green Book (FDA)
Drugs with leaching/adsorption issues with PVC containers
Lorazepam, Amiodarone, Taxanes, Tacrolimus, Insulin, Nitroglycerin
Only compatible in saline
("A DIAbetic Can't Eat Pie")
Ampicillin, Daptomycin, Infliximab, Amp/Sulbactam, Caspofungin, Ertapenem, Phenytoin
Only compatible in dextrose
("Obese Bakers Avoid Salt")
Oxaliplatin, Bactrim, Amphotericin B, Synercid
Common drugs with filter requirements
Pushy Guys (and gals) in LA LA land
P
henytoin
G
olimumab
L
ipids (1.2 micron - larger pore size filter required)
A
mphotericin B (lipid formulations - prepare using 5 micron filter)
L
orazepam
A
miodarone
Most require 0.22 micron filter during administra
Do not refrigerate
(Dear Sweet Pharmacist, Freezing Makes Me Edgy)
Dexmedetomidine, SMX/TMP, Phenytoin, Furosemide, Moxifloxacin, Metronidazole, Enoxaparin
Protect from light during administration
(Protect Every Necessary Med from Daylight)
Phytonadione, Epoprostenol, Nitroprusside, Micafungin, Doxycycline
Others: Ampho B Deoxycholate, Anthracyclines, Dacarbazine, Pentamidine, Thiotepa
Continuous data
ratio or interval data:
ratio - age, height, weight, time BP
interval - Celsius or F temp scales
Discreet data
also categorical data:
nominal - gender, ethnicity, marital status, mortality
ordinal - NYHA Functional Class, pain scale
Type I error
false positive, the incorrect rejection of a null hypothesis, related to alpha level
found a difference when there actually is not one
Type II error
false negative, incorrectly accept the null hypothesis
not finding a difference when there actually is one
study power
The ability to detect a difference btw study groups if one actually exists.
Indirectly related to the likelihood of making a Type II (b) error
...As power increases, chance of type II error decreases
interpretation of 95% confidence interval
We are 95% confident that the true population value lies somewhere between ___ and ___ (range).
interpretation of NNT 45
For every 45 patients who receive [treatment] for [one year], [outcome (e.g. HF progression)] is prevented in one patient
(
ROUND UP NNT
so you don't overestimate benefit)
interpretation of NNH 90
One additional case of [major bleeding] is expected to occur for every 90 patients taking [drug] instead of [placebo/other drug].
(
ROUND DOWN NNH
so you don't underestimate harm)
What kind of statistical analysis should be performed for continuous data that is normally distributed between a single group compared to known data from the population?
one-sample t-test
What kind of statistical analysis should be performed for before and after continuous data that is normally distributed between a single group?
dependent/paired t-test
What kind of statistical analysis should be performed for continuous data that is normally distributed between two groups (e.g. treatment and control comparison for BP reduction)?
unpaired student t-test
What kind of statistical analysis should be performed for continuous data that is normally distributed between three or more groups?
ANOVA
What kind of statistical analysis should be performed for discreet/categorical data between a single group or two groups (e.g. mortality data)?
Chi-square test
(Fisher's exact for a very small trial)
Cost-minimization analysis
used when two or more interventions have already demonstrated equivalency in outcomes and the costs of each intervention are being compared
cost-benefit analysis
compares the costs and benefits between unrelated or related programs, as long as the outcome is monetary
cost-effectiveness analysis
outcomes are measured in natural units (e.g. life years gained, mmHg blood pressure, % at treatment goal)
cost-utility analysis
measured in QALY
What is the focus of USP <797>?
minimize the risk of microorganisms or other contaminants in sterile preparations
What is the focus of USP <800>?
keep the compounder safe and reduce risk of exposure to the HD
What are the physical space basics for non-sterile compounding?
*needs to be separate and distinct from any sterile compounding
*can be performed in ambient (room) air
*must have adequate space for orderly work with shelving and storage & no storage on the floor
*needs to be adequate plumbing and 2 types of water: pot
What are the physical space basics for sterile compounding?
*anteroom, buffer area and a PEC (hood) with specific ISO air requirements
*all surfaces must be smooth, impervious, free from cracks or crevices and non-shedding so they are easy to clean
*walls - locked, sealed panels
*floors overlaid with wide, sheet v
What are the physical space basics for hazardous drugs?
Containment
-PEC or SEC (vertical flow hood)
*permissible to perform both sterile and non-sterile HD compounding in same area as long as ISO 7 air is maintained, kept 1 meter apart, no HD powders at the same time as sterile compounding
negative air pressu
Air quality for sterile compounding
*PEC/hood/isolator/glove box is ISO 5 air: < 3,520 particles/m^3
*SEC/buffer area/room where the hood is located is ISO 7 air: < 352,000 particles & anteroom if open to negative pressure SEC
*anteroom/where you garb & wash hands is ISO 8 if open to positi
HEPA filters
>99.97% efficient at removing particles
0.5 microns
or larger (including bacteria, viruses, fungi, dust)
-located at the
top
in a vertical biological safety cabinet
-located at the
back
in a horizontal LAFW
-must be recertified by a specialist
every 6 mon
Non-HD sterile compounding: working inside the hood/PEC
-always work 6 inches from the front edge of the hood
-wipe off the outside of vials, syringes, etc with 70% IPA before bringing them inside the hood
-line up items side by side in a horizontal LAFW to protect critical sites exposed to first air and avoid
HD sterile compounding: working inside the Class II BSC/CACI
-will be externally vented
-negative air pressure, vertical flow
-do not block first air coming from the top; hold horizontal or underneath
-waste buckets are yellow for trace HD waste, such as empty vials and syringes
-garb:
2 pairs ASTM-rated gloves
(po
Personnel training requirements for sterile compounding
-initial training (didactic + hands-on), any time work is new or different must have additional training
-PRIOR to compounding, must demonstrate adequate aseptic technique in hand hygiene, garbing and gloving by passing the
gloved fingertip test
and in st
What is considered passing a gloved fingertip test?
Perform garbing and gloving, then must have
three consecutive
gloved fingertip samples with zero CFUs for both hands (6 total plates with TSA)
How do you pass a media fill test?
TSB takes place of the drug being prepared. The growth medium must stay clear after 14 days of incubation
How often should the temperature be monitored?
daily
for the cleanroom/SEC (20 C/68 F or colder)
twice daily
, minimum daily for the fridge (2-8 C) and freezer (-50 to -15 C)
How often should air and surface testing be performed?
-air sampling: at least
every 6 months
-surface sampling: periodically; TSA plates with polysorbate 80 and lecithin cannot have > 3 CFUs in ISO 5 or > 5 CFUs in ISO 7, preferably -
zero CFUs
-air pressure:
every SHIFT
or
daily
at a minimum
When can you shut down the hood/PEC?
Ideally it should be kept running at all times
-if power outage, all compounding must STOP and all hoods will need to be
cleaned with germicidal detergent THEN disinfected with 70% IPA
and allowed to
run for 30 mins
prior to resuming compounding
-C-PECs w
What is the cleaning schedule for the sterile compounding area?
DAILY
: clean and disinfect counters, floors & carts; for HDs sanitize the work area at the end of each shift
WEEKLY
: walls, windows, shelving, bins, chairs
MONTHLY
: ceiling
How often should you clean ISO 5 PECs?
-before each shift
-
every 30 minutes
while working
-before and after each batch of CSPs
-whenever needed, including after spills
What do the different colors of waste bins mean?
RED
: infectious waste, including IV tubing and culture dishes
YELLOW
: trace hazardous waste, including sharps
BLACK
: bulk hazardous waste with a visible amount of HD drug left, supplies used to administer HDs or clean up HD spills
Steps for garbing
Outside the ante area
: remove all jewelry, make up, coat
Ante area
: put on shoe covers, head and facial hair covers, and face mask (eye shield if preparing HDs), wash hands with soap and warm water for 30 seconds, scrubbing in circular motions up to elb
BUD for nonaqueous formulations
Not later than the time remaining until the earliest expiration date of any API or
6 months
, whichever is earlier
BUD for water-containing oral formulations
14 days refrigerated
BUD for water-containing topical/dermal and mucosal liquid and semisolid formulations
30 days at room temperature
BUD for hazardous drugs compounded in a segregated compounding area
12 hours at room temp or fridge
BUD for low risk CSPs
48 hrs room temp
14 days fridge
45 days freezer
BUD for medium risk CSPs
30 hrs room temp
9 days fridge
45 days freezer
BUD for high risk CSPs
24 hrs room temp
3 days fridge
45 days freezer
Binders
acacia, starch paste, sucrose syrup
diluent or fillers
-tablets/capsules: lactose, mannitol, sorbitol,
starches, calcium salts
, gelatin, bentonite
powdered
cellulose
(also a thickener, adsorbent, disintegrant, suspending agent)
-liquid: water, glycerin, alcohol
-topical: mineral oil, petrolatum, lanolin, wax
Disintegrants
alginic acid/alginates, polacrillin potassium (Amberlite), cellulose products, starches, compressible sugar (Nu-Tab)
lubricant/glidant/anti-adherent
magnesium stearate
, calcium, PEG, glycerin, mineral oil, stearic acid, talc,
colloidal silica
preservatives
benz" "cetyl" "phenyl/ols" "
parabens
"
chlorhexidine
topical/nasal: alcohols, acids, chlorhexidine
sorbic acid/potassium sorbate,
thimerosal
sodium benzoate, benzoic acid
buffers
potassium phosphate/metaphosphate
sodium acetate/citrate
hydrochloric acid/sodium hydroxide
boric acid/potassium chloride
potassium (biphthalate or phosphate)/water
hydrophilic solvents
-purified water: distilled, deionized, reverse osmosis, carbon-filtered
-sterile water for injection (SWFI)
-bacteriostatic water for injection (SWFI + preservatives)
-sterile water for irrigation
hydrophobic solvents
-alcohols: ethanol (grain alcohol, ethyl alcohol, drinking alcohol), isopropyl alcohol
-oils and fats: almond, borage, canola, castor coconut, mineral oils, omega-3, omega-6
-glycols: glycerin, propylene glycol,
PEG, Polybase
-emollients (moisturizers): p
humectants
glycerin, glycerol, propylene glycol, PEG, urea, hyaluronic acid
-draw water into the skin, less greasy but can feel sticky
hydrocarbon base ointments
white petrolatum, white ointment (
Vaseline
)
-forms occlusive barrier, feels greasy
-
oleaginous, no water
adsorption base ointments
hydrophilic petrolatum, lanolin
-used for water-in-oil emulsions or as emollients
water-removable bases
oil-in-water emulsions, hydrophilic
-more easily diluted, washed off the skin more easily
-per USP, more correctly called
creams
water-soluble bases
polyethylene glycol ointment
-do not contain petrolatum
-per USP, more correctly called
gels
adsorbants
magnesium oxide/carbonate, kaolin
anti-foaming agents
Simethicone, dimethicone
Coatings (regular)
shellac, gelatin, gluten
enteric-coating
cellulose acetate phthalate, shellac
Gelling (thickening) agent, stabilizer
agar, alginates, guar gums, acacia, gelatins
, tragacanth,
bentonite, carbomer, cellulose, starches
, acrylates, cetyl alcohol, magnesium aluminum silicate (Veegum), poloxamer (pluronic) gels, polyvinyl alcohol
-increases the viscosity of a substance; sta
levigating agents
glycerin/glycerol, mineral oil
, glycols, PEG, propylene glycol
comminution
reducing particle size by grinding, crushing, milling, vibrating, or other processes
-trituration
-levigation and spatulation
-pulverization by intervention
trituration
mix thoroughly" or make product homogenous
-grinding tablets in a mortar with a pestle
-shaking/triturating an emulsion
levigation
triturating a powder with mortar and pestle and incorporating a small amount of liquid/levigating agent/wetting agent to help with the grinding process
-turns the solid into a uniform paste
spatulation
similar to levigation, performed on an ointment slab with a spatula instead of with a mortar and pestle
Pulverization by intervention
the reduction of a solid (crystalline powders that will not crush easily) by combining it with a solvent (alcohol) that will evaporate after pulverization is complete
types of solutions
-syrups: contain sucrose or other sugars
-elixirs: sweet hydroalcoholic solutions used for drugs that would be insoluble in aqueous formation
-tinctures: plant or animal extracts dissolved in alcohol or hydroalcohol
-spirits: alcohol or hydroalcohols of v
emulsifiers
acacia, agar, carbomers, glyceryl monostearate, pectin, PEG, sodium laurel sulfate, sorbitan liphophlic ester (Arlacel, Span), sorbitan hydrophilic esters (Myrj, Tween)
Continental Gum Method
-also called the
dry gum
method uses 4 parts oil, 2 parts water, and 1 part emulsifier (acacia or other gum-type emulsifier)
-the
gum is levigated with the oil
, then the
water is added all at once
-the mixture is triturated by shaking it until a
cracking
English Gum Method
-also called the
wet gum
method also uses 4:2:1 oil, water, emulsifier
-triturate the gum and water to form a
mucilage
then
add the oil slowly
while triturating to form the emulsion
-add other ingredients by dissolving in the solution and QS water to fina
Nephron: hot spot diagram
PCT: SGLT2 inhibitors, acetazolamide (filters bicarb)
thick ascending Loop of Henle: loop diuretics
DCT: thiazides, K-sparing diuretics
CD: K-sparing diuretics (amiloride, triamterene)
Select drugs that cause kidney disease
aminoglycosides, amphotericin B, cisplatin, cyclosporine, loop diuretics, NSAIDs, polymyxins, contrast dye, tacrolimus, vancomycin
Key drugs that require dose reduction or increasing the interval in CKD
-anti-infectives:
aminoglycosides, beta-lactams
(most),
fluconazole, quinolones
(except moxi),
vancomycin
-CV drugs:
LMWHs (enoxaparin), rivaroxaban
(for AFib)
-GI drugs:
metoclopramide, H2RAs
-Others:
bisphosphonates, lithium
Other drugs that require dose reduction or interval increase in CKD
anti-infectives: amphotericin B, ethambutol, pyrazinamide, acyclovir, (valacyclovir, ganciclovir, valganciclovir), oseltamivir, aztreonam, NRTIs, polymyxins, sulfamethoxazole/trimethoprim
CV drugs: antiarrhythmics (digoxin, disopyramide, dofetilide, proca
Drugs contraindicated with CrCl < 60
-nitrofurantoin
-do not initiate TDF if < 70
-glyburide not recommended in CKD
Drugs contraindicated with CrCl < 50
-
tenofovir disoproxil fumarate
: Stribild, Complera, Symfi/Symfi Lo, Atripla, Truvada (during treatment)
-
voriconazole
IV
-meperidine (reduce dose to avoid accumulation of toxic metabolites)
Drugs contraindicated with CrCl < 30
-
tenofovir alafenamide
: Genvoya, Odefsey, Descovy, Biktarvy, Symtuza
-NSAIDs
-dabigatran (DVT/PE)
-rivaroxaban (DVT/PE)
-Others: bisphosphonates, duloxetine, fondaparinux, K-sparing diuretics, tadalafil, tramadol ER, avanafil
-sotalol (Betapace AF) at <
Drugs contraindicated with GFR < 30
-SGLT2 inhibitors
-metformin
Treatment for CKD induced hyperphosphatemia
1. calcium-based phosphate binders
2. aluminum-free, calcium-free phosphate binders (expensive) or
sevelamer carbonate/HCl
3. aluminum-based phosphate binders LAST LINE and duration limited to 4 weeks due to toxicity ("dialysis dementia")
Treatment for CKD induced Vitamin D deficiency and secondary hyperparathyroidism
-vitamin D2 (dietary) or D3 (synthesized in the skin after sunlight) supplementation in CKD stage 3 or 4
-vitamin D analogs (calcitriol - active D3) for later stages of CKD or ESRD to increase calcium absorption from the gut and inhibit PTH secretion
-cal
Key drugs that raise potassium levels
ACE inhibitors, ARBs, aliskiren, aldosterone-receptor antagonists, canagliflozin, drospirenone-containing COCs, Bactrim, calcineurin inhibitors
(cyclosporine, tacrolimus, everolimus)
Others: glycopyrrolate, heparin (chronic use), NSAIDs, IV fluids, K supp
Steps for treating severe hyperkalemia
1. Stabilize the heart
- prevent arrhythmias with calcium gluconate
2. Move it
- shift excess K intracellularly with albuterol. bicarb, insulin/dextrose
3. Remove it
- enhance K elimination with Kayexalate/SPS, dialysis, loop diuretics
Warning for sofosbuvir-containing products
serious symptomatic bradycardia when taken with
amiodarone
-Sovaldi, Harvoni, Epclusa
HCV treatment that is pan-genotypic and approved for treatment-naive patients
Epclusa
Mavyret
Acid Suppressive therapy should be avoided or minimized during therapy (HCV)
Harvoni,
Epclusa-avoid
, Vosevi
Avoid ethinyl estradiol-containing medications with (HCV)
Technivie
Viekira
(
ritonavir
in each)
key drugs with boxed warnings for liver damage
Acetaminophen (high doses, acute or chronic), isoniazid, ketoconazole, methotrexate, nefazodone, nevirapine, NRTIs, propylthiouracil, tipranavir, valproic acid
Others: amiodarone, bosentan, felbamate, flutamide, leflunamide, lomitapide, maraviroc, mipomer
Live vaccines
Cholera (Vaxchora), Typhoid (Vivotif), Zoster (Zostavax), Yellow fever (YF-VAX), Varicella (Varivax), Rotavirus, MMR, Intranasal influenza
Antibiotic hot spot: MOA
-cell wall inhibitors: Beta-lactams, aztreonam, vancomycin, dalbavancin, oritavancin, telavancin
-cell membrane inhibitors: polymyxins, daptomycin, telavancin, oritavancin
protein synthesis inhibitors: aminoglycosides, macrolides, tetracyclines, clindamyc
HIV Life cycle: hot spot MOA
Stage 1: binding/attachment - maraviroc
Stage 2: fusion - enfurvitide
Stage 3: reverse transcription - NRTIs/NNRTIs
Stage 4: integration - INSTIs
Stage 5: transcription and translation - no drugs (yet)
Stage 6: assembly - no drugs (yet)
Stage 7: budding a
Hydrophilic antibiotics
-Beta-lactams
-Aminoglycosides
-Glycopeptides
-Daptomycin
-Polymyxins
*Small Vd, poor tissue penetration, renal elimination, increased Cl or Vd in sepsis, poor to moderate bioavailability
Lipophilic antibiotics
quinolones, macrolides, rifampin, linezolid, tetracyclines, chloramphenicol
*large Vd, excellent tissue penetration, hepatic metabolism (more DDI and hepatotoxicity), active against atypical pathogens, Cl/Vd minimally changed in sepsis, excellent bioavail
Which beta-lactams do not require renal dose adjustments?
anti-staph PCNs: nafcillin, oxacillin, dicloxacillin
ceftriaxone
Penicillins spectrum of activity
natural: streptococci, enterococci, G+ anaerobes
amino: above plus HNPEK; BLI adds MSSA and G- anaerobes
Zosyn: above plus MSSA, SPACE, Pseudomonas, G- anaerobes
antistaph: MSSA, streptococcus
Penicillin allergy exceptions
1. syphilis in pregnancy
2. children with acute otitis media - use cephalosporin
Cephalosporins spectrum of activity
1st gen: streptococci, MSSA, PEK, G+ anaerobes
2nd gen: above plus "HN"PEK; cefotetan/cefoxitin: G- anaerobes
3rd gen (except ceftaz): above plus more resistant Strep and HNPEK
ceftazidime: Pseudomonas; BLI adds MDR G- rods (PsA)
4th/cefepime: HNPEK, SPAC
Cephalosporins: outpatient indications
1st gen (Keflex): strep throat, MSSA skin infections
2nd gen (cefuroxime): AOM, CAP, sinus infections
3rd gen (cefdinir): CAP, sinus infections
Cephalosporins: inpatient indications
1st gen: surgical prophylaxis
2nd gen: surgical prophylaxis (GI procedures)
3rd gen (CTX/cefotaxime): CAP, meningitis, SBP, pyelonephritis
ceftazidime/cefepime: Pseudomonas
ceftaroline: MRSA
Key Features of Carbapenems
Class effects:
-all cover ESBL-producing organisms
-Do not use with PCN allergy on NAPLEX!!
-All except ert
APE
nem cover Pseudomonas
-seizure risk with higher doses, renal failure, or imipenem/cilastatin
-do NOT cover atypicals, VRE, MRSA, C. diff, Steno
Key features of aminoglycosides
-Spectrum: G- bacteria (including PsA), synergy for G+ infections (usually with beta lactam)
-dosing:
extended-interval
vs traditional, weight-based
-toxicities: nephrotoxicity, ototoxicity
-monitoring: peaks, troughs, random for extended-interval
Quinolones: coverage
My Good Lungs" / respiratory FQs: levofloxacin, moxifloxacin, gemifloxacin
-used for Strep pneumo, pneumonia
antipseudomonal FQs: ciprofloxacin, levofloxacin
-used for Pseudomonas infections (including pneumonia), UTIs, intra-abdominal infections, travel
Quinolones: safety issues
All the black box warnings:
tendonitis/tendon rupture
peripheral neuropathy
CNS effects:
seizures*
*avoid in patients with myasthenia gravis
*use LAST LINE for acute bacterial sinusitis, uncomplicated UTI, bronchitis
Warnings:
-QT prolongation (moxi worst
ciprofloxacin is contraindicated with
tizanidine
clinical pearls of moxifloxacin
-some anaerobic coverage (B fragilis)
-no renal dose adjustment
-cannot be used to treat UTI because it does not reach adequate concentration in the urine
-highest risk of QT prolongation
Key features of macrolides
-atypical coverage
-QT prolongation
-drug interactions: clarithromycin and erythromycin contraindicated with simvastatin and lovastatin
-azithromycin and erythromycin do not require renal dose adjustments
Key features of tetracyclines
-atypical coverage
-avoid in pregnancy and children < 8 years
except
Rocky Mountain Spotted Fever in children
-photosensitivity, separate from cations
Bactrim: key features
-5:1 ratio of sulfamethoxazole to trimethoprim
-dosed on trimethoprim component
-side effects:
photosensitivity, hemolytic anemia, hyperkalemia
-interacts with
warfarin
Vancomycin: key features
-covers MRSA, C. diff (PO)
-use TOTAL BODY WEIGHT for dosing
-target trough for MRSA cellulitis 10-15
-more severe infections (pneumonia, endocarditis, osteomyelitis, meningitis) target trough 15-20
-MRSA
MIC cutoff 2
- use another drug
-infusion-related
key features of lipoglycopeptides
("-vancin"): red man syndrome (all)
-telavancin: fetal risk, nephrotoxicity
-oritavancin, dalbavancin: single-dose
-oritavancin: do not use IV heparin
5 days
after dose -falsely elevated aPTT
key features of daptomycin
elevated CPK/rhabdomyolysis, only compatible in NS, can't be used in pneumonia, watch statin drug interactions
key features of linezolid
serotonergic drug interactions, thrombocytopenia, covers MRSA and VRE
key features of Synercid
quinupristin/dalfopristin: arthralgias/myalgias, must be given via central line, only compatible in D5W
key features of tigecycline
BBW use last line (increased risk of DEATH), 3T's tissue (good tissue penetration), tangerine (orange in color), three P's not covered -Pseudomonas, Proteus, Providencia
Which antibiotics cover Pseudomonas?
cefepime, Zosyn, ceftazidime, ceftolozane/tazobactam, ceftazidime/avibactam, ciprofloxacin, levofloxacin, carbapenems (except erta), aminoglycosides, aztreonam, Colistin, polymyxin B
Which antibiotics cover MRSA?
-community-acquired MRSA SSTIs: Bactrim, clindamycin, doxycycline, minocycline, linezolid
-more severe SSTI, need IV treatment or hospitalization: vancomycin (unless MIC>2), linezolid, tedizolid, daptomycin, ceftaroline, telavancin, oritavancin, dalbavanc
Which antibiotics cover VRE?
daptomycin, linezolid, Synercid, tigecycline
-cystitis only: nitrofurantoin, fosfomycin, doxycycline
Which antibiotics cover B fragilis?
metronidazole, Augmentin, Unasyn, cefotetan, cefoxitin, carbapenems, tigecycline
-others with reduced activity: clindamycin, moxifloxacin
Which antibiotics cover CRE?
ceftazidime/avibactam, Colistin, polymyxin B
Drugs that increase LDL and triglycerides
protease inhibitors, steroids, diuretics, cyclosporine, tacrolimus
drugs that increase only LDL
fibrates, SGLT2 inhibitors
drugs that increase only triglycerides
IV lipid emulsions, propofol, beta blockers, atypical antipsychotics
CAP guidelines category 1 patients
no comorbidities or risk factors for MRSA or Pseudomonas
-no heart, liver, lung dz, alcoholism, not immunocompromised
-no abx in last 90 days, hospitalizations
-treatment: high dose amoxicillin, doxycycline or macrolide (if local R<25%)
monotherapy
CAP guidelines category 2 patients AND nonsevere inpatient CAP (non-ICU)
comorbidities, immunocompromised, risk factors for MRSA or Pseudomonas
-treatment: beta-lactam + macrolide/doxycycline OR respiratory FQ monotherapy (cannot have a seizure history!!!)
severe (ICU) inpatient CAP treatment
1. beta lactam + macrolide (NO doxycycline)
2. beta lactam + respiratory quinolone
HAP/VAP treatment
everybody gets Pseudomonas coverage
-double cover if high risk of mortality or received abx in the last 90 days + MRSA coverage
cover for MRSA or MSSA based on risk
tuberculosis active disease treatment
RIPE therapy x 2 months then 2 drugs for 4 months
RIPE therapy pearls
R
ifampin - turns fluids orange/red, strong inducer, hemolytic anemia, flu-like syndrome, hepatotoxicity
I
soniazid - peripheral neuropathy (take with B6/pyridoxine to decrease), hepatotoxicity, DILE, hemolytic anemia
P
yrazinamide - hyperuricemia/gout, h
opportunistic infections: CD4+ < 200
PCP: Bactrim prophylaxis
alternative: dapsone or dapsone + pyrimethamine + leucovorin
until CD4 recovers to 200 for at least 3 months while on ART
opportunistic infections: CD4+ < 100
toxoplasmosis: Bactrim DS prophylaxis
alternative: dapsone + pyrimethamine + leucovorin
until CD4 recovers to 200 for at least 3 months on ART
opportunistic infections: CD4+ < 50
MAC: azithromycin (if not on ART)
Recommended initial HIV regimens
INSTI-based (preferred):
-Biktarvy
-Isentress + Truvada/Descovy
-Tivicay + Truvada/Descovy
-Triumeq
-Dovato (if VL <500,000, no HBV, genotype results)
Major safety issues of NNRTIs
hepatotoxicity and rash
, including SJS/TEN
-nevirapine > others
-monitor for erythema, facial edema, skin necrosis, blisters and tongue swelling
rilpivirine
: QT prolongation, depression and suicidality, take with full meal of ~500 kcals, no PPIs
efavire
Major safety issues of NRTIs
warning for lactic acidosis and hepatomegaly with steatosis
-zidovudine, stavudine, didanosine > others
abacavir
: hypersensitivity reactions; test for HLA-B*5701; careful with CVD
tenofovir
: nephrotoxicity, osteoporosis, Fanconi syndrome
-less with TAF
Major safety issues of protease inhibitors
-metabolic abnormalities such as hyperlipidemia, lipohypertrophy (least with ATV, DRV), insulin resistance/hyperglycemia (highest with LPV/r and IDV)
-hepatotoxicity (highest with TPV)
-increased CVD risk (lowest with ATV, DRV)
-GI upset:
take with food
t
Major safety issues with INSTIs
-increased CPK, rhabdo (most with
RAL
)
-separate from polyvalent cations
-headaches, insomnia
Major safety issues with PK boosters
-lots of drug interactions (both strong inhibitors): 3A4 (both); 2C8, 2D6, 2C9, 2C19, P-gp (RTV)
-
contraindicated
with alfuzosin, amiodarone, carbamazepine, dronedarone, lova/simvastatin, rifampin, phenytoin, phenobarbital, St. John's wort
-must be taken
Drugs that can lower the seizure threshold
bupropion, clozapine, theophylline, varenicline, carbapenems (esp. imipenem), lithium, meperidine, penicillin, quinolones, tramadol
Drug references for Y-site compatibility
-ASHP's Handbook on Injectable Drugs/Trissel's
-King Guide to Parenteral Admixtures
-general: Micromedex, Lexicomp, Clinical Pharmacology
-Pharmacy Practice News
-Hospital Pharmacy
Drug references for Pregnancy and Lactation
-Briggs'
-CDC
-Hale's
-LactMed: NLM TOXNET
-Reprotox and Reprorisk: Micromedex
-MotherToBaby
Drug references for Pediatrics
-NeoFax and Pediatrics: Micromedex
-Lexicomp
-Red Book (AAP)
-Harriet Lane Handbook
-American Academy of Pediatrics
-ASHP's Pediatric Injectable Drugs (The Teddy Bear Book)
-Nelson Textbook of Pediatrics
Reputable consumer drug resources
-Drugs.com
-CDC
-FDA For Consumers
-US Dept of Health and Human Services (healthfinder.gov)
-Mayo Clinic
-MedlinePlus: NLM
-SafeMedication
-WebMD
-Traveler's Health
Chronic seizure drugs: major side effects
-
bone loss
- all AEDs; take Ca + Vit D
-
serious rash
- lamotrigine, carbamazepine (& cousins), ethosuximide
-
fetal harm
- carbamazepine, phenytoin, topiramate, valproic acid, phenobarbital
-
alopecia
- lamotrigine, valproic acid (Se + Zn)
-hepatotoxici
Hypertension: when to treat?
-Stage 1 (130-139 SBP or 80-89 DBP)
with
Clinical CVD or ASCVD risk 10% or greater
-Stage 2 (>/= 140/90)
-Pregnancy SBP 160+ or DBP 105+ chronically
Initial drug selection in hypertension
-Non-black: thiazide, CCB, ACE inhibitor or ARB
-black: CCB or thiazide
-CKD (all races): ACE inhibitor or ARB
-Diabetes
+ albuminuria
(all races): ACE inhibitor or ARB
-Start
2 drugs
in Stage 2 if average BP
>150/90
-Pregnancy: labetalol, nifedipine ER,
Thiazides key features
-contraindicated with sulfa allergy
-side effects:
decrease
K, Mag, sodium;
increase
calcium, uric acid, blood glucose, LDL, triglycerides
-not effective if CrCl < 30 (except metolazone)
-drug interactions: NSAIDs, lithium
-max HCTZ 50 mg, chlorthalidone
DHP Calcium Channel Blockers (CCBs) key features
-vasodilatory side effects (reflex tachycardia, flushing, headache, peripheral edema)
-gingival hyperplasia
-CYP3A4 drug interactions
-do not use nifedipine IR
-ghost tablet: Procardia XL, Adalat CC
-safe/preferred for heart failure: amlodipine or felodip
Non-DHP calcium channel blockers key features
-bradycardia, constipation, edema
-AVOID in heart failure (decreased cardiac output)
-CYP3A4 drug interactions
-gingival hyperplasia
ACE inhibitors and ARBs key features
-contraindications: angioedema, bilateral renal artery stenosis, pregnancy, ACE inhibitors within 36 hours of Entresto
-side effects: cough (ACEi), hyperkalemia, renal impairment
-olmesartan: sprue-like enteropathy
-drug interactions: lithium
Beta blockers key features
-not first line unless heart failure, MI, or ischemic heart disease
-common side effects: bradycardia, fatigue, dizziness, depression
-metoprolol tartrate IV:PO = 1:2.5
Centrally acting alpha-2 agonists key features
-side effects: dry mouth, somnolence, fatigue, dizziness, constipation, bradycardia, hypotension
-clonidine patch: weekly, remove before MRI, skin rash, pruritis, erythema
-warning: do not stop abruptly (rebound HTN), taper gradually over 2-4 days
-methyl
Drug-induced causes of heart failure
(DI NATION)
D
PP-4 inhibitors (alogliptin, saxagliptin)
I
mmunosuppressants (TNF inhibitors-etanercept, rituximab; interferons)
N
on-DHP CCBs
A
ntiarrhythmics (Class I: procainamide, quinidine, flecainide)
T
hiazolidinediones
I
traconazole
O
ncology agent
Loop diuretics key features
-for fluid overload, no mortality benefit in HF
-work in the thick ascending limb of the Loop of Henle
-sulfa allergy: choose ethacrynic acid
-ototoxicity, calcium-wasting (monitor long-term), decreases K, Na, Mg, Cl, Ca, increases uric acid, bicarb, bloo
digoxin key features
-for symptoms and morbidity, but not mortality
-therapeutic range for HF: 0.5-0.9 ng/mL (AFib is 0.8-2)
-renal clearance
-initial signs of toxicity:
nausea, vomiting, loss of appetite, bradycardia
-severe toxicity: yellow-green vision, halos, confusion, d
Who gets a high-intensity statin?
-Clinical ASCVD (ACS/MI, angina/SIHD, revascularization, stroke/TIA, PAD)
-LDL 190 or greater
-10-year ASCVD risk 20% or greater
-Diabetes at high risk
High-intensity statins:
atorvastatin 40-80 mg
rosuvastatin 20-40 mg
Who gets a moderate-intensity statin?
-any patient with diabetes
-10-year ASCVD risk 7.5-19%
Moderate intensity statins: atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, pravastatin 40-80 mg, lovastatin 40 mg
What are the statin equivalent doses?
(Pharmacists Rock At Saving Lives and Preventing Fatty-deposits)
P
itavastatin 2 mg
R
osuvastatin 5 mg
At
orvastatin 10 mg
S
imvastatin 20 mg
L
ovastatin 40 mg
Pr
avastatin 40 mg
F
luvastatin 80 mg
What increases the risk for rhabomyolysis with statins?
-simvastatin 80 mg
-statin + gemfibrozil
-statin + niacin 1 gram
-CYP3A4 drug interactions
How do you manage myalgias with statins?
-hold statin, check CPK, investigate other possible causes
-after 2-4 weeks: re-challenge with
same
statin at the same or decreased dose
-if myalgias return, discontinue and use a low dose of a different statin once symptoms resolve; gradually increase th
Max dose of simvastatin with dronedarone, verapamil, or diltiazem
10 mg
Max dose of simvastatin with amiodarone,
amlodipine
, lomitapide, or ranolazine
20 mg
amiodarone key features
-works on K-channels (primarily), sodium and calcium-channels, blocks alpha and beta receptors
-
boxed warnings
: pulmonary toxicity, hepatotoxicity, patients should be hospitalized when a loading dose is given
-
contraindications
: iodine hypersensitivit
amiodarone drug interactions
3A4, 2D6, 2C9, P-gp
-decrease digoxin by 50% and warfarin by 30-50% when starting amiodarone
-do not exceed 20 mg/day of simvastatin or 40 mg/day of lovastatin
-do not use with sofosbuvir (increased bradycardia)
-additive bradycardia with diltiazem, verap
Contraindications to alteplase in stroke
-active bleed (ICH, SAH, internal bleeding)
-head injury, intracranial or intraspinal surgery within the last 3 months
-aneurysm, AVM
-BP > 185/110
additional exclusion criteria:
-stroke within the past 3 months
-INR > 1.7
-aPTT > 40 seconds
-Platelets <1
Where in the coagulation cascade do anticoagulants work?
warfarin: inhibits factors VII, IX, X, and II
UFH: equal anti-Xa and anti-IIa
LMWH: anti-Xa > anti-IIa
DOACs, fondaparinux: Xa
DTIs: IIa
converting warfarin to DOACs
stop warfarin and convert to
R
ivaroxaban when INR < 3
E
doxaban with INR < 2.5
A
pixaban when INR < 2
D
abigatran when INR < 2
Who should you start warfarin at a dose of no more than 5 mg in?
-heart failure
-liver disease
-elderly
-malnutrition
-high risk of bleeding
warfarin drug interactions
2C9 (major), 1A2 (minor), 2C19 (minor), 3A4 (minor)
-major inhibitors that increase INR: Flagyl, amiodarone, azole antifungals, Bactrim, Fluoroquinolones, macrolides
-major inducers that decrease INR: rifampin, phenytoin, St. John's wort, phenobarbital
-a
Key drugs that cause hemolytic anemia
dapsone, methylene blue, primaquine, pegloticase, rasburicase, valproic acid
others: cephalosporins, penicillins, nitrofurantoin, levodopa, methyldopa, rifampin, quinine, quinidine
Cough and cold products should be avoided in
< 6 (AAP), < 4 (package labeling), < 2 (FDA)
avoid promethazine < 2 years
avoid topical menthol and camphor < 2 (package labeling)
codeine is contraindicated in
children < 12
< 18 after tonsillectomy
Drugs that can worsen BPH
anticholinergics, antihistamines, caffeine, decongestants, diuretics, SNRIs, TCAs, testosterone products