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1. Describe the changes in renal and hepatic function and other biological changes that occur 2. Identify factors that must be considered when determining adult medication dosages. 3. Calculate adult drug dosages using appropriate methods. 4. Discuss problems that may be encountered in administering medications to adults. 5. Identify medication-related problems that may occur in adults. 6. Identify factors that increase the potential for medication-related problems in adults and describe precautions that can minimize these factors. 7. List factors important in the selection and monitoring of medication therapy for adults. Drug Disposition in Adults Biological processes responsible for drug disposition are fully developed in adult patients (18-65 years of age). However, throughout adulthood these functions may experience changes that can alter the pharmacokinetic and pharmacodynamic parameters of medications. Renal and hepatic function begin to decline as adults age resulting in changes in the body’s ability to metabolize and excrete medications. Other age-related changes that can affect drug disposition include increased gastric pH, decreased total body water, and increased adipose tissue. Because physiological changes that develop with age do not occur consistently among individuals or consistently in all organ systems within one person, their effect on drug disposition may not be predictable. Therefore, individualized drug therapy is necessary. Other factors that may affect biological function include acute or chronic disease states and lifestyle choices (e.g., substance abuse, nutritional habits, and physical activity). Adult Drug Dosing Recommended drug dosages for adults have been established and are reported in the package labeling for medications and drug information references. Doses are usually reported as micro- gram (mcg), milligram (mg), or gram (g) per dose, but may be expressed in other ways such as equations. The following is commonly used: BSA ( m 2 ) Height (inches) < Weight (pounds) BSA ( m 2 ) Height (cm) < Weight (kg) There are also nomograms to calculate BSA available in the published literature. However, recommended dosages may not be appropriate for patients with impaired biologi- cal processes that consequently affect parameters such as absorption, distribution, metabolism, and excretion. For example, hepatic or renal dysfunction can reduce the elimination of some medications (e.g., anti-infectives,) requiring reductions in doses or increases in the dosage interval. Dosages may also be based on serum drug concentrations. Examples of medications that can be initial y dosed and then monitored and adjusted using pharmacokinetic data and the patient’s response include aminoglycosides, vancomycin, and phenytoin. Dosage adjustments may be needed when switching from one dosage form or route of ad- ministration to another because of differences in physiochemical and pharmacokinetic properties (e.g., salt form and bioavailability). Medications that require dosage adjustments from one dosage form to another include levothyroxine, phenytoin, verapamil, diltiazem, and propranolol. For example, the intravenous dose of levothyroxine is 50% of the oral dose. Medication Administration in Adult Patients In general, adults tolerate all dosage forms and routes of administration. However, the choice of dosage form, route and method of administration, and other components of drug administra- tion are dependent on patient-specifi c factors (e.g., concurrent disease states) and the availability of appropriate drug preparations. Seriously ill patients may not be able to take medications by mouth, requiring the use of alternative routes of administration such as parenteral and rectal routes or via a nasogastric tube that necessitates the use of liquid dosage forms. In these in- stances medications not available as oral liquid formulations must be modifi ed for use. Crushed tablets and the contents of emptied capsules may be mixed with beverages, soft foods, enteral formulas, or extemporaneously prepared in syrups and other liquid vehicles. However, problems can occur when some products are altered. Sustained-release and enteric-coated products should not be crushed because the bioavailability of the medication will be altered. Foods, enteral for- mulas, and liquid vehicles can interact with medications and alter bioavailability and other phys- iochemical properties. Some patients susceptible to fl uid overload (e.g., those with renal failure) may require oral liquid and parenteral medications to be prepared in more concentrated forms when appropriate concentrations are not commercially available. Care must be taken to ensure that appropriate concentrations and diluents are used. Medication-related problems that may occur in adults include1 Many factors increase the potential for ADRs and other medication-related problems in adults. Adults often take a large number of medications to treat concurrent chronic illnesses such diabetes and hypertension. Multiple diseases often mean more medications thereby increasing the potential for ADRs because of possible additive drug effects, interactions, nonadherence, and other medication-related problems. The presence of concurrent disease states can affect the dis- position of, as well as response to, medications. For example, renal and hepatic insuffi ciency may lead to decreased metabolism and elimination of medications, resulting in drug accumulation and toxicity. Polypharmacy may also interfere with laboratory tests used in monitoring disease states and medication therapy. Certain factors of an individual’s lifestyle, such as the presence of substance abuse (e.g., tobacco, alcohol, or illicit drugs), the use of nutritional supplements, and the level of physical activity may also produce physiological changes that affect drug kinetics and dynamics. Examples include decreased serum theophylline concentrations resulting from smoking tobacco or consuming alcohol, and acetaminophen toxicity in chronic alcohol users. Inactive ingredients in medication formulations (e.g., ethanol, sucrose, sorbitol, and dyes) may have adverse effects on adult patients. For example, drug formulations containing ethanol can negatively affect some disease states (e.g., diabetes mellitus and alcoholism) and produce a disulfiram-like reaction when given in combination with certain medications (e.g., metronida- zole). Formulations containing large amounts of sucrose (e.g., some psyllium products) may impact glycemic control in patients with diabetes. Excess sorbitol may produce diarrhea and abdominal cramping. Nonadherence is another factor that may cause medication-related problems. Methods of administration, frequency of dosing, and combinations of medications all affect patient adherence to medication therapy. Nonadherence generally increases as the number of different medications increases and the frequency of dosing increases. Unpleasant side effects and the cost of medications are other factors that may cause therapy to be interrupted or discontinued. Patients may be nonadherent with medication regimens that are complex, inconvenient, or require lifestyle changes. In addition, patients may not understand or recall medication therapy information or they may not understand how to use measuring and administration devices correctly. The use of multiple physicians and pharmacies and self-medication with nonprescription (OTC) medications, herbal products, and dietary supplements can also increase medication- related problems, such as therapeutic duplication, drug-drug interactions, and the incidence and severity of ADRs. Managing Medication Therapy for Adults Medication therapy for adults should be carefully managed to ensure positive therapeutic outcomes and minimize medication errors and other medication-related problems. Proper selection and monitoring of medication therapy includes consideration of the following factors: 1. Presence of concurrent disease states 2. Renal and hepatic function and other factors involved in drug disposition 3. Physical and psychological considerations (e.g., physical and mental abilities and hearing or 4. Socioeconomic factors (e.g., income, education level, family relationships and support systems, 5. Lifestyle choices (e.g., substance abuse, nutritional habits, and level of physical activity) 6. Drug characteristics (e.g., kinetic and dynamic characteristics, dosage form, dosing frequency, side effect profile, method of administration, monitoring requirements, and cost) Precautions that can minimize medication-related problems in adults include the following: 1. Ensure complete and accurate medication orders and records. Orders should include medi- cation name, dose, dosage form, strength, route, frequency or rate, the site of administra- tion (when appropriate), and the intended use of the medication. 2. Use appropriate doses. Modify doses for patients with renal insufficiency or hepatic dys- function as wel as those who are obese or severely underweight. Adjustments may also be necessary when changing from one dosage form or route of administration to another. Adjust doses, if necessary, to ensure that doses are appropriate. 3. Use a system of double checks. Have another individual check the accuracy of calculations, 4. Use unit-dose or unit-of-use packages. These minimize the need for calculations and prepa- ration of medications outside of the pharmacy. 5. Avoid polypharmacy whenever possible, and keep medication regimens simple. Some medications can benefit multiple conditions, reducing the number of drugs used or the required dosage of another medication because of additive effects. For example, an ACE inhibitor can treat congestive heart failure and hypertension, plus protect renal function in a patient with diabetes and heart disease. If possible, choose drugs with a low dosing frequency. Nonpharmacological management should be considered when appropriate (e.g., 6. Monitor for adverse drug reactions and drug-drug, drug-food, drug-laboratory test, and 7. Monitor the patient’s response and serum drug concentrations, when appropriate. This ensures therapeutic efficacy and reduces the potential for ADRs. 8. Educate patient’s. A critical part of patient education is the assessment of the patient’s (or caregiver’s) level of comprehension and tailoring communication to meet the patient’s needs. For each therapy, counsel patients and caregivers about dosing schedules, side effects, and expected therapeutic outcomes as well as demonstrate administration techniques and measurement of doses. Use communication methods that overcome barriers to effective counseling. Discourage nonprescription medication use, unless directed by a physician or pharmacist, and encourage patients to inform healthcare providers if using nonprescription medications, herbal products, or dietary supplements. Reference 1. Strand LM, Morley PC, Cipol e RJ, et al. Drug-related problems: their structure and function. Resources American Society of Health-System Pharmacists. Clinical S kil s Program: Pharmacotherapy S eries. 2nd ed. Bethesda, MD: American Society of Health-System Pharmacists; 1992-3. Cohen MR, ed. Medication E rrors. 2nd ed. Washington, DC: American Pharmaceutical Association;

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Nanostructured and Multilayered Active Materials for Clinical Applications S. FACCA1, A. DIERICH2, J.-C. VOEGEL1, N. BENKIRANE-JESSEL1 1Institut National de la Santé et de la Recherche Médicale, Unité 977, Faculté de Médecine, 11 rue Humann, 67085, Strasbourg Cedex, France and Faculté de Chirurgie Dentaire, UDS, Strasbourg 2Institut de Génétique et de Biologie Moléculaire et Cellulaire

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DIREKTORAT JENDERAL PELAYANAN KEFARMASIAN DAN ALAT KESEHATAN UNDANG – UNDANG REPUBLIK INDONESIA NOMOR 5 TAHUN 1997 P S I K O T R O P I K A DENGAN RAHMAT TUHAN YANG MAHA ESA PRESIDEN REPUBLIK INDONESIA, Menimbang : a. bahwa pembangunan nasional bertujuan untuk mewujudkan suatu masyarakat adil dan makmur yang merata materil dan spiritual berdasarkan Pancasila dan Undang

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