Pharm II Week 1

Components of promoting adherence in the pediatric population (developmentally appropriate care)

Effective two-way communication Individualized patient education Provide patient education in several ways always in writing in addition to verbal, infomercial, class, etc Demonstration techniques should be included when/if appropriate "Teach Back"  Patient/ caregiver/ family need to know: Name of medication Purpose of medication Dosage size and timing (r/t meals, other meds, time of day, symptom onset, and so forth) Administration route and technique Special considerations Treatment duration Drug storage- safety for children in household Nature and time course of desired responses Nature and time course of adverse effects:teach possible adverse effects, how to respond, when and how to follow-up with provider,and when to call 911

Teratogenesis - stages of development (in general) and result of teratogen exposure in each stage (in general)

Teratogenesis = the process by which congenital malformations are produced in an embryo or fetus greatest concern for many Teratogenesis: produce birth defects (cleft palate, neurobehavioral) Major structural abnormalities, internal organ abnormalities, minor structural abnormalities

Drug related adverse events in pregnancy

1. Pregnant women subject to same adverse effects as non-pregnant women 2. Physiologic state of being pregnant may itself impose additional issues for mother 3. Potential adverse effects to reproductive structures (uterus, cervix, placenta) & fetus (organogenesis, functional development) Ex// aspirin increases risk of serious bleeding during childbirth Ex// drugs can impact uterine contractions (cocaine & prostaglandins stimulate, aspirin can suppress but increases risk of serious bleeding) Ex// drugs can cause bleeding Ex// drugs can lead to dependence production

Effect of teratogens at various stages of development

1. Preimplantation (conception-week 2): all or nothing 2. Embryonic period (week 3-week 8): gross malformations, anatomic abnormalities 3. Fetal period (week 9-term): effects are usually functional (not anatomic structure)

Types of impact of drugs on fetal growth & development

1. major structural abnormalities (life threatening, require surgical correction 2. minor structural abnormalities 3. functional abnormalities (growth delays, learning/intellectual differences, neurobehavioral anomalies) Note: vast majority of birth defects have unidentified causes

Pregnancy risk categories - understand what the classification categories mean.

A: Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester, and the possibility of fetal harm appears remote. B: animal studies don't indicate risk and no controlled human studies (or animal studies show risk, but studies in pregnant women don't indicate risk) C: Drug excerts animal teratogenic effects, no controlled studies in women, or no animal studies D: Positive evidence of human fetal risk, benefits in certain situations may make use of drug acceptable X: Fetal abnormalities that outweigh possible benefit Ex// Drugs to avoid- aspirin, ibuprofen on frequent basis drugs of choice - acetaminophen, but not too excessively

Existence of dosage determination for children (if only have adult dose information)

Approximate dosage for a child = Body surface area of the child × adult dose 1.73 m² Initial pediatric dosing is, at best, an approximation. After an initial dose, pt must be monitored carefully  Subsequent doses must be adjusted on the basis of: clinical response/outcome presence of adverse effects plasma drug concentrations

Significance of reaching 1 year of age in terms of pharmacokinetic processes (from lecture)

As a consequence of organ immaturity, newborns and babies in the first year of life have very different pharmacokinetics from adults Fewer albumin proteins greater concentrations of free drug Elevated free drug levels more intense response Decreased hepatic metabolism prolonged response Decreased renal elimination prolonged response Blood-brain-barrier not well-formed CNS effects At the age of 1 year, most pharmacokinetic parameters in children are similar to those of adults children 1 year and older metabolize drugs faster than adults until age 2 years gradually declines sharper decline at puberty (adult values reached) Various stages of ongoing growth and development also put children at risk for unique or age-related adverse effects Examples : Growth suppression (caused by glucocorticoids) Discoloration of developing teeth (tetracyclines) Kernicterus (sulfonamides)

Basic considerations of drug therapy during pregnancy (availability of data, treat vs not treat, therapeutic goals, etc.)

Certain health conditions in the mother may be (are) more dangerous to the fetus than drug(s) used to control the condition Conditions that threaten the mother's health may well impact the fetus/baby as well Rule: avoid unnecessary drugs during pg/BF, but all drug therapy cannot and should not be avoided

Pediatric patients: differences in absorption

Differences: Drug absorption GI emptying is prolonged & irregular in early infancy adult values by 6-8 months Delayed gastric emptying in stomach enhanced absorption in stomach & delayed absorption in small intestine Low gastric acidity until 2 years old increased absorption of acid-labile drugs Protein binding of drugs Limited protein binding b/c low serum albumin levels & endogenous compounds compete w/ drugs for available binding sites higher free levels of drugs intensifies effects reduce dosing. Adult values by 10—12 months. Exclusion of drugs from central nervous system BBB not fully developed at birth access to CNS Hepatic drug metabolism Drug metabolizing capacity of newborns is low (complete maturation of liver by 1 years old) Renal drug excretion Reduced renal excretion at birth (adult levels by 1 years old)

Placental drug transfer - what types of drugs cross? How does this affect what should or should not be given to pregnant women?

For practical purposes, the clinician should assume any drug taken during pregnancy will reach the fetus Essentially all drugs can cross the placenta. Factors are the same as factors that determine drug passage across all other membranes. Assume that any drugs taken reach fetus. Factors: Lipid solubility (more easily) Ionized, highly polar, protein bound (less easily)

Pediatric patients: hepatic metabolism

Hepatic metabolism The drug-metabolizing capacity of newborns is low Neonates are especially sensitive to drugs that are eliminated primarily by hepatic metabolism The liver's capacity to metabolize many drugs increases rapidly about 1 month after birth The ability to metabolize drugs at the adult level is reached a few months later Complete liver maturation occurs by 1 year of age

What are reasons pharmacokinetics in children differ from adults? E.g., muscle mass, protein binding, renal excretion, etc.

Inadequate research data currently exists for prescribers to ensure safe dosing for infants/children. Two thirds of drugs used in pediatrics have never been tested in pediatric patients 20 % of drugs were ineffective for children (even though they were effective for adults) 30 % of drugs caused unanticipated side effects, some of which were potentially lethal 20 % of drugs required dosages different from those that had been extrapolated from dosages used in adults Younger patients are more sensitive to drugs than adult patients & show greater individual variation. Drug sensitivity largely due to organ system immaturity. Ex// IV injection: levels decline more slowly --> effects are prologued Ex// SubQ: levels rise higher & decline more slowly

What types of drugs cross into breast milk? How does this affect what should or should not be given to nursing women?

Nearly all drugs can enter breast milk, but the extent of drug entry into breast milk varies greatly Relatively few instances where drugs are secreted into breast milk that cause injury to patients. Post-pone pharmacotherapy until baby is weaned, or use non-pharm strategies. Have mother take medication after feeding baby (reduces amount of drug in breast milk), avoid breastfeeding during peak effect, avoid drugs with long half-life / active metabolites, drugs that are highly protein bound are preferred Use caution if baby is severely ill / neonate / preterm (may not have adequate drug metabolizing enzymes) Factors that determine entry into breast milk are same factors that determine passage of drugs across membranes (lipid soluble enter readily, ionized/highly polar/protein bound don't enter readily)

Physiological changes during pregnancy along with the implications for drug dosing (what happens in the liver and kidney? How does this affect dosing?)

Physiologic changes occur during pregnancy alter drug disposition. Changes in: kidney, liver, GI tract. By third trimester renal blood flow has doubled large increase in glomerular filtration rate accelerated clearance of drugs that are eliminated by glomerular filtration (ex// lithium) & reduced plasma concentration of drug dosage must be increased Hepatic metabolism increases during pregnancy Tone & motility of bowel decreases in pregnancy intestinal transit time increases more time for drug absorption (& more time for reabsorption of drugs that undergo enterohepatic recirculation prolongation of drug effects) reduction of drug dosage Blood volume: By the third trimester, blood volume doubles, thereby reducing the plasma concentration of drug. RBF: By the third trimester, renal blood flow doubles, thereby more rapidly eliminating renal-excreted drugs. Liver: For some drugs, hepatic metabolism increases (enzyme induction), thereby decreasing amount of drug. Bowel: Tone & motility decrease, thereby prolonging transit time. Increased time in the bowel allows greater drug absorption and enterohepatic cycling to occur.

Differences in pharmacokinetic processes during the various stages of growth and development (as discussed in class)

Premature infants: <36 weeks gestational age Full term: 36-40 weeks gestational age Neonates: First 4 postnatal weeks Infants: Week 5-52 postnatal Children: 1-12 years old Adolescents: 12-16 years old 2/3 of drugs used in paediatrics have never been tested in children.

Pediatric patients: differences in distribution

Protein binding Binding of drugs to albumin and other plasma proteins is limited in the infant Amount of serum albumin is relatively low Consequence? _______________ Blood-brain barrier Not fully developed at birth Drugs and other chemicals have relatively easy access to the CNS Infants especially sensitive to drugs that affect CNS function Dosage should also be reduced for drugs used for actions outside the CNS if those drugs are capable of producing CNS toxicity as a side effect Endogenous compounds compete with drugs for available binding sites Limited drug/protein binding in infants Reduced dosage needed Adult protein binding capacity by 10 to 12 months of age

How do considerations for breast-feeding women differ from what should or should not be given to pregnant women?

Relatively few instances where drugs are secreted into breast milk that cause injury to patients. Drugs with serious adverse effects: Immune suppressants (e.g., cyclosporine. methotrexate) Amiodarone & antithyroid drugs Benzodiazepines, anticonvulsants, antihistamine - watch for sedation Caffeine - high infant exposure = irritability All drugs of abuse, controlled substances Herbs to avoid: Fenugreek Comfrey

Pediatric patients: renal excretion

Renal excretion Significantly reduced at birth Low renal blood flow, low glomerular filtration, and low active tubular secretion Drugs eliminated primarily by renal excretion must be given in reduced dosage and/or at longer dosing intervals Adult levels of renal function achieved by 1 year

Teratogens - minimizing risk & responding to exposure

Teratogen = a medicine or other chemical capable of producing a permanent structural or functional birth defect, growth impairment, or fetal death

Reason for drug sensitivity in pediatric patients (for example, consider development/ maturity of organ systems; blood brain barrier)

Younger patients are more sensitive to drugs than adult patients & show greater individual variation. Drug sensitivity largely due to organ system immaturity. Intramuscular administration During the first few days of life: Slow, Erratic, Delayed absorption as a result of low blood flow During early infancy, absorption of intramuscular drugs more rapid than in neonates and adults Transdermal absorption Stratum corneum of infant's skin is very thin Blood flow to skin greater in infants than in older patients More rapid and complete for infants than for older children and adults Infants at increased risk of toxicity from topical drugs

Maternal morbidity

physical and psychologic conditions that result from pregnancy, or are aggravated by pregnancy, and have an adverse effect on a woman's health.  --> severe complications of pregnancy, generally referred to as severe maternal morbidity (SMM), affect more than 50,000 women in the United States every year. Based on recent trends, this burden has been steadily increasing.