Clinical treatment often requires taking blood samples for the pur- pose of recording physiologic markers related to protein-binding. The following markers provide interpretive data related to drug dosage, organ blood flow, and fundamental function of the liver and kidneys (Katzung, 2018, p. 53). The primary proteins utilized for this purpose are albumin and alpha-acid glycoprotein. Patho- logic conditions can decrease concentrations of serum albumin, thereby reducing total drug concentration. Conversely, acute and/or chronic inflammatory responses can increase alpha-acid glycoprotein concentrations, which can induce changes in total plasma concentration of certain drugs. In addition, drug concen- tration may be dependent on the capacity of a specific binding protein. Higher drug concentrations can lead to saturation when no unbound proteins are available and/or present, which leads to an increased presence of unbound drug in plasma. Some phar- maceuticals demonstrate a higher affinity to red blood cells. In turn, fluctuations in red blood cell concentrations, correlated with hematocrit levels, may lead to changes in whole blood concentra- tions of a drug without changes in pharmacological activity. Measurement peak pharmacological concentration is relatively weak in terms of validity, and complicated by pharmacodynam- ics as well as pharmacokinetic variability. Greater effort is placed upon timing lab values to establish achievement of steady-state concentration. Although initial predictions for volume of distribu- tion and clearance can be calculated, clinically significant differ- ences in observed drug concentrations require dosing revisions.
ogy, tend to present with lower volumes of distribution for many pharmaceuticals that bind to muscle proteins (Katzung, 2018, p.52). On the other hand, pharmaceutical distribution for patients presenting with obesity depends largely on chemical drug prop- erties, specifically whether or not the drug is hydrophobic versus hydrophilic. Volume of distribution may appear greater for hydro- philic drugs administered to patients with obesity. The opposite may be true for hydrophobic drugs, which enter fatty tissues more easily. Even though volume of distribution in this scenario may present as relatively low, the concern is that prolonged storage of pharmaceuticals in adipose tissue can lead to toxicity. In addition, volume of distribution may significantly increase for patients with pathologic fluid collection, such as ascites, pleural effusion, and/ or edema, when hydrophilic drugs are administered. Maximum effect refers to the point at which increasing drug con- centration does not produce changes in drug action. Determin- ing maximum effect provides a quantitative marker with which to avoid overdosage and resultant toxicity. Sensitivity is the concen- tration of drug required to produce 50 percent of the maximum ef- fect. The relationship between sensitivity and drug concentration also provides clinical data in the presence of pathological states. Increased drug sensitivity is associated with small amounts of a drug producing embellished responses. On the other hand, de- creased drug sensitivity would be associated with larger amounts of a drug producing relatively weak responses. Sensitivity values may be indicative of physiologic impairment and/or pharmaceuti- cal antagonism. It is important to recognize and understand that every medica- tion presents risks of side effects. In turn, side effects must be prevented, minimized and managed by allied health professionals (Watkins, 2013, p. 18). Mild pharmaceutical side effects include nausea, drowsiness, dizziness, constipation and sensitivity to light. An adverse reaction is a critical side effect, which may include shock and/or death, and often causes prescribers to amend medi- cation prescriptions. Side effects may be unique to an individual patient and are termed idiosyncratic . In general, topical drugs present fewer side effects than systemic drugs. Side effects can also be described further by categorizing effects on specific or- gan systems. Neurologic drug effects can include hallucinations, agitation, depression, sedation, disorientation and even coma. As the primary cite of metabolism, side effects on the liver are gener- alized to organ damage due to local accumulation of a drug. Most common side effects are observed in the gastrointestinal system and include diarrhea, constipation, inflammation, nausea and vomiting. Gastrointestinal side effects can be mediated by food ingestion and dietary amendments. One of the most notable gas- trointestinal side effects may include ulceration associated with long-term application of nonsteroidal anti-inflammatory drugs. Kidney damage may be implicated for specific medications that are metabolized primarily in the kidney as opposed to the liver. Impaired kidney function can lead to toxic pharmaceutical build- up in the body. Other medications are associated with ototoxicity, leading to hearing and/or balance loss. The hematological system is of notable concern as well. Certain drugs can lead to problems with coagulation, bleeding, clotting and/or immunosuppression (Watkins, 2013, p. 19). Damage to bone marrow is of specific con- cern with regard to anticancer drugs, as blood cell production is required for effective immune system response. Additional considerations for medication administration include age, gender and cultural background. Geriatric patients, defined as those 55 and older, present with decreased functional capac - ity for absorption and distribution. This can be attributed to de- creased gastrointestinal performance, abdominal blood vessel blockage, decreased plasma protein levels with consideration to nutritional status, and reduced liver and kidney function (Watkins, 2013, p. 31). Specific drug categories that present additional risk to elderly patients include sedative-hypnotics, such as non-steroi- dal anti-inflammatory drugs and anticoagulants, antihypertensive pharmaceuticals and thrombolytics (These categories will be fur-
PHYSIOLOGIC VARIABILITY
ther defined later in the course). Geriatric patients often require regimens of multiple medications, which increase the risk of ad- verse polypharmacy reactions due to drug interactions and side effects. On the other end of the age spectrum, pediatric patients pres- ent with increased metabolism, decreased body weight, reduced blood-brain barrier, and immature renal, endocrine and nervous system function. In turn, drug metabolism and excretion are rela- tively limited. Medication dosing can be complicated and dynam- ic due to rapid physiologic development, requiring an extraor- dinarily specific prescription to avoid potentially adverse effects. Considerations for injections include reduced arm muscle size, fragile blood vessels and general fear of needles. This presents needs for thigh muscle injection sites, careful monitoring dur- ing intravenous fluid administration, and gentle explanation and sensitivity in terms of approach (Watkins, 2013, p. 32). Absorp- tion rates for neonates are reduced due to higher gastric pH, and more variable due to irregular stomach emptying times. As well infants secrete less lipase, which reduces absorption for lipid-for- mulated medications. Infants also have thinner striatum corneae, which increases absorption rates for ophthalmic pharmaceuticals. Pharmaceuticals that are introduced rectally are absorbed faster in pediatric patients, which can lead to rapid toxicity. The percent- age of extracellular, total water and ratio of water to lipids is also higher for this population. In turn, drugs become more widely dis- tributed throughout the body, though with reduced relative levels in the bloodstream (Watkins, 2013, p 32). Gender-based pharmaceutical variability can be affected by body water content, metabolic rates and gonadal hormone variations (Watkins, 2013, p. 32). Males generally present with more muscle than fat as compared to females, which speeds up drug absorp- tion and distribution. In addition, female pharmaceutical manage- ment may continue during pregnancy, which adds concern for the blood-placental barrier. This physiologic interface prohibits water- soluble medications, while allowing passage of many lipid-soluble drugs. Historical pharmaceutical practice has led to a number of drugs that are teratogenic, meaning they cause deformity and/ or death of the fetus. Heightened periods of fetal vulnerability include the first and last trimesters. The first trimester is critical for organ development, while the third trimester can be associated with increased accumulation of drugs before birth.
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