Week 1 Flashcards
Pediatric vital signs in comparison to adults
Newborn:
HR: ~120-160
RR: 30-50
BP: ~60/37
Infant (1-12 months)
HR: ~100-140
RR: 20-40
BP:~70-100/ 50-70
Temp:
Toddlers (1-3 years)
HR: 100-130
RR:20-30
BP: 80-110/50-70
Temp:
Preschooler (3-5 years)
HR: 80-120
RR:20-30
BP: ~95/70
Temp:
School Age (6-12)
HR: 70-110
RR: 20-25
BP:100-120/75
Temp:
Adolescent
HR: 60-100
RR: 12-20
BP:110-120/80
Temp:
Vital sign differences in peds vs adults
HR and RR are higher in peds than adults, lower and normalize when they become adult ages
BP is lower in peds than adults, increase as they get older
How to Assess pain in Peds patients
physiologic markers
*RR, HR, O2 sat, behvior (grimacing, highi pitched crying)
Standardized scales
children </4:
*neonate pain scale (NIPS)
*Face, Legs, Activity, Cry , Consolability (FLACC)
Children>4 y.o :
*wong baker FACES
Children >10 y.o:
*visual analog scale
*numeric pain scale
common caculations for peds
BSA:
BMI: (weight/height^2)x10000
IBW: (height^2)x1.65)/1000
***eGFR:
use bedside Schwartz equation in <18 y.o
[0.413xheight]/SCr
challenges in ped pharmacotherapy
PKPD differences
*drug sleection
*dosage
psychosocial influences on drug therapy
*child vs adolescent
caregiver mediation administraion hesitance
*cultural beliefs
*socioeconomic status
dosage formulation selections
off label medicaion use
what is off-label medication use
use of a medicationoutside of FDA approved labeled indication
only 1/4 fda approved drugs indicated for ped patients
limitations to off label drug usage
potential for denied insurance proider coverage
liability for adverse effects
limited experience in specific conditions or age gorups
limited available dosage formulations
evidence Considerations for off label med use
use guidelines (NAEPP and NHlbi when available
use of primary literatureis critical in providing evidence based care to infants, children and adolescents (most data fro retrospecive cohort studies
medication adherance reasons
apprehension regarding med AE
caregiver inability or unavailability to adminster drugs
caregivers may be overwhelmed confused
inappropriate measurements of medication dose
straegies to improve adherance in peds
educatin of caregiver at several points
ease of amdinistration (palatable dosage forms, less frequent dosing)
decreased child resistance (reward systems, positive reinforcement
empowering older children adolescents
Dosage form considerations
Parenteral
volume of iv fluids
(infants and newborns susceptible to volume overload) pick concentrated versions of doses
vehicle safety (ex: propylene glycol can ccumulate in newborns and infnts causing AE)
iv acces ( difficult to obtain and maintain in newborns and infants)
dosage form considerations
oral
manufactured liquid preparations
extemporaneously compounded liquid preparations
volume of po fluids
chewable tablets
tablets
capsules
granules
*make sure these solid dosage forms can be manipulated
dosage form considerations
palatbility
children have different preferences
mixing with food
*peanut butter
*crystal lite
flavoring
*flavor rx
Considerations for extemporaneous preparations
USP:water containing formulations prepared from solid ingredients should have a bud no later than 14 days when stored at cold temps
*ISMP: List of oral dosage forms that should not be crushed)
injectable solutions administered orally
*ok if both formulations (IV and PO) contain same salt form w. similar bioavailability
*ex: glycopyrrolate broide injection (adminstered PO)
determining pediatric dosages
ALWAYS ASK FOR WEIGHT
*max pediatric dose=adult dose
doses may be also based on gestational age, actual age, patient weight ranges
Assessment of kidney function in peds
calculate eGFR: bedside schwartz equation
Uurine output: reported ml/kg/day for intake
ml/kg/hr: for output
anuria: zero output
oligouria: <0.5-1mL/kg/hr
normal urine output: 1mL/kg/hr
polyuria= 4mL/kg/hr
Peds PK
Absorption-Oral
*most common route for drug delivery
*children will reject meds based on color, taste, texture, and temperature
taste:
birth: ability to detect sweet
by 2y.o: can detect bitter/salty/sour
by1-2 y.o: can detect texture and temp
smell: by 5-7 y.o: affective response to colors
Effects of gastric pH on oral absorption in peds
varies with growth.
after birth, ph in stomach is high (basic)
can effect acid labile medications (ex acid labile med such as PCN can have higher concentrations in newborns)
effects of gastric emptying on oral absorption in peds
increased gastric emptyingduring first week of life . increased drug delivery to site of absoprtion
frequency and amplitue of intstinal contractions reduced in newborns and young infant
*adult motility occurs by 6-8 mo.)
reduced gastirc eptying and poorly coordinated intestinal contractility = decreased rate of drug absoprtion
extra-oral routes of adminisration considerations
rectal: higher amplituse contractions in infants which expells drug. maydecrease drug absoprtion time. decreases bioavaiabilty
percutaneous: ;arger surface area per unit mass, greater degree of hydratation of skin, higher perfusion rates, enhanced drug permeability
IM: greater capillary densiy in young children compared to older childrn: greater iM bioavailability.
refresher on pka and ph
if drug is basic in a basic environment, the drug will notionize
if drug is basic in an acid environment, the drug will ionize
if drug is acid in an acidic environment, will not ionize
if drug is acid in a basic environment, drug will ionize
ped consdierationds for distribution
increased tbw in neonates (75-85% vs adults (55-60%)
extracellul;ar fluid is greater in neonates (35-45% vs adults (20%)
new borns have much less muscle fat.
overall, increase of vs for hydrophyllic drugs and decrease of vd for lipophyllic drugs
examples: AG’s are hydrophyllic drugs… so will need more drug to achieve same conc as adult.
neonates: 4-5 mg/kg/dose
infants: 2.5 mg/kg/dose
adults: 1-2.5 mg/kg/dose
protein binding and distribution
in new borns, decreased concentration of albumins and binding affinity of fetal albumin to substances…
increases the free fraction of drug, enhancing pharmacologic effects
also increases risk to adverse effects…
ex: ceftriaxone and sulfonamides in infants <2 months of age can displace bilirubin form fetal albumin,,, puts baby at risk for kernicterus (albumin deposits in the brain) can cause cell atrophy and neurologic damage.
drugs that may be affected: phenytoin which is 90-95% bound to albumin and tp range of 10-20
metabolism considerations in peds
hanges in phase 1 and phase 2 preesent in new borns in conmparison to adults
CYP3A4: doesnt reach adult acitivty levels until 1 year of age. causes decreased metabolism
CYP2C19: activity increased during first 6 months of life( ex PPIs may need to be given more frequently
CYP2E1: approx 80% of adult levels by year 1 of age
CYP1A2: absent in neonates, 25% pf adult levels by year 1, 55% of adult levels by year 9
UGT: in children <12 years of age, less susceptable to APAP toxicity due to use of sulfation pathway for metabolism into nontoxic metabolite instead of just saturating regular glucuronic pathway
elimination considerations in peds
nephrogenesis completes by 26 weeks
decreased renal blood flow, leads to decreased substrate delivery to kidneys
decreased gfr
decreased tubular secretions
overall causes lower clearance of drugs and longer half lives. drugs can be given at longer dosing intervals, or less frequently.
ex: fluconazole t1/2 in prematur infants: =88 hrs
t1/2 in full term is less
challenges peds pts face for drug deliuvery and dosage forms
nay require manipulation form tailored to ability to swallow
may require dosage forms tailed to smaller dose
may require alteration sin stability
may not be palatable
considerations for enteral formulation use
tablets
is manipulation feasble or alters med delivery
is it extended relewase? can it be split
considerations forenteral formulations
capsules
must determine contents
ex: powder, beads, enteric coating, gel capsules
considerations for eneteral formulations
liquid dosage forms: pros and cons
most used dosage form in children
pros: dose flexibility
easy to swallow
cons: lack of controlled release mechanisms
volume required
accuracy of measuring devices
challenges: not all meds have commercially available suspensions, single concentrations vs extemporaneous compounds
additional enteral formulation sthat are ideal but not perfect in peda
chewable tabs: pro minimizes need for additional liquids
con: relies on ability to chew
minitablets: eases swallowing tabs
con: limited dosage flexibility
ODT:L quick dissolve
orodispersible films (ODFs)
powder packets
sprinkle capsules/granules
Special considerations for enteral formulations in peds
palability!!!
depends on preferences of the individual pt
manipulation can change taste
flavor rx: commercially available
- admin via tube
*ex: gtube, jtube, ngtube, ndtube
what is the site of absorption of the drug, can medication contact plastic?
will med clog the tube (
parenteral formulations used in peds
IV administration
allows for immediate entry into bloodstream
most common parenteral admin used
parenteral formulations used in peds
IM or SQ
muscle and fat mass are factors affecting utility
can be used in ana emergency or for single med asmin such a svaccines
limitations exist related to volume allowed per injection based on age
additonal considerations for parenteral formulations
volume is a common challenge: is dose measurable ?
IV access-central vs peripheral vs number of lines available
other formulations that pose challenges in peds
inhalation: devices designed for adults
nebulizers preffered but cumbersome and require additonal education
nasal: devices designed for adults
difficult to admin based on age
rectal: lmited dosage forms, neonates/infants size restrictions, increased stool count
topical:
need to consider BSA ratio, potential for systemic absorption
transdermal:
lmited dosage forms
ability to cut/cover
age restrictions
behavior
risiks associated w. excipiennts
benzoyl alcohol
role as excipient:
effects:
example:
risiks associated w. excipiennts
role as excipient: preservative, to protect microbial contamination
effects:neurotoxicity and metabolic acidosis, especially in concerning neonatal population
example: IV lorazepam (2% benzoyl alcohol)
risiks associated w. excipiennts
ehtNOL
role as excipient:
effects:
example:
risiks associated w. excipiennts
role as excipient: solvent
effects: neurotoxicity
example: dexamethasone intensol solution (30%) alcohol
risiks associated w. excipiennts
polysorbate
role as excipient:
effects:
example:
risiks associated w. excipiennts
role as excipient: surfactant, increases solubility of one agent w. another agent
effects: liver and kidney failure, thrombocytopenia, ascites, and pulmonary deterioration
example: IV amiodarone (PS80 300mg and PS20 20mg)
BUD Dating of extemporaneous compounding in peds
USP 795
non preserved aqueous dosage forms: 14 days in fridge
preserved acquous dosage forms: 35
risiks associated w. excipiennts
propylene glycol
role as excipient:
effects:
example:
risiks associated w. excipiennts
role as excipient: solvent
effects:seizures, hyperosmorality, metabolic acidosis, and neurotoxicity
example:IV phenobarbitol (67.8% propylene glycol)
other ocmpounded preparations benficial for peds pts
powder papers (used crushed tablets, may or may not need filter
injectable meds used as oral solution (ph dependent)
oral suspensio: when not commercially available. can use crushed tablets, bulk powders, or filled capsules. need to avoid using extended release products, hard geletin capsules, or capsules w. time released beads
risiks associated w. excipiennts
Sorbitol
role as excipient:
effects:
example:
risiks associated w. excipiennts
role as excipient: sweetner, to mask taste and palatability
effects:seizures, hyperosmorality, metabolic can lead to osmotic diarrhea
example:loperamide
age ranges
neonate: birth -30 days old
infant: 1mo-1yr
child: 1-12 y.o
adolescent: 12-18 years old
neonatal dosing
gestational age: “how for along in pregnancy
post -natal age: chronilogical age, time in days, weeks, months from birth
post menstrual age: combo of GA and PNA
important eq for peds
weight ocnversion: 1kg=2.205 lbs
1 inch=2.54 cm
bsa
m^2=(weightxheight/3600)^1/2
commonly used components of a drug monograph
dosing section: recommendations
preparation for administration
*info on concentrations and appropriate diluents for reconstitution/dilution of parenteral meds
administration:
*instructions for mixing w. food, missed doses, parenteral info
adverse reactions
extemporaneous compiunding: if applicable, provided published reference for compounding recommendations into oral solution/suspension from tabs or capsules
PK/moa
dosage forms, US and canada : shows available products on market, brand name and generic strengths availability
