Neonatal Pharm Flashcards
Gestational Age
Definition
3 ways to determine GA
Estimated time since conception
- LMP
- Early ultrasound
- Dubowitz/Ballard – done within first 48 hour
Corrected Age
(actual age – weeks premature = Corrected age)
Helps anticipate complications and expectations
General Principles for Pharm (2)
Age – consider GA and PMA
Weight – update weekly (if not daily)
Normal weight gain
20-40grams/day in first 6 months
Enteral absorption
pH affects gastric absorption
o pH approaches neutrality at birth
o Highest gastric pH within first 1-10 days
o Lowest gastric pH within first 10-30 days
o Gastric secretion approaches lower limit of adult values by 3 months of age
o Better absorption of weak bases (Penicillin, ampicillin, erythromycin)
o Poor absorption of weak acids (Phenytoin, phenobarbital)
Enteral Absorption
Decreased Intestinal Motility
(3)
o Possible increase absorption of drugs absorbed in the stomach
o Delayed absorption of drugs absorbed in small intestine
o Gastric emptying normalizes quickly but intestinal emptying lags behind until 4-6 months of age
Enteral Absorption
Pancreatic Enzyme Activity (2)
- Important for meds that require cleavage from its salt form prior to absorption (clindamycin)
- Absorption is highly variable during the first 3 months of life
Enteral Absorption
Preemies should be receiving ½ of total fluid intake enterally before PO meds are introduced (2) WHY?
- Indicates GI function = tolerating feeds
- Provides diluent and buffer for medications
Intramuscular absorption (5)
- Pain
- Low blood flow/supply Slower absorption rates
- Decreased muscle mass in newborns (especially preemies)
- Immobility
- Volume of administration reserved for emergencies or situations in which slower absorption is desired and /or safer (ie-vitamin K at birth)
Absorption
Increased topical absorption (5)
o Increased skin hydration
o Low fat stores
o Immature epidermis (thinner stratum corneum)
o Increased risk of toxicity (povidone iodine)
o Sensitive to environmental changes
Absorption
Rectal (2)
o Useful for N/V, induction of anesthesia, status epilepticus
o Avoids first pass effect
Distribution
Volume of distribution (2)
o Hydrophilic drugs (vanco, gentamicin) are confined to extracellular fluid or total body water (low Vd)
o Lipophilic drug (digoxin) widely distribute to all tissues (large Vd)
Distribution
Volume of distribution in neonates (7)
- Increased total body water (85% vs 50%) – may need higher doses (mg/kg) to achieve same outcome
- Increased extracellular water (40% vs 20%)
- Decreased fat in neonates/infants
- Lipophilic drugs (digoxin) may have lower Vd
o 1% in 29 week preterm neonate
o 12%-16% in full term neonate
o 2-%-25% at 1 year of age
Distribution
Decreased protein binding (2)
o Decreased albumin and decreased affinity for drug binding
o Therefore – increased free drug
Albumin bound meds (4)
Phenytoin, phenobarbital, PCNs, morphine
High affinity for albumin – may displace drugs and increase free drug levels
Ex. Sulfonamides, ceftriaxone, may displace bilirubin = kernicterus
Distribution
Increased concentrations of (2)
Free fatty acids
Unconjugated (indirect) bilirubin
Metabolism (3)
Hepatic enzyme activity is…
- Hepatic enzyme activity is decreased
- Enzymatic microsomal systems responsible for drug metabolism are present at birth
- Their activities increase with advancing gestational age
Metabolism
Phase I hepatic reactions (3)
- Oxidation, reduction, hydroxylation develop rapidly during infancy
- Adult capacities by 6 months of life
- Ex.prolonged elimination for phenobarbital and cocaine
Metabolism
Phase II hepatic reactions (3)
- Synthesize a more water soluble compound to augment elimination
- Glucuronidation, Acetylation, Sulfation
- Glucuronidation – takes up to 1 year to develop= leads to decreased glucoronide = decreased GFR= leading to accumulation of drug (and can lead to death)
EX- chloramphenical – gray baby syndrome
Metabolism (4)
- Different metabolic pathways
- Enzymatic systems responsible for metabolism
- Mature at different times – this coupled with the diminished volume of distribution in the newborn = prolonged effect of certain drugs
- Local anesthetics during delivery
Elimination (4)
- CrCl is proportional to gestational age
- Nephrons begin forming in utero at 9 weeks and formation is complete at 36 weeks- but functionally immature
- Infants born before 34 weeks have a more pronounced decrease in renal function
- Drugs are often dosed according to post conceptual and postnatal age
Normal CrCl = in newborns
newborns ~40-65ml/min
Elimination reaches 50% of adult GFR by 1 month of age
3
Fullterm newborns have decreased renal function which approaches adult by 3-5 months
Decreased daily doses of meds which are renally eliminated
Gentamicin – Q12-24 hours
Decreased ability to concentrate urine
3
Normal urine output – 1-2 cc/kg/hour
Renal insufficiency - <1cc/kg/hr
Drugs dosing has to be adjusted with decreased urine output
Calculation of CrCl – Schwartz Method
CrCl (ml/min/1.73m2)= K x length (cm)
// SCr
K- age specific proportionally constant preterm – 0.34 (1st year) fullterm – 0.44 (1st year) L- length in cm SCr- serum creatinine in mg/dl
Elimination REMEMBER (4)
Adjust medications based on GA and weight
Aminoglycosides, cephalosporins
GFR changes with age
Premature infant -11ml/min
Fullterm infant -33ml/min
1 month old - 50ml/min
Look at what your patient is doing clinically
Reasons for renal impairment?
Always check your dosages
Factors leading to ADRs in neonates
5
- Decreased plasma proteins- result in increased free (unbound) drug
- Immature renal function – decreased elimination of renally excreted drugs
- alteration in number of drug receptor sites
- immature hepatic metabolism
- increased permeability of skin
Common conditions Preterm Neonates (8)
Respiratory Distress Syndrome (RDS) Bronchopulmonary dysplasia (BPD) Patent Ductus Arteriosus (PDA) Apnea of Prematurity (AOP) Sepsis Necrotizing Enterocolitis (NEC) Seizures PPHN
Respiratory Distress Syndrome (RDS)
3 requirements
Hyaline membrane disease
Requirements
- Central cyanosis in room air
- Requiring supplemental oxygen to maintain a pulse oximeter saturation over 85%
- Characteristic chest Xray – uniform reticulogranular pattern to lung fields with or without low lung volumes/air bronchogram- within the 1st 24 hours of life
Patho RDS (4)
- Surfactant deficiency is the primary cause of RDS
- Complicated by overly compliant chest wall
- Leads to progressive atelectasis – failure to develop effective FRC
- Surfactant is a surface active material produced by epithelial cells
Type II pneumocytes (4)
- Begins at 24-28 weeks gestation
- Type II cells are sensitive to/decreased by… asphyxial insults in the perinatal period
Maturation of this cell line is delayed in presence of fetal hyperinsulinemia (DM)
Type II enhanced by
Administration of antenatal corticosteroids
Chronic intrauterine stress (HTN, IUGR)
Surfactant (3)
- Composed of phospholipids (75%) and protein(10%)
- Produced and stored in the Type II pneumocytes
- This lipoprotein is released into the airways where it functions to decrease surface tension and maintain alveolar expansion
what happens when neonates
LACK surfactant
The small airways collapse- each expiration results in progressive atelectasis – cell damage – debris build up in the airway – directly decrease total lung capacity
RDS
Prematurity leads to….
Prematurity leads to overly compliant chest wall – weak structural support- allows negative pressures cause retraction of the chest wall – (instead of inflation)- collapse!
Risk factors for RDS (5)
Prematurity Male sex C-section without labor Perinatal asphyxia Maternal diabetes
RDS Physical Exam (5)
Tachypnea Grunting Flaring Retractions Cyanosis in room air
Management RDS(4)
Administer surfactant
Reduces surface tension in lungs (anti-stick)
Improves gas exchange
? Decrease in BPD. LOS, or mechanical ventilation- ??
Surfactant Products
Synthetic (1)
Surfaxin
Surfactant Products
Natural (3)
Curosurf – porcine
Infasurf - bovine
Survanta – bovine
Natural surfactant characteristics (3)
- Natural ( derived from animal lungs) surfactant preparations are better than synthetic (protein free)
- They have a quicker onset of action and reduced number air leaks (pneumothorax)
Natural are treatment of choice
Surfactant Replacement Therapy
Early administration
Key to restore pulmonary function
Prevents tissue injury
Decreased mortality
Surfactant Replacement Therapy
Composition
Animal origin
All contain hydrophilic surfactant properties SpB and SpC
Surfactant Replacement Therapy
Actions
(3)
Intended to replace missing or inactivated natural surfactant
Surface tension reduction and stabilization of the alveolar air-water interface are the basic functions
Air-water interface stability lower alveolar surface tension–> prevents atelectasis
Surfactant Replacement Therapy
Efficacy (3)
Can be seen with clinical conditions with both early and long-term effects
Early: reduction in Fio2 need-improved PaO2-improved lung function decreased ventilator pressure
Long-Term: decreased length of respiratory support, less severe CLD
