Drug Therapy Across the Lifespan

Geriatric clients experience more adverse drug reactions because.....

- Altered pharmacokinetics (more sensitive to drugs) - Multiple and severe illnesses - Multiple drug therapy - Poor adherence

Predisposing ADR Factors

- Drug accumulation secondary to reduced renal function. - Polypharmacy - Greater severity of illness - Multiple pathologies - Greater use of drugs that have a low therapeutic index (digoxin) - Increased individual variation secondary to altered pharmacokinetics - Inadequate supervision of long term therapy - Poor patient adherance

Pharmacokinetics: Metabolism

- Hepatic metabolism declines with age. - Reduced hepatic blood flow, reduced liver mass, and decreased activity of some hepatic enzymes occur. - Half life of some drugs may increase, and responses are prolonged. - Responses to oral drugs (those that undergo extensive first pass effect) may be enhanced.

Pharmacokinetics: Distribution

- Increase percentage of body fat storage depot for lipid soluble drugs - decreased percentage of lean body mass - decreased total body water distributed in smaller volume; thus concentration is increased and effects are more intense. - reduced concentration of serum albumin may be significantly reduced in the malnourished. causes decreased protein binding of drugs and increase in levels of free drugs.

Geriatric clients have altered drug distribution for three primary reasons....

- Increased percentage of body fat. - Decreased percentage of lean body mass. - Decreased total body water.

Geriatric Patients

- Individualization of treatment is essential - Each patient must be monitored for desired and adverse responses - Regimen must be adhered to - Goal of treatment: reduce symptoms and improve quality of life. Cure is generally possible.

Drug Therapy During Pregnancy

- Physiologic changes during pregnancy and their impact on drug disposition and dosing THIRD TRIMESTER: - renal blood flow doubled and renal excretion accelerated - Tone and mobility of bowel decrease - prolonged transit: increase in absorbtion

Pregnancy and Breastfeeding

- Shortage of reliable data on toxicity from drug use during pregnancy or breast feeding. (unethical to test on unborn child) However: - two thirds of pregnant women take at least one medication; most take more. used to treat: - pregnancy related problems: nausea, constipation, and preeclampsia. - chronic disorders: HTN, diabetes, epilepsy. infectious diseases or cancer - drugs of abuse: alcohol, cocaine, heroin

Promoting Compliance with Unintentional Nonadherence

- Simplified drug regimens - Clear, concise verbal and written instructions - Appropriate dosage form - Clearly labeled and easy to open containers - daily reminders - Support system - Frequent monitoring Most cases (75%) of geriatric non compliance are intentional, reasons include: expense, side effects, patients conviction that the drug is unnecessary or the dosage is too high.

Measures to Reduce ADRs

- Take thorough drug history, including OTCs - Consider pharmacokinetic and pharmacodynamics changes due to age. - Monitor clinical response/plasma drug levels. - Use the simplest regimen possible. - Monitor for drug-drug interactions. - Periodically review the need for continued drug therapy. - Encourage patient to dispose of old meds. - Take steps to promote adherence and avoid drugs on the beers list.

Placental Drug Transfer

- all drugs can cross placenta. - some can cross more easily than others.

Pharmacokinetics: Absorption

- altered GI absorption is not a major factor in drug sensitivity. - percentage of an oral dose that is absorbed does not change with age. - rate of absorption may slow - delayed gastric emptying and reduced splanchnic blood flow occur.

Adverse Reactions During Pregnancy

- can adversely affect both pregnant patient and fetus. some unique effects: - heparin causes osteoporosis. - prostaglandins stimulate uterine contraction. - certain pain relievers used during delivery can depress respiration in the neonate.

Dosage Determination

- dosing is most commonly based on body surface areas (BSA) - initial pediatric dosing is, at best, an approximation. - subsequent doses need to be adjusted approximate dosage for a child = BSA of child X adult dose _________________________________ 1.73 m^2(squared)

Drug Therapy During Breast Feeding

- drugs can be excreted in breast milk, and effects can occur in the infant. How to decrease risk to the infant: - take drugs immediately after breast feeding. - avoid drugs that tend to be excluded from milk and are least likely to affect the infant. - avoid drugs known to be hazardous.

what are the three age related adverse effects?

- growth suppression (caused by glucocorticoids) - discoloration of developing teeth (tetracyclines) - kernicterus (sulfonamides)

Teratogenesis

- incidence and causes of congenital anomalies: less than 1% of all birth defects caused by drugs. - identification of teratogens very difficult - as a result, only a few drugs are considered proven teratogens. Minimizing risk for teratogenesis: - avoid unnecessary drug use - 50% of pregnancies are unintended Responding to teratogen exposure: - identifying details of exposure - ultrasound scans

Pharmacokinetics: Children age 1 and older

- most pharmacokinetic parameters similar to those in adults - drug sensitivity more like that for adults than for children younger than one ONE IMPORTANT DIFFERENCE IS THAT THIS AGE CLIENT WILL METABOLIZE DRUGS FASTER THAN AN ADULT - markedly faster until age 2, then gradual decline - sharp decline at puberty - may need to increase dosage or decrease interval between doses

Promoting Adherence

- provide patient education in writing. - demonstration techniques should be included as appropriate. Effective education should include: - dosage size and timing - route and technique of administration - duration of treatment - drug storage - the nature and time course of desired responses - the nature and time course of adverse responses

Why are beta blockers less effective for geriatric clients?

- reduction of number in beta receptors. - reduction in the affinity of beta receptors for beta receptor blocking agents.

Adverse Drug Reactions

- vulnerable to unique adverse effects related to organ immaturity and ongoing growth and development. Age Related Effects - growth suppression (caused by glucocorticoids) - discoloration of developing teeth (tetracyclines) - kernicterus (sulfonamides)

Children

1 - 12 years old

Pediatric patients respond differently to drug therapy for four reasons; name them

1. more sensitive to drugs 2. show greater individual variation 3. sensitivity due to organ immaturity 4. increased risk for adverse reaction

Adolescents

12 - 16 years old

Full Term Infants

36 - 40 weeks gestational age

Adverse Drug Reactions in Elderly

Adverse Drug Reactions in Elderly: - Seven times more likely in the elderly. - Account for 16% of hospital admissions. - Account for 50% of all medication related deaths. - Majority are dose related, not idiosyncratic. - Symptoms in elderly often non specific (dizzy, cognitive impairment)

Pharmacodynamic Changes in the Elderly

Alterations on receptor properties may underlie altered sensitivity to some drugs. - Drugs with more intense effects in the elderly (warfarin, certain CNS depressants) - Beta blockers less effective in the elderly, even in the same concentrations. Reduction in number of beta receptors. Reduction in the affinity of beta receptors for beta receptor blocking agents

Geriatric Patients and Adverse Drug Reactions

Altered Pharmacokinetics - more sensitive to drugs than younger adults and have wider variation Multiple and Severe Illnesses - severity of illness, multiple pathologies Multiple Drug Therapy - excessive prescribing Poor Adherence

What is teratogenesis?

Birth Defects

Teratogenesis & Stage of Development

Development occurs in three stages: - Conception through week 2 - Embryonic Period: weeks 3-8 gross malformations produced by teratogens - Fetal Period: week 9 to term functions disrupted with teratogen exposure CNS is most important. takes longest to develop. fetus is at risk during entire pregnancy.

Drug Therapy in Geriatric Patients

Disproportionately high prescription drug use exists in the elderly. - 12% of Americans are 65 years or older - this 12% consumes 31% of prescribed drugs Geriatric patients experience more adverse drug reactions and drug-drug interactions than younger patients do.

Neonates

First 4 postnatal weeks

Drug Therapy in Neonates and Infants

Increased sensitivity in infants due to immature state of five pharmacokinetic processes: - absorption - protein binding of drugs - blood-brain barrier - hepatic metabolism - renal drug excretion

Drug Therapy in pediatric Patients

Pharmacokinetics: neonates and infants - absorption - distribution - hepatic metabolism - renal excretion Determining the concentration of a drug at its sites of action Determining the intensity of duration of response: - elevated drug levels = more intense response - delayed elimination = prolonged response - immaturity of organs puts patient at risk for both of these responses

Pharmacokinetics: Excretion

Renal function undergoes progressive decline beginning in early adulthood. - reductions in renal blood flow, GFR, active tubular secretion, and number f nephrons. - renal function should be assessed with drugs that are eliminated primarily by the kidneys. In elderly patients: - use creatinine clearance, not serum creatinine, because leave muscle mass (source of creat) declines in parallel with kidney function. - creat levels may be normal even though kidney function is greatly reduced. Drug accumulation secondary to reduced renal excretion is the most important cause of adverse drug reactions in the elderly.

Teratogenesis/ Birth Defects

Teras = a greek word meaning "monster" Teratogenesis = literally, "to produce a monster" Birth Defects: -Gross Malformations: cleft palate, clubfoot, and hydrocephalus - Neurobehavioral and Metabolic Anomalies/

Infants

Weeks 5 - 52 postnatal

what drugs cross the placenta?

all drugs cross the placenta. some more easily than others.

How can teratogenesis be reduced?

avoid taking medications

Pharmacokinetics for pediatric patients 2 and younger are different than for adults in what way?

children 2 and under metabolize drugs faster than adults

why is there a shortage of reliable data related to drug use during pregnancy?

due to ethics there is a shortage of reliable data related to drug use during therapy. It is unethical to test on an unborn child.

Premature Infants

less than 36 weeks gestational age

how does this effect dosing for the pediatric client

may need to increase dosage or decrease interval between doses

third trimester changes impact the renal system in what way?

medications move through body faster and they are excreted faster.

Pediatric Patients

patients younger than 16 years. Respond differently to drugs than the rest of the population: 1. more sensitive to drugs than other patients 2. show greater individual variation 3. sensitivity due mainly to organ system immaturity 4. increased risk for adverse drug reaction -ongoing growth and development - different age groups: different challenges - two thirds of drugs used in pediatrics have never been tested in pediatrics.

Geriatric clients are how many times more likely to experience adverse drug responses?

seven times more likely

Non Complience

usually intentional reasons: expense, side effects, patient thinks drug is unnecessary or dose is too high