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Diarrhea or dysentery is associated with infestations by Oxamniquine has a restricted range of efficacy cheap gabapentin 600mg with amex treatment eczema, being S gabapentin 600mg on-line medications look up. In Oxamniquine is given orally and is readily absorbed the chronic form of the disease buy cheap gabapentin 400 mg online medicine 3 times a day, fibrosis and hyperplasia from the intestinal tract buy 300mg gabapentin with visa treatment hyperkalemia. The drug increases calcium permeability Bithionol through parasite-specific ion channels, so that the Bithionol (Actamer) is a phenolic derivative whose tegmental and muscle cells of the parasite accumulate mode of action is related to uncoupling of parasite- calcium. This action is followed by vacuolization and the specific fumarate reductase–mediated oxidative phospho- exposure of hitherto masked tegmental antigens, lipid- rylation. Peak blood levels are achieved in the fluke’s lipid bilayer causes conformational changes, 4 to 8 hours. It is highly active after oral administration, with serum concentrations be- against the adult worm but exerts no action against the ing maximal in 1 to 3 hours; the drug has a half-life of migratory stages. Side effects are generally mild and transient; they Dexamethasone decreases plasma praziquantel levels include nausea, vomiting, diarrhea, headache, dizziness, by 50%. It is the most effec- Metrifonate tive of the drugs used in the treatment of schistosomia- sis, possessing activity against male and female adults Metrifonate is an organophosphorous compound that and immature stages. In addition, it has activity cholinesterase and potentiates inhibitory cholinergic ef- against other flukes, such as C. It is contraindicated in preg- of clonorchiasis and paragonimiasis and is an effective nancy, previous insecticide exposure, or with depolariz- alternative agent to niclosamide in the treatment of ing neuromuscular blockers. Initially he (B) Praziquantel thought he was recovering from stomach flu; his ex- (C) Albendazole amination is significant for conjunctival hemor- (D) Surgery rhage, bilateral periorbital edema, and severe ten- (E) Thiabendazole derness of neck muscles and jaws. Which of the following as- the West Coast is admitted with abdominal pain, pects of trichinosis are particularly important? Diphyllobothriasis is diagnosed after stool studies are (C) Suramin is used in its treatment with consider- done. While serving with Doctors Without Borders in (E) Piperazine Malaysia, you are seeing a patient who has intermit- tent cough, shortness of breath, and wheezing. Trichinosis should be suspected in a patient who filaria in the blood, and a chest radiograph showing has any of the cardinal features of periorbital scattered reticulonodular infiltrates. Muscle biopsy from (B) Absence of microfilariae in blood makes the a tender, swollen muscle (preferably deltoid or gas- diagnosis unlikely. Paroxysmal respiratory symptoms blood count showing anemia and 22% eosinophils may fluctuate in severity. A stool specimen revealed the character- ways present, is usually very high, and the absence istic eggs of A. No prior history of fever, chills, trauma, or Piperazine or pyrantel pamoate may be used for the headaches was reported on admission. Mebendazole is an effective tomography reveals three ring-enhancing cystic le- drug to be taken for 3 days. Thiabendazole is not sions in the brain parenchyma, and a diagnosis of used in this condition but is used commonly in neurocysticercosis is made. Albendazole at a single dose of management of this condition should include 400 mg is the preferred mode of therapy. The quantel should be considered later to eliminate the Sanford Guide to Antimicrobial Therapy (32nd adult tapeworm in the gut and prevent further rein- ed. The biochemical basis of anthelmintic action Ivermectin is effective for filarial infections, espe- and resistance. Hunter’s Tropical Medicine and ifestations (subacute combined degeneration of Emerging Infectious Diseases (8th ed. Case Study An Extensive History: Always Useful he patient is a 64-year-old male resident of a area, with no masses. His skin examination revealed Tmental institution with a chief complaint of a migratory serpiginous urticarial rash distributed cough and rash. He was a Vietnam veteran with a over the lower abdomen, lower trunk, and buttocks history of non-Hodgkin’s lymphoma treated with (larva currens). His chest radiograph showed diffuse pul- what he describes as an itchy rash on the lower ab- monary infiltrates. The patient’s physical examination showed eosinophilic granulomatous inflammation revealed a thin man in mild distress with a temper- of the bronchial epithelium. Microscopic mmHg, pulse 120, and respiratory rate 25 per examination of the stool revealed rhabditiform lar- minute. His abdomen was soft and flat, with hypoactive stercoralis hyperinfection syndrome, which agent or bowel sounds. There was marked tenderness with- agents would be a logical choice for treatment of out rebound noted on palpation of the epigastric this life-threatening disease? It presents a serious potential for severe needed to make a timely diagnosis of patients who disease in the many military servicemen who were spent time in endemic areas. In fact, it was first described in complicate therapy with thiabendazole (even when 1876 as “diarrhea of China” in French colonial given over 7 to 10 days). Alternative therapy with troops in Indochina by Louis Alexis Norman, physi- ivermectin appears as effective (64–100% cure cian first class in the French Navy. Sikic Modern cancer chemotherapy originated in the The mitotic index is the fraction or percentage of 1940s with the demonstration that nitrogen mustard cells in mitosis within a given cell population. The possessed antitumor activity against human lymphomas thymidine labeling index is the fraction of cells incorpo- and leukemias. They represent cells in M- cer have 40 to 80% “cure” rates using chemotherapy phase and S-phase and define the proliferative charac- alone or chemotherapy plus surgery or radiation (Table teristics of normal and tumor cells. For this purpose cure is defined as the disappear- ance of any evidence of tumor for several years and a The Tumor Cell Cycle high actuarial probability of a normal life span. Patients with other types of unresectable cancer also The duration of the S-phase in human tumors is 10 to 20 may benefit from chemotherapy, as evidenced by pro- hours. This period is followed by the G2-phase, or period longation of life, shrinkage of tumor, and improvement of preparation for mitosis, in which cells contain a in symptoms. The G2-phase lasts lial and breast carcinomas, oat cell (small cell undiffer- only 1 to 3 hours for most cell types, with mitosis itself entiated) carcinoma of the lung, and acute myelocytic lasting approximately 1 hour. Cancers that are for the most part resistant to then enter the G1-phase, whose duration varies from today’s agents include melanoma, colorectal and renal several hours to days. The factors that influence daughter cells to enter the G0, or resting The normal cell cycle consists of a definable sequence of stage, are not well understood. The ability to cause such events that characterize the growth and division of cells resting cells to reenter the cell cycle would be quite use- and can be observed by morphological and biochemical ful, since proliferating cells generally are more sensitive means. Age Type of Cancer Unfortunately, many human cancers have a large Childhood Acute lymphocytic leukemia Burkitt’s sarcoma proportion of cells in the resting phase, and these cells Ewing’s sarcoma are also resistant to the class 3 agents, which include cy- Retinoblastoma clophosphamide, dactinomycin, and fluorouracil. For instance, it may be difficult to generalize Adult Hodgkin’s disease Non-Hodgkin’s disease about the phase specificity of a particular drug, since Trophoblastic choriocarcinoma this may vary among cell types. Several techniques are Testicular and ovarian germ cell cancers available to synchronize cell populations in such a way that most cells will be in the same phase of the cell cy- cle. After synchronization, one can treat cells in each phase and determine their relative sensitivity to drugs classification divides the anticancer drugs into three cat- throughout the cell cycle. Such a dosage regimen would increase increasing tumor size is related both to a decrease in the the number of tumor cells exposed to the drug proportion of cancer cells actively proliferating (termed during the sensitive phase of their cell cycle.
J Gastroenterol Hepatol 2006;21(1 Pt Has been hospitalized nearly every 6 months of his life for cystic 1):22–25 gabapentin 600mg symptoms depression. Meta-analysis of prophylactic antibi- Patient does not drink alcohol order 600mg gabapentin overnight delivery symptoms 14 days after iui, smoke cigarettes buy 400mg gabapentin visa medications ms treatment, or use illicit drugs otic use in acute necrotizing pancreatitis generic gabapentin 600 mg online medicine for stomach pain. 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. Survey several pharmacies to estimate the approximate retail Diseases; Poster 514, April 26–30, 2006, Vienna, Austria. Non-smoker; denies illicit drug or inhalant use; drinks two to four glasses of wine once From Fibrosis to Cirrhosis. She still drinks alcohol occasionally (2–4 glasses of wine once or twice a week), but otherwise has been Neck/Lymph Nodes “drug free” since her mid-twenties when she was married. She Neck supple; no lymphadenopathy or thyromegaly; no carotid states that she feels fine much of the time, but sometimes has bruits fatigue, fluid retention, headaches, and difficulty sleeping. She has lost about 10 Lungs pounds in the last 2 months, which she attributes to reduced Normal breath sounds appetite, since her activity level has diminished. What other laboratory tests should be obtained to better monitor Chronic hepatitis C her drug therapy tolerance? Based on this new information, what changes would you recom- Desired Outcome mend for the treatment of chronic hepatitis C for this patient, 2. Outline a plan for vaccination of this patient against other forms Therapeutic Alternatives of viral hepatitis. Perform a literature search to compare the differences in phar- ered contraindications to receiving the treatments discussed in macokinetic properties and tolerance between interferon and the previous question? With respect to the patient’s other drug therapy, are there any drug related interventions that need to be made other than The course of chronic hepatitis C infection and treatment response acetaminophen use? Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treat- as predictors of poor response to the treatment you recom- ment of chronic hepatitis C: a randomised trial. What actions can be taken if the patient develops intolerable ribavirin for chronic hepatitis C virus infection. What information should be provided to this patient regarding ment: management of hepatitis C: 2002—June 10–12, 2002. Three days post-operation, purulent drainage was noted from the surgical Gen site, and he was subsequently diagnosed with mediastinitis. Based on the patient’s estimated creatinine clearance and clinical presentation, do any of his medications require dosage adjust- ment? What risk factors did the patient have for gentamicin-induced Basilar crackles, inspiratory wheezes acute kidney injury? What feasible pharmacotherapeutic alternatives are available 2+ Ankle/sacral edema for treating acute kidney injury in this patient? What clinical and laboratory parameters are necessary to evaluate Cl 104 mEq/L Plt 263 × 10 /mm Phos 4. Recommend an appropriate dosage of digoxin for this patient feeling normal until last night when he felt more tired than usual given a trough digoxin concentration of 2. Before retirement, the outcome measures, animal models, fluid therapy and information technol- patient was employed as an accountant. Estimation of creatinine clearance in patients with unstable renal Furosemide 40 mg po once daily function, without a urine specimen. Pharmacokinetics and therapeutic drug monitoring of Enalapril 20 mg po once daily gentamicin in the elderly. His subsequent hospital course was uneventful, and his Weak pulses; no peripheral edema kidney function gradually improved. No tobacco use but occasional alcohol (2 or 3 glasses of wine or beer on weekends or when out with friends). Previous diet included eggs and bacon for breakfast, chicken sandwiches for lunch, and pasta 50 and salad for dinner with snacks mid-afternoon and in the evening (usually a couple diabetic treats or a muffin). Occasional dizziness, weakness, and mild diaphoresis during mid- After completing this case study, students should be able to: afternoon.
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Adverse Effects Second- and Third-generation The principal adverse effect associated with throm- Thrombolytic Drugs bolytic therapy is bleeding due to fibrinogenolysis or fibrinolysis at the site of vascular injury discount 400mg gabapentin visa medications migraine headaches. Life-threatening intracra- solute; circulating plasminogen also may be activated nial bleeding may necessitate stoppage of therapy gabapentin 300 mg fast delivery medications given before surgery, by large doses or lengthy treatment buy 800 mg gabapentin amex symptoms kidney disease. After intravenous administration of whole blood generic gabapentin 800 mg otc medicine look up drugs, platelets or fresh frozen administration, alteplase is more efficacious than strep- plasma, protamine (if heparin is present), and an an- tokinase in establishing coronary reperfusion. Reocclusion may be lessened by administration diopulmonary resuscitation (trauma to thorax is possi- of heparin and antiplatelet drugs. Streptokinase (Streptase, Kabikinase), a nonenzymatic Reteplase (Retavase) contains only the peptide domains protein from Lancefield group C -hemolytic strepto- required for fibrin binding and protease activity. These 22 Anticoagulant, Antiplatelet, and Fibrinolytic (Thrombolytic) Drugs 265 changes increase potency and speed the onset of action. They also are useful adjuncts to co- Reteplase may penetrate further into the fibrin clot agulation factor replacement during dental surgery in than alteplase. Anistreplase (Eminase) consists of streptokinase in a Agents for Controlling Blood Loss noncovalent 1:1 complex with plasminogen. Anistreplase is catalytically inert because of acylation of the catalytic Cardiopulmonary bypass, with extracorporeal circula- site of plasminogen. However, the affinity of plasmino- tion during cardiac artery bypass graft or heart valve re- gen binding to fibrin is maintained. It has a long catalytic placement surgery, causes transient hemostatic defects half-life (90 minutes), and the time required for nonen- in blood cells and perioperative bleeding. Anistreplase is more effective than lation phase) and plasmin (fibrinolysis) and protects streptokinase in establishing coronary reperfusion, but it platelets from mechanical injury. Several biological agents are used intravenously to maintain coagulability in the face of factor deficiencies Antifibrinolytic Drugs in hemophilia or Von Willebrand’s disease patients. Hyperplasminemia resulting from thrombolytic therapy Manufacture of these substances involves extraction exposes fibrinogen and other coagulation factors, plas- from human blood or recombinant technology. Consumption of these factors and extensive fibrin concentrate (Bebulin, AlphaNine, Mononine, others) dissolution leads to hemorrhage. Warfarin does not produce an anticoagulant blood collection devices used at blood donating effect in vitro. Warfarin does not require conversion into an (B) The anticoagulant effect of warfarin occurs active drug. Warfarin is metabolized in the liver by P450 (E) Warfarin is chemically unstable and is de- enzyme system and is appreciably metabolized be- graded unless made fresh and used immediately. Thrombocytopenia is a frequent side effect as- (D) Warfarin is eliminated from the body un- sociation with heparin. Which of the following is an adverse effect associ- may be administered to pregnant mothers without ated with pharmacotherapy using heparin? Altering therapy by removing the placenta and has not been reported to produce heparin and adding warfarin is not a viable option, effects in the fetus. Argatroban is discontinued at because warfarin can cross the placenta and exert the time of delivery, and thrombosis is then man- an anticoagulant effect in the fetus. In fact, a re- cent study employing intensive lifestyle changes in pa- Atherosclerosis is the primary cause of coronary heart tients with coronary heart disease achieved a 37% disease. A be the goal, with the focus on decreasing elevated prescription for lifestyle changes should accompany the blood cholesterol. Although hypercholesterolemias are linked to spe- cific genetic mutations, most have a multifactorial basis Principal risk factors for heart disease are elevated lev- that can respond to lifestyle changes. C-Reactive protein tion of body weight; decreased dietary total fat, choles- is a marker for cellular inflammation. Guidelines for initiation and goals of treatment Dietary treatment of hypercholesterolemias are outlined in Table 23. As a consequence, all other hypocholes- mg/dL), diabetes mellitus, definite cerebrovascular or peripheral terolemic drugs have been relegated to secondary status. Clinical trials with lovastatin (Mevacor), simvastatin dRoughly equivalent to total cholesterol level 200 mg/dL. An consequences of inhibiting the cholesterol synthesis overview of lipoprotein metabolism and the sites where pathway. Drug-induced inhibition of hepatic cholesterol drugs can influence plasma lipoprotein levels is pro- synthesis leads to lowering of liver cholesterol concen- vided in Figure 23. However, the statins probably should not be given with the fibrates (triglyceride- lowering drugs, discussed later), since this combination may greatly increase statin toxicity. The statins also have been claimed to reduce blood cholesterol levels modestly in some patients with homozygous familial hy- percholesterolemia, a condition often fatal in childhood density in postmenopausal women. Lovastatin decreased elevated plasma levels of C- reactive protein, a marker for cellular inflammation, and Adverse Effects acute coronary events in patients with relatively low The statins generally appear to be well tolerated, plasma cholesterol levels. Recent studies also suggest with muscle pain and liver dysfunction seen in 1 to 2% that use of statins may decrease the risk of stroke, de- of patients. However, the consequences of 20 to 30 years mentia, and Alzheimer’s disease and may improve bone of continuous use are unknown. Type I is a rare elevation of chylomicrons treatable only by diet (removing long chained fatty acids). A relatively liver by the enterohepatic circulation results in dere- common side effect of the statins (perhaps 1% of pa- pression of 7- -hydroxylase, the rate-limiting enzyme tients) is myositis, that is, inflammation of skeletal mus- for conversion of cholesterol to bile acids. This results in cle accompanied by pain, weakness, and high levels of increased use of cholesterol to replace the excreted bile serum creatine kinase. Thus, similar to the statins, the ultimate kidney damage, was considered to be a rare and extreme actions of the bile acid–sequestering resins are up- toxic outcome. The risk of muscle damage is said to increase with simultaneous use of the triglyceride-lowering fibrates. Drugs that inhibit P450 3A4, such as itra- Adverse Effects conazole, cyclosporine, and erythromycin, can vastly (10- The resins are interesting drugs because they have fold) increase plasma statin levels and thus increase the profound metabolic effects without truly entering the risk of toxicity. Perhaps for this reason they are relatively safe, intestinal metabolism of the statins and can result in an with constipation being the chief complaint. Since resins are given as the chloride salt and the chloride is fluvastatin is metabolized by cytochrome P450 2C9, exchanged for the negatively charged bile salt, bile acid which is also responsible for metabolism of warfarin, resins can lead to hyperchloremic acidosis in vulnerable warfarin toxicity may be increased if these drugs are si- patients (children and patients with kidney failure). Grapefruit juice should obviously not be consumed within several hours of statin adminis- Drug Interactions tration. Drugs that induce the P450 3A4 system, such as The principal precaution with use of the bile acid barbiturates, can accelerate statin metabolism and sup- resins is the possibility of impaired absorption of other press statin blood levels. Cholestyramine and colestipol can bind many other drugs, such as digitoxin, phenobarbital, chlorothiazide, and warfarin, and delay Other Hypocholesterolemic Drugs or prevent their absorption. For this reason, other drugs Resins should always be taken at least 1 hour before or 4 to 6 hours after the resin. Prior to the introduction of the statins in the mid to late 1980s, the bile acid–sequestering drugs cholestyra- Nicotinic Acid (Niacin) mine (Questran) and colestipol (Colestid) were primary drugs for lowering plasma cholesterol. Today they are Nicotinic acid has three special features as a hypolipi- second-line drugs that can safely be given with a statin demic drug: it has multiple beneficial effects on serum to enhance cholesterol lowering or as an alternative for lipoproteins, it is the least expensive, and it is the least patients intolerant to a statin or concerned with statin’s well tolerated. This ac- These drugs are basically anion exchange resins that tion appears secondary to its ability to inhibit fatty acid remain in the gut, bind intestinal bile acids, and greatly mobilization from adipose tissue.
