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To prepare answers or appropriate therapeutic • Actively integrating what you read with previous parts of the text methocarbamol 500 mg free shipping spasms on right side of head. The active learning strategies outlined previously allow In writing order discount methocarbamol on-line muscle relaxant with alcohol, consider summarizing the major points of each class buy methocarbamol 500mg lowest price spasms upper left quadrant. In classes that involve active learning order methocarbamol 500 mg otc xanax spasms, you To implement active learning strategies in the classroom, teachers may write for “think-pair-share” exercises, quizzes, summary para- must overcome the anxiety that change often creates. Stopping to write allows you to reflect ing with active learning methods such as the pause technique and on the information you have just heard and reinforces learning. Discussing material Using any of the active learning strategies requires teachers to helps you to apply your knowledge, verbalize the medical and encourage as much classroom discussion as possible instead of pharmacologic terminology, engage in active listening, think criti- lecturing. Teaching others is effort to learn the names of all students so they can more easily an excellent way to learn the subject matter. In addition, teachers should have a precon- ceived plan for how the class discussion will go and stick to it. It is important for students to realize that Taking initiative is the key to deriving the benefits of active learning. Students are encouraged to solve each of the cases individ- laziness, fear of change, and force of habit. The student will begin In active learning, you are expected to talk about what you are to appreciate the variety and complexity of diseases that are encoun- learning, write about it, relate it to previous patient cases, and apply it tered in different patient populations. In a sense, you repeatedly manipulate the information from the patient will play a pivotal role in drug therapy information until it becomes a part of you. In others, some diagnoses can be resolved when studying are to compare, contrast, and summarize similarities through use of laboratory analysis or specific medical tests. Some and differences among disease states, drug classes, and appropriate cases may require a much more in-depth assessment of the patient’s pharmacotherapy. Attempt to relate personal experiences or initiation of both nonpharmacologic and pharmacologic therapy, outside events to topics discussed in class, and always be an active ranging from single to multiple drug regimens. These will be your personal set of notes medicinal chemistry, pharmacology, pharmacokinetics, pharmaco- to study for the course exams and to review for the pharmacy state economics, drug literature evaluation, ethics, physical assessment). While taking notes in class, leave a wide margin on As a consequence, students may need to review previous notes, the left to write down questions that you generate later when reviewing handouts, or textbooks. When time allows, seek out recent information on subjects Pharmacotherapy: A Pathophysiologic Approach are essential in sup- that interest you. Use Web-based cases and other online resources to porting each student’s ability to solve the cases successfully. Under- extend your knowledge on a particular disease state and drug ther- standing the usefulness and limitations of these resources will be apy. Likewise, discussions in study groups and Some other methods for maximizing active learning are to review class should lead to a further understanding of disease states and corrected assignments and exams for information that you do not treatment strategies. You will probably find that you read more, but you will gain The use of case studies and other active learning strategies will understanding from reading. At the same time, you are developing enhance the development of essential skills necessary to practice in 10 any setting, including community, ambulatory care, primary care, 11. Using the pause procedure to enhance health-systems, long-term care, home health care, managed care, lecture recall. Quick-thinks: active-thinking tasks in lecture strategies into the classroom are facilitating the development of classes and televised instruction. Acad Med based learning: Students’ comments on the value of using real, as 2000;75(10, Suppl):S90–S92. While all pharmacists are well versed in the traditional approach never verifies that the patient understands how to technical aspects of the profession, many are not well prepared properly use his or her medication, which can lead to poor outcomes. Given the low level of patient health literacy in the United States, In contemporary pharmacy practice, good communication skills are reliance on written patient handouts may also lead to a similar level of critical for achieving optimal patient outcomes and increasing poor patient outcomes. The focus of tional approach, the “teachback” method, the Indian Health Service this chapter is limited to the essential skills needed for symptom Pharmacy program developed a needs-based interactive medication assessment, medication consultation, and strategies to improve counseling technique, with the goal of verifying patient understanding. Readers are encouraged Using open-ended questions to initiate dialogue negates the to review aspects of basic communication skills in other sources. Finally, the consultation is One of the most important techniques to effectively communicate quicker, and you maintain the patient’s attention span because you with patients is the primary use of open-ended questions. Closed-ended can be answered with either a simple One is for new prescriptions (Prime Questions), and the other is for yes or no answer and start with can, do, did, are, would, or could. Open-ended questions have numerous advantages compared to These open-ended questions make the patient an active participant in closed-ended questions. They provide an organized approach to ascertain siveness and accuracy of patient responses compared to closed- what the patient already knows about the medication. Open-ended questions help readily identify systematic approach has been associated with improved recall of patients with special needs requiring interventions, including prescription instructions. It spares the pharmacist from repeating patients with special needs to go undetected by hiding behind their information already known by the patient, which is an inefficient use yes or no answers. Finally, Open the Consultation open-ended questions force the patient to answer with something When the patient is called for counseling, introduce yourself by name other than yes or no, encouraging dialogue or further conversation and state the purpose of the consultation. Closed-ended questions are perceived by patients identity, either by asking for identification or at least by asking, “And as discouraging further response and are used to bring closure to you are…? Whether collecting information regarding a patient’s otherwise unable to provide his or her name, or answers inappropri- symptoms or verifying that patients understand how to take their ately to a question, you have identified a barrier in the consultation medication during medication counseling, the use of open-ended that must be overcome before discussing the medication. Consultation on prescription medication use is a fundamental and important activity of the pharmacist and is mandated by both state 6 Conduct the Counseling Session and federal law or regulation. The primary goal of traditional meth- for New Prescriptions ods of medication counseling is to provide information: the pharma- cist “tells” and the patient “listens. If there are gaps in the patient’s understanding, the Prime questions pharmacist “fills in the gap” by providing the missing information 1. If the patient is able to or tell you what the medication is for (the first question), move to the What were you told the medication is for? Rather than providing facts, consider asking the patient, What should you do if a bad reaction occurs or if the medication doesn’t work? After verifying patient understanding about how to take the medi- The pharmacist begins the process by showing the medication to the cation, proceed to the third prime question. Note that the doctor verifies the patient’s understanding of potential common and uncom- is omitted as a reference, because the patient should have been mon (but serious) adverse effects plus what to do if a bad effect occurs. The show- the pharmacist should warn about mild cough (talk with your physi- and-tell technique enables the pharmacist to detect problems with cian) and any sudden swelling in the face, mouth, or tongue (get to an compliance or unwanted drug effects. If the patient answers incor- emergency room), which may represent the uncommon but poten- rectly to the second question, the patient may be noncompliant, or tially serious adverse effect of angioedema. The pharmacist will patients want information about their medications, especially adverse need to further define the reason for the discrepancy. The second effects, and that providing such information does not lead to the 9–11 show-and-tell question also allows the pharmacist to ask the patient development of those reactions.
When the dosing interval is 12 hours cheap methocarbamol 500mg with mastercard muscle relaxant drug class, the size of each maintenance dose would be: A tablet or capsule size close to the ideal dose of 350 mg would then be prescribed at 12-hourly intervals cheap methocarbamol 500 mg on line spasms 1983 movie. If an 8- hour dosing interval was used discount methocarbamol 500 mg otc spasms hands fingers, the ideal dose would be 233 mg; and if the drug was given once a day cheap 500mg methocarbamol amex spasms from catheter, the dose would be 700 mg. For the theophylline example given in the Box, Example: Maintenance Dose Calculations, the loading dose would be 350 mg (35 L × 10 mg/L) for a 70-kg person. Up to this point, we have ignored the fact that some drugs follow more complex multicompartment pharmacokinetics, eg, the distribution process illustrated by the two-compartment model in Figure 3–2. However, in some cases the distribution phase may not be ignored, particularly in connection with the calculation of loading doses. If the rate of absorption is rapid relative to distribution (this is always true for rapid intravenous administration), the concentration of drug in plasma that results from an appropriate loading dose—calculated using the apparent volume of distribution—can initially be considerably higher than desired. This may be particularly important, eg, in the administration of antiarrhythmic drugs such as lidocaine, where an almost immediate toxic response may occur. Thus, while the estimation of the amount of a loading dose may be quite correct, the rate of administration can sometimes be crucial in preventing excessive drug concentrations, and slow administration of an intravenous drug (over minutes rather than seconds) is almost always prudent practice. When intermittent doses are given, the loading dose calculated from equation (12) will only reach the average steady- state concentration and will not match the peak steady-state concentration (Figure 3–6). In addition, it may be necessary to consider two pharmacodynamic variables: maximum effect attainable in the target tissue and the sensitivity of the tissue to the drug. Diseases may modify all of these parameters, and the ability to predict the effect of disease states on pharmacokinetic parameters is important in properly adjusting dosage in such cases. Input The amount of drug that enters the body depends on the patient’s adherence to the prescribed regimen and on the rate and extent of transfer from the site of administration to the blood. The Target Concentration Strategy Recognition of the essential role of concentration in linking pharmacokinetics and pharmacodynamics leads naturally to the target concentration strategy. Pharmacodynamic principles can be used to predict the concentration required to achieve a particular degree of therapeutic effect. This target concentration can then be achieved by using pharmacokinetic principles to arrive at a suitable dosing regimen (Holford, 1999). The target concentration strategy is a process for optimizing the dose in an individual on the basis of a measured surrogate response such as drug concentration: 1. Overdosage and underdosage relative to the prescribed dosage—both aspects of failure of adherence—can frequently be detected by concentration measurements when gross deviations from expected values are obtained. If adherence is found to be adequate, absorption abnormalities in the small bowel may be the cause of abnormally low concentrations. Variations in the extent of bioavailability are rarely caused by irregularities in the manufacture of the particular drug formulation. Clearance Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. However, for many other drugs known to be eliminated by hepatic processes, no changes in clearance or half-life have been noted with similar hepatic disease. At present, there is no reliable marker of hepatic drug-metabolizing function that can be used to predict changes in liver clearance in a manner analogous to the use of creatinine clearance as a marker of renal drug clearance. Volume of Distribution The apparent volume of distribution reflects a balance between binding to tissues, which decreases plasma concentration and makes the apparent volume larger, and binding to plasma proteins, which increases plasma concentration and makes the apparent volume smaller. Changes in either tissue or plasma binding can change the apparent volume of distribution determined from plasma concentration measurements. Older people have a relative decrease in skeletal muscle mass and tend to have a smaller apparent volume of distribution of digoxin (which binds to muscle proteins). The volume of distribution may be overestimated in obese patients if based on body weight and the drug does not enter fatty tissues well, as is the case with digoxin. Adipose tissue has almost as much water in it as other tissues, so that the apparent total volume of distribution of theophylline is proportional to body weight even in obese patients. Abnormal accumulation of fluid—edema, ascites, pleural effusion—can markedly increase the volume of distribution of drugs such as gentamicin that are hydrophilic and have small volumes of distribution. Half-Life The differences between clearance and half-life are important in defining the underlying mechanisms for the effect of a disease state on drug disposition. The increasing half-life for diazepam actually results from changes in the volume of distribution with age; the metabolic processes responsible for eliminating the drug are fairly constant. No matter how high the drug concentration goes, a point will be reached beyond which no further increment in response is achieved. If increasing the dose in a particular patient does not lead to a further clinical response, it is possible that the maximum effect has been reached. Recognition of maximum effect is helpful in avoiding ineffectual increases of dose with the attendant risk of toxicity. Sensitivity The sensitivity of the target organ to drug concentration is reflected by the concentration required to produce 50% of maximum effect, the C50. Diminished sensitivity to the drug can be detected by measuring drug concentrations that are usually associated with therapeutic response in a patient who has not responded. This may be a result of abnormal physiology—eg, hyperkalemia diminishes responsiveness to digoxin—or drug antagonism—eg, calcium channel blockers impair the inotropic response to digoxin. Increased sensitivity to a drug is usually signaled by exaggerated responses to small or moderate doses. The pharmacodynamic nature of this sensitivity can be confirmed by measuring drug concentrations that are low in relation to the observed effect. The interpretation of measurements of drug concentrations depends on a clear understanding of three factors that may influence clearance: the dose, the organ blood flow, and the intrinsic function of the liver or kidneys. Each of these factors should be considered when interpreting clearance estimated from a drug concentration measurement. It must also be recognized that changes in protein binding may lead the unwary to believe there is a change in clearance when in fact drug elimination is not altered (see Box: Plasma Protein Binding: Is It Important? Albumin concentration: Drugs such as phenytoin, salicylates, and disopyramide are extensively bound to plasma albumin. Alpha -acid glycoprotein concentration:1 a -Acid glycoprotein is an important binding protein with binding sites for1 drugs such as quinidine, lidocaine, and propranolol. It is increased in acute inflammatory disorders and causes major changes in total plasma concentration of these drugs even though drug elimination is unchanged. Therapeutic concentrations of salicylates and prednisolone show concentration-dependent protein binding. Because unbound drug concentration is determined by dosing rate and clearance—which is not altered, in the case of these low-extraction- ratio drugs, by protein binding—increases in dosing rate will cause corresponding changes in the pharmacodynamically important unbound concentration.
The exact mechanism of met- formin’s action is not clear methocarbamol 500mg with amex muscle relaxant erectile dysfunction, but it does decrease hepatic glucose production and increase peripheral glucose up- Meglitinides take methocarbamol 500mg online spasms everywhere. When used as monotherapy order methocarbamol 500 mg without a prescription muscle relaxant high, metformin rarely Though structurally unrelated to sulfonylureas best buy for methocarbamol muscle relaxant natural remedies, the causes hypoglycemia. The incapable of stimulating insulin secretion in nutrient- United Kingdom Prospective Diabetes Study demon- starved -cells, but in the presence of glucose, they strated a marked reduction in cardiovascular comor- demonstrate hypoglycemic effects by augmenting the bidities and diabetic complications in metformin- release of insulin. Insulin ing, anorexia, metallic taste, abdominal discomfort, and levels transiently rise postprandially after repaglinide diarrhea) occur in up to 20% of individuals taking met- administration but generally return to baseline by the formin; this can be minimized by starting at a low dose next meal. Like fer any advantage over the sulfonylureas, it may be phenformin, metformin can cause lactic acidosis, but its helpful in patients with a known allergy to sulfa drugs. Glucovance is a combination of metformin and in conjunction with metformin, sulfonylureas, and and glyburide that may be helpful for diabetics who re- insulin. Met- whether this has any clinical signiﬁcance or persists in formin is usually given two to three times a day at meal- the long term. Thiazolidinediones (sometimes termed glitazones) are Consequently, frequent monitoring of liver transami- a novel class of drugs that were initially identiﬁed for nases is recommended for rosiglitazone and pioglita- their insulin-sensitizing properties. They all act to de- zone, and these drugs should be stopped if transami- crease insulin resistance and enhance insulin action in nases rise to more than two to three times the upper target tissues. There is often a other nuclear receptors to modulate the expression of modest amount of weight gain that is independent of insulin-sensitive genes. In laboratory animals, thiazo- Thiazolidinediones are readily absorbed from the lidinediones at high doses are associated with ultrastruc- gastrointestinal tract following oral administration and tural histopathological changes in cardiac tissue; there- are rapidly metabolized by the liver. Plasma elimination fore, thiazolidinedione use is contraindicated in patients half-life is 2 to 3 hours for rosiglitazone (Avandia) and with signiﬁcant heart failure. The biological effect of Hypoglycemia is rare with thiazolidinedione mono- these drugs takes several weeks to develop, although therapy; however, these drugs may potentiate the hypo- patients may see some beneﬁt within a few days to a glycemic effects of concurrent sulfonylurea or insulin week. For betic’s regimen, the sulfonylurea or insulin dosage that reason, upward adjustments in dosage are made should be decreased to compensate for any enhanced gradually to avoid hypoglycemia. Improvements in -Glucosidase Inhibitors diabetic control are variable, ranging from a 1% reduc- tion in hemoglobin A1c when used as monotherapy to The -glucosidase inhibitors primarily act to decrease greater reductions ( 2% reduction in hemoglobin A1c) postprandial hyperglycemia by slowing the rate at which when used in combinations with other agents, such as carbohydrates are absorbed from the gastrointestinal sulfonylureas or metformin. They act by competitively inhibiting -glucosi- Rosiglitazone is approved for use as monotherapy dases, a group of enzymes in the intestinal brush border and in conjunction with metformin, though it is some- epithelial cells that includes glycoamylase, sucrase, mal- times combined with a sulfonylurea or insulin. To be effective, -glucosidase inhibitors must it is unclear whether this effect has any clinical signiﬁ- be taken before or with meals. Systemic ab- counseled that these side effects will occur and that tol- sorption of acarbose is very low (~2%), with most being erance should develop; otherwise, compliance will be broken down in the intestine to several metabolites. Unlike the sulfonylureas, insulin, and the thia- creted unchanged in the feces, while the remainder, zolidinediones, -glucosidase inhibitors do not cause some of which is systemically absorbed, is renally ex- weight gain. Acarbose may be associated with hepatotoxicity of -glucosidase inhibitors, so fasting hypoglycemia in rare instances. Although the -glucosidase inhibitors but in contrast to acarbose, miglitol is systemically ab- may be used as monotherapy, they are usually used in sorbed prior to its activity in the small intestine. Leaving aside their gastroin- Gastrointestinal disturbances (loose stools, ﬂatu- testinal side effects, -glucosidase inhibitors appear to lence, and abdominal cramping) are the most frequently be relatively safe. The main reason metformin should not be used in (A) Thiazolidinediones may be hepatotoxic in patients with renal failure is that some individuals. Metformin causes lactic acidosis in patients with (D) Glucagon is a hormone that counteracts many renal failure and severe congestive heart failure. Lispro insulin displays a similar (D) Glyburide afﬁnity and action with the insulin receptor as regu- (E) A, B, and C lar insulin. The most common side effects are sulin signaling and the molecular mechanisms of in- edema and weight gain that is independent of the sulin resistance. Since on awakening his fasting glucose pattern in his blood sugar measurements: is in the normal range and after taking his morning 8 A. When his blood sugar is about 55, he feels shaky Regular insulin is short-acting and would not result and sweaty, but this goes away if he has something in a 5 P. Which of the following changes would you insulin given in the morning would continue to recommend to his regimen? Not all of the vitamins can be synthe- quate to meet the known nutritional needs of practically sized in the body, and therefore, some vitamins must be all healthy persons, were the primary reference value for obtained from an external source, such as a proper well- vitamins and other nutrients. Since these recommendations are ingestion, irregular absorption, or impaired metabolic given for healthy populations in general and not for indi- use of these nutrients. The ingestion or administration viduals, special problems, such as premature birth, inher- of excessive quantities of vitamins, also known as hy- ited metabolic disorders, infections, chronic disease, and pervitaminosis, may result in toxicity. Vitamin supplementation may be re- quired by patients with special conditions and for those who do not consume an appropriate diet. Bone development and growth in children as the highest level of intake of a nutrient that will not have also been linked to adequate vitamin A intake. Medical personnel who work in afﬂuent areas are un- An early sign of hypovitaminosis A is night blind- likely to see large numbers of people with vitamin deﬁ- ness. Biochemical, physiological, and behavioral conditions include biliary tract disease, pancreatic dis- changes can occur in the marginal deﬁciency state with- ease, sprue, and hepatic cirrhosis. Acute hypervitaminosis A results in drowsiness, headache, vomiting, papilledema, and a bulging fon- tanel in infants. Anorexia, irritability, and swelling of Toxic effects have been observed when large dosages of the bones have been seen in children. Liver toxicity has been associ- vitamins are less toxic, since excess quantities are usu- ated with excessive vitamin A intake. Excessive amounts of fat- atogenic in large amounts, and supplements should not soluble vitamins, however, are stored in the body, which be given during a normal pregnancy. The fat-soluble vitamins are generally metabolized min D2) are formed by irradiation of the provitamins 7- slowly and are stored in the liver. The soluble vitamins are rapidly metabolized and are read- conversion to vitamin D3 occurs in the skin. Additional hydroxylation to form 1,25-dihydroxyvita- Fat-Soluble Vitamins min D occurs in the kidney in response to the need for Vitamin A calcium and phosphate. A discussion of the role of vita- Vitamin A, or retinol, is essential for the proper main- min D in calcium homeostasis is provided in Chapter 66. The low blood calcium and 68 Vitamins 779 phosphate levels that occur during vitamin D deﬁciency ous plants, especially green vegetables. The mena- stimulate parathyroid hormone secretion to restore cal- quinones that possess vitamin K2 activity are synthe- cium levels (see Chapter 66). In children, this deﬁciency sized by bacteria, particularly gram-positive organisms; leads to the formation of soft bones that become de- the bacteria in the gut of animals produce useful quan- formed easily; in adults, osteomalacia results from the tities of this vitamin. Vitamin D deﬁciency sized quinone that possesses the same activity as vita- may occur in patients with metabolic disorders, such as min K1.