PHARM chapter 10

Oral administration

*Oral administration- GI physiology in infant is different from adult. As a result drug absorption may be enhanced or impeded depending on the physiochemical properties of the drug involved. -gastric empying is prlonged and irregular in early infancy and then gradually reaches adult values by 6 to 8 months. -for drugs absorbed primarily from the stomach, delayed gastric emptying enhances absorption. -drugs absorbed primarily though intestine, absorption is delayed gastric emptying time is not predictable. -gastric acidity is very low 24hrs after birth and doesn't reach adult levels till about 2yrs. Because of low acidity. Absorption of acid-labile drugs is increased.

Percutaneous absorption

Because the skin of the very young is thin, percutaneous drug absorption is significantly greater than in older children and adults. This increase the reisk of toxicity from topical drugs.

Protein binding

Binding of drugs to albumin and other plasma proteins is limited in the infant. Because (1) amount of albumin Is low (2) endogenous compounds compete with drugs for available binding sites. So drugs that ordinarily undergo extensive protein binding in adults undergo much less binding in infants. As a result, concentration of free levels of such drugs is relatively high in the infant, thereby intensifying effects. To ensure effects are not too intense, dosages in infants should be reduced. Proteinapacity reaches adult values within 10 to 12 months.

Pediatrics

Covers all patients up to the age of 16. Because of ongoing growth and development, _______ patients is different age groups present different therapuetic challenges. Subdivided into 6 groups: -premature infants (less than 36wks gestational) -full-term infants (36-40wks gestational age) -neonates(first 4 postnatal weeks) -infants(5wks to 52 postnantal wks) -children (1 to 12yrs) -Adolescents (12 to 16yrs) As young grow older, they become more like adults physiologically and hence more like adults with regard to druh. Therapy. ?ery young (less than.wyr) and esp those less than 1mth are very differnt than adults. If drug is to be safe and effective, we must account for those differences. ________ therapy is made even more difficult by insufficient drug information. 2\3. Of drugs used in ______ have never been tested in kids.

Intramuscular administration

Drug absorption following I'm injection in neonate is slow and erratic. Delayed absorption is due is part to low blood flow through muscle during first days on postnatal life. By early infancy absorption of I'm drugs becomes more rapid than in neonates and adults.

Very young and very old

Patients of this age group respond differently to drugs than the rest of the population. Most differences are quantitative. Patients inn both age groups are more sensitive to drugs than other patients. And show greater individual variation. Drug sensitivity in the very yooung results largely from organ sysem immaturity. Drug sensitivity in the elderly results from organ system degeneration. Because of heightend drug sensitivity patients in both groups are at high risk of adverse drug reactions.

Pharmacokinetics neonates and infants

When a drug is administered intervenously, level decline more slowly in the infant than adult. As a result drug levels in ifnat remain above MEC longer than in adult. Therby causing effects to be prolonged. When a drug is administered subcutaneously, not only do levels in the infant remain above the MEC longer than adult but levels also rise higher causing effects to be more intense as well as prolonged. From these points it is clear that adjustment of dosage for infants on the basis of body size alone is not sufficient to achieve safe results. Increased sensitivty of ifants is due largely to the immature state of 5 pharmacokinetic processes (1) drug absorption (2) protein binding of drugs (3) exclusion of drugs from the central nervous sysem by the blood brain barrier (4) hepatic drug metabolism (5) renal drug excretion

Blood-brain barrier

___________ is not fully developed at birth. As a result, drugs and other chemicals have relatively easy access to the cns, making the infant especially sensitive to drugs that affect CNS function. So these drugs should be given in reduced dosage. Drugs should also be reduced with actions outside the CNS if those drugs are capable of producing CNS toxicity as a side effect.

dosage determination

______________ for pediatric patients is difficult. Selecting a dosage is especially difficult in the very young, since pharmacokinetic factors are under going rapid change. Pediatric doses have been established for a few drugs, but not for most. For drugs that do not have an established pediatric dose, dosage can be extrapolated from adult doses. body surface area x adult dose / 1.73 m2 = approx childs dose. pediatric doses are an approximation subsequent doses must be adjusted on the basis of clinical outcome and plasma drug concentrations, these adjustments are especially important in neonates and younger infants. Clearly if dosage adjustments are to be optimal, it is essential that we monitor the patient for therapeutic and adverse responses.

renal excretion

__________________ is significantly reduced at birth. Renal blood flow, glomerular filtration, and active tubular secretion are all low during infancy -because the drug excreting capacity of infants is limited, drugs that are eliminated primarily by renal excretion must be given in reduced dosage. Adult levels of ______________ are achieved by 1 year.

Promoting adherence

achieving accurate and timely dosing requires informed participation of the childs parents or gaurdian and to the extent possible, active involvement of the child. Effective education is critical. Issues should be addressed: -dosage size and timing (spills & spitting are common causes of inaccurate dosing, parents should be taught to estimate amount of drug lost and re-administer amount) -route and technique of administration (demonstration should be made) -duration of treatment -drug storage -the nature and time course of desired responses -the nature and time course of adverse responses. ***written instructions should be provided. -selecting the most convenient dosage form and dosing schedule -suggesting mixing oral drugs with food or juice (when allowed) to improve palatibility -providing a calibrated medicine spoon or syringe for measuring liquid formulations -taking extra time with young or disadvantaged parents to help ensure conscientious and skilled participation.

1 year

by the age of ____. most Pharmacokinetic parameters in children are similar to those in adults so drug sensitivity over this age is similar to those of adults. however children do metabolize drugs much faster than adults. Drug metabolism is markedly elevated until 2 yrs and then gradually declines. A further sharp decline takes place at puberty, when adult values are reached. because of enhanced drug metabolism in children, an increase in dosage or a reduction in dosing interval may be needed for drugs that are eliminated by hepatic metabolism.

adverse drug reactions in pediatrics

like adults, pediatric patients are subject to adverse drug reactions when drug levels are too high. in addition pediatrics patients are vulnerable to unique adverse effects related to oragn system immaturity and to ongoing growth and development. Among these age related effects are growth suppression, discoloration of developing teeth, and kernicterus.

hepatic-metabolism

the drug-metabolizing capacity of newborns is low. As a result, neonates are especially sensitive to drugs that are eliminated primarily by ___________________. When these drugs are used. Dosages must be reduced. The capacity of the liver to metabolize many drugs increases rapidly about 1 month after birth, and approaches adult levels a few months later. Complete maturation of the liver develops by 1 year.