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It has been suggested that these drugs may Saline laxatives are soluble inorganic salts that contain act by stimulating afferent nerves to initiate a reflex in- multivalent cations or anions (milk of magnesia generic chloroquine 250 mg amex symptoms flu, mag- crease in gut motility cheap 250 mg chloroquine fast delivery treatment 360. These charged particles do not readily cross the senna purchase generic chloroquine canada medications pain pills, and rhubarb) are among the oldest laxatives intestinal mucosa and therefore tend to remain in the known. Cascara sagrada is one of the mildest of the the colon and producing a physiological stimulus for anthraquinone-containing laxatives. This Phenolphthalein is partially absorbed (about 15% explanation of the mechanism by which the saline laxa- of a given dose) and excreted into the bile; hence, if it tives exert their effects, however, may be too simplistic, is taken constantly, it will accumulate and exert too since active secretion of fluid into the gut lumen has drastic an action. The ricinoleic acid acts larly dopamine) stimulation, is connected to the emetic on the ileum and colon to induce an increased fluid se- center through the fasciculus solitarius. There is minimal Emetics net absorption or excretion of fluid or electrolytes, and The most commonly used emetics are ipecac and apo- thus these are safe to use in patients with renal insuffi- morphine. The patient has repeated liquid stools until the emptying the stomach in awake patients who have in- administered solution has been expelled. If gastric emp- gested a toxic substance or have recently taken a drug tying is slow, patients may have abdominal distention overdose. This preparation should not be used if a has central nervous system depression or has ingested bowel obstruction or impaired gag reflex is present. If emesis does not occur, nating in the forceful expulsion of gastric contents gastric lavage using a nasogastric tube must be per- through the mouth. Duodenal and jejunal tone is increased, while gastric first administered before oral or subcutaneous dosing. Opioid antagonists such as nalox- lows nausea, during which the abdominal muscles con- one usually reverse the depressant actions of apomor- tract with simultaneous attempts at inspiration against a phine. The resultant high intragastric pressure moves more or by preventing peripheral or cortical stimulation of gastric contents into the esophagus, and with continued the emetic center. These events are coordinated by the emetic center, Antihistamines which lies within the lateral reticular formation of the medulla oblongata close to the respiratory and salivary The antihistamines appear to block peripheral stimula- centers. Dimenhydrinate, diphenhy- suggesting that they inhibit stimulation of peripheral dramine, and meclizine hydrochloride are the three an- vagal and sympathetic afferents. Sedation will fre- tihistamines primarily used in the prevention of nausea quently occur following their administration. A more complete discussion also may have problems with acute dystonic reactions, of the H1antihistamines can be found in Chapter 38. Headache is the most fre- tion with other antiemetics for treating chemotherapy- quently reported adverse effect of these medications. The oxyntic (parietal) gland area, which fective in the elderly, primarily because of its side ef- corresponds to the fundus and body of the stomach, se- fects. The antiemetic effect is associated with a high, and cretes hydrogen ions, pepsinogen, and bicarbonate. Ataxia, drowsiness, dry mouth, or orthostatic hypoten- The parietal cells secrete H in response to gastrin, sion may be seen in up to 35% of the older patient pop- cholinergic, and histamine stimulation (Fig. The bioavailability is not as vari- bring about a receptor-mediated rise in intracellular cal- able if the agent is smoked. The coadministration of cium, an activation of intracellular protein kinases, and prochlorperazine may prevent some of the central nerv- eventually an increased activity of the H –K pump ous system side effects seen with the use of tetrahydro- leading to acid secretion into the gastric lumen. After food is ingested, Phenothiazine Derivatives gastric distention initiates vagal stimulation and short Phenothiazine derivatives, which include prochlorper- intragastric neural reflexes, both of which increase acid azine (Compazine) and promethazine (Phenergan), act secretion. The pathways by which secretagogues are believed to stimulate hydrogen ion production and secretion are shown. Evidence from animal studies suggests that the mucosal surface, both the local blood supply and the after protein amino acids are converted to amines, gas- ability of the local cells to buffer this ion will ultimately trin is released. With Gastric acid secretion is inhibited in the presence of duodenal and gastric peptic ulcer disease, a major acid itself. A negative feedback occurs when the pH ap- causative cofactor is the presence of gastric Helico- proaches 2. Ingested carbohydrates and Medications that raise intragastric pH are used to fat also inhibit acid secretion after they reach the intes- treat peptic ulcer disease and gastroesophageal reflux tines; several hormonal mediators for this effect have disease. The integrity of the mucosal lining of the stomach The rationale for the use of antacids in peptic ulcer dis- and proximal small bowel is in large part determined by ease lies in the assumption that buffering of H in the the mucosal cytoprotection provided by mucus and bi- stomach permits healing. The use of both low and high carbonate secretion from the gastric and small bowel doses of antacids is effective in healing peptic ulcers as mucosa. In ad- with those observed after the use of histamine (H2) dition, the bicarbonate that is secreted into the layer be- blocking agents. The buffering agents in the various tween the mucus and epithelium permits a relatively antacid preparations consist of combinations of ingredi- high pH to be maintained in the region next to the mu- ents that include sodium bicarbonate, calcium carbon- cosal surface. If 40 Drugs Used in Gastrointestinal Disorders 479 diarrhea occurs or if there is renal failure, a magnesium- long-term therapy. Since cimetidine is partly me- are generally safe, but some patients resist because some tabolized by the cytochrome P450 system, coadminis- of the formulations are unpalatable and expensive. Calcium carbonate may induce hypercalcemia tion, with a peak plasma level achieved 1 to 3 hours af- and a rebound increase in gastric secretion secondary to ter ingestion. About 90% of an oral dose is absorbed, hydroxide is associated with constipation; serum phos- with a peak plasma concentration occurring after 0. The elimination half-life is 1 to 2 hours, and general may interfere with the absorption of a number more than 90% of an oral dose is excreted in the urine. Famotidine has an onset of effect within 1 hour after oral administration, and inhibition of gastric secretion is present for the next 10 to 12 hours. Elimination is by renal (65–70%) and he- The histamine receptor antagonists (H2 blockers) mar- patic (30–35%) routes. Ranitidine, famotidine, and niza- keted in the United States are cimetidine (Tagamet), tidine do not alter the microsomal cytochrome P450 ranitidine (Zantac), famotidine (Pepcid), and nizatidine metabolism of other drugs, nor do they cause gyneco- (Axid). A reduction in dosage of any of the H2-blockers cell membranes of parietal cells and prevent histamine- is recommended in the presence of renal insufficiency. After pro- longed use, down-regulation of receptor production oc- Proton Pump Inhibitors curs, resulting in tolerance to these agents. H2-blockers are approved for the treatment of gastroesophageal re- The proton pump inhibitors available in the United States flux disease, acute ulcer healing, and post–ulcer healing are omeprazole (Prilosec), lansoprazole (Prevacid), pan- maintenance therapy. Although there are substantial toprazole (Protonix), rabeprazole (Aciphex), and es- differences in their relative potency, 70 to 85% of duo- omeprazole (Nexium). These are substituted benzimida- denal ulcers are healed during 4 to 6 weeks of therapy zole prodrugs, which accumulate on the luminal side with any of these agents. These drugs markedly inhibit particularly important in healing, nighttime-only dosing gastric acid secretion. The proton pump inhibitors are also used to sorbed following oral administration, with peak blood treat patients with Zollinger-Ellison syndrome, which is levels 45 to 90 minutes after drug ingestion.

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Superior to each valve is tumors: a tumor in the pelvis cheap chloroquine online symptoms yeast infection, for example cheap chloroquine online amex professional english medicine, could invade a depression termed an anal sinus buy chloroquine with a visa treatment renal cell carcinoma. Assessing whether spread has together form a circle around the anal canal at a occurred may involve ultrasound scanning, computed location known as the pectinate line, which marks tomography, and magnetic resonance imaging. Urinary system • Inferior to the pectinate line is a transition zone known The pelvic parts of the urinary system consist of the termi­ as the anal pecten, which is lined by nonkeratinized nal parts of the ureters, the bladder, and the proximal part stratifed squamous epithelium. The ureters enter the pelvic cavity from the abdomen by Given the position of the colon and rectum in the passing through the pelvic inlet. On each side, the ureter abdominopelvic cavity and its proximity to other organs, it crosses the pelvic inlet and enters the pelvic cavity in the area anterior to the bifurcation of the common iliac artery. The anal mucosa can be palpated for abnormal masses, and in women, the posterior wall of the vagina and the cervix can be palpated. In many instances the digital rectal examination may Ureter Common iliac arery be followed by proctoscopy or colonoscopy. An ultrasound probe may be placed into the rectum to Internal iliac artery assess the gynecological structures in females and the prostate in the male before performing a prostatic biopsy. In the clinic Carcinoma ofthe colon and rectum Carcinoma of the colon and rectum (colorectum) is a common and often lethal disease. Recent advances in surgery, radiotherapy, and chemotherapy have only slightly improved 5-year survival rates. The overall prognosis is related to: • the degree of tumor penetration through the bowel wall, Neck of bladder • the presence or absence of lymphatic dissemination, and Urethra • the presence or absence of systemic metastases. The two ureters enter The bladder is the most anterior element of the pelvic the bladder at each of the upper corners of the base, viscera. Although it is entirely situated in the pelvic cavity and the urethra drains inferiorly from the lower corner when empty, it expands superiorly into the abdominal of the base. The superior continues from it superiorly up the anterior abdominal surface is slightly domed when the bladder is empty; it wall to the umbilicus. Trigone Superior surface Median umbilical lnferolateral suraces A Ureters Trigone Internal urethral B orifice Fig. The neck ofthe bladder surrounds the origin ofthe urethra • In men, the paired fbromuscular bands are known as at the point where the two inferolateral surfaces and the puboprostatic ligaments because theyblend withthe base intersect. At birth, the bladder is almost entirely abdominal; the urethra begins • In women, these fbromuscular bands aretermedpubo­ approximately at the upper margin of the pubic symphysis. Together with the peri­ With age, the bladder descends until after puberty when it neal membrane and associated muscles, the levator ani assumes the adult position. Pubovesical ligament A Vaginal opening in deep perineal pouch and perineal membrane Puboprostatic ligament 8 Prostate Fig. These may pass down the ureter, causing ureteric If small enough, the stones may be removed via obstruction, and into the bladder (Fig. Often, these patients develop (or may a suprapubic incision and enter the bladder already have) problems with bladder emptying, which retroperitoneally to remove them. For The procedure of suprapubic catheterization is example, when the prostate is markedly enlarged and it is straightforward and involves the passage of a small impossible to pass a urethral catheter, a suprapubic catheter on a needle in themidline approximately 2 em catheter may be placed. The catheter passes easily The bladder is a retroperitoneal structure and when full into the bladder without compromise of other structures lies adjacent tothe anterior abdominal wall. Approximately one-third of bladder tumors are multifocal; fortunately, two-thirds are superfcial tumors and amenable to local treatment. Bladder tumors may spread through the bladder wall and invade local structures, including the rectum, uterus (in women), and lateral walls of the pelvic cavity. Difuse tumors may be treated with local chemotherapy; more extensive tumors may require radical surgical removal of the bladder and, in men, the prostate. The paths taken by The urethral opening is anterior tothe vaginal opening the urethra differ signifcantly in women and men. Each drains via a duct travels a slightly curved course as it passes inferiorly that opens onto the lateral margin of the external urethral 466 through the pelvicfloor into the perineum, where it passes orifce. Preprostatic part of urethra Internal urethral sphincter (smooth muscle) Deep perineal pouch Perineal membrane Bulbo-urethral gland and duct 2nd bend when penis is flaccid 3. In men The urethra in men is divided into preprostatic, pros­ Inmen, the urethra is long, about 20em, and bends twice tatic, membranous, and spongy parts. Beginning at the base of the bladder and passing inferiorly through the prostate, it Preprostatic part. The preprostatic part of the urethra is passes through the deep perineal pouch and perineal mem­ about 1 em long, extends from the base of the bladder to brane and immediately enters the root of the penis. As the the prostate, and is associated with a circular cuff of urethra exits the deep perineal pouch, it bends forward to smooth muscle fbers (the internal urethral sphincter). When the penis Contraction of this sphincter prevents retrograde move­ is flaccid, the urethra makes another bend, this time infe­ ment of semen into the bladder during ejaculation. In this region, the lumen of the urethra is marked by a longitudinal midline fold of mucosa (the urethral Membranous part. The depression on each side of the crest is thepros­ is narrow and passes through the deep perineal pouch tatic sinus; the ducts of the prostate empty into these two (Fig. The spongy urethra is surrounded by position of the prostate gland during transurethral tran­ erectile tissue (the corpus spongiosum) of the penis. It is enlarged to form a bulb at the base of the penis and A small blind-ended pouch-the prostatic utricle again at the end of the penis to form the navicular fossa (thought to be the homologue of the uterus in women)­ (Fig. On each perineal pouch are part of the male reproductive system side of the prostatic utricle is the opening of the ejacula- and open into the bulb of the spongy urethra. In children under 1 year of The relatively short length of the urethra in women makes age, infection from the bladder may spread via the ureters them more susceptible than men to bladder infection. The to the kidneys, where it can produce renal damage and primary symptom of urinary tract infection in women is ultimately leadto renal failure. In women, it is much simplerto passcatheters and In men: cystoscopes because the urethra is short and straight. Urine may therefore be readily drained from a distended • The spongy urethra is surrounded bythe erectile bladder without signifcant concern for urethral rupture. The wall of this short instrumentation through the urethra to drain the bladder, segment of urethra is relatively thin and angles usually because there is a urethral stricture or prostatic superiorly to pass through the deep perineal pouch; enlargement. In such cases, an ultrasound of the lower at this position the urethra is vulnerable to damage, abdomen will demonstrate a full bladder (Fig. A suprapubic catheter • The membranous part of the urethra runs superiorly may be inserted into the bladder with minimal trauma as it passes through the deep perineal pouch. The major In the clinic components are a testis, epididymis, ductus deferens, and Testicular tumors ejaculatory duct on each side, and the urethra and penis in the midline. In addition, three types of accessory glands Tumors of the testis account for a small percentage of malignancies in men. However, they generally occur in are associated with the system: younger patients (between 20 and 40years ofage).

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Identification of real or potential drug that all feasible pharmacotherapeutic alternatives available for therapy problems achieving the predefined therapeutic outcome(s) are considered The first step in the patient-focused approach is to collect pertinent before choosing a particular therapeutic regimen chloroquine 250mg with amex medicine 8 letters. Some authors prefer to divide this be included in the list of therapeutic alternatives when appropriate order chloroquine toronto stroke treatment 60 minutes. It is important to differentiate the There has been a resurgence of interest in dietary supplements process of identifying the patient’s drug therapy problems from and other alternative therapies in recent years chloroquine 250mg amex treatment quietus tinnitus. In fact, the medical billions of dollars each year on supplements to treat diseases for diagnosis is known for most patients seen by pharmacists. Furthermore, pharmacists must be capable of assessing the patient’s database to some products are hazardous, and others may interact with a determine whether drug therapy problems exist that warrant a patient’s prescription medications or aggravate concurrent disease change in drug therapy. On the other hand, scientific evidence of efficacy does exist such as asthma or rheumatoid arthritis, one must be able to assess for some dietary supplements (e. Health care providers must be knowledgeable about these products This process involves reviewing the patient’s symptoms, the signs of and prepared to answer patient questions regarding their efficacy disease present on physical examination, and the results of labora- and safety. Each scenario Monitoring for adverse events should be directed toward pre- involves one or more questions asked by a patient about a specific venting or identifying serious adverse effects that have a reasonable remedy. For example, it is not cost-effective to reader provide a scientifically based answer to the patient’s ques- obtain periodic liver function tests in all patients taking a drug that tion(s). Eleven different dietary supplements are included in this causes mild abnormalities in liver injury tests only rarely, such as section: garlic, omega-3 fatty acids, Ginkgo biloba, St. On the other hand, serious patient harm may be valerian, black cohosh, saw palmetto, glucosamine, kava kava, averted by outlining a specific screening schedule for drugs associ- Echinacea, and coenzyme Q10 (Co-Q10). Provision of patient education The purpose of this step is to determine the drug, dosage form, dose, The concept of pharmaceutical care is based on the existence of a schedule, and duration of therapy that are best suited for a given covenantal relationship between the patient and the provider of care. Individual patient characteristics should be taken into Patients are our partners in health care, and our efforts may be for consideration when weighing the risks and benefits of each available naught without their informed participation in the process. For example, an asthma patient who chronic diseases such as diabetes mellitus, hypertension, and asthma, requires new drug therapy for hypertension might better tolerate patients may have a greater role in managing their diseases than do treatment with a thiazide diuretic rather than a β-blocker. Self care is becoming widespread as other hand, a hypertensive patient with gout may be better served increasing numbers of prescription medications receive over-the- by use of a β-blocker rather than by use of a thiazide diuretic. For these reasons, patients must be provided with Students should state the reasons for avoiding specific drugs in sufficient information to enhance compliance, ensure successful their therapeutic plans. Chapter 3 describes patient include drug allergy, drug–drug or drug–disease interactions, interview techniques that can be used efficiently to determine the patient age, renal or hepatic impairment, adverse effects, poor patient’s level of knowledge. In the questions The specific dose selected may depend upon the indication for posed with individual cases, students are asked to provide the kind of the drug. For example, the dose of aspirin used to treat rheumatoid information that should be given to the patient who has limited arthritis is much higher than that used to prevent myocardial knowledge of his or her disease. An alternative plan should also be in place that would be appropriate if the initial therapy fails or • Dosage, dosage form, route of administration, and duration of cannot be used. If the goal is to cure a bacterial sions for new and refill prescriptions during case discussions to pneumonia, students should outline the subjective and objective practice medication education skills. Communication and implementation of the should be collected are dependent on the outcome parameters pharmacotherapeutic plan selected and should be established prospectively. It should be noted that expensive or invasive procedures may not be repeated after the The most well-conceived plan is worthless if it languishes without initial diagnosis is made. For example, it is insufficient to state that one will monitor for mentation of significant recommendations in the medical record is potential drug-induced “blood dyscrasias. These references may be useful to optimal process for learning to solve drug therapy problems because students for answering the questions posed. The Pharmacotherapy several important steps taken by experienced clinicians are not textbook contains a more comprehensive list of references pertinent always apparent and may be overlooked. Students should be advised to be wary of informa- ful consideration has been given to all available feasible diagnostic or tion posted on the Internet that is not from highly regarded health therapeutic alternatives. Finally, there is often little suggestion provided as to the treatment information that should be conveyed to the most important individual involved: the patient. For this reason, method of consistently documenting therapeutic recommendations students may find it difficult at first to devise complete answers to and implementing plans. The authors of the cases contributed the recommended preparation of written communication notes is not included in writ- answers provided in the appendix, but they should not be consid- ten form with each set of case questions, instructors are encouraged to ered the sole “right” answer. In addition to communicating with other health care profession- With diligent self-study, practice, and the guidance of instructors, als, practitioners of pharmaceutical care must also develop a per- students will gradually acquire the knowledge, skills, and self- sonal record of each patient’s drug therapy problems and the health confidence to develop and implement pharmaceutical care plans for care provider’s plan for resolving them, interventions made, and their own future patients. Chapter 4 of this casebook discusses the philosophy of care planning and describes their creation and use. Perceptions and misperceptions of skin The process of pharmaceutical care entails an assessment of the color. Pharmaceutical care practice: The Some cases follow the progression of the patient’s disease over clinician’s guide, 2nd ed. Drug-related problems: their Follow-up questions directed toward ongoing evaluation and prob- structure and function. Large-group problem-based learning: a revision from traditional to pharmaceutical care-based therapeutics. To teach students to be lifelong learners, it is professional organizations, they may need to do a service project that essential to stimulate them to be inquisitive and actively involved requires identifying an idea, developing a project plan, assigning with the learning that takes place in the classroom. This requires that tasks to different group members, and, finally, finishing the project teachers move away from more comfortable teaching methods and and evaluating the results. On practice rotations, students often need learn new techniques that will help students “learn to learn. Active learning has numerous definitions, and various methods are Students who finish their formal training in health care must recog- described in the educational literature. Scores of new drugs are approved the process of having students engage in activities that require reflec- every year, and innovative research changes the way that many diseases 5 tion on ideas and how students use them. Drug use practices change yearly, and students will have the learning formats, students are involved in much more than listening. They must be The transmission of information is deemphasized and replaced with prepared to take direct responsibility for patient outcomes by practicing the development of skills. Health care providers work in interprofessional allows students to become engaged in the learning process while environments that require active participation to provide optimal care. Learning is reinforced when students actu- They will need to use their skills in communications, problem solving, 5 ally apply their knowledge to new situations. Willing students, inno- independent learning, drug information retrieval, and knowledge of 1–3 vative teachers, and administrative support within the school are disease state management. Control of learning must manner, many health care educators are using active learning strategies 4,5 be shifted from the teacher to the students; this provides an opportu- in the classroom. In many therapeutics courses, students are given nity for students to become active participants in their own learning. Students may be Although it sounds frightening at first, students can take control of asked to identify the significant subjective and objective findings; to their own learning. Knowledge of career and life goals can help develop a drug therapy problem list; to create an assessment statement; students make decisions about how to spend their educational time.

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To avoid side effects cheap chloroquine master card 8h9 treatment, the starting dose would be 50% of this antici- pated maintenance dose (50 mg every 6 hours) and would be titrated to the full dose over 1–2 weeks purchase on line chloroquine medications dispensed in original container. Steady-state trough primidone and phenobarbital serum concentrations should be measured after steady state for both agents is attained in 3–5 half-lives chloroquine 250 mg free shipping medicine man pharmacy. Since the patient is expected to have a phenobarbital half-life equal to 60 hours or more, the steady-state concentrations could be obtained any time after 2 weeks of dosing at the full primidone maintenance dose (5 phenobarbital half-lives = 5 ⋅ 60 h = 300 h or 13 d). Primidone and phenobarbital serum concentrations should also be measured if the patient experiences an exacerbation of their epilepsy, or if the patient develops potential signs or symptoms of primidone toxicity. The suggested initial mainte- nance dosage rate for primidone in a pediatric patient is 12–23 mg/kg/d. To avoid side effects, the starting dose would be 50% of this anticipated maintenance dose (50 mg every 8 hours) and would be titrated to the full dose over 1–2 weeks according to response and adverse effects. Steady-state trough primidone and phenobarbital serum concentrations should be measured after steady state for both agents is attained in 3–5 half-lives. Since the patient is expected to have a phenobarbital half-life equal to 60 hours or more, the steady- state concentrations could be obtained any time after 2 weeks of dosing at the full primidone maintenance dose (5 phenobarbital half-lives = 5 ⋅ 60 h = 300 h or 13 d). Primidone and phenobarbital serum concentrations should also be measured if the patient experiences an exacerbation of their epilepsy, or if the patient develops poten- tial signs or symptoms of primidone toxicity. Using linear pharmacokinetics, the primidone dose necessary to cause the change in steady-state concentration would equal Dnew = (Cssnew/Cssold) Dold = (8 μg/mL / 5. The dosage regimen would be titrated to this value over a period of 1–2 weeks to avoid adverse effects. Using linear pharmacokinetics, the resulting steady-state phe- nobarbital serum concentration would equal Css,new = (Dnew/Dold) Css,old = (300 mg/d / 225 mg/d) 18 μg/mL = 24 μg/mL. A steady-state trough primidone and phenobarbital serum concentration should be measured after steady state is attained in 2 weeks. Primidone and phenobarbital serum concentrations should also be measured if the patient experiences an exacerba- tion of their epilepsy, or if the patient develops potential signs or symptoms of primi- done toxicity. The patient would be expected to achieve steady-state conditions for both primi- done and phenobarbital after 2 weeks of therapy. Primidone clearance can be computed using a steady-state primidone concentra- tion: Cl = [F(D/τ)] / Css = [1(75 mg/8 h)] / (5. Steady-state trough primidone and phenobarbital serum concentrations should be measured after steady state is attained in 2 weeks. Primidone and phenobarbital serum concentrations should also be measured if the patient experiences an exacerbation of their epilepsy, or if the patient develops potential signs or symptoms of primidone toxicity. Enter patient’s demographic, drug dosing, and serum concentration/time data into the computer program. The pharmacokinetic parameters computed by the program are a volume of distri- bution of 36 L, a half-life equal to 217 hours, and a clearance equal to 0. The one-compartment model first-order absorption equations used by the program to compute doses indicates that a dose of 60 mg every 24 hours will produce a steady-state phenobarbital concentration of 21 μg/mL. Enter patient’s demographic, drug dosing, and serum concentration/time data into the computer program. The pharmacokinetic parameters computed by the program are a volume of distri- bution of 44 L, a half-life equal to 97 hours, and a clearance equal to 0. The one-compartment model first-order absorption equations used by the program to compute doses indicates that a dose of 240 mg every 24 hours will produce a steady-state phenobarbital concentration of 29 μg/mL. Phenylethylmalonamide serum levels in patients treated with primidone and the effects of other antiepileptic drugs. Update on drug sieving coefficients and dosing adjustments during continuous renal replacement therapies. While the exact mechanism of action is not known, the antiepileptic effect of ethosuximide is thought to result from its ability to decrease low-threshold calcium currents in thalamic neurons. Generally, administration of smaller doses and more frequent dosing of the drug produce relief from these side effects. In the upper end of the therapeutic range (>70 μg/mL) some patients will begin to experience the concentration-dependent adverse effects of ethosux- imide treatment: drowsiness, fatigue, lethargy, dizziness, ataxia, hiccups, euphoria, and headaches. Idiosyncratic side effects that are independent of concentration include rash, systemic lupus-like syndromes, and blood dyscrasias (leukopenia, pancytopenia). Simple partial seizures Drugs of choice locally) (without impaired Carbamazepine consciousness) Phenytoin a. Absence seizures (typical or Drugs of choice or nonconvulsive) atypical; also known as petit Ethosuximide mal seizures) Valproic acid Alternatives Lamotrigine Clonazepam Zonisamide Levetiracetam 2. While it is desirable to entirely abolish all seizure episodes, it may not be possible to accomplish this in many patients. Patients should be monitored for concentration-related side effects (drowsiness, fatigue, lethargy, dizziness, ataxia, hiccups, euphoria, headaches) as well as gastrointestinal upset associated with local irritation of gastric mucosa (gastric distress, nausea, vomiting, anorexia). Serious, but rare, idiosyncratic side effects include systemic lupus-like syn- dromes, leukopenia, and pancytopenia. Because epilepsy is an episodic disease state, patients do not experience seizures on a continuous basis. Thus, during dosage titration it is difficult to tell if the patient is responding to drug therapy or simply is not experiencing any abnormal central nervous system discharges at that time. Patients are more likely to accept drug therapy if adverse reactions are held to the absolute minimum. At concentrations exceeding 100 μg/mL, the drug may follow nonlinear pharmacokinetics, presumably owing to Michaelis-Menten (concentration dependent or saturable) metabolism. However, based on animal studies, ethosuximide oral bioavailability of capsules (250 mg) and syrup (250 mg/5 mL) is assumed to be 100%. Because of this, patients with liver cirrhosis or acute hepatitis may have reduced ethosuximide clearance because of destruction of liver parenchyma. This loss of functional hepatic cells reduces the amount of enzymes avail- able to metabolize the drug and decreases clearance. An index of liver dysfunction can be gained by applying the Child-Pugh clinical classification system to the patient (Table 14-2). Each of these areas is given a score of 1 (normal) to 3 (severely abnormal; Table 14-2), and the scores for the five areas are summed. The Child-Pugh score for a patient with normal liver func- tion is 5 while the score for a patient with grossly abnormal serum albumin, total biliru- bin, and prothrombin time values in addition to severe ascites and hepatic encephalopathy is 15. A Child-Pugh score greater than 8 is grounds for a decrease of 25–50% in the initial daily drug dose for ethosuximide. As in any patient with or without liver dysfunction, ini- tial doses are meant as starting points for dosage titration based on patient response and avoidance of adverse effects. Ethosuximide serum concentrations and the presence of adverse drug effects should be monitored frequently in patients with liver cirrhosis. Similarly, a small amount (20–30%) of ethosuximide is usually eliminated unchanged by the kidneys so patients with renal dysfunction (creatinine clearance <30 mL/min) receiving ethosuximide should be closely monitored. It allows individualized target serum concen- trations to be chosen for a patient, and each pharmacokinetic parameter can be customized to reflect specific disease states and conditions present in the patient. Doses are based on those that commonly produce steady-state concentrations in the lower end of the therapeutic range, although there is a wide variation in the actual concentrations for a specific patient.

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Despite its better solubility (which eliminates the need for an organic solvent) proven 250mg chloroquine medicine plies, midazolam may also produce pain on injection purchase generic chloroquine from india medications japan travel. Clinical Uses & Dosage Benzodiazepines are most commonly used for preoperative medication generic chloroquine 250 mg mastercard kerafill keratin treatment, intravenous sedation, and suppression of seizure activity. The slow onset and prolonged duration of action of lorazepam limit its usefulness for preoperative medication or induction of anesthesia, especially when rapid and sustained awakening at the end of surgery is desirable. The amnestic, anxiolytic, and sedative effects of benzodiazepines make this class of drugs the most popular choice for preoperative medication. Midazolam has a more rapid onset, with greater amnesia and less postoperative sedation, than diazepam. The synergistic effects between benzodiazepines and other drugs, especially opioids and propofol, can be used to achieve better sedation and analgesia but may also greatly enhance their combined respiratory depression and may lead to airway obstruction or apnea. Because benzodiazepine effects are more pronounced with increasing age, dose reduction and careful titration may be necessary in elderly patients. Delayed awakening is a potential disadvantage, limiting the usefulness of benzodiazepines for induction of general anesthesia despite their advantage of less pronounced circulatory effects. Although its pharmacokinetics are favorable, endocrine side effects limit its use for continuous infusions. Etomidate is a carboxylated imidazole derivative that is poorly soluble in water and is therefore supplied as a 2 mg/mL solution in 35% propylene glycol. A Pharmacokinetics An induction dose of etomidate produces rapid onset of anesthesia, and recovery depends on redistribution to inactive tissue sites, comparable to thiopental and propofol. Metabolism is primarily by ester hydrolysis to inactive metabolites, which are then excreted in urine (78%) and bile (22%). Clearance of etomidate is about five times that of thiopental, as reflected by a shorter elimination half-time (Table 25–2). Because of etomidate’s minimal effects on hemodynamics and short context-sensitive half- time, larger doses, repeated boluses, or continuous infusions can safely be administered. Etomidate, like most other intravenous anesthetics, is highly protein bound (77%), primarily to albumin. Cardiovascular Effects A characteristic and desired feature of induction of anesthesia with etomidate is cardiovascular stability after bolus injection. In this regard, decrease in systemic blood pressure is modest or absent and principally reflects a decrease in systemic vascular resistance. Therefore, the systemic blood pressure-lowering effects of etomidate are probably exaggerated in the presence of hypovolemia, and the patient’s intravascular fluid volume status should be optimized before induction of anesthesia. Its depressant effects on myocardial contractility are minimal at concentrations used for induction of anesthesia. Respiratory Effects The depressant effects of etomidate on ventilation are less pronounced than those of barbiturates, although apnea may occasionally follow rapid intravenous injection of the drug. Depression of ventilation may be exaggerated when etomidate is combined with inhaled anesthetics or opioids. Endocrine Effects Etomidate causes adrenocortical suppression by producing a dose-dependent inhibition of 11β-hydroxylase, an enzyme necessary for the conversion of cholesterol to cortisol (see Figure 39–1). Despite concerns regarding this finding, no outcome studies have demonstrated an adverse effect when etomidate is given in a bolus dose. Clinical Uses & Dosage Etomidate is an alternative to propofol and barbiturates for the rapid intravenous induction of anesthesia, especially in patients with compromised myocardial contractility. Similar to propofol, during intravenous injection of etomidate there is a high incidence of pain, which may be followed by venous irritation. Involuntary myoclonic movements are also common but may be masked by the concomitant administration of neuromuscular blocking drugs. Awakening after a single intravenous dose of etomidate is rapid, with little evidence of any residual depressant effects. Etomidate does not produce analgesia, and postoperative nausea and vomiting may be more common than after the administration of thiopental or propofol. The characteristic state observed after an induction dose of ketamine is known as “dissociative anesthesia,” wherein the patient’s eyes remain open with a slow nystagmic gaze (cataleptic state). As with other intravenous induction drugs, the effect of a single bolus injection is terminated by redistribution to inactive tissue sites. Norketamine, the primary active metabolite, is less potent (one third to one fifth the potency of ketamine) and is subsequently hydroxylated and conjugated into water-soluble inactive metabolites that are excreted in urine. Organ System Effects If ketamine is administered as the sole anesthetic, amnesia is not as complete as with the benzodiazepines. Reflexes are often preserved, but it cannot be assumed that patients are able to protect the upper airway. Frequently, lacrimation and salivation are increased, and premedication with an anticholinergic drug may be indicated to limit this effect. Nevertheless, these perceived undesirable effects on cerebral blood flow may be blunted by the maintenance of normocapnia. Despite the potential to produce myoclonic activity, ketamine is considered an anticonvulsant and may be recommended for treatment of status epilepticus when more conventional drugs are ineffective. Such reactions may include vivid colorful dreams, hallucinations, out-of-body experiences, and increased and distorted visual, tactile, and auditory sensitivity. These reactions can be associated with fear and confusion, but a euphoric state may also be induced, which explains the potential for abuse of the drug. Combination with a benzodiazepine may be indicated to limit the unpleasant emergence reactions and also increase amnesia. Cardiovascular Effects Ketamine can produce transient but significant increases in systemic blood pressure, heart rate, and cardiac output, presumably by centrally mediated sympathetic stimulation. These effects, which are associated with increased cardiac workload and myocardial oxygen consumption, are not always desirable and can be blunted by coadministration of benzodiazepines, opioids, or inhaled anesthetics. Though the effect is more controversial, ketamine is also considered to be a direct myocardial depressant. This property is usually masked by its stimulation of the sympathetic nervous system but may become apparent in critically ill patients with limited ability to increase their sympathetic nervous system activity. When it is used as a single drug, the respiratory response to hypercapnia is preserved and blood gases remain stable. Transient hypoventilation and, in rare cases, a short period of apnea can follow rapid administration of a large intravenous dose for induction of anesthesia. The ability to protect the upper airway in the presence of ketamine cannot be assumed despite the presence of active airway reflexes. Especially in children, the risk for laryngospasm because of increased salivation must be considered; this risk can be reduced by premedication with an anticholinergic drug. Ketamine relaxes bronchial smooth muscles and may be helpful in patients with reactive airways and in the management of patients experiencing bronchoconstriction. Clinical Uses & Dosage Its unique properties, including profound analgesia, stimulation of the sympathetic nervous system, bronchodilation, and minimal respiratory depression, make ketamine an important alternative to the other intravenous anesthetics and a desirable adjunct in many cases despite the unpleasent psychotomimetic effects. Moreover, ketamine can be administered by multiple routes (intravenous, intramuscular, oral, rectal, epidural), thus making it a useful option for premedication in mentally challenged and uncooperative pediatric patients. Induction of anesthesia can be achieved with ketamine, 1–2 mg/kg intravenously or 4–6 mg/kg intramuscularly.

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