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American hospital formulary ser- acidic gastric environment for absorption; any drug vice drug information 2001. However, the patient remained profoundly Afor initiation of chemotherapy for acute myel- neutropenic for the next several weeks. Several weeks after completing supplemental intravenous potassium and magne- induction chemotherapy, he developed profound sium to replace electrolytes lost in the urine to am- neutropenia (absolute granulocyte count of less photericin B–induced renal tubular acidosis. After 4 weeks then had a temperature elevation to 103°F of profound neutropenia, the patient was noted to (39. Vancomycin However, the patient once again developed high empirical coverage was added 2 days later as high fever and appeared ill. A computed fevers continued, and 3 days later the patient began tomographic scan of the abdomen revealed multiple empirical therapy with amphotericin B for possible small low-density lesions in the liver and spleen. With the addition of amphotericin B, Antifungal therapy with a lipid formulation of am- the patient appeared to improve clinically, with less photericin B was continued. The patient had a 52 Antifungal Drugs 605 Case Study Chronic Disseminated Candidiasis stormy course requiring 4 additional weeks of anti- nia. Eventually the patient’s liver en- could generate an inflammatory response, fever zymes returned to normal and follow-up abdominal reappeared and the patient worsened clinically. A computed tomography showed resolution of hepatic new elevation in serum transaminases provided the and splenic abscesses. He was discharged home af- clue that led to abdominal imaging and the detec- ter a 2- month hospitalization. This patient was appropriately up to 50% of blood cultures falsely negative in this treated for possible fungal sepsis when antibacterial setting. Chronic disseminated candidiasis in neu- therapy failed to resolve fever in the setting of neu- tropenic leukemia patients is a life-threatening in- tropenia.

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The low pH of the gastric contents (pH 1–2) may The large intestine has a considerably smaller absorp- have consequences for absorption because it can dra- tive surface area than the small intestine, but it may still matically affect the degree of drug ionization. The most distal portion of the large intestine, the Intestinal Motility rectum, can be used directly as a site of drug adminis- tration. This route is especially useful where the drug Increased gastrointestinal motility may facilitate drug may cause gastric irritation, after gastrointestinal sur- absorption by thoroughly mixing intestinal contents gery, during protracted vomiting, and in uncooperative and thereby bringing the drug into more intimate con- patients (e. The processes may also occur in that an increase in motility may re- involved in rectal absorption are similar to those de- duce contact time in the upper portion of the intestine scribed for other sites. Conversely, a Although the surface area available for absorption decrease in gastrointestinal motility may promote ab- is not large, absorption can still occur, owing to the ex- sorption by increasing contact time. Serious in- sorbed from the rectum largely escape the biotransfor- testinal diseases, particularly those associated with mation to which orally administered drugs are subject, intestinal sloughing, can be expected to alter drug ab- because a portion of the blood that perfuses the rectum sorption dramatically. Absorption of most drugs from the gastrointestinal tract is reduced or delayed by the presence of food in the gut. For drugs that are ionized in the drugs, local blood flow, and intestinal surface area, other stomach and un-ionized in the intestine, overall ab- factors may affect absorption from the gastrointestinal sorption will be delayed by any factor that delays gas- tract. Finally, increased splanchnic blood flow, as occurs during eating, will increase the rate of drug Gastric Emptying Time absorption. The rate of gastric emptying markedly influences Formulation Factors the rate at which drugs are absorbed, whether they are acids, bases, or neutral substances. In general, fac- The ability of solid drug forms to dissolve and the sol- tors that accelerate gastric emptying time, thus permit- ubility of the individual drug in the highly acidic gas- ting drugs to reach the large absorptive surface of the tric juice must be considered. For example, although small intestine sooner, will increase drug absorption the anticoagulant dicumarol has a very high lipid– unless the drug is slow to dissolve. Taken together, the absorbed faster and more completely than tablet or Pgp transporter and the cytochrome P450 enzymes suspension forms. Suspensions of fine particles (mi- form a mechanism to reduce the amount of drug reach- crocrystalline) are better absorbed than are those of ing the systemic circulation. Until recently, only gut mi- The lungs serve as a major site of administration for a croflora were implicated in the metabolism of drugs in number of agents given for both local and systemic ef- the gastrointestinal system, affecting drug absorption. Absorption of agents from the lung is zymes, play a major role in determining the extent of facilitated by the large surface area of the pulmonary drug absorption of some drugs.

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Kamak, 55 years: Several obvious features are visible on the posterior Inner layer of the eyeball surface of the optic part of the retina. The laboratory abnormalities of a mildly elevated serum aminotransferase or creatine kinase level may be present but are nonspecific. Agents that block production or action of angiotensin and thereby reduce peripheral vascular resistance and (potentially) blood volume.

Rathgar, 21 years: These confrmatory tests demonstrated that the patient patients therefore have a high risk of bleeding. Evidence is accumulating that resistance rates do not rise Some strains have been associated with particularly severe inevitably and irreversibly (see page 169). The upper portion of the figure shows the population of channels moving through a cycle of activity during an action potential in the absence of drugs: R (rested) → A (activated) → I (inactivated).

Silvio, 49 years: The berries them- selves are less well absorbed than the extract and are Conclusion therefore believed to be less effective. He has not adult and pediatric patients receiving chemotherapy or radiation ther- apy or undergoing surgery. Pseudolinear Pharmacokinetics Method A simple, easy way to approximate new total serum concentrations after a dosage adjust- ment with valproic acid is to temporarily assume linear pharmacokinetics, then subtract 10–20% for a dosage increase or add 10–20% for a dosage decrease to account for nonlinear, concentration-dependent plasma protein binding pharmacokinetics: Dnew = (Cssnew/Cssold) Dold, where Cssnew is the expected steady-state concentration from the new valproic acid dose in μg/mL, Cssold is the measured steady-state concentration from the old valproic acid dose in μg/mL, Dnew is the new valproic acid dose to be prescribed in mg/d, and Dold is the cur- rently prescribed valproic acid dose in mg/d.

Farmon, 63 years: Pharmacokinetics: Infliximab is given as an intravenous infusion with “induction” at 0, 2, and 6 weeks and maintenance every 8 weeks thereafter. Prolonged usage of some bismuth compounds may rarely lead to bismuth toxicity, resulting in encephalopathy (ataxia, headaches, confusion, seizures). Thus, writes a critic: ‘We are asked to put may rest within an understanding of the complex nature aside the whole edifice of evidence concerning the physical of the placebo response and, in particular, its biology nature of materials and the normal concentration–response (see below).

Quadir, 57 years: Because the patient has a rapid theophylline clearance and half-life, the initial dosage interval (τ) will be set to 8 hours: D = (theophylline dose ⋅ Wt ⋅τ)/S = (0. When prorenin binds to the (pro)renin receptor, the prorenin undergoes a conformational change and becomes enzymatically active without cleavage of the prosegment. The most important potential cause of failure to achieve a satisfactory response is that the diagnosis is wrong or physiologically incomplete.

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