Exam 4 - Peds, Gers, & Rx Writing Flashcards
Gestational Age
- Maturity at birth
- Based on dates (LMP) and PE
Postnatal Age
-Chronologic age of child after its born
Post conception age:
-Gestational age and post natal age
Preterm infant
< 37 weeks GA
Full-term infant
37-42 weeks GA
Post-term infant
> 43 weeks GA
Newborn or neonate
0 to 1 month of age
First month of life
Infant
1-12 month of age
Toddler
1 -2 years of age
Young child
2 - 5 years of age
Older child
6 - 12 years of age
Adolescent
13 - 17 years of age
Absorption
- Molecular weight
- Particle size
- pH and pKa
- Dosage form (Need to be able to tolerate).
Two major determinants of gastrointestinal absorption of drugs:
- Gastric acidity
- Gastric emptying time
Differ greatly between infants and adults
pH dependent passive diffusion:
-Nonpolar, lipophillic states are better absorbed
↑ pH in pre-term infant compared to term infants; not producing as much acid yet.
↑ Gastric acid production with ↑ GA (lowers pH - acidic).
Gastric pH: 6-8 in full-term infant for 1-3 days (amniotic fluid).
Highest acid: 1-10 days
Lowest acid: 10-30 days
Lower limit of adult values by 3 months!
Effects drug absorption: Acidic/Basic
Acidic drugs Increased ionization (more polar), which decreases absorption.
Basic drugs
Decreased ionization, will have increased absorption.
Gastrointestinal emptying time (GIT):
-GIT determines rate of absorption; much slower in infants less than 6 mos of age.
Congenital heart disease = ↓ blood flow = ↓ GIT.
Type of feeding
Gestational and postnatal age(more preterm = slower gastric emptying time).
How does a shorter gut in a neonate/infant affect absorption?
-Shorter transit time decreases duration of drug contact with absorptive surfaces!
- Extended release formulations are incompletely absorbed!
- Leads to serum concentration variations
Intramuscular Absorption
Often easier than IV access in infants/neonates.
Blood perfusion to the area of injection
Rate of drug penetration through the capillaries
Apparent volume into which the drug has been distributed
Neonates and infants differ from older children and adults:
- ↓ blood flow to muscles
- ↓ extent of muscular contractions
- ↓ rate of drug penetration
- ↑ percent of water in muscles (high apparent volume of distribution due to high body water)
- Peripheral vasomotor instability - Can’t regulate temperature well (blood flow is erratic).
Rectal absorption in infants/neonates:
- ↑ bioavailability of some medications (thin mucosa).
- ↑ mucosal translocation.
- Neonates/children have ↑ amplitude of rectal contractions
- Can cause suppositories to be pooped back out (re-dose if happens).
Intraosseus absorption in infants/neonates:
-Useful in emergent situations
- Performed by inserting an intraosseous needle into bone marrow
- Children have soft outer cortex of long bones with rich vascular bed of marrow
- Full drug absorption
- Easy administration - can do fluids, pressors, abx.
Percutaneous absorption in infants/neonates:
- Children have underdeveloped stratum corneum; the skin thickness is inversely related to absorption.
- Ex: Hypothyroidism from betadine (iodine).
- Skin is well hydrated with ↑ perfusion.
- Skin hydration directly proportional to absorption.
- Ratio of body surface area (BSA) to body mass is significantly ↑ compared with adults.
- May result in toxicity of topically applied drugs.
- Seizures and anticholinergic toxidromes from antihistamine lotions
- Hypoglycemia and lethargy from isopropanol baths
Volume of distribution (Vd)
- Relates amount of drug in body to serum concentration.
- Adipose tissue, lipophillic drug, has a large volume of distribution.
Vd = X0/C0
X0 = dose administered C0 = initial serum concentration
Hydrophillic - low volume of distribution, can’t distribute into fat, etc.
General factors affecting Vd:
-The more lipid soluble, the higher the volume of distribution.
- Plasma protein binding (i.e. Albumin; doesn’t distribute far from blood stream, low VOD).
- Tissue binding (Increases in VOD).
Disease state conditions affecting Vd:
-Critically ill states (e.g., burn victims/edema)
Distribution in newborn infant:
- Water 70 – 75% of the body weight
- High extracellular water component
40% in infants vs. 20% in adults
- Less fat tissue
- Less muscle tissue
-Results in increased Vd for hydrophilic medications
“The Pediatric Bucket”
In order to get a similar blood concentration of drug in hydrophilic medications, pediatrics require HIGHER mg/kg dose than adults.
Why? Bc they have a higher water volume.
Gentamicin
Used for neonatal sepsis
Neonates have higher body water; goes down as you get older and have more fat tissue.
Dose:
- Neonate: 4-5 mg/kg (high)
- Infants/Children: 2.5-3 mg/kg
- Adults: 1-2 mg/kg
Plasma proteins:
Neonates:
↓ plasma proteins
↓ protein binding/lower protein stores
Compounds that compete for protein binding; i.e. Bilirubin and Rocephin.
Examples:
Phenytoin (used for seizures)
-Decreased protein binding results in higher free fraction of drugs.
-Free levels are higher than you expect without protein binding, which leads to TOXICITY.
Why can’t Rocephin be given to neonates?
JAUNDICE
Displaces bilirubin from protein binding sites.
Albumin
Albumin
- Reduced in neonate
- Infants near adults
- Children near adults
Neonates have higher free drug, less protein binding.
Bilirubin
Bilirubin
- Increased in neonate
- Infants/children normal
Which is why you won’t see reactions with ceftriaxone after neonatal period
What factors alter drug metabolism in neonates/children?
↑ GA & postnatal age: more mature, able to metabolize drugs.
Changes in hepatic blood flow
↑ size of the liver
↑ in quantity & quality of hepatic enzymes
Phase 1 Reactions
Net effect: Add sulfur, hydroxyl, carboxyl, or amino group to make water soluble compounds
- To be excreted by bile, lungs, & kidneys
- Prepare for Phase 2
Cytochrome (CYP) P450 mixed-oxidative system is most important pathway in Phase 1.
What are the other specific pathways?
CYP450 activity of full-term infants is approx. HALF of that of adults.
- Oxidation: example phenytoin. By 1 year of age postnatal activity increases to 2-5 times that of an adult. Metabolize phenytoin more quickly.
- Reduction: example chloral hydrate
- Hydrolysis: example procaine/tetracaine. Less metabolism, bc hepatic and plasma esterase activity are reduced in infants.
- Demethylation: example theophylline
CYP450
CYP2E1?
CYP2D6?
CYP2C?
CYP3A4?
Within hours after birth CYP2E1 activity increases rapidly. CYP2D6 is detectable soon after.
CYP2C and 3A4 are present within first month.
CYP3A4 activity in young infants may exceed adult levels
Phase 2 Reactions
Net effect: Addition of endogenous chemical groups to drugs
Excreted by bile or kidneys
Sulfation
- Ex: acetaminophen
- Well developed/functional pathway at birth
Methylation
- Ex: epinephrine
- Well developed/functional pathway at birth
- Not significantly utilized in hepatic metabolism of drugs in adults
Glucuronide conjugation
-Ex: morphine, chloramphenicol
-Undeveloped conjugation at birth (longer duration of activity -
high risk of toxicity), mature around 3 years of age
Glycine conjugation
- Ex: benzyl alcohol (preservative)
- Cannot conjugate it; will get toxic build up.
- Neonatal Gaffing? Syndrome
Excretion of drugs:
GFR in infants?
Preterm infants?
-Most drugs are renally excreted
GFR & infants:
- ↑ serum creatinine (SrCr) for 1st week of life (Detecting what mom’s was).
- Renal function ↑ during 1-2 wks of life
Pre-term infants have ↓ GFR:
- Immature quality & quantity of glomeruli
- Immature proximal tubules
- Reduced renal blood flow
Measure urine output to see how kidneys are functioning.
1ml/kg/hr = Normal; less we are concerned.
6 months of age, they’ll have normal kidney function. 100ml/min.
How does GFR affect half life of gentamicin?
Gentamicin
- Eliminated through kidneys
- Drugs have longer half-life
- Takes longer to clear through their kidneys
Preterm babies will take longer to clear it; need to adjust dose accordingly.
Neonate < 1 wk, 3-11.5 hrs 1wk to 1mo 3-6 hrs Infant 4 hrs *Declines as kidneys develop. *Dose based on gestational age
Ex: Neonate 0-28 days
< 36 wks, every 48hrs.
> 36 wks, every 24hrs.
Tubular secretion & reabsorption
-Both are significantly ↓ in 1st year of life
General concerns with renal tubular development:
↓ renal blood flow
↓ ability to concentrate urine in kidney
Low urinary pH values
Low urine pH will be acidic to reabsorb acidic meds (aspirin, phenobarb) - increases half-life
How do pharmacogenetics affect codeine metabolism?
-CYP2D6: converts codeine to morphine (active form)
- Poor CYP2D6: slow metabolizer, less effective drug
- Ultra CYP2D6: convert a lot, drug is more effective
- Mother (exaggerated response)
- Child (exaggerated or diminished response)
- Black box warning: Death Related to Ultra-Rapid Metabolism of Codeine to Morphine.
- Respiratory depression and death have occurred in children who received codeine post-tonsillectomy and/or adenoidectomy and were ultra-rapid CYP2D6 metabolizers.
Aged-Based Dosing Regimens
- Advantage: Easy to use in practice
- Disadvantage: Assumes maturation of ADME principles is “equal” in all patients; can cause under/overdose.
Body weight dosing regimens:
What are the advantages?
Need to know how to dose pediatrics patients on exam
Neonates/infants: 20-30 mg/kg/day PO divided q 12 h
Infants > 3 mo/children: 25-50 mg/kg/day PO divided q 8-12 h
Adults: 200-500 mg PO q 8 h
Advantage:
- MOST COMMON dosing scheme utilized
- Children have ↑ med clearance based on weight.
If you have a large child whose dose is calculated greater than adult dose (500mg), how do you treat them?
Cap dose at the adult dose: 500mg.
What are disadvantages of dosing via body weight of child?
Disadvantages
- Potential for over-dosing or under-dosing in overweight children
- ↑ incidence of overweight children (1/3)
Body Surface Area Dosing:
Ex: corticotropin—150 mg/m2 IM divided bid
Advantage:
- More precise for meds requiring calculations
- Limits potential for OD based on weight
Disadvantage:
- Difficult to estimate length, height in children (contractures)
- Numerous BSA calculations
Intravenous Drug Administration
- Difficult to get access
- Volume - Give drug as concentrated as possible; prevents fluid shift.
-Multiple drugs & frequency
- Intraosseous access easiest in emergencies.
- Therapeutic drug monitoring (e.g. drug sampling) - Blood can affect hemoglobin, so get as many labs as possible from one sample.
IV admin: important to use?
Syringe pumps, to make sure you’re infusing right amount into patient.
Rapid infusions can cause pulmonary edema, this is controlled in pumps to prevent.
Oral Administration
- Need accurate measuring devices
- Dosage forms: tablets or liquids; suppositories used in infants.
- Sensory appeal (gross tasting)
- Drug-food interactions
- Inactive ingredient (lactose, dyes, etc).
How do you prescribe medications to pediatric patients?
- Obtain current weight
- Check dose with available references
Consider counseling points with children:
- Provide child specific language if needed
- Provide counseling to older children/guardians
Drug Dosing
IMPORTANT
IMPORTANT
IMPORTANT
15 kg child requires amoxicillin for acute otitis media
90 mg/kg/day divided BID
Amoxicillin suspension: 400 mg/5 mL (5 mL = tsp).
How much should this child receive per dose?
Dose per day = 15 kg x 90 mg/kg/day = 1350 mg/day
1350 mg/day divided BID = 675 mg/dose
Convert to volume:
400 mg/5 mL = 80 mg/mL
675 mg/dose ÷ 80 mg/mL = 8.4 mL/dose
18 kg patient needs ranitidine for GERD symptoms
4 mg/kg/day divided BID
Ranitidine syrup= 15 mg/mL
How much should they receive per dose?
18kg * 4mg/kg/day = 72mg/day
72mg/day / BID = 36mg/dose
36mg/dose divided by 15mg/mL
2.4mL BID (round to 2.5mL)
12 kg patient is receiving trimethoprim/sulfamethoxazole for cellulitis
4 mg TMP/kg/dose BID
Suspension: sulfamethoxazole 200 mg and trimethoprim 40 mg/5 mL
How much should this child receive?
12kg * 4mg TMP/kg/dose = 48mg/dose given BID
40/5 = 8mg/mL
48mg TMP / 8 = 6mL
6mL in AM and PM
20 kg child is receiving 2 tsp acetaminophen 4 times a day for fever
Usual dose 15 mg/kg/dose
Acetaminophen suspension: 160 mg/5 mL
Is this child being dosed appropriately?
160mg/5ml = 32mg/ml
2 * 5 ml = 10mL QID
32mg/mL * 10mL = 320mg per dose
320mg /20kg = 16mg/kg
He’s getting 1mg extra per dose. Should be getting 15mg/kg/dose.
What’s the measurement for a fluid bolus?
Fluid bolus: 20 mL/kg
Maintenance IV Fluid Calculations
4:2:1 Rule
4 mL/kg/hr for the first 10 kg
2 mL/kg/hr for the second10 kg
1 mL/kg/hr for every subsequent kg
Bolus and Maintenance fluid rates for: 8 kg infant 1200 g neonate 45 kg adolescent 100 kg teenager
Bolus: 160mL, 24mL , 900mL, 2000mL (give 1L and see how he does before giving 2L).
Maintenance: 32mL/hr, 4.8mL/hr, 85mL/hr, 140mL/hr
A 24 kg patient is receiving lidocaine 1% solution for intradermally for a laceration to the face.
The max dose the patient can receive is 5 mg/kg at one time.
How many mL can this patient receive?
5mg/kg * 24kg = 120mg
MAX DOSE
1% = 10mg/mL 2% = 20mg/mL
120mg / 10mg/mL = 12 mL injected before toxicity
GERIATRICS
Geriatric: 65 years of age or older
US life expectancy – 79 y/o
Comprehensive Geriatric Assessment (CGA)
Focuses on elderly individuals with complex problems
It emphasizes functional status and quality of life. Assess psychosocial, medical, and functional capabilities and limitations.
- Basic ADLs
- Intermediate ADLs - taking meds by themselves
- Advanced ADLs - volunteering at hospital
Nutritional Assessment
Decreased appetite
- Loneliness, depression, medications, ill-fitting dentures
- Constipation, CHF, cancer
- Finance
- Unable to prep meals
Supplements
-Recall food, drinks, vitamins, or supplements in last 24 hrs and amount.
- Eat varied foods, vegetables, milk, fruits
- Balanced diet
- Drinks of beer, liquor, or wine daily
- Takes 3 or more Rx or OTC drugs per day
- Has lost 10 lbs without trying over the last 6 months
Ginseng
Ginseng has anticoagulants on top of warfarin, patient had massive head bleed and died from it.
Lab tests in CGA:
CMP – kidney, liver, electrolytes, fasting glucose, protein (albumin), and acid/base balance
Renal function: (Albumin, BUN/Creatinine Ratio [calculated], Calcium, Carbon Dioxide, Creatinine, Estimated Glomerular Filtration Rate [calculated], Glucose, Phosphate [as Phosphorus, Potassium, Sodium, Urea Nitrogen)
Liver function: (Total Protein, Albumin, Total Bilirubin, Direct Bilirubin, Alkaline Phosphatase, AST, ALT) Serum cholesterol/lipid panel A1C CBC - Hemoglobin/hematocrit/WBC/plt Vitamin B12 levels UA
Polypharmacy
Polypharmacy – the use of five or more regular medications
Reasons
- Longer life expectancy
- Increase chronic diseases
- Evidence-based clinical practice guidelines (EB CPG)
Polypharmacy causes:
Age and Co-morbidity 8% increase in number of medications with each additional disease
Example: pt w/ osteoporosis, osteoarthritis, T2DM, HTN, & COPD – 12 different medications at 5 different times per day.
- Evidence-based guidelines
- Hospitalizations: 57.4% of pts were prescribed more Rx on discharge than they were on prior to admission
Consequences of polypharmacy
- ADR
- Falls - sedation, hypotension, lightheaded, decreased alertness
- Decreased compliance
Why do patients have decreased compliance?
Complex dosing schedule
Multiple medications
Economics – cost of Rx
Lack of Support (formal or informal) – someone to ensure they take the Rx
Mental decline – can’t remember right drug/time
Visual impairment – can’t see right drug or dose
Decreased swallowing ability
Decreased venous access – IV dose
Pt willingness to adhere to treatment
End of life
Pts have less than 6 months to live; when treating those over 65y/o, tailor to patient’s goals.
Cardiac age related changes
- Higher systolic arterial pressure
- Impedance to left ventricular ejection
- Reduced heart rate
Renal age related changes
- Decrease renal mass
- Reduced blood flow to the afferent artery
- Decline in glomerular filtration rate (GFR)
- Decrease ability to maintain acid-base balance
GI age related changes
- Decrease hydrochloric acid and pepsin; decreased gastric emptying
- Small intestine – decreased absorption
- Colon – decreased motility
- Pancreas – decrease lipase and trypsin
- Liver – decreased blood flow, metabolism, elimination, and liver mass(size)
PK age-related changes
Absorption
Drug distribution
Protein binding
Absorption
- Dietary changes, increased OTC meds (laxatives, antacids)
- Impaired gastric emptying (diabetics)
Drug distribution
- Reduced lean body mass (muscle decrease, fat increase)
- Reduced body water
Protein binding
- Decreases in serum albumin, less drug binding so higher free fraction
- Increase in α-acid glycoprotein
Geriatric drug clearance - kidney
- Reduced renal function
- Increase in serum creatinine not proportional to decrease in creatinine clearance
- Less muscle mass in old age
- Prolonged half-life of drugs
- Increased risk of toxic concentrations
- Affected by hydration status
Creatinine Clearance
Cockcroft-Gault equation
CrCl = (140-age) * (weight in kg)
-THEN DIVIDED BY 72*SCr
-Multiply by 0.85 for women
MDRD equation better for older patients.
Creatinine = 0.8
When estimating renal function > 70yo, if Cr < 1.0, round up to one anyway
Do not want to over estimate their renal function.
PK age-related changes
Drug Clerance
First pass metabolism
Phase 1 and 2
- Drug clearance – liver (capacity of the liver to extract drug from the blood based on hepatic blood flow)
- First-pass metabolism and bioavailability
- Decreased function of phase I reactions (CYP450)
- Minimal changes in phase II reactions
- Decreased metabolism due to impaired liver blood flow
Are geriatric patients more “sensitive?”
Can’t eliminate as well, etc.
Can’t compensate for changes in BP, poor homeostatic response
May change pattern or intensity of drug response
-CO, postural hypotension, temperature, FBG
SPECIFIC DRUG CLASSES
…
Sedative hypnotic agents
- CNS depression: causes ataxia, falls, altered mental status
- Half-life increased 50-150%
- Accumulate metabolites (altazepram)
Analgesics - opioids
- Susceptible to respiratory depression, esp with OSA, COPD, obese
- Accumulation of metabolites
What dont you use on geriatrics?
DRUGS WITH METABOLITSE
Lithium
- Decreased clearance with renal function
- Concomitant diuretics can increase accumulation
Antidepressants
Older agents put patients at risk for altered mentation and falls
Newer agents (selective serotonin reuptake inhibitors, SSRIs) are much safer
Prevent sedative ones, avoid MAOI and TCA - hypotension, sedation, altered mental status
Antihypertensives
- increased risk orthostatic hypotension
- electrolyte imbalance from diuretics, can affect arrythmias
antiarrythmics
- poor hemodynamic reserve
- electrolyte imblance
-Extended half life of quinidine, procrainamide, lidocaine
more likely to see toxicity with them
Tecasin
Class 3 antiarrythmic
Mg, K levels need to be normal or leads to TORSADES
ADR probability
single med = 10%
10 meds = 100%
Patients may not recognize drug prodts as medicine:
BC powders “Goody’s”
RX WRITING
…
Prescription
Prescription = written, verbal, or electronic order from a practitioner to be fulfilled by a pharmacist, lab, etc.
Prescribing practitioners MDs, DO PA, ARNP Podiatrist Veterinarian Optometrist
State vs. Federal laws
Go with whichever is stricter
If not addressed in state law, follow federal law
State: OK to marijuana
Feds can shut down at any time
If not addressed in state law, follow federal law
Prescription Requirements
Basic requirements (non-controlled substances)
If written or typed, must be LEGIBLE
- Name of practitioner
- Name and strength of drug prescribed
- Quantity of drug to dispense
- Directions for use
- Must be dated
- Signed by prescriber on date issued
Rules
-No pre-signing prescriptions
- Scripts can be called in or communicated electronically
- Must be reduced to written Rx if called in
-All prescriptions are only good for one year (at most)
Can you write more than one med on a script?
-Multiple non-controlled orders may go on the same prescription
- Keep controlled substances SEPARATED
- CII must be by themselves
According to FL statute for non-controlled prescriptions, ____ is not required on script:
Name
Date of birth
Not on FL statute
Indications preferred
How long does a script last?
365 days
FL LAW
Automatically dispenses a generic unless script says
“Dispense as written”
Additional requirements for controlled substances
- Name AND full address of the patient (or owner of the animal)
- If for an animal, the SPECIES must be specified
- Full name and address of the prescribing practitioner along with DEA number
- Written and numerical quantity to dispense
40 (forty)
Schedule II substances
Must be written/typed - No electronic or verbal transmittal!!!! C2
No refills – may be written up to 90 days worth or as 3 different prescriptions to be filled on different dates.
Must be HAND-signed by provider. NO EXCEPTIONS.
Schedule III-V
III-IV: May only have 5 refills (total of 6 months after Rx written).
May be communicated by phone or facsimile
- benzos, seizure meds
Counterfeit Proof Paper
- Produced by specific vendors
- Must be used for controlled substances not electronically transmitted.
- Must be hand signed by provider
- Photocopy = VOID
How to keep the pharmacist from calling you… :)
Include strength and dosage forms
Don’t write in teaspoon or tablespoon. Use mL only.
Avoid trailing zeros - 5.0 mg read as 50.
Always use leading zeros .1 misread as 1.
How to keep the pharmacist from calling you… :)
Include quantity of drug
Make sure quantity makes sense based on what’s prescribed (tabs, caps, etc. per day x treatment days)
If you want brand name, must write DAW = Dispense as written
Pharmacies will automatically substitute if possible
phone calllllls
Include indications
Clarifies instructions for pharmacists. Clarifies instructions for patients.
Review patient’s med profile to make sure there are no:
- Antagonistic combinations
- Duplicate therapies
- Allergies
- Make sure things are legible
- Write within your scope of practice
- Dermatologist writing for ADHD meds
