Intrathecal

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

Oral treatment offers the advantage of bringing all the lesions at all sites under control, in addition to the absence of unpleasant cosmetic effects. In certain cases, it may be preferable to use oral treatment for C. albicans vaginitis and for extensive and persistent pityriasis versicolor, a skin disorder caused by Pityrosporum orbiculare. In the case of onychomycosis, a combination treatment, topical plus systemic, is required. It is preferable to use oral treatment for deep and systemic mycoses, though intravenous or intrathecal treatment is sometimes required. 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

The drug is metabolized rapidly in the liver, kidney, intestinal mucosa, and even red blood cells. Therefore it has a plasma half-life of only 10 min after bolus intravenous application. The major metabolite, uracil arabinoside (ara-U), can be detected in the blood shortly after cytarabine administration. About 80% of the dose is excreted in the urine within 24 h, with less than 10% appearing as cytarabine the remainder is ara-U. After continuous infusion, cytarabine levels in the liquor (cerebro-spinal fluid) approach 40% of that in plasma. Continuous infusion schedules allow maximal efficiency, with uptake peaks of 5-7 pM. It can be administered intrathecally as an alternative to methotrexate. 

The intrathecal space is located between the arachnoid and the pia mater of the spinal cord. It contains the cerebrospinal fluid, spinal nerves and blood vessels. 

Intracellular Transport Intrathecal Application Intrathecal Space Intrinsic Efficacy Intron... 

Intrathecally or epidurally for pain relief for extended periods without apparent loss of motor, sensory, or sympathetic function... 

Succinylcholine-induced rhabdomyolysis Hypoxic encephalopathy Intrathecal administration of constant agents Defective temperature-monitoring devices Stimulation during light anesthesia... 

Dobrydnjov I, Axelsson K, Berggren L, et al Intrathecal and oral clonidine as prophylaxis for postoperative alcohol withdrawal syndrome a randomized double-blinded study. Anesth Analg 98 738—744, 2004... 

MUligan ED, O Connor KA et al (2001) Intrathecal HlV-1 envelope glycoprotein gpl20 induces enhanced pain states mediated by spinal cord proinflammatory cytokines. J Neurosd 21(8) 2808-2819... 

Johnston IN, Milligan ED, Wieseler-Frank J, Frank MG, Zapata V, Campisi J (2004) A role for proinflammatory cytokines and fractaUdne in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine. J Neurosci 24(33) 7353-7365 Kim YS, Panganiban AT (1993) The full-length tat protein is required for TAR-independent, post-transcriptional trans activation of human immunodeficiency virus type 1 env gene expression. J Virol 67(7) 3739-3747... 

Most injections are formulated as aqueous solutions, with Water for Injections BP as the vehicle. The formulation of injections depends upon several factors, namely the aqueous solubility of the active ingredient, the dose to be employed, thermal stability of the solution, the route of injection and whether the product is to be prepared as a multidose one (i.e. with a dose or doses removed on different occasions) or in a singledose form (as the term suggests, only one dose is contained in the injection). Nowadays, most injections are prepared as single-dose forms and this is mandatory for certain routes, e.g. spinal injections such as the intrathecal route and large-volume intravenous infusions (section 2.2). Multidose injections may require the inclusion of a suitable... 

Third-line Intrathecal baclofen Pre- and postsynaptic y-aminobutyric acid P receptor blocker Titrated individually, usual range 62-749 mcg/day... 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

Dexamethasone therapy may reduce antibiotic penetration, so antimicrobial drug dosing may have to be increased (especially vancomycin) to achieve adequate CSF levels. Serum levels of vancomycin should be measured and doses titrated to ensure adequate CNS concentrations. Evaluate whether intraventricular or intrathecal antibiotics are indicated. 

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