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The most commonly used androgenic effects occur in women (acne generic cytotec 100 mcg on-line treatment nail fungus, hirsutism and order cheap cytotec medications varicose veins, antiandrogen is cyproterone acetate buy 100 mcg cytotec with visa symptoms 7 days post iui. Flutamide is a potent non-steroidal antiandrogen that is effective in the treatment of Fertility regulation hirsutism buy cytotec with american express medicine descriptions. Metformin may be a safe and effective • Anterior pituitary hormones: follicle stimulating means of improving metabolic profile in both lean and hormone (p. Numerous field trials have shown that progestogen– The requirements of a successful hormonal contraceptive oestrogen combinations, if taken precisely as directed, are are stringent, for it will be used by millions of healthy the most reliable reversible contraceptive known. Carcinomas of the breast and cervix are slightly increased • 2 in incidence; the incidence of hepatoma (very rare) is in- creased. The risk to life seems to be less than that of mod- erate smoking (10 cigarettes/day) and than that of a normal Combined contraceptives (the ‘pill’) pregnancy, as the risks of pulmonary embolus are higher in Combined oestrogen–progestogen oral contraceptives a normal pregnancy. The overall inci- cipal mechanism is inhibition of ovulation through sup- dence of cancer is unaltered. In The effect on menstruation (it is not true menstruation, addition the endometrium is altered, so that implantation see above) is generally to regularise it, and often to dimin- is less likely and cervical mucus becomes more viscous and ish blood loss, but amenorrhoea can occur. Premenstrual tension and dysmenorrhoea are ued for 21 days (this is immediately effective, inhibiting much reduced. It is followed by a period of 7 days when no pill is taken, and during which bleeding usually Libido is greatly subject to psychosocial influences, and occurs. Thereafter, regardless of bleeding, a new 21-day removal of fear of pregnancy may permit enthusiasm for course is begun, and so on, i. There is evidence that the normal in- combined pills are packaged so that the woman takes crease in female-initiated sexual activity at time of ovula- one tablet every day without interruption (21 active then tion is suppressed. The incidence of venous In some instances, the course is not started on the first thromboembolism is increased in pill users. It is lowest in day of menstruation but on the second to the fifth day the 20–35-microgram pill and rises progressively with the (to give a full month between the menses at the outset). The small increase in hypertension, cerebro- cholestatic jaundice, Dubin–Johnson and Rotor vascular events and acute myocardial infarction is confined syndromes. The progestogen-only pill does not • Other conditions including: systemic lupus significantly affect coagulation. Because of the added risk of venous thromboem- Relative contraindications or uses with caution, bolism (surgery causes a fall in antithrombin levels), oral include: contraceptives should be withdrawn, if practicable, 4 weeks beforealllowerlimboperationsoranymajorelectivesurgery • Family history of venous thromboembolism, arterial (and started again at the first menstruation to occur more disease or a known prothrombotic condition, e. But increase in clotting factors factor V Leiden (pretreatment coagulation may persist for many weeks and there is also the risk of preg- investigation is advised). An alternative for emergencies is • Diabetes mellitus, which may be precipitated or to use low molecular weight heparin (although this may become more difficult to control (avoid if there are not reverse all the oestrogenic effects on coagulation) and diabetic complications). Cyclical bleeding will continue to occur under the influence of the drugs even after the natural men- Often more prominent at the outset and largely due to oes- opause. Thus the only way of deciding whether contracep- trogen, these include: nausea and, rarely, vomiting; breast tion can be permanently abandoned is by discontinuing it discomfort, fluid retention, headache (including increase (and using another technique) for 3 months annually to in migraine), lethargy, abdominal discomfort, vaginal dis- see whether natural menstruation is resumed, or by stop- charge or dryness. Depression may occur but most depres- ping the combined pill for 1 month and measuring lutei- sion in pill users is not due to the contraceptive. Menses are accompanied by less premenstrual tension and • Transient cerebral ischaemic attacks without headache. When oestrogen is combined with the • Infective hepatitis, until 3 months after liver function antiandrogen cyproterone acetate as the progestogenic test results have become normal, and other liver disease agent Dianette, the combined pill is useful treatment for including disturbances of hepatic excretion, e. Although the protective effect of cervical mucus returns within 48 h, Progestogen: this 7-day period is needed to ensure effective • Second generation: norethisterone, levonorgestrel. If vomiting occurs more than 3 h Combined oral contraceptives are defined as second or after a pill, behave as for a missed pill (above). The hor- third generation by the progestogen component (first- mones are rapidly absorbed and only severe diarrhoea generation progestogens are obsolete). In case of doubt, a fixed amount of oestrogen and progestogen in each active it would be prudent to use a barrier method during and for tablet are termed ‘monophasic’. The dose of progestogen is low at the beginning one preparation she may be changed to another containing and higher at the end, the oestrogen remaining either con- a different dose of oestrogen and/or progestogen. The objective is to preparation should start the day after she has finished a cy- achieve effective contraception with minimal distortion cle on the previous preparation. The advantages claimed for these techniques are dimin- Breakthrough bleeding (bleeding on days of active pill ished adverse metabolic changes, e. It is now appreciated that the earlier preparations had much more oestrogen than was necessary for efficacy. It seems probable that 20 micrograms is about the limit Progestogen-only contraception below which serious loss of efficacy can be expected. Progestogens render cervical mucus less easily pen- taining 50 micrograms oestrogen or more to avoid loss etrable by sperm and induce a premature secretory change of efficacy due to increased oestrogen metabolism (elim- in the endometrium so that implantation does not occur. Ectopic pregnancy may be more unwanted effects) and should make a start with the first frequent due to a fertilised ovum being held up in a func- preparation given above, recognising that compliance is tionally depressed fallopian tube. Medroxyprogesterone acetate and its metabolites are ex- cretedinbreastmilk,sowomenwhobreastfeedshouldwait Common problems until 6 weeks postpartum before starting Depo-Provera, when the infant’s enzyme system should be more mature. The following refers to the combined pill (see Norethisteroneenantate 200 mg(Noristerat)isshorter-acting later for the progestogen-only pill): than Depo-Provera, 8 weeks, and is used to provide contra- • If an omitted dose is remembered within 12 h, it ceptionafteradministrationoftherubellavaccine,anduntil should be taken at once and the next dose at the usual a partner’s vasectomy has taken effect. Medroxy- tives by diminishing the bacterial flora that metabolise progesterone (Depo-Provera) (t½ 28 h) is a sustained- ethinylestradiol in the large bowel and make it available release (aqueous suspension) deep intramuscular injection for recycling. When injected between day1 and day 5 of be taken during a short course of antimicrobial, and for the menstrual cycle, contraception starts immediately. Postcoital (‘morning after pill’) and emergency contraception Hypothalamic/pituitary hormone The overall risk of pregnancy following a single act of un- protected intercourse on any day in the menstrual cycle is approach to contraception 2–4%. Pregnancy may be pre- vented before implantation by disrupting the normal hor- monal arrangements; the mode of action is probably by Other methods of contraception delaying or preventing ovulation or by preventing implan- tation of the fertilised ovum. Levonorgestrel effective (>99% at 1 year) for 5 years, and some for 1500 micrograms is taken within 72 h of unprotected 10 years. Some women complain of nausea and vomiting, as a contraceptive, as a medical treatment for idiopathic which responds best to domperidone. Mirena Drug interaction with steroid contains 52 mg levonorgestrel surrounded by a Silastic cap- contraceptives sule, and releases 20 micrograms/day over 5 years, after Particularly now that the lowest effective doses are in use which the device should be changed. Any addi- micide) spermatozoa, are used to add safety to various me- tional drug-taking must be looked at critically lest it reduces chanical contraceptives. The rifamycins, rifampicin and rifa- used include non-oxinols (surfactants that alter the perme- butin, are potent inducers of hepatic drug-metabolising ability of the sperm lipoprotein membrane) as pessary, gel enyzmes. The or baby creams, wash off readily, but are nevertheless oil- enhanced metabolism of the steroids results in contracep- based. The levonorgestrel releasing intrauterine system Despite the small risk of thromboembolism, the death rate (Mirena) is advocated as an alternative to surgery. Sometimes there are press- ing reasons to prevent menstruation at the normal time but obviously this cannot be done at the last moment. Menstrual disorders Menstruation can be postponed by giving oral norethister- one 5 mg three times daily, starting 3 days before the expected onset; bleeding occurs 2–3 days after withdrawal. Amenorrhoea, primary or secondary, requires specialist Users of the combined oral contraceptive pill (having a endocrinological diagnosis.

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The physician asks whether this is a toxic dose of acetaminophen and whether any specific therapies are recom- 1 trusted cytotec 100mcg symptoms diagnosis. Comparison of rifaximin and lactitol in the Significant for an overdose 2 months earlier; details not available treatment of acute hepatic encephalopathy: results of a randomized buy cytotec discount medications routes, double- blind discount cytotec medications vs grapefruit, double-dummy purchase cytotec 200 mcg otc medicine assistance programs, controlled clinical trial. Evaluation of the efficacy í All and safety of rifaximin in the treatment of hepatic encephalopathy: a Not available double-blind, randomized, dose-finding multi-centre study. The poi- Possible acetaminophen poisoning son specialist determines that the correct dosage was administered and that no adverse effects occurred. Physical examination is normal, although she was complaining of a severe headache the previous evening. Which pain medications would the poison specialist want to Desired Outcome make sure are not being administered to this patient? Gray’s history of drug overdoses, should other medi- cations be considered for the management of her hypertension? What feasible pharmacotherapeutic alternatives are available for treating acetaminophen toxicity in this patient? Defend the argument that all patients with an intentional drug Optimal Plan overdose, no matter what their stated history, should have an acetaminophen level drawn to rule out acetaminophen toxicity. Show all calcu- acetylcysteine in addition to the oral N-acetylcysteine currently lations including how the total dose needed was obtained and on formulary. What clinical and laboratory parameters are necessary to evaluate evidence-based consensus guideline for out-of-hospital management. What is the rate of adverse events Patient Education after oral N-acetylcysteine administered by the intravenous route to 6. What should the patient be told about the effectiveness of N- patients with suspected acetaminophen poisoning? The sister has a remote history of inhalant N-acetylcysteine used as an intravenous solution for the pancreatitis as well. Prothrombin time prolongation he reports sharing a couple of pitchers with two friends last night in paracetamol poisoning: a relevant marker of hepatic failure? Skin Dry with poor skin turgor • Recommend appropriate pharmacologic and nonpharmaco- logic therapies for patients with acute pancreatitis. Neck/Lymph Nodes • Outline monitoring parameters to assist in realization of desired Supple; no bruits, lymphadenopathy, or thyromegaly therapeutic outcomes. No rebound tenderness, masses, or hepatospleno- midnight on a Friday night because of intense mid-epigastric pain megaly. He states that the pain started shortly after dinner the night before but has progressively worsened, and he Ext began vomiting around midnight tonight. When this patient is stable, what information should be provided to him to reduce the likelihood of recurrent pancreatitis? The pancreas itself appears relatively normal with the exception of small non-enhancing areas Problem Identification (Fig. How should these new therapies be monitored for efficacy and Therapeutic Alternatives adverse effects? Summarize published information regarding opioid effects on • Understand the rationale for “pancreatic rest” in the resolution the sphincter of Oddi. Review the Ranson scoring method for predicting the severity of • Discuss therapeutic alternatives and outline a patient-specific acute pancreatitis, and outline its advantages and disadvantages plan for pain management during an acute exacerbation of when clinically applied. Compose a list of drugs believed to aggravate or cause pancrea- • Recommend appropriate pancreatic enzyme replacement titis and assess the level of association for each agent. Jones management of acute pancreatitis: diagnostic criteria for acute pancre- vomited twice while in the waiting room and admits in the exam atitis. J Gastroenterol Hepatol 2006;21(1 Pt Has been hospitalized nearly every 6 months of his life for cystic 1):22–25. Meta-analysis of prophylactic antibi- Patient does not drink alcohol, smoke cigarettes, or use illicit drugs otic use in acute necrotizing pancreatitis. What feasible pharmacotherapeutic alternatives are available for treating this acute exacerbation of chronic pancreatitis? What drug, dosage form, and duration of therapy are best for this breath sounds in all lung fields patient? What clinical and laboratory parameters are necessary to evaluate Abd the therapy for achievement of the desired therapeutic outcome and to detect or prevent adverse effects? Chronic pancreatitis Cystic fibrosis is classically associated with pulmonary disease, diagnosis during childhood, and a lifespan generally not exceeding 2. What subjective and objective information is consistent with manifestations of cystic fibrosis in the adult patient. No adenopathy or goiter • Counsel eligible patients on the benefits of hepatitis A vaccina- Chest tion and the possible adverse effects associated with its use. Is Samantha’s daughter a candidate for the hepatitis A vaccina- changes in bowel habits, melena, hematochezia, urinary urgency or tion? Determine what other vaccines can be given simultaneously with increased risk for infection with hepatitis A? Compare the cost of administering the Havrix and Engerix-B Desired Outcome vaccines separately versus the combination product Twinrix for 2. What commercial products are available for vaccination against hepatitis A, and how effective are they in providing protective efficacy? Prevention of hepatitis A with the hepatitis A administration, and the number of doses required for Saman- vaccine. What adverse effects may be experienced with the regimen you recommended, and how may these events be treated? However, her husband Jorge who also accompanied them on the trip has progres- • Outline a pharmacologic and nonpharmacologic regimen for sively developed severe abdominal pain and yellow skin and eyes for patients with chronic hepatitis B. Jorge was admitted to the hospital for medical • Determine clinical and laboratory endpoints for treatment of attention. There are small cysts in the right kidney, and gallstones are present with non-obstructing nephrolithiasis. Which baseline parameters suggest that this patient may have a Abd favorable response to treatment. Soft, nontender; liver span 10 cm; no evidence of ascites; spleen is not palpable Patient Education Rect 6. Include the drug name, dose, dosage form, schedule, and childhood, the Immunization Practices Advisory Committee of the duration of therapy. What adverse effects may occur with this new therapy, and how newborn infants be vaccinated regardless of the hepatitis B status of the mothers. Hepatitis virus B: a Follow-Up Questions (continued) comprehensive immunization strategy to eliminate transmission of 4. If yes, include the doses, dosage prehensive immunization strategy to eliminate transmission of hepatitis schedule, and doses in micrograms for Mandy and the baby. Describe the ideal hepatitis B candidate to respond to entecavir treatment of hepatitis B e antigen-positive chronic hepatitis B.

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The anatomic structures caudal portion receives blood supply from peduncu- studied are the diencephalic structures as previously lar branches of the posterior cerebral artery buy generic cytotec 200 mcg on line medications quizlet, the medi- described order cytotec 200 mcg with amex medicinenetcom symptoms, to which the lenticular nuclei as well as al posterior choroidal artery purchase genuine cytotec medicines, and the superior cerebel- the caudate nuclei purchase cytotec 100 mcg on-line medications causing hair loss, and the related ventral striatopal- lar arteries (Duvernoy 1978; Rhoton et al. These classical orientation, as represented in the anatomic basal nuclei derive largely from the telencephalon. The basal ganglia: axial anatomic cut at the level of the insular and frontal horns, displaying the caudate and lenticular nuclei, and including the thalami and the internal capsules. The basal ganglia: axial anatomic cut through the bodies of the lateral ventricles, displaying the rostrocaudal extent of the caudate nuclei, superior to the level of lenticular nuclei. The basal ganglia: axial anatomic cut through the roof of the lateral ventricles and the body of the corpus callosum, displaying the corona radiata lateral to the caudate nuclei. The ventral striatum in- riorly enlarged portion is termed the head and pro- cludes the nucleus accumbens septi and the anterior trudes into the frontal horn of the lateral ventricle perforated substance and the ventral pallidum cor- (Figs. The remaining portion, called of the Lenticular Nucleus the tail of the caudate, follows the curvature of the temporal horn of the lateral ventricle, penetrates into The lentiform or lenticular nucleus refers to the the temporal lobe, and ends in the region of the putamen and pallidum. In all portions of the lateral ventri- lens completely buried in the hemispheric white cle, the caudate nucleus is covered by the ependyma. Above this infe- the form of a wedge with the apex directed medially rior fusion, the putamen and the head of the caudate and the base laterally. This nucleus is divided into are connected by strands of gray matter traversing two portions: a larger outer portion, the putamen, the anterior limb of the internal capsule (Figs. The This striped appearance of these gray matter anterior-posterior and superior margins of the lenti- bridges suggested the term corpus striatum. In the temporal lobe, the tail of portion of the putamen is continuous with the head the caudate nucleus is separated from the inferior of the caudate nucleus (Figs. The lateral striate arteries penetrat- The intrinsic architecture of the caudate nucleus ing the brain at this level are clearly seen on the coro- and the putamen is similar; both are highly cellular nal slices (Fig. Morphometric data has The globus pallidus, which forms the medial portion shown that the putamen is around 13% larger than of the lenticular nucleus, is subdivided into two seg- the caudate nucleus in humans and the external glo- ments separated by the internal medullary lamina. It is bus pallidus constitutes 70% of the volume of the traversed by numerous heavily myelinated fibers which pallidum (Parent 1996). The pallidum is separated from the putamen by the ex- D Functional Aspects ternal medullary lamina (Figs. The corticostriatal projections arise from large matter related throughout its extent to the lateral areas of the cerebral cortex and project to the cau- 210 Chapter 7 A B C D E F Fig. Note the high contrast resolution due partly to the relatively rich vascularization of most of the basal ganglionic structures, mainly, the ventral striatum-accumbens complex, the striatum, the pulvinar and dorsomedian thalamic nuclei. A The ventral striatum-accumbens and pulvinar level; B the striatum, inferior level; C the striatum, mid-level; D the striatum, upper level; E,F the body of the caudate nucleus. The cortical stri- atal fibers arising from area 4 project bilaterally and somatotopically to the putamen and use glutamate as a neurotransmitter. The thalamostriatal projections constitute an- other profuse afferent system, arising mainly from the centromedian, but also other intralaminar and midline nuclei. The nigrostriatal fibers originate from the cells of the pars compacta of the substantia nigra, ascend to the subthalamic region to reach the internal capsule, and end in the caudate and the putamen nuclei. Dissection of the major fiber bundles in the basal ing from serotoninergic cell groups located in the ganglia. The striatopallidal fibers are to- pographically organized; the lateral portion of the project to the putamen as part of a feed-back system. Topographically organized fibers arising from the The basal ganglia functionally include the puta- subthalamic nucleus project to both segments of the men, the globus pallidus, the caudate nucleus, the globus pallidus. The fron- represented by the pallidofugal system which is tal cortex, in turn, exerts motor control, mainly con- comprised of thick and heavily myelinated fibers to- tralaterally, at all levels of the central nervous sys- pographically organized in a series of pathways in- tem. Note that the basal ganglia do not project fibers cluding: the ansa lenticularis, the lenticular fascicu- directly to the level of the spinal cord. The basal gan- lus, the thalamic fasciculus, the subthalamic glia control system is organized in circuits and acts fasciculus, and between other pallido-tegmental, as a modulating system, inhibiting or facilitating pallido-nigral, and pallidohabenular projections motor activities. Pallidothalamic and nigroth- exception of the pallidosubthalamic fibers that arise alamic projections may result in inhibition of the from the external segment of the pallidum. The main destination of the pallidotha- ic nuclei and the raphe nuclei of the midbrain, all of lamic crossed and uncrossed fibers is to the ventral which are projections mediated by different neu- anterior and ventral lateral thalamic nuclei, which in rotransmitters. Thalamostriatal Pathologic conditions are observed when the bal- fibers arising from the centromedian nucleus also ance in this complex, modulating and interrelated The Basal Forebrain, Diencephalon and Basal Ganglia 213 system is disrupted. Movement disorders consecu- per and Bravo 1958; Hassler 1959, 1982; Martin and tive to the basal dysfunction comprise a wide spec- McCaul 1959; Talairach et al. Such surgical at- trum of abnormalities, ranging from hypokinesia to tempts to alleviate various forms of involuntary hyperkinesia or dyskinesia. The pathophysiologic movements are based on the hypothesis that dyski- basis of the associated disease processes is often the nesias are the physiologic expression of release phe- consequence of a deficiency in one or more involved nomena, the involuntary movements observed being neurotransmitters. Parkinson’s disease is the best representative of Experimental models clarified part of the patho- hypokinetic disorders. It is characterized by a reduc- physiology of hypokinetic disorders, which seem to tion or loss of movement with reduction of initia- be due to increased thalamic inhibition caused by in- tion, implementation and facility of execution of creased excitatory effects acting on the internal glo- movements, as well as in the velocity of voluntary bus pallidus and the substantia nigra reticulata and movements known as bradykinesia. Clinical re- usually associated with muscular rigidity and trem- sults obtained from selective lesioning of the subtha- or at rest. The positive role of the subthalamic the pathologic changes affect mainly the substantia nucleus in the genesis of akinesia as postulated is also nigra and are characterized by a reduced dopamin- supported by experimental high frequency stimula- ergic input from the cells of the pars compacta to the tion of this nucleus (Benazouz et al. The clinical picture of this syndrome in- cludes akinesia and bradykinesia with little facial expression and slowness of movements, flexed pos- E Functional Neurosurgery ture and immobility, muscular rigidity, and static or postural tremor. This treatment modality has recently re- 1-2–5-6-Tetrahydropyridine), a neurotoxin, which ceived much attention and consists of lesional sur- produces a chronic form of parkinsonism in mon- gery directed to specific targets or neuro-augmenta- keys, the signs of which are identical to human Par- tive procedures using high frequency stimulation. Using the standard to the release of pallidal and thalamic activities fol- brain atlases, which are incorporated frequently in lowing the degeneration of striatal neurons which the stereotaxy software, the approximate location of normally modulate the pallidum. The precise location tex plays an important role in the neural mecha- of the target is selected, based on stimulation studies nisms, causing dyskinesias. At present, Most of the abnormal involuntary movements most units performing functional neurosurgery and dyskinetic states are abolished with interrup- supplement the coordinates derived by neuroimag- tion of the corticospinal pathway or surgical ablation ing with intraoperative physiological testing to de- of the motor cortex (Bucy 1958; Carpenter et al. More recently, structures have significantly reduced, and even abol- the treatment is individualized based on the most ished, some forms of dyskinesia (Cooper 1956; Coo- disabling symptoms. In addition, high frequency 214 Chapter 7 stimulation has been found to produce the same ef- eotactic atlas. The specific thalamic nuclei are located in the branches of the anterior choroidal artery (Gillilan parallelogram drawn between these two lines and 1968; Dunker and Harris 1976). The dorsolateral nal role in the pathogenesis of motor disturbances portion of the head and the body of the caudate associated with Parkinson’s disease. Consequently, nucleus are supplied by the lateral striate branches of recent work has demonstrated that high frequency the middle cerebral artery.

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Bayes’ theorem is used in the computer algorithm to balance the results of the computations between values based solely on the patient’s serum drug concentrations and those based only on patient popula- tion parameters buy cytotec 100 mcg without a prescription medicine zoloft. Results from studies that compare various methods of dosage adjustment have consistently found that these types of computer dosing programs perform at least as well as experienced clinical pharmacokineticists and clinicians and better than inexperi- enced clinicians purchase 200mcg cytotec with mastercard medicine 50 years ago. Some clinicians use Bayesian pharmacokinetic computer programs exclusively to alter drug doses based on serum concentrations order cytotec pills in toronto severe withdrawal symptoms. An advantage of this approach is that consis- tent dosage recommendations are made when several different practitioners are involved in therapeutic drug monitoring programs order 100 mcg cytotec overnight delivery medications you cant drink alcohol with. However, since simpler dosing methods work just as well for patients with stable pharmacokinetic parameters and steady-state drug concentrations, many clinicians reserve the use of computer programs for more difficult situations. Those situations include serum concentrations that are not at steady state, serum concentrations not obtained at the specific times needed to employ simpler meth- ods, and unstable pharmacokinetic parameters. When only a limited number of phenytoin concentrations are available, Bayesian pharmacokinetic computer programs can be used to compute a complete patient pharmacokinetic profile that includes Vmax, Km, and vol- ume of distribution. These are distinct advantages compared to the other methods used to adjust phenytoin dose based on one steady-state serum concentration. Many Bayesian pharmacokinetic computer programs are available to users, and most should provide answers similar to the one used in the following examples. The patient was prescribed 400 mg/d of extended phenytoin sodium capsules for 1 month, and the steady-state phenytoin total concentration equals 6. Suggest an initial phenytoin dosage regimen designed to achieve a steady-state phenytoin concentration within the therapeutic range. 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 distribu- tion of 53 L, a Vmax equal to 506 mg/d, and a Km equal to 4. Extended phenytoin sodium capsules would be prescribed as 400 mg/d on even days alternating with 500 mg/d on odd days. A steady-state trough total phenytoin serum concentration should be measured after steady state is attained in 7–14 days. Phenytoin 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 phenytoin toxicity. The patient was prescribed 300 mg/d of extended phenytoin sodium capsules for 1 month, and the steady-state phenytoin total concentration equals 10. Suggest an initial phenytoin dosage regimen designed to achieve a steady-state phenytoin concentration of 18 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 distribu- tion of 34 L, a Vmax equal to 354 mg/d, and a Km equal to 5. The one-compartment model Michaelis-Menten equations used by the program to compute doses indicates that a dose of 304 mg/d of phenytoin will produce a total steady- state concentration of 19. Extended phenytoin sodium capsules would be prescribed as 330 mg/d (three 100 mg capsules + one 30 mg capsule). A steady-state trough total phenytoin serum concentration should be measured after steady state is attained in 7–14 days. Phenytoin 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 phenytoin toxicity. The patient was prescribed 300 mg/d of extended phenytoin sodium capsules for 1 month, and the steady-state phenytoin total concentration equals 8. Suggest a new phenytoin dosage regi- men increase designed to achieve a steady-state phenytoin concentration within the upper end of the therapeutic range. 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 distribu- tion of 43 L, a Vmax equal to 586 mg/d, and a Km equal to 13. The one-compartment model Michaelis-Menten equations used by the program to compute doses indicates that a dose of 396 mg/d of phenytoin will produce a total steady- state concentration of 20. Extended phenytoin sodium capsules would be prescribed as 430 mg/d (four 100 mg capsules + one 30 mg capsule). A steady-state trough total phenytoin serum concentration should be measured after steady state is attained in 7–14 days. Phenytoin 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 phenytoin toxicity. Some dosing schemes link together logically when considered according to their basic approaches or philosophies. In this setting, it would not be acceptable to simply increase the maintenance dose and wait for therapeutic steady-state serum concentrations to be established in the patient. If the volume of distribution for phenytoin is known for the patient, it can be used in the calcula- tion. For obese individuals 30% or more above their ideal body weight, the volume of distribution can be estimated using the following equation: V = 0. Concurrent with the administration of the booster dose, the maintenance dose of phenytoin is usually increased. Clinicians need to recognize that the administration of a booster dose does not alter the time required to achieve steady-state conditions when a new phenytoin dosage rate is prescribed. However, usually the difference between the postbooster dose phenytoin concentration and the ultimate steady-state concentration has been reduced by giving the extra dose of drug. After receiving an initial loading dose of phenytoin sodium (1000 mg) and a maintenance dose of 300 mg/d of phenytoin sodium for 5 days, his phenytoin concen- tration is measured at 5. Clinicians should always con- sult the patient’s chart to confirm that current anticonvulsant therapy is appropriate. Addi- tionally, all other medications that the patient is taking, including prescription and nonprescription drugs, should be noted and checked to ascertain if a potential drug inter- action with phenytoin exists. Suggest an initial extended phenytoin sodium capsule dosage regimen designed to achieve a steady- state phenytoin concentration equal to 10 μg/mL. Suggest an ini- tial phenytoin suspension dosage regimen designed to achieve a steady-state pheny- toin concentration equal to 15 μg/mL. Suggest an initial intravenous fosphenytoin regimen designed to achieve a steady-state phenytoin concentration equal to 12 μg/mL. A phenytoin serum concentration was obtained just before the fourth dose of this regimen and equaled 4. Assuming the phenytoin concentration was zero before the first dose, compute a new intravenous fosphenytoin injection that will provide a steady-state concentration of 12 μg/mL. Suggest an initial intravenous phenytoin sodium dosage regimen designed to achieve a steady-state phenytoin concentration equal to 12 μg/mL.