Drug Action Across the Life Span Chapter 3 Drug Action Across the Life Span Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Chapter 3 Lesson 3.1 Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Objectives Discuss the effects of patient age on drug action Discuss the role of genetics and its influence on drug action Cite major factors associated with drug absorption, distribution, metabolism, and excretion in the pediatric and geriatric populations Cite major factors associated with drug absorption, distribution, metabolism, and excretion in men and women Gender-specific medicine is a developing science that looks at how men and women perceive and experience disease, as well as how pharmacokinetics affect each gender. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Therapeutic Drug Monitoring Entails measurement of a drug’s concentration in biologic fluids to correlate the dosage administered and the level of medicine in the body with the pharmacologic response Timing of drug’s administration and collection of specimen are crucial to accurate interpretation Essential in neonates, infants, and children, given the major physiologic changes that affect drug ADME. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Use of Monitoring Parameters Before administering medicine Assess expected therapeutic actions, side effects, reportable adverse effects, and probable drug interactions Monitor parameters related to patient’s age Absorption, distribution, metabolism, and excretion of drugs are different for infants and children These parameters often change; therapeutic drug monitoring is very important for pediatric patients. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Use of Monitoring Parameters: Pediatric Patients Infants and young children are more susceptible to dehydration Weight variation affects dosage Aspirin is never administered to children Allergic reactions occur rapidly in children, most commonly to antibiotics Why should aspirin not be given to children? (Reye’s syndrome) What two common drugs are appropriate analgesics and antipyretics for children? (Ibuprofen and acetaminophen) What is it called when a medication is prescribed for a child but there is no FDA-approved use for children? (Off-label use) What symptoms may be indicative of an allergic reaction? (Urticaria, difficulty breathing, swelling in the oropharynx) If the patient is exhibiting signs of a severe allergic reaction, what is the appropriate nursing intervention? Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Use of Monitoring Parameters: Geriatric Patients Drug therapy Take thorough drug history and nutritional assessment Determine whether new symptoms have been induced by existing medicines Gradually taper dosage when discontinuing drug Start at 1/3 to 1/2 normal dosage when initiating therapy; gradually increase Review regimen periodically Use calendars or pill boxes to avoid confusion with multidrug regimens. Offer assistance in destroying old medicines. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Changing Drug Action With Gender Considerations In nearly every body system, men and women function differently Men and women perceive and experience disease differently Pharmacogenetics Fundamental questions remain about how humans function and the effect of disease on function Polymorphisms Naturally occurring variations in the structures of genes Having parameters or guidelines for both men and women is one of the goals of this research. Women’s studies need to include the different phases of the menstrual cycle, as well as pre- and post-menopausal women. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Absorption: Age Considerations Special considerations for pediatric and older adult patients Differences in muscle mass, blood flow, and inactivity affect medicines given intramuscularly Topical and transdermal administration differs in the very young and the very old Factors that place older patients at risk Reduced renal and hepatic function Polypharmacy – multiple-drug therapy required by chronic illness A greater likelihood of malnourishment Discuss why the amount of muscle mass and blood flow affect the absorption of IM drugs. Describe why IM drugs may be absorbed differently in older adults compared with younger adults. Explain why topical and transdermal medications may be absorbed differently in children and older adults. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Absorption: Age Considerations (cont’d) Gastrointestinal absorption influenced by: Gastric pH Gastric emptying time Enzymatic activity Blood flow of mucous lining and intestines Discuss why intestinal blood flow influences drug absorption. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Absorption: Age Considerations for Infants Topical administration in infants is effective because: Outer layer of skin (stratum corneum) not fully developed Skin more fully hydrated; plastic diaper increases skin hydration Inflammation (diaper rash) increases absorption Drugs are fat soluble or water soluble. Drugs that are water soluble will be absorbed more readily through an aqueous medium. Discuss how diaper rash increases absorption of topical medications as well as why a plastic diaper increases the water content of the skin. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Absorption: Age Considerations for Geriatric Patients Difficult to predict in geriatric patients Dermal thickness decreases with age and may enhance absorption Drying, wrinkling, and decreased hair follicles decrease absorption Decreased cardiac output and diminishing tissue perfusion also affect absorption Why does wrinkling of the skin and a decrease in the number of hair follicles affect the absorption of topical medications? (Because they alter the surface area available for drug absorption) Why does diminished tissue perfusion decrease absorption of topical medications? (Because blood flow enhances absorption of drugs) Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

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 The adverse effects of these drugs are more common. Use these medications with older adults only as a last resort (e.g., when treatment with other medications has failed). Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Absorption: Gender Considerations Increased potential for toxicity and slower absorption times in women Empty solids more slowly Have greater gastric acidity Have lower gastric levels of alcohol dehydrogenase needed to metabolize alcohols The exact contribution of gender to drug absorption has not been completely outlined. Discuss the effect of a low level of alcohol dehydrogenase in women. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Distribution Depends on pH, body water concentrations, presence and quantity of fat tissue, protein binding, cardiac output, and regional blood flow Infants have larger volume of water content and require higher dose With age, total body water decreases and fat increases Highly fat-soluble drugs take longer to act and accumulate in fat tissues, increasing potential for toxicity Infants have higher body water concentrations. What effect does this have on drug distribution? (Increases drug distribution) Women have a higher percentage of body fat than men. What effect does this have on drug distribution? (May decrease drug distribution) Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Distribution (cont’d) Protein binding Drugs that are relatively insoluble are transported in circulation by binding to plasma proteins Age considerations Some drugs have lower protein binding in neonates and require larger loading dose Albumin levels decrease with age Gender considerations Some differences between men and women in globulin proteins Drugs that are highly fat soluble include antidepressants, phenothiazines, benzodiazepines, and calcium channel blockers. Lower protein binding may lead to greater immediate pharmacologic effect. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Metabolism Drug metabolism Process by which the body inactivates medicine Affected by genes, diet, age Liver weight and hepatic blood flow decrease with age Explain why a decrease in liver weight and hepatic blood flow affect drug metabolism. (Because it may cause a decline in the liver’s ability to metabolize a drug) Discuss the effect liver disease has on drug metabolism and why. (It will affect the patient’s ability to metabolize a drug, increasing the risk for drug toxicity) Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drug Excretion Metabolites of drugs (and sometimes the drug itself) eventually excreted Preterm infant has 15% of adult renal capacity; fully functional by 9 to 12 months Decreased renal function with age No prediction of renal function can be based solely on age because of wide individual variation in changes Occasionally drug metabolites can be pharmacologically active. Why is it important to know that the renal capacity of an infant is less than that of an adult? (Because it will affect excretion of drugs) What are the two common blood tests that measure renal function? (Blood urea nitrogen [BUN] and creatinine [Cr]) Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

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 Alcohol and tobacco are not essential nutrients, and have been proven to have detrimental effects on the fetus. Herbal medications are not regulated by the FDA and pose a risk to the pregnant patient, including miscarriage. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Drugs Known to be Teratogenic Drug classifications known to be teratogenic Androgenic and estrogenic hormones ACE inhibitors, ethanol, tetracycline Thalidomide, vitamin A, warfarin Angiotension II receptor antagonists Anticonvulsants, antimanic agent, antithyroid Chemotherapy, statins, cocaine Discuss teratogenic drugs or any substances that cause birth defects. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

Use of Monitoring Parameters: Breast-Feeding Infants Some drugs are known to enter breast milk and harm the nursing infant Discuss all medications with physician Take medicine immediately after breast-feeding or just before infant’s longest sleeping period For many drugs that are excreted in breast milk, no one knows with certainty what effect they will have on the infant. Medications include prescription, nonprescription, and herbal products. Mosby items and derived items © 2010, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.