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By: A. Farmon, M.B. B.A.O., M.B.B.Ch., Ph.D.
Deputy Director, Rowan University School of Osteopathic Medicine
Because of these immunosuppressant activities medicine bow cheap 100 mg persantine with mastercard, hydroxychloroquine is used to treat some autoimmune disorders medications descriptions buy persantine no prescription, eg symptoms torn rotator cuff generic persantine 25 mg visa, rheumatoid arthritis and systemic lupus erythematosus treatment lead poisoning purchase persantine 25mg with mastercard. It has also been used to both treat and prevent graft-versus-host disease after allogeneic stem cell transplantation. Other Cytotoxic Agents Other cytotoxic agents, including vincristine, methotrexate, and cytarabine (see Chapter 54), also have immunosuppressive properties. Methotrexate has been used extensively in rheumatoid arthritis (see Chapter 36) and in the treatment of graftversus-host disease. Although the other agents can be used for immunosuppression, their use has not been as widespread as the purine antagonists, and their indications for immunosuppression are less certain. The use of methotrexate (which can be given orally) appears reasonable in patients with idiosyncratic reactions to purine antagonists. The antibiotic dactinomycin has also been used with some success at the time of impending renal transplant rejection. Vincristine appears to be quite useful in idiopathic thrombocytopenic purpura refractory to prednisone. The related vinca alkaloid vinblastine has been shown to prevent mast cell degranulation in vitro by binding to microtubule units within the cell and to prevent release of histamine and other vasoactive compounds. Pentostatin is an adenosine deaminase inhibitor primarily used as an antineoplastic agent for lymphoid malignancies, and produces a profound lymphopenia. It is now frequently used for steroid-resistant graft-versus-host disease after allogeneic stem cell transplantation, as well as in preparative regimens prior to those transplants to provide severe immunosuppression to prevent allograft rejection. Antilymphocyte & Antithymocyte Antibodies Antisera directed against lymphocytes have been prepared sporadically for over 100 years. With the advent of human organ transplantation as a therapeutic option, heterologous antilymphocyte globulin (ALG) took on new importance. ALG and antithymocyte globulin (ATG) are now in clinical use in many medical centers, especially in transplantation programs. The antiserum is usually obtained by immunization of horses, sheep, or rabbits with human lymphoid cells. ALG acts primarily on the small, long-lived peripheral lymphocytes that circulate between the blood and lymph. With continued administration, "thymus-dependent" (T) lymphocytes from lymphoid follicles are also depleted, as they normally participate in the recirculating pool. As a result of the destruction or inactivation of T cells, an impairment of delayed hypersensitivity and cellular immunity occurs while humoral antibody formation remains relatively intact. Monoclonal antibodies directed against specific cell surface and soluble proteins such as CD3, CD4, CD25, CD40, IL-2 receptor, and TNF- (discussed below) much more selectively influence T-cell subset function. The high specificity of these antibodies improves selectivity and reduces toxicity of the therapy and alters the disease course in several different autoimmune disorders. In the management of transplants, ALG and monoclonal antibodies can be used in the induction of immunosuppression, in the treatment of initial rejection, and in the treatment of steroidresistant rejection. There has been some success in the use of ALG and ATG plus cyclosporine to prepare recipients for bone marrow transplantation. ALG appears to destroy the T cells in the donor marrow graft, and the probability of severe graft-versus-host syndrome is reduced. The adverse effects of ALG are mostly those associated with injection of a foreign protein. Local pain and erythema often occur at the injection site (type III hypersensitivity). Since the humoral antibody mechanism remains active, skin-reactive and precipitating antibodies may be formed against the foreign IgG. Similar reactions occur with monoclonal antibodies of murine origin, and reactions thought to be caused by the release of cytokines by T cells and monocytes have also been described. Anaphylactic and serum sickness reactions to ALG and murine monoclonal antibodies have been observed and usually require cessation of therapy. Complexes of host antibodies with horse ALG may precipitate and localize in the glomeruli of the kidneys. The incidence of lymphoma as well as other forms of cancer is increased in kidney transplant patients. It appears likely that part of the increased risk of cancer is related to the suppression of a normally potent defense system against oncogenic viruses or transformed cells. The preponderance of lymphoma in these cancer cases is thought to be related to the concurrence of chronic immune suppression with chronic low-level lymphocyte proliferation. Immune Globulin Intravenous (IGIV) A different approach to immunomodulation is the intravenous use of polyclonal human immunoglobulin. This immunoglobulin preparation (usually IgG) is prepared from pools of thousands of healthy donors, and no single, specific antigen is the target of the "therapeutic antibody. IGIV in high doses (2 g/kg) has proved effective in a variety of different applications ranging from immunoglobulin deficiencies to autoimmune disorders to HIV disease to bone marrow transplantation. It has also brought about good clinical responses in systemic lupus erythematosus and refractory idiopathic thrombocytopenic purpura. Possible mechanisms of action of IGIV include a reduction of T helper cells, increase of regulatory T cells, decreased spontaneous immunoglobulin production, Fc receptor blockade, increased antibody catabolism, and idiotypic-anti-idiotypic interactions with "pathologic antibodies. Rho(D) Immune Globulin Micro-Dose One of the earliest major advances in immunopharmacology was the development of a technique for preventing Rh hemolytic disease of the newborn.
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Also available in antihistamine symptoms 4 weeks 3 days pregnant buy persantine overnight, antitussive symptoms cervical cancer buy persantine with a mastercard, expectorant treatment gastritis persantine 100 mg discount, and analgesic combination products medications canada purchase persantine online. Federal regulations established to discourage the illicit manufacture of methamphetamine specify that all drug products containing pseudoephedrine must be stored in locked cabinets or behind the pharmacy counter and can only be sold in limited quantities to consumers after they provide photo identification and sign a logbook. Reduces the chance of pregnancy by up to 89% when taken as directed within 72 hours after unprotected intercourse. Plan B is available behind the counter at pharmacies and sold under the supervision of a licensed pharmacist. Often used with antihistamines, decongestants, and antitussives in combination products. Minoxidil appears to directly stimulate hair follicles resulting in increased hair thickness and reduced hair loss. If new hair growth is observed, continued treatment is necessary as hair density returns to pretreatment levels within months following drug discontinuation. Senna, dosage varies, consult product labeling Product Examples Citrucel, Fibercon, Konsyl, Metamucil, various generic Comments the safest laxatives for chronic use include the bulk formers and stool softeners. Saline laxatives and stimulants may be used acutely but not chronically (see text). Polyethylene glycol formulations are large, poorly absorbed molecules that induce an osmotic effect causing distention and catharsis. Stimulant laxative actions include direct irritation of intestinal mucosa or stimulation of the myenteric plexus, resulting in peristalsis. These agents may also cause alteration of fluid and electrolyte absorption, resulting in luminal fluid accumulation and bowel evacuation. Linens, pajamas, combs, and brushes should be washed daily until the infestation is eliminated. Permethrin products have residual effects for up to 10 days; therefore, reapplication is not required unless live nits are visible 7 days or more after the initial treatment. Diphenhydramine and doxylamine are antihistamines with well-documented CNS depressant effects. Because insomnia may be indicative of a serious underlying condition requiring medical attention, patients should consult a physician if insomnia persists continuously for longer than 2 weeks. Nicotine replacement products in combination with behavioral support approximately double long-term cessation rates compared with placebo. Review directions for use carefully, since product strengths vary and self-titration and tapering may be necessary. Fleet Glycerin Suppository, various generic; Dulcolax Balance, MiraLax Colace, Dulcolax, Surfak, various generic Dulcolax, Ex-Lax, Senokot, various generic Pediculicides (head lice) Permethrin 1% Pyrethrins (0. Orlistat is a nonsystemically absorbed inhibitor of gastrointestinal lipase that blocks the absorption of dietary fat. Furthermore, acute ingestion of large amounts of acetaminophen by adults or children can cause serious, and often fatal, hepatotoxicity. Antihistamines may cause sedation or drowsiness, especially when taken concurrently with sedativehypnotics, tranquilizers, alcohol, or other central nervous system depressants. Antihistamines and other substances contained in OTC topical and vaginal products may induce allergic reactions. Finally, use of OTC cough and cold preparations in the pediatric population has been under scrutiny by the FDA based on a lack of efficacy data in children less than 12 years of age and reports of serious toxicity in children. In 2008, the FDA issued an advisory alert recommending that OTC cough and cold agents (eg, products containing antitussives, expectorants, decongestants, and antihistamines) not be used in infants and children less than 2 years of age because of the potential for serious and possibly lifethreatening adverse events. More recently, in October 2008, leading pharmaceutical manufacturers voluntarily modified product labels on OTC cough and cold preparations to state, "do not use" in children under 4 years of age. Further safety reviews by the FDA regarding the use of these agents in children between the ages of 2 and 11 are ongoing. Handbook of Nonprescription Drugs is the most comprehensive resource for OTC medications; it evaluates ingredients contained in major OTC drug classes and lists the ingredients included in many OTC products. Nonprescription Drug Therapy is an online reference that is updated monthly; it provides detailed OTC product information and patient counseling instructions. Any health care provider who seeks more specific information regarding OTC products may find useful the references listed below. Lessenger JE, Feinberg SD: Abuse of prescription and over-the-counter medications. Sharfstein JM, North M, Serwint JR: Over the counter but no longer under the radar-pediatric cough and cold medications. Systemic nasal decongestants (c ontained in Alka-Seltzer and Sudafed) stimulate 1 -adrenoceptors and may raise blood pressure through direct vasoconstrictor effects. Alka-Seltzer cold preparations should be avoided in patients with heart failure due to the high sodium content, which can lead to fluid retention. The sodium content in one dose of Alka-Seltzer Plus cold medicine (948 mg/dose) provides approximately half of the maximum recommended sodium allowance for patients with heart failure. His most recent laboratory values show that his low-density lipoprotein (LDL) cholesterol is still slightly above goal at 120 mg/dL (goal < 100 mg/dL) and his hemoglobin A1C is well controlled at 6%. He asks you if taking a garlic supplement could help to bring his LDL cholesterol down to less than 100 mg/dL.
For hookworm infections medicine 93 7338 order 25 mg persantine visa, a single dose is effective against light infections; but for heavy infections symptoms vitamin d deficiency buy persantine 100mg with visa, especially with Necator americanus treatment variable purchase persantine once a day, a 3-day course is necessary to reach 90% cure rates symptoms gluten intolerance generic persantine 100mg without a prescription. Adverse Reactions, Contraindications, & Cautions Thiabendazole is much more toxic than other benzimidazoles and more toxic than ivermectin, so other agents are now preferred for most indications. Less common problems are epigastric pain, abdominal cramps, diarrhea, pruritus, headache, drowsiness, and neuropsychiatric symptoms. The drug should not be used in pregnancy or in the presence of hepatic or renal disease Adverse Reactions, Contraindications, & Cautions Adverse effects are infrequent, mild, and transient. Mebendazole (generic, Vermox) Oral: 100 mg chewable tablets; outside the USA, 100 mg/5 mL suspension Metrifonate (trichlorfon, Bilarcil) 1 Niclosamide (Niclocide) 1 1 Additional information may be obtained from the Parasitic Disease Drug Service, Parasitic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, 30333. Bethony J et al: Soil-transmitted helminth infections: Ascariasis, trichuriasis, and hookworm. Bockarie MJ et al: Efficacy of single-dose diethylcarbamazine compared with diethylcarbamazine combined with albendazole against Wuchereria bancrofti infection in Papua New Guinea. Cochrane Database Syst Rev 2008:CD000053 Dayan AD: Albendazole, mebendazole and praziquantel. Flohr C et al: Low efficacy of mebendazole against hookworm in Vietnam: Two randomized controlled trials. Garcia HH et al: Current consensus guidelines for treatment of neurocysticercosis. Garcia HH et al: A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. Horton J: Albendazole: A broad spectrum anthelminthic for treatment of individuals and populations. Keiser J, Utzinger J: Efficacy of current drugs against soil-transmitted helminth infections: Systematic review and meta-analysis. Matthaiou DK et al: Albendazole versus praziquantel in the treatment of neurocysticercosis: A meta-analysis of comparative trials. Osei-Atweneboana MY: Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: A two-phase epidemiological study. Ramzy RM et al: Effect of yearly mass drug administration with diethylcarbamazine and albendazole on bancroftian filariasis in Egypt: A comprehensive assessment. Reddy M et al: Oral drug therapy for multiple neglected tropical diseases: A systematic review. Supali T et al: Doxycycline treatment of Brugia malayi-infected persons reduces microfilaremia and adverse reactions after diethylcarbamazine and albendazole treatment. Taylor MJ et al: Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: A double-blind, randomised placebo-controlled trial. Tisch DJ, Michael E, Kazura JW: Mass chemotherapy options to control lymphatic filariasis: A systematic review. Other causes of liver fluid collections include amebic and pyogenic abscesses, but these are usually not cystic in appearance. For echinococcosis, a typical cystic lesion and positive serology support the diagnosis, and treatment generally entails albendazole in conjunction with cautious surgery or percutaneous aspiration. One approach entails treatment with albendazole followed by aspiration to confirm the diagnosis and, if it is confirmed, to remove most of the infecting worms. This page intentionally left blank C Cancer Chemotherapy Edward Chu, MD, & Alan C. Colonoscopy identifies a mass in the ascending colon, and biopsy specimens reveal well-differentiated colorectal cancer (CRC). He undergoes surgical resection and is found to have high-risk stage III CRC with five positive lymph nodes. The patient receives a combination of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin as adjuvant therapy. One week after receiving the first cycle of therapy, he experiences significant toxicity in the form of myelosuppression, diarrhea, and altered mental status. Is there any role for genetic testing to determine the etiology of this level of toxicity Cancer continues to be the second leading cause of mortality from disease in the USA, accounting for nearly 500,000 deaths in 2008. Cancer is a disease characterized by a loss in the normal control mechanisms that govern cell survival, proliferation, and differentiation. Cells that have undergone neoplastic transformation usually express cell surface antigens that may be of normal fetal type, may display other signs of apparent immaturity, and may exhibit qualitative or quantitative chromosomal abnormalities, including various translocations and the appearance of amplified gene sequences. It is now well established that a small subpopulation of cells, referred to as tumor stem cells, reside within a tumor mass. They retain the ability to undergo repeated cycles of proliferation as well as to migrate to distant sites in the body to colonize various organs in the process called metastasis. Such tumor stem cells thus can express clonogenic (colony-forming) capability, and they are characterized by chromosome abnormalities reflecting their genetic instability, which leads to progressive selection of subclones that can survive more readily in the multicellular environment of the host. This genetic instability also allows them to become resistant to chemotherapy and radiotherapy. The invasive and metastatic processes as well as a series of metabolic abnormalities associated with the cancer result in tumor-related symptoms and eventual death of the patient unless the neoplasm can be eradicated with treatment. Exposure to ionizing radiation has been well documented as a significant risk factor for a number of cancers, including acute leukemias, thyroid cancer, breast cancer, lung cancer, soft tissue sarcoma, and basal cell and squamous cell skin cancers. Chemical carcinogens (particularly those in tobacco smoke) as well as azo dyes, aflatoxins, asbestos, benzene, and radon have all been well documented as leading to a wide range of human cancers. Expression of virus-induced neoplasia may also depend on additional host and environmental factors that modulate the transformation process. These mammalian cellular genes, known as oncogenes, have been shown to code for specific growth factors and their corresponding receptors.
Treatment: As remission often occurs within 2 years symptoms quitting tobacco generic 100mg persantine mastercard, antiepileptic medication is often not needed symptoms adhd buy generic persantine on-line. Think of these as age-specific epileptic reactions to non-specific exogenous CNS insults symptoms 0f a mini stroke generic persantine 100mg mastercard, acting at specific developmental stages symptoms zoning out purchase persantine master card. Monitor ECG OR (if on regular phenytoin) Phenobarbital 18mg/kg over 5min Call PICU & your anaesthetist-prepare for intubation locate ET tube,etc p626. Lorazepam 5min these times refer to elapsed time on the clock from the 1st drug, not gaps between each drug. Some authorities recommend starting ventilation earlier, and always be ready to do this to protect the airway. Consider anticonvulsant levels, toxicology screen, blood ammonia (requires special blood bottle), lumbar puncture (after resolution), culture blood and urine, virology, EEG, MRI, CT, carbon monoxide level, lead level, amino acid levels, metabolic screen. Once the crisis is over Refer to a specialist: is MRI or prophylaxis, eg with sodium valproate or carbamazepine (p209) needed Out of the context of status, prophylaxis is typically started after the 2nd seizure. Choice of anti-epileptic drug (AED) should be based on epilepsy syndrome/presenting seizure type. Rare hepatotoxicity can be fatal (eg if coexisting unsuspected metabolic disorder). When prescribing to girls of childbearing potential, warn of teratogenic risk (carbamazepine also). SE: Drowsiness, depression, psychosis, amnesia, diplopia, and field defects (test every year). Levetiracetam licensed for used as monotherapy for focal seizures-but thought not cost-effective (NICE 522). Increasingly used in preference to phenytoin for status epilepticus SE: depression; lethargy; weakness. Diet Consider a high-fat ketogenic diet under speciliast supervision if 2 drugs fail to work (it can fits by). Emphasize compliance/concordance (one seizure may the threshold for the next, referred to as kindling). If unsuitable try lamotrigine (may exacerbate myoclonic seizures) or carbamazepine (may exacerbate myoclonic and absence seizures). Carbamazepine, gabapentin, oxcarbazepine, phenytoin, tiagabine, and vigabatrin are not recommended for absence seizures. If drugs fail Do not use ever more toxic combinations: refer for neurosurgical advice and MRI. The risk of seizure recurrence during the tapering down process is no greater if the tapering Newer anticonvulsants NICE reserves gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and vigabatrin (as an adjunct for partial seizures) for children not benefiting from (or able to tolerate) older drugs (p208) or older drugs have contraindications/interactions (the Pill)-or the child is of childbearing potential or is likely to need drugs into her childbearing years. If the child can win, be more subtle, eg consistent rewards, not inconsistent punishments. Reducing pressure on the child, discouraging parental over-reaction, and gradual enlarging of tiny portions of attractive food are usually all that is needed. Overeating: Eating comforts, and if the child is short on comfort, or if mother feels inadequate, the scene is set for overeating and lifelong patterns are begun. Pica is eating things which are not food, eg plastic, or faeces (coprophagia); if persistent, look for other disturbed behaviours, autism, or IQ. Ask about onset of constipation and precipitants (fissure/change in diet/timing of potty training/fears and phobias/moving house/acute infections/family upheavals). Abnormal appearance of anus / skin in sacral/gluteal region (look for sacral dimples/hairy patches/flattening of gluteal muscles/multiple fissures). Break the vicious cycle of: large faeces pain/fissure fear of the pot rectum overstretched call-to-stool sensation dulled soiling parental exasperation coercion. Exonerate the child to boost confidence for the main task of obeying calls-to-stool to keep the rectum empty. If >12y use Movicol or equivalent (lacks electrolytes and contains a higher dose of polyethylene glycol 3350) at 4 sachets on day 1, escalating by 2 sachets/day to a maximum of 8. NB: behaviour therapy in combination with laxatives is effective, 542 but biofeedback methods are not. It is usually due to overflow in constipation, but may occasionally be a behavioural response to sexual abuse. Try behaviour therapy and referral to a child and adolescent psychiatrist for non-retentive soiling-it is part of an emotional disorder. This is important because we know that encopresis is associated with anxiety, depression, attention difficulties, and environments with less expressiveness and poor organization, and social problems (disruptive behaviour, poorer school performance etc). Enuresis: 550 Infrequent bedwetting (<2 nights/week) occurs in ~15% at 5yrs and 5% at 10yrs.
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