Ch.3: Drug Action Across the Life Span

Polymorphins

naturally occurring variations in the structures of genes and instructions that they give to the organism

Use in Pregnancy Categories - X

Studies: adequate, well-controlled, or observational; in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or who may become pregnant

Use in Pregnancy Categories - D

Studies: adequate, well-controlled, or observational; in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk

Illness

pathologic conditions may alter rate of absorption, distribution, metabolism, and excretion of drug - ex. pt w/ reduced peripheral vascular circular absorb IM or subcut drugs slowly

Use in Pregnancy Categories - C

•Animal studies have shown an adverse effect, and there are no adequate and well-controlled studies in pregnant women OR no animal studies have been conducted, and there are no adequate and well-controlled studies in pregnant women

Potentially Inappropriate Medications for Geriatric Patients

•Includes medications that should be avoided and those that are rarely appropriate -Some barbiturates, benzodiazepines, and some narcotics •Some are considered appropriate to give only with certain indications but may have potentially adverse reactions

Factors That Affect Drug Therapy

- Age - Body Weight - Gender - Metabolic Rate - Illness - Psychology - Tolerance - Dependence - Cumulative Effect

Use of Monitoring Parameters: Pregnant Women

- Avoid drugs if at all possible - When taking woman's history, be alert to possibility of pregnancy - Instruct patient to avoid drugs, alcohol, and tobacco - Try nonpharmacologic treatments before using medicines - Avoid herbal medicines

Nursing Implications when Monitoring Drug Therapy - Geriatric Patients

- Complete a thorough drug history, including prescription, OTC, herbal medications, and nutritional status - Evaluate vision and motor skills - When evaluating a new symptom, determine whether it was induced by a medication already prescribed - Start with smaller doses and gradually increase - Keep multidrug regimen simple - Review if any medications can be discontinued - Assess ability to pay for medications - Make tablets/Mix capsules for easier administration - Polypharmacy: multidrug therapy

Factors Affecting Drug Action - Excretion (Age)

- Drug metabolites and the drug itself are excreted from the body - Preterm infants have 15% of the renal capacity of an adult - Neonates have 35% - Full adult function occurs at 9 to 12 months - Serum creatinine levels give estimate of renal function Geriatric: - Decreased renal blood flow - Reduced cardiac output - Loss of glomeruli - Decreased tubular function

Nursing Implications when Monitoring Drug Therapy - Pregnant Patients

- Fetus exposed to substances in mother's blood Teratogens: - Drugs that cause abnormal development of fetal tissues

Factors Affecting Drug Action - Metabolism (Gender)

- Males and females differ with regard to concentrations of enzyme systems throughout life - CYP3A4 component of cytochrome P450 system of enzymes metabolizes more than 50% of all drugs and is more active in women

Therapeutic Drug Monitoring

- Measurements of drug concentration in blood sample to correlate the dosage administered and the level of medicine in the body - Very essential in neonates, infants, children to ensure appropriate therapeutic range - Dosage and frequency of medications can be adjusted to maintain therapeutic level of potentially toxic drugs

Nursing Implications when Monitoring Drug Therapy - Pediatric Patients

- More susceptible to dehydration from fever, vomiting or diarrhea - Dosage adjustments expected during growth - Therapeutic drug monitoring essential - Measure liquid medications using mL - Use appropriate dilution - Verify dosage prior to giving - Aspirin use linked with Reye's syndrome - Common analgesics: ibuprofen, acetaminophen - Allergic reactions occur rapidly in children

Drug Dependence

- Person is unable to control his/her ingestion of drugs - Physical: person develops withdrawal symptoms if drug withdrawn - Psychological: a person is emotionally attached to a drug

Factors Affecting Drug Action - Metabolism (Age)

- Process whereby the body inactivates medications; primarily occurs in the liver Infants: - Enzymes take several weeks to a year to develop Older adults: - Liver cells decrease, blood flow decreases All ages: - Genetics, smoking, diet, other medications, liver disorders

Use of Monitoring Parameters: Breastfeeding Infants

- Some drugs are known to enter breast milk and harm the nursing infant - Discuss all medications with health care provider - Take medicine immediately after breastfeeding or just before infant's longest sleeping period

Genetics

- Study of how living organisms inherit the traits of their ancestors, including function of metabolic pathways - Pharmacogenetics: study of how drug response may vary according to inherited differences - Significant differences can occur among racial and ethnic groups

Factors Affecting Drug Action - Distribution (Age)

- Ways in which drugs are transported to site of action - Depends on pH, body water concentrations, fat tissues, protein binding, cardiac output, and blood flow Infants: - Higher total body water content, requiring higher dose on mg/kg basis - Lower body fat - Reduced protein binding in neonates Geriatric patients - Total body water content decreases

Psychology

- attitudes and expectations play role in patient's response to therapy and in willingness to take medication - Placebo effect - Nocebo effect

Drug Accumulation

- next dose is given before the previously given drug has been metabolized or excreted - May result in drug toxicity

Nocebo effect

A patient's negative expectations can result in a less-than-optimal outcome

Placebo effect

A patient's positive expectation can positively affect the outcome

Use in Pregnancy Categories

A, B, C, D, and X.

Use in Pregnancy Categories - A

Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities

Factors Affecting Drug Action: - Absorption - Distribution - Metabolism - Excretion

Age Gender

Factors Affecting Drug Action - Absorption (Age)

Age: - Neonates: IM absorption erratic, reduced gastric acidity - Infant: Topical absorption increased Geriatric: - IM absorption erratic - Reduced salivary flow makes swallowing difficult - Transdermal absorption hard to predict - Timed-release/enteric-coated tablets cannot be crushed - Reduced GI acidity affects absorption - Slower gastric emptying time - Decreased GI motility and blood flow

Use in Pregnancy Categories - B

Animal studies have revealed no evidence of harm to the fetus; however, there are no adequate and well-controlled studies in pregnant women OR animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus

Drugs Known to be Teratogenic

Drug classifications known to be teratogenic - Androgenic and estrogenic hormones - ACE inhibitors, ethanol, tetracycline - Thalidomide, vitamin A, warfarin - Angiotensin II receptor antagonists - Anticonvulsants, antimanic agents, antithyroid - Chemotherapy, statins, cocaine

Gender

Gender-Specific medicine: studies differences in normal function of men and women and how people of each gender perceive and experience disease Women: consider premenopausal, postmenopausal and menstrual cycles

Factors Affecting Drug Action - Distribution (Gender)

Gender: - Total body fat higher in females

Factors Affecting Drug Action - Absorption (Gender)

Gender: - Women's stomach empties solids more slowly than men, greater gastric acidity = slow absorption of medicines - Women have lower gastric levels = higher BAC and state of intoxication

Metabolic Rate

Higher-than-avg metabolic rate: metabolize drugs more rapidly, requiring larger doses or more frequent doses - ex. pt w/ hyperthyroidism, smoker Lower-than-avg: smaller doses/less frequent - ex. pt w/hypothyroidism

Age

Infants and older adults are most sensitive to effects of drugs Infants: differences in absorption, distribution, metabolism, and excretion of drugs in premature neonates, full-term newborns and children Older adults: aging causes changes in body composition and organ function, affecting responses to drug therapy

Body Weight

Overweight: require increase in drug dosage to attain same response Underweight: require lower dosages to attain same response Pediatric: mg/kg

Tolerance

a person begins to require a higher dosage of a medication to produce the same effects that a lower dosage once provided

Due to the decreased protein-binding capacity in preterm infants, what adjustment in dosage of protein-binding drugs would need to made? a) The dosage should be decreased. b) The dosage should be increased. c) The dosage should be kept at the same level. d) Protein-binding drugs are not administered to infants.

b) The dosage should be increased. Rationale: Drugs that are relatively insoluble are transported in the bloodstream bound to plasma proteins (albumin and globulins). There is a decreased affinity for binding in infants, especially preterm infants. These drugs are then distributed over a wider area of the neonate's body. They will therefore require a higher dosage of these medications in order to achieve a therapeutic effect.

Which type of topical drug is more readily absorbed by infants? a) Fat-soluble b) Water-soluble c) Emollient d) Protective

b) Water-soluble Rationale: Topical administration with percutaneous absorption is usually quite effective in infants because the outer layer of skin is not fully developed. Because the skin is more fully hydrated at this age, water-soluble drugs are absorbed more readily.

Which patient has the greatest percentage of body water? a) Older adult b) Middle-aged person c) Infant d) Toddler

c) Infant Rationale: An infant has a total body water percentage of 74%, whereas a premature infant has an even higher percentage at 83%. As we age, our total percentage of body water decreases and our percentage of total body fat increases.

It is important to maintain therapeutic levels of drugs to avoid the complications of being over- or undermedicated. If a drug level of 0.5 to 2 ng/mL is considered therapeutic, a drug level of 0.45 ng/mL is considered to be what? a) Toxic b) Therapeutic c) Subtherapeutic d) Tolerant

c) Subtherapeutic Rationale: Drugs are therapeutic when maintained within the normal range for the drug. In this example, the level is below that indicated for the drug, or subtherapeutic. A subtherapeutic level would require increasing the dose for the patient to achieve the maximum benefit of the drug.

Genome

complete package of genetic coding of an organism Human Genome: - composed of 23 chromosome pairs - 22 autosomal pairs - 1 pair = X or Y chromosome for sex characteristics

Which form of medication is more easily administered for a toddler who requires a course of antibiotics? a) Enteric b) Capsules c) Tablets d) Liquid

d) Liquid Rationale: Very small children are not able to swallow solids such as tablets or capsules. They should receive medications carefully measured in a calibrated dropper or oral syringe.