When you have wide variation in drug plasma level from a given dose.
When the medication has a narrow therapeutic range.
When the desired effects cannot be assessed by other simple means.
A medications duration of action is often related to it’s half-life and may also indicate when another dose should be given.
It takes approximately 5 half-lives to reach steady state or 5 half-lives once a medication has been discontinued to be considered out of the system.
Usually drawn after adequate time has been allowed for the drug to distribute throughout the body
Usually drawn just before the next dose is due.
These drug levels are often used when patients have a changing renal function.
The characteristics of the receptors are responsible for the selective nature of medication response.
This allows for an explanation for medication antagonists limiting of inhibiting the response to the original medication
Some medications do not act through receptors .
Regulating Gene Expression
these medications generally do not have a rapid response
cell membrane permeability
have a short lag time between administration and administration response
increasing the intracellular concentration of a medication
stimulate a rapid response in changing cell characteristics
variation in antagonist substances
alteration in the numbers or function of receptor molecules
changes in the concentration of molecules other than receptor molecules
All medications have some side-effects. minor to serious
regardless of route, medications must cross the cell membrane
absorption of a medication is dependent on route
Gastric emptying and intestinal transit times
GI tract acidity
GI enzyme activity
GI tract perfusion
Underlying disease states
reaches adult values at 6-8 months
motility in reduced by: prematurity, asphyxia, reflux, and RDS
administration of hypocaloric feeds, human milk, and metacloprrmide can increase transit times.
Prolonged transit and enterohepatic recirculation may increase bioavaliability
some medication concentrations mat decrease because of increased first-pass loss.
the stomach acidity gradually increase to adult levels by age 2
net effect is depend ant on the medication and preperation
may inhibit absorption of some medications
one compensating mechanism neonates have is an increased Beta-gluronidase secretion.
also capable to metabolize some medications.
Up to 7 times higher concentrations than adults.
colonization is dependent on oral intake, antibiotic administration and disease states.
normal colonization take place in 4-6 days
intestinal flora are required to produce vitamin K
genetic diseases (CF) or circulatory (NEC) will alter pancreatic enzymes or intestinal mucosa, decreasing absorption.
serum levels may be as high as IV route
This route is discouraged because of volume and fragility of the rectum
retention time is the rate-limiting step
when the site of action is the tracheobronchial tree this route is preferred. (albuterol, terbutaline)
fewer side-effects because the medication may not be absorbed systemically.
certain medications can be delivered during an emergency
may be ineffective in infants with PPHN or abnormal circulation
limited to medications that do not cause tissue damage.
response time is dependent on blood flow.
bypasses all absorptive barriers
most reliable route of administration
serum concentrations achieved rapidly
adequate and equal levels are not guaranteed
rapidly reaching toxic levels may require that medications be delivered over prolonged periods.
determined by: size of the compartment, number and type of binding sited, amount of medication.
may be altered if the medication is highly protein bound or tissue bound.
expressed in units of L or mL;
important indicator of drug distribution into body fluids and tissues
a large value indicates drug distributes extensively into body tissues and fluids
less mature infants may require a higher dose to achieve the same peak concentration
in the first days after birth infants will have a rapid change in volume of distribution for water soluble medications
diuretics and indomethacin may have a major impact on water loss.
changes in water loss may make gentamicin difficult to dose. frequent monitoring may be necessary
medications with more lipid solubility have a greater affinity for these tissues
reduced fat% causes lower volume of distribution.
Plasma concentration will be higher because less will be bound (morpheine and lorazepam)
results in higher dose by wieght
amount bonded effects the available to achieved desired effect.
serum levels may be altered in the sick neonate, or ELBW
causes increased medication availability for action.
Some medications will displace UCbilirubin from albumin and increase risk for brain injury. (cefitriaxone, sulfonamides) and should be avoided with increased blilrubin or 2 months of age.
may be beneficial in treating meningitis
high-lipid solubility medications are the opposite
relative solubility may make some medications inappropriate because they may not reach an organ that is “fatty”.
-increase the polarity of drug molecule (making more ionized, more polar, more charged.) if you reveal a COOH, or OH it makes it more water soluble. this is purpose of metabolism
-hepatic microsomal enzyme drug metabolism:cytochrome P-450: smooth endoplasmic reticulum is where this is housed.
-purpose is to increase the water solubility of the drug
-cytochrome p-450 system can be inhibited and induced. this is a major reason why we get a lot of drug interactions
requires conjugation reaction
glucuronidation: addition of glucouronic acid. catalyzed by UGTs (expressed in tissue dependant manner and are inducible. highest in GI)
neonates deficient in conjugating system making them vulnerable to drugs such as antibiotics with are inactivated by glucouronic acid
very limited sweat production makes this route insignificant
less important for other medications
renal blood flow, GFR and tubular secretion iare important parts of this system
influenced by renal blood flow, glomerular membranes and water solubility of the medication
limited in neonates
related to gestational age
Important to: indomethacin, digoxin, aminoglycocides, and vancomycin
-may occur passive or actively
-reabsorption matures more slowly than GFR
-caffeine, glucose, phosphate and sodium are dependent
Ex. Clyndamycin, fluconazole
ainoglycocieds, penicillin, cephalosporin
-dose it takes to kill bacteria
decreased cellular penetration
altered taget proteins
readily achievable and maintainable
relative permeability of the target tissue (blood-brain barrier)
-Skin permeability in the extremely premature neonate may allow topical antibiotics to be adsorbed systemically.
-Blood flow changes may affect absorption or distribution. (Repeaed administration of aminoglycosides IM an SQ antibiotics may damage tissue)
-increases the intracellular calcium
-increases cardiac contractility
-decreases conduction through the AV and SA node to slow the ventricular rate
epinephrine, ISO, DopAmine and dobutamine)
-stimulates mucociliary activity
-some inhibitory action on inflammatory mediator release(antihistamine)
-BRONCHODILATION/VASODILATION IS DESIRED EFFECT
-increased fluid, mucin(submucosal glands)
-reduce vascular resistance
-decrease pulmonary vascular resistance
-captopril and propranolol
-digoxin, lidocane, esmolol
-desired response in one organ may lead to undesired effect in another
-some medications are highly albumin bound and may lead to hyperbilirubinanemia
-one of several derivatives of barbituric acid
may need tapering of dose
-assessment for need is ongoing and needs to be monitored carefully
-consideration for risk/benefit
-long term effects are not known
-other methods should be used first
-oral administration highly unpredictable (morphine)
-oral/rectal Tylenol may be enough
-as neonate body fat increases the dose will increase
-slower hepatic metabolism or disease may markedly increase half-life
-renal failure may cause toxic effects or nedications may hase a direct effect on renal function
-effects is base on function of renal tissue
-any medication that increases GFR may have an indirect diuretic effect
-larger dose may be required to achieve the same effect
-limited tubular function potentates electrolyte loss
-some provide a complete protection, some partial, some must be readministerd
-hep B immune globulin, varicella immune glogulin, palivizumab
-the does should NOT be decreased in neonates
-when vacceine is given at birth this does will not be counted. Hep B would need 4 doses rather than 3
-antibody titers will be inadequate to determine response
-current antibiotics or convalescence from illness
-reaction to DPT with fever less than 105F
-pregnancy within the household
-allergies other than neomycin or streptomycin other than anaphalyxis
-family history of seizure with pertussis or measles vaccine
-family Hx. SIDS