S. Snorre. Southern Utah University.

Initial dose of 5 µg/24h order tofranil 50 mg with mastercard, then titrate by 5 µg/24h increments at 1–2-wk intervals; maintenance 25–75 µg/24h PO qd SUPPLIED: Tabs 5 order tofranil 50 mg otc, 25 discount tofranil 75 mg line, 50 µg; inj 10 µg/mL NOTES: ↓ Dose in elderly; monitor TFT Lisinopril (Prinivil, Zestril) COMMON USES: HTN, heart failure, and AMI ACTIONS: ACE inhibitor DOSAGE: 5–40 mg/24h PO qd–bid. AMI: 5 mg within 24h of MI, followed by 5 mg after 24h, 10 mg after 48 h, then 10 mg/d SUPPLIED: Tabs 2. High lipid solubility translates into excellent penetra- tion into the CNS Loperamide (Imodium) COMMON USES: Diarrhea 22 ACTIONS: Slows intestinal motility 22 Commonly Used Medications 563 DOSAGE: Adults. Status epilepticus: 4 mg/dose IV may be re- peated at 10–15-min intervals; usual total dose 8 mg. Supplement: 1–2 g IM or IV; repeat dosing based on response and continued hy- pomagnesemia. Highly volatile; must be administered within 30–60 min of preparation Meclizine (Antivert) COMMON USES: Motion sickness; vertigo associated with diseases of the vestibular system ACTIONS: Antiemetic, anticholinergic, and antihistaminic properties DOSAGE: Adults & Peds >12 y. Abnormal uterine bleeding: 5–10 mg/d PO for 5–10 d beginning on the 16th or 21st d of the menstrual cycle. Appetite: 800 mg/d PO SUPPLIED: Tabs 20, 40 mg; soln 40 mg/mL NOTES: May induce DVT; do NOT abruptly discontinue therapy Meloxicam (Mobic) COMMON USES: Osteoarthritis ACTIONS: NSAID agent DOSAGE: 7. ABMT: 140–240 mg/m2 IV SUPPLIED: Tabs 2 mg; inj 50 mg NOTES: Toxicity symptoms: Myelosuppression (leukopenia and thrombocytopenia), secondary leukemia, alopecia, dermatitis, stomatitis, and pulmonary fibrosis; very rare hypersensitivity reac- tions Meperidine (Demerol) [C-II] COMMON USES: Relief of moderate to severe pain ACTIONS: Narcotic analgesic DOSAGE: Adults. Concurrent allopurinol therapy requires a 67–75%↓of 6-MP because of interference with metabolism by xanthine oxidase Meropenem (Merrem) COMMON USES: Serious infections caused by a wide variety of bacteria including intraabdominal and polymicrobial; bacterial meningitis ACTIONS: Carbapenem; inhibition of cell wall synthesis, a β-lactam DOSAGE: Adults. Oral: 800–1000 mg PO 3–4×/d 22 SUPPLIED: Tabs 400 mg; caps 250 mg; supp 500 mg; rectal susp 4 g/60 mL 22 Commonly Used Medications 567 Mesna (Mesnex) COMMON USES: ↓ Incidence of ifosfamide and cyclophosphamide-induced hemorrhagic cystitis ACTIONS: Antidote DOSAGE: 20% of the ifosfamide dose (+/–) or cyclophosphamide dose IV at 15 min prior to and 4 and 8 h after chemotherapy SUPPLIED: Inj 100 mg/mL Mesoridazine (Serentil) COMMON USES: Schizophrenia, acute and chronic alcoholism, and chronic brain syndrome ACTIONS: Phenothiazine antipsychotic DOSAGE: Initially, 25–50 mg PO or IV tid; ↑ to a max of 300–400 mg/d SUPPLIED: Tabs 10, 25, 50, 100 mg; oral conc 25 mg/mL; inj 25 mg/mL NOTES: Low incidence of extrapyramidal side effects Metaproterenol (Alupent, Metaprel) COMMON USES: Bronchodilator for asthma and reversible bronchospasm ACTIONS: Sympathomimetic bronchodilator DOSAGE: Adults. Inhal: 1–3 inhal q3–4h to a max of 12 inhal/24h; allow at least 2 min between inhal. Mandelate: 50–75 mg/kg/d ÷ qid SUPPLIED: Methenamine hippurate (Hiprex, Urex): 1-g tabs. Methenamine mandelate: 500 mg/1 g EC tabs NOTES: Contra in patients with renal insufficiency, severe hepatic disease, and severe dehydration Methimazole (Tapazole) COMMON USES: Hyperthyroidism and preparation for thyroid surgery or radiation ACTIONS: Blocks the formation of T3 and T4 DOSAGE: Adults. Maintenance: 1⁄3–⁄23 of the initial dose PO qd SUPPLIED: Tabs 5, 10 mg NOTES: Follow patient clinically and with TFT Methocarbamol (Robaxin) COMMON USES: Relief of discomfort associated with painful musculoskeletal conditions ACTIONS: Centrally acting skeletal muscle relaxant DOSAGE: Adults. High-dose therapy requires leucovorin rescue to prevent severe hematologic and mucosal toxicity (see page 559); monitor blood counts and MTX levels carefully Methoxamine (Vasoxyl) COMMON USES: Support, restoration, or maintenance of blood pressure during anesthesia; for ter- mination of some episodes of PSVT ACTIONS: α-Adrenergic DOSAGE: Adults. Metoclopramide (Reglan, Clopra, Octamide) COMMON USES: Relief of diabetic gastroparesis; symptomatic GERD; relief of cancer chemother- apy-induced nausea and vomiting ACTIONS: Stimulates motility of the upper GI tract and blocks dopamine in the chemoreceptor trig- ger zone DOSAGE: Adults. Diabetic gastroparesis: 10 mg PO 30 min ac and hs for 2–8 wk PRN; or same dose given IV for 10 d, then switch to PO. Antiemetic: 1–3 mg/kg/dose IV 30 min prior to antineoplastic agent, then q2h for 2 doses, then q3h for 3 doses. Antiemetic: 1–2 mg/kg/dose IV on the same schedule as for adults SUPPLIED: Tabs 5, 10 mg; syrup 5 mg/5 mL; soln 10 mg/mL; inj 5 mg/mL NOTES: Dystonic reactions common with high doses; can be treated with IV diphenhydramine; can also be used to facilitate small bowel intubation and radiologic evaluation of the upper GI tract Metolazone (Mykrox, Zaroxolyn) COMMON USES: Mild to moderate essential HTN and edema of renal disease or cardiac failure ACTIONS: Thiazide-like diuretic; inhibits reabsorption of sodium in the distal tubules DOSAGE: Adults. Amebic dysentery: 35–50 mg/kg/24h PO in 3 ÷ doses for 5–10 d SUPPLIED: Tabs 250, 500 mg; ER tabs 750 mg; caps 375 mg; topical lotion and gel 0. Day 2: ACTH test, administer 50 U of ACTH infused over 8 h and measure 24-h urinary steroids. Day 6: Determine 24-h urinary steroids SUPPLIED: Tabs 250 mg (Limited availability in U. Maintenance dose: 2–3 g/d ÷ qid SUPPLIED: 250 mg caps NOTES: Administer at least 5–7 d preop Mexiletine (Mexitil) COMMON USES: Suppression of symptomatic ventricular arrhythmias; diabetic neuropathy ACTIONS: Class IB antiarrhythmic DOSAGE: Administer with food or antacids; 200–300 mg PO q8h; do not exceed 1200 mg/d SUPPLIED: Caps 150, 200, 250 mg NOTES: Do NOT use in cardiogenic shock or 2nd- or 3rd-degree AV block if no pacemaker; may worsen severe arrhythmias; monitor LFT during therapy; drug interactions with hepatic enzyme in- ducers and suppressors requiring dosage changes Mezlocillin (Mezlin) COMMON USES: Infections caused by susceptible strains of gram (−) bacteria (including Kleb- siella, Proteus, E. Candidiasis: 600–1800 mg/day ÷ Q8h Intravaginally: Insert 1 applicatorful or supp hs for 7 d SUPPLIED: Topical cream 2%; lotion 2%; powder 2%; spray 2%; vaginal supp 100, 200 mg; vaginal cream 2%, IU forms NOTES: Antagonistic to amphotericin B in vivo; rapid IV infusion may cause tachycardia or ar- rhythmias; may potentiate warfarin drug activity Midazolam (Versed) [C-IV] COMMON USES: Preoperative sedation, conscious sedation for short procedures, and induction of general anesthesia ACTIONS: Short-acting benzodiazepine DOSAGE: Adults. DOSAGE: 15 mg PO hs, up to 45 mg/d hs SUPPLIED: Tabs 15, 30, 45 mg NOTES: Do NOT ↑ dose at intervals of less than 1–2 wk; may cause agranulocytosis Misoprostol (Cytotec) COMMON USES: Prevention of NSAID-induced gastric ulcers ACTIONS: Synthetic prostaglandin with both antisecretory and mucosal protective properties DOSAGE: 200 µg PO qid with meals SUPPLIED: Tabs 100, 200 µg NOTES: Do NOT take during PRG; can cause miscarriage with potentially dangerous bleeding; GI side effects common Mitomycin C (Mutamycin) COMMON USES: Adenocarcinomas of the stomach, pancreas, colon, and breast; non-small-cell lung cancer; head and neck cancer; cervical cancer; squamous cell carcinoma of the anus; and blad- der cancer (intravesically) ACTIONS: Alkylating agent; may also generate oxygen free radicals, which induce DNA strand breaks DOSAGE: 20 mg/m2 q 6–8 wk or 10 mg/m2 in combination with other myelosuppressive drugs; bladder cancer 20–40 mg in 40 mL of NS via a urethral catheter once/wk for 8 wk, followed by monthly treatments for 1 y SUPPLIED: Inj NOTES: Toxicity symptoms: Myelosuppression, which may persist up to 3–8 wk after a dose and may be cumulative (minimized by a lifetime dose <50–60 mg/m2), nausea and vomiting, anorexia, stomatitis, and renal toxicity. Microangiopathic hemolytic anemia (similar to hemolytic-uremic syndrome) with progressive renal failure. Venoocclusive disease of the liver, interstitial pneumonia, and alopecia (rare); extravasation reactions can be severe. Adjust dose in renal impairment Mitotane (Lysodren) COMMON USES: Palliative treatment of inoperable adrenal cortex carcinoma ACTIONS: Exact action unclear; induces mitochondrial injury in adrenocortical cells DOSAGE: 8–10 g/d in 3–4 ÷ doses (begin at 2 g/d with full glucocorticoid replacement therapy) SUPPLIED: Tabs 500 mg NOTES: Toxicity symptoms: Anorexia, nausea and vomiting, and diarrhea. Acute adrenal insuffi- ciency may be precipitated by physical stresses (shock, trauma, infection), in which case cortico- steroid replacement necessary.

Solu- tion 2 is designed to be given at a maximum rate of 125 mL/h generic tofranil 75mg without prescription, but this only provides 1275 Cal from dextrose and must be supplemented with a fat emulsion (10% 500 mL = 550 Cal generic tofranil 50mg line, 20% 500 mL = 1000 Cal) order tofranil 25mg with amex. Many hospitals have adopted a “three-in-one” solution for the standard house formula. This involves the administration of protein, carbohydrate, and fat from the same TPN bag over a 24-h period; in other words, the fat is not administered peripherally through a sepa- rate site. Caution should be used when altering the standard formula in this situation be- cause the fat emulsion may be less stable to additives and makes incompatibilities less visible. For example, the solution will be milky in color, and a calcium–phosphate problem, normally easily seen, would not be apparent. Additions to these formulations should be done in conjunction with a pharmacist to ensure that precautions are taken for appropriate addi- tive concentrations. Remember, the solutions described in Table 12–1 contain full concentrations of elec- trolytes and are for patients with normal renal function. For patients with renal impairment, the concentrations of potassium, magnesium, phosphorus, and protein should be reduced (see page 235). PERIPHERAL PARENTERAL NUTRITION If a deep line is contraindicated or impossible, a peripheral TPN solution (<7% dextrose with 2. A posi- 12 Total Parenteral Nutrition 231 tive nitrogen balance will not be achieved in most patients receiving parenteral nutrition by this route. A product conforming to recommen- dations of the American Medical Association Nutrition Advisory Group is usually used, such as multivitamin infusion-12 (MVI-12). In addition to MVI-12, 5–10 mg of vitamin K (phytonadione) must be given IM weekly. Trace element deficiencies are rare in hospitalized patients receiving short-term TPN supplements. Supplementation should be routine, however, to ensure trace element avail- ability for cell restoration. In patients receiving long-term support or home TPN, additional trace element supplementation may be necessary. Note, however, that owing to the inconvenience of its administration, many clinicians avoid in- jectable iron–dextran. A complete medical and hematologic work-up is often indicated be- fore instituting parenteral iron replacement. Anaphylaxis is rare, but a period of 1h should elapse before the therapeutic dose of iron is administered. Use the following equation to determine the dose of iron: Total replacement dose (mL) = 0. The calculated dose should be added to TPN at 2 mL/L until the entire dose has been given. TABLE 12–2 Typical Vitamins Provided in 1 L of TPN by Adding 2 Vials of Standard MVI–12 Ascorbic acid 100 mg Pyridoxine (B6) 4 mg Vitamin A 3300 IU Dexpanthenol 15 mg Vitamin D 200 IU Vitamin E (α tocopherol) 10 IU Biotin 60 µg Thiamine (B1) 3 mg Folic acid 400 µg Riboflavin (B2) 3. Insulin, when required, can be given subcutaneously as regular insulin using a sliding scale, as shown in Table 12–4. This allows a constant infusion of insulin along with the infusion of dex- trose, which avoids the peaks and valleys in blood glucose that occur when the sliding scale is used. Insulin drips are not advised because TPN can be tem- porarily or permanently discontinued, which would then stop the insulin. This could be done with minimal supplementation; as little as 4% of total calories per day would prevent the syndrome of EFAD. Most clinicians prescribe 500 mL of 10% lipid emulsion three times weekly to prevent this syndrome. The signs and symptoms of this deficiency include scaling skin rash, alopecia, and wound healing failure. TABLE 12–4 Sliding Scale for Insulin Orders Regular Insulin Dose Urine Glucose* (Units, given SQ) 0–1+ 0 2+ 5 3+ 10 4+ 15 Any acetone: call house officer *Should be checked every 6 h as part of standing TPN orders.

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For example generic tofranil 75 mg otc, concerns about acceptable actions buy tofranil 75mg on line, religious beliefs order tofranil 75mg with mastercard, and knowledge of beneficence motivate physicians, pharmacologists, phar- the law are frequently insufficient to guide moral ac- macists, and clinical investigators, all of whom share the tion, in the realm of health care. Solving problems that goal of conducting studies that will ultimately benefit arise in the scientific and clinical contexts requires society by producing or refining effective treatments. While bioethical analysis is multifac- sionals have an obligation to prevent harm or if harm is torial, four moral principles play key roles in establish- unavoidable, minimize that harm. This principle plays an 73 74 I GENERAL PRINCIPLES OF PHARMACOLOGY important role in clinical research, as it entails an obli- • Proposed studies must have sufficient scientific gation to minimize risks to each participant. The principle of justice states that individuals should • Researchers are obligated to stop the study if be given what they deserve, be that benefit or burden. The The guidelines further require that research on hu- principle of justice does not specifically state what dis- man subjects be conducted by qualified individuals and tinctions are fair or which criteria are reasonable; it sim- that most clinical research be reviewed by an independ- ply requires that, once criteria are determined, they be ent committee, which is generally an institutional re- applied fairly. For example, researchers must guard against of Helsinki, The International Ethical Guidelines for distributing the burdens of participation disproportion- Biomedical Research Involving Human Subjects was ately among populations that are poorly equipped to issued in 1982 and revised in 1993 by the Council for give informed consent, such as children or the mentally the International Organization of Medical Sciences incompetent. Those guidelines define national policies for The principles of autonomy, beneficence, nonmalefi- biomedical research, apply ethical standards to the cir- cence, and justice form a foundation for analysis of eth- cumstances often present in research in economically ical quandaries. In addition, a comprehensive ethical developing nations, and define mechanisms for ethical analysis will include considerations of cultural and reli- review of human subjects research. In ternational medical research, especially that done with 1948, in response to the atrocities perpetrated by Nazi patients in economically developing nations. For ex- experimentation, the Nuremberg Code was developed ample, one controversy focused on a highly publicized to set forth guidelines for the acceptable conduct of sci- placebo-controlled study in Africa examining the pre- entific research. In 1964 the World Medical Association vention of perinatal transmission of HIV using azi- adopted the Declaration of Helsinki, which specifically dothymidine (AZT). These docu- ically developed nation would probably not have a ments specify basic moral guidelines ultimately founded placebo arm, critics argue that this reflects a double on concerns for autonomy, beneficence, and justice. They assert that one standard guidelines require the following: for ethical research should prevail, regardless of the social and economic conditions of the subjects. The pharmaceutical industry com- efit over and above the status quo, they assert, and did bines a desire for discovery and development with not deprive subjects of anything they could otherwise profit-motivated marketing and sales goals. Yet such “studies in nature” pose complex ethi- scientists and physicians share the desire for drug dis- cal issues. If the research relies on the continuation of covery and development and are motivated by the de- undesirable social conditions, such as the general lack of sire to contribute to scientific advancement and im- prenatal care, critics assert that there is a fundamental proved patient care, pharmaceutical companies are obligation to improve those background conditions simultaneously under strong commercial pressures. In some cases, this financial so, is that the role of pharmaceutical research or a support may compromise professional judgment in con- broader social role that goes beyond what researchers ducting, analyzing, or reporting research. While it would be foolhardy to For example, often a pharmaceutical company will insist that the only ethically acceptable research is done contract with a private physician to recruit patients into on patients with full access to comprehensive health a drug study. While this arrangement frequently offers care, we do not want to make those who are already de- patients access to treatment that might otherwise be un- prived and in poverty into “lab rats” who participate in available, the potential conflict may ultimately result in research that ultimately benefits primarily those in the lack of objectivity in study design, data interpretation, developed world. For example, a Clinical research can target the needs of those in 1986 study in the Journal of General Internal Medicine economically developing nations and those who are found a statistically significant relationship between medically underserved in the United States. Yet we drug company funding and outcomes favoring a new must be cautious in the design and implementation of therapy. The doctor assumes a position of re- must satisfy the needs of the population in which it is sponsibility to the company while simultaneously main- undertaken, and the products developed during the taining the usual duties to protect and benefit his or her course of the research must subsequently be made rea- patients. The pharmaceutical industry depends on scientists enroll and advised of any potential conflicts between and clinicians for research, development, and marketing. Although disclosure to patients is important, pa- While this interdependence often benefits industry, re- tients are generally ill suited to assess how a potential search, and patient care, conflicts of interest may arise in conflict of interest actually affects their treatment. In two main areas: (1) drug research and development and addition to disclosure to patients, we need rigorous re- (2) clinical education and product marketing. Although such visits may keep clini- cians informed about current products, they may also Clinical Education and Product precipitate conflicts of interest. Gifts of more than to- Marketing ken value, trips to resort areas for “educational” pro- The second area for ethical concern is clinical education grams with little scientific merit, and cash incentives for and product marketing.

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Although surgical research has focused on pathology since the 19th century purchase 25mg tofranil fast delivery, largely following the Virchow tradition tofranil 25 mg with amex,9 purchase tofranil 25 mg mastercard,10 pathology is not linearly associated with the final clinical outcomes noticed by patients and surgeons. It is therefore necessary to consider pathological findings with other outcome measures such as impairment. Pathological measures are often primary methods (separate from the symptoms associated with the primary disease) for understanding whether a treatment is © 2005 by CRC Press LLC working. For example, measurement of the size of a brain tumor on MRI scans can form a primary data source with which to compare various chemotherapy treatment regimens. In spine studies, radiographic fusion is often used as a surrogate marker for success of a fusion procedure, even though this marker does not appear to correlate with patient outcomes in most other respects. Clearly, the use of pathological measures may be an important basis to decide on treatment efficacy at a basic level, but these measures likely require supplementation with other types of outcomes to decide whether a treatment on the whole is worthwhile at patient level. Active pathology may result in some type of impairment, but not all impairments are associated with active pathology (e. Impairments can usually be objec- tively specified by an observer such as a physician or surgeon, and are classified in a standard text, the American Medical Association Guide to Impairment. For example, a limitation in shoulder range of motion secondary to a cerebral vascular accident may greatly affect the life of an active patient and be of little importance to a sedentary elderly patient. We will focus our discussion on the disablement model developed by Saad Nagi, a sociolo- gist,12 the International Classification of Impairments, Disabilities and Handicaps (ICIDH-1),13 and its current revision, the International Classification of Functioning, Disability and Health (ICF). It may not constitute a disability for some occupations (manual laborer) but would produce complete disability for others (concert pianist, surgeon). This is a fundamental distinction of critical importance to scholarly discussion and research related to disability phenomena. We will not review the ICIDH-1 classification except to note that in principle this original system was designed as a model for coding and manipulating data on the consequences of health conditions. Part 1 covers functioning and disability including body functions, structures, activities, and participation. Each component consists of various domains and, within each domain, categories that are the units of classification. This view fails to recognize that disablement is more often a dynamic process that can fluctuate in breadth and severity across the life course; it is anything but static or unidirectional. More recent disablement formulations and elaborations of earlier models have explicitly acknowledged that the disablement process is far more dynamic. In these newer concepts, a given disablement process may lead to further downward spiraling consequences. Pope and Tarlov15 use secondary conditions to describe any type of secondary consequence of a primary disabling condition. Commonly reported sec- ondary conditions include pressure sores, contractures, depression, and urinary tract infections, but it should be understood that they can be pathologies, impairments, functional limitations, or additional disabilities. Longitudinal analytic techniques now exist to incorporate secondary conditions into research models and are beginning to be used in disablement epidemiologic investigations. Because patient satisfaction is a multidimensional concept, it is important to start by understanding its multiple definitions. Patient satisfaction is a complex concept that may incorporate sociode- mographic, cognitive, and affective components. Although many theories for patient satisfaction have been proposed, few have been extensively tested and validated in different health care settings. Moreover, few studies have been conducted to explain associations between patient satisfaction and patient characteristics or subsequent patient behaviors. Although theories of patient satisfaction are difficult to categorize in an organized and easily comprehensible fashion, one may group these theories into intrapatient comparisons (disconfirmation theory) and differences between individual patients and health care providers (attribution theory) or other patients (equity theory). Intrapatient comparison theories explain the satisfaction phenomenon by a match between patient expectations and perceptions of medical care. Differences between what is expected and what is perceived to occur will contribute to patient satisfaction or dissatisfaction.

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