NURS1140: CH.3 Drugs Across the Lifespan

Cumulative Effect

drug may accumulate in the body if the next dose is administered before the previously administered dose has been metabolized or excreted. drug accumulation- may result in toxicity

pharmacogenetics

study of how drug response may vary in accordance with inherited differences

Tolerance

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

(Distribyution) Drugs that are highly fat soluble

(e.g., antidepressants, phenothiazines, benzodiazepines, calcium channel blockers) require a longer onset of action and accumulate in fat tissues, thereby prolonging their action and increasing the potential for toxicity. -Highly fat-soluble medicines (e.g., diazepam) must be given in smaller milligram-per-kilogram dosages to low-birth-weight infants, because there is less fat tissue to bind the drug, thereby leaving more drug to be active at receptor sites

(Distribution) Drugs that are water soluble

(e.g., ethanol, aminoglycoside antibiotics), a woman's greater proportion of body fat produces a higher blood level compared with that of a man when the drug is given as an equal dose per kilogram of body weight

Albumin

-Little difference exists between albumin protein in men and women, although there are some differences between the globulin proteins (i.e., corticosteroid-binding and sex-hormone-binding globulins). -In adults who are more than 40 years old, the composition of body proteins begins to change. -albumin concentrations gradually decrease and other protein levels (e.g., globulins) increase. -As albumin levels diminish, the level of unbound active drug increases. -Increased levels of naproxen and valproate have been found in older adults, presumably as a result of decreased albumin levels. -cirrhosis, renal failure, and malnutrition can lower albumin levels. -Initial doses of highly protein-bound drugs (e.g., warfarin, phenytoin, propranolol, diazepam) should be reduced and then increased slowly if there is evidence of decreased serum albumin.

Metabolism Influence Drug Action

-Liver weight, the number of functioning hepatic cells, and hepatic blood flow decrease with age; this results in the slower metabolism of drugs in older adults. -Reduced metabolism can be seriously aggravated by the presence of liver disease or heart failure. -Drugs that are extensively metabolized by the liver (e.g., morphine, lidocaine, propranolol) can have substantially prolonged durations of action if hepatic blood flow is reduced. -Drug metabolism can be affected in all age groups by genetics, smoking, diet, gender, other medicines, and diseases (e.g., hepatitis, cirrhosis). Liver enzymes are monitored to determine any elevated levels during the course of drug therapy. -erythromycin, prednisolone, verapamil, and diazepam are metabolized faster in women than in men.

Absorption Influence Drug Action-AGE

-Medicines given intramuscularly are usually erratically absorbed in neonates and older adults. Differences in muscle mass, blood flow to muscles, and muscle inactivity in patients who are bedridden make absorption unpredictable. -Topical administration with percutaneous absorption is usually effective for infants because their outer layer of skin (the stratum corneum) is not fully developed. Because the skin is more fully hydrated at this age, water-soluble drugs are absorbed more readily. Infants who wear plastic-coated diapers are also more susceptible to skin absorption because the plastic acts as an occlusive dressing that increases the hydration of the skin. Inflammation (e.g., diaper rash) also increases the amount of drug that is absorbed. -Transdermal administration in geriatric patients is often difficult to predict. Although dermal thickness decreases with aging and may enhance absorption, factors that may diminish absorption can be seen, including drying, wrinkling, and a decrease in the number of hair follicles. With aging, decreased cardiac output and diminishing tissue perfusion may also affect transdermal drug absorption. -Geriatric patients often have reduced salivary flow, which makes chewing and swallowing more difficult

Illness

-Pathologic conditions may alter the rate of absorption, distribution, metabolism, and excretion of a drug -patients who are in shock have reduced peripheral vascular circulation and will absorb intramuscularly or subcutaneously injected drugs more slowly. -Patients who are vomiting may not be able to retain a medication in the stomach long enough for dissolution and absorption. -Patients with conditions such as nephrotic syndrome or malnutrition may have reduced amounts of serum proteins in the blood that are necessary for adequate distribution of drugs. -Patients with kidney failure generally will excrete drugs at a slower rate and must have significant reductions in dosages of medications that are excreted by the kidneys

Absorption: Passive Diffusion

-across the membranes and gastric emptying time depend on the pH of the environment. Newborns and geriatric patients have reduced gastric acidity and prolonged transit time compared with adults. -Premature infants have a high gastric pH (6 to 8) as a result of the immature acid-secreting cells in their stomachs. -Geriatric patients often have a higher gastric pH because of the loss of acid-secreting cells. Drugs that are destroyed by gastric acid (e.g., ampicillin, penicillin) are more readily absorbed in older adults because of the decrease in acid production, which results in higher serum concentrations. By contrast, drugs that depend on an acidic environment for absorption (e.g., phenobarbital, acetaminophen, phenytoin, aspirin) are more poorly absorbed, thereby resulting in lower serum concentrations in older adults.

Drug dependence,

-addiction -when a person is unable to control his or her desire for ingestion of drugs. -physiologic, in which the person develops withdrawal symptoms if the drug is withdrawn for a certain period, --psychological, in which the patient is emotionally attached to the drug.

Gender-specific medicine

-developing science that studies differences in the normal function of men and women and addresses how people of each gender perceive and experience disease. -angina (heart pain), women will present with nausea, indigestion, and upper back and jaw pain, whereas men will generally present with left-sided chest pain or pressure.

Metabolic Rate

-higher-than-average metabolic rate (e.g., patients with hyperthyroidism) tend to metabolize drugs more rapidly, thus requiring larger doses -Chronic smoking enhances the metabolism of some drugs (e.g., clozapine, olanzapine), thereby requiring larger doses to be administered more frequently for a therapeutic effect.

Therapeutic drug monitoring

-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 -Therapeutic drug monitoring is routine for conditions such as epilepsy (e.g., phenytoin, carbamazepine, valproic acid, phenobarbital), stroke (e.g., warfarin), heart failure (e.g., digoxin), and antimicrobial therapy (e.g., gentamicin, tobramycin, vancomycin) to prevent toxicities and to ensure that dosages are adequate to provide appropriate therapeutic levels -trough=lowest blood level -peak=highest blood level

Excretion Influence Drug Action

-preterm infant has up to 15% of the renal capacity of an adult, whereas a full-term newborn has approximately 35% of that capacity. -The filtration capacity of an infant increases to about 50% of adult capacity at 4 weeks of age and is equivalent to full adult function at 9 to 12 months. -Drugs that are excreted primarily by the kidneys (e.g., penicillin, gentamicin, tobramycin, vancomycin) must be administered in increased dosages or given more often to maintain adequate therapeutic serum concentrations as renal function matures. -As the body ages, important physiologic changes take place in the kidneys, including decreased renal blood flow caused by atherosclerosis and reduced cardiac output, a loss of glomeruli, and decreased tubular function and urine-concentrating ability.

Hydrolysis

-process that uses water to initiate a chemical reaction. -affects drug absorption in the newborn is the absence of the enzymes needed for hydrolysis. -Infants cannot metabolize palmitic acid from chloramphenicol palmitate (an antibiotic), thereby preventing the absorption of the chloramphenicol. Oral phenytoin dosages are also greater in infants who are less than 6 months old because of poor absorption (i.e., in neonates, the dosage is 15 to 20 mg/kg/24 hr compared with infants and children, in whom the dosage is 4 to 7 mg/kg/24 hr).

Metabolites

-products of metabolism—and, in some cases, the active drug itself—are eventually excreted from the body. The primary routes are through the renal tubules into the urine and through the GI tract into the feces. -Other generally minor routes of excretion include evaporation through the skin, exhalation from the lungs, and secretion into the saliva and breast milk.

protein binding

-reduced in preterm infants because of decreased plasma protein concentrations, lower binding capacity of protein, and decreased affinity of proteins for drug binding. -Drugs that are known to have lower protein binding in neonates than in adults include phenobarbital, phenytoin, theophylline, propranolol, lidocaine, and penicillin.

intestinal transit

-speed at which the intestine moves foods, secretions, and other ingested matter along, and this rate varies with age. -Premature and full-term newborns have a slower transit time. As the healthy newborn matures into infancy, the GI transit rate increases to a relatively standard rate by about 4 months of age. -Older adults develop decreased GI motility and intestinal blood flow. This has the potential for altering the absorption of medicines and for causing constipation or diarrhea, depending on the medicine.

Distribution Influence on Drug Action

-total body water content of a preterm infant is 83%, whereas that of an adult man is 60%; this drops to 50% in older persons. -The significance of this is that infants have a larger volume of distribution for water-soluble drugs and thus require a higher dose on a milligram-per-kilogram basis than an older child or an adult -The body weight of a preterm infant may be composed of 1% to 2% fat, whereas a full-term newborn may have 15% fat. Adult total body fat ranges from 18% to 36% for men and 33% to 48% for women between the ages of 18 and 35 years.

Absorption Influence Drug Action-GENDER

-woman's stomach empties solids more slowly than a man's does, and it may have greater gastric acidity, thus slowing the absorption of certain types of medicines (e.g., aspirin). -Women also have lower gastric levels of the enzyme alcohol dehydrogenase, which is needed to metabolize ingested alcohol. Thus larger amounts of ingested alcohol may be absorbed instead of metabolized in the stomach, thereby leading to a higher blood alcohol level in a woman than in a man for equal amounts of ingested alcohol.

Age Table

<38 wk gestation Premature 0-1 mo Newborn, neonate 1-24 mo Infant, toddler 3-5 yr Young child 6-12 yr Older child 13-18 yr Adolescent 19-54 yr Adult 55-64 yr Older adult 65-74 yr Elderly 75-84 yr The aged 85 yr or older The very old

Carcinogenicity

ability of a drug to induce living cells to mutate and become cancerous.

genome

complete package of genetic coding of an organism.

Polymorphisms

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

Psychology

placebo nocebo- negative expectations about therapy and the care