Intrathecal administration

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. 

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

Hammond DL, Stapelfeld A, Drower EJ, Savage MA, Tam L, Mazur RH. Antinociception produced by oral, subcutaneous or intrathecal administration of SC-39566, an opioid dipeptide arylalkylamide, in the rodent. J Pharmacol Exp Ther 1994 268 607-615. 

Remifentanil For epidural or intrathecal administration hypersensitivity to fentanyl analogs. 

Limit epidural or intrathecal administration of morphine to the lumbar area. 

Epidural/Intrathecal administration Limit epidural or intrathecal administration of preservative-free morphine and sufentanil to the lumbar area. Intrathecal use has been associated with a higher incidence of respiratory depression than epidural use. Asthma and other respiratory conditions The use of bisulfites is contraindicated in asthmatic patients. Bisulfites and morphine may potentiate each other, preventing use by causing severe adverse reactions. Use with extreme caution in patients having an acute asthmatic attack, bronchial asthma, chronic obstructive pulmonary disease or cor pulmonale, a substantially decreased respiratory reserve, and preexisting respiratory depression, hypoxia, or hypercapnia. Even usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Reserve use for those whose conditions require endotracheal intubation and respiratory support or control of ventilation. In these patients, consider alternative nonopioid analgesics, and employ only under careful medical supervision at the lowest effective dose. 

Intrathecal administration Because of the possibility of potentially life-threatening CNS depression, cardiovascular collapse, or respiratory failure, physicians must be adequately trained and educated in chronic intrathecal infusion therapy. 

In the treatment of fungal meningitis or Candida urinary bladder infections, IV infusion alone is inadequate. It must be supplemented with intrathecal administration or bladder irrigation. 

Not for intrathecal use. Severe injury with permanent sequelae can result from intrathecal administration (see Warnings). 

Baclofen is a GABA agonist at GABA B receptors and it has a presynaptic inhibitory function by reducing calcium influx. Its indication is increased extensor tone and clonus. Intrathecal administration may control severe spasticity pain. It is used for the treatment of spastic movement, especially in instances of spinal cord injury, spastic diplegia, multiple sclerosis and amyotrophic lateral sclerosis. Its central nervous system effects include drowsiness, somnolence and seizure activity in epileptic patients. 

Ziconotide is a non-opioid, non-NSAID, non-local anesthetic used for the amelioration of chronic pain. In December 2004 the FDA approved ziconotide for intrathecal administration. The drug is derived from a marine snail toxin. Its mechanism of action has not yet been elucidated. Due to serious side effects or lack of efficacy when delivered through more conventional routes ziconotide must be administered in-trathecally. It s use is considered appropriate only for management of severe chronic pain in patients for whom intrathecal therapy is indicated. 

Myelosuppression is a major toxicity, as is severe bone marrow hypoplasia. Nausea and mucositis also may occur. Intrathecal administration occasionally produces arachnoiditis or more severe neurological toxicity. 

Tumor response Objective remissions are usually associated with a 50% decrease in the size of solid tumor as measured by physical measurement or test parameter (e.g., chest X-ray). After intrathecal administration, clearing of malignant cells in the cerebrospinal fluid indicates a positive response... 

The minor adverse effects include nausea, vomiting, pain and inflammation at the site of injection after intramuscular administration has been reported. After intrathecal administration (which is a contraindication) it may lead to convulsions, arachnoiditis and encephalopathy. 

Most of the ester-linked local anaesthetics are rapidly hydrolysed by plasma cholinesterases and liver esterases. Because the cerebrospinal fluid contains little or no esterase, intrathecal administration of these drugs produces a prolonged effect, which persists until the agent is absorbed into the bloodstream. 

Shi, L., Tang, G.P., Gao, S.J., et al. (2003). Repeated intrathecal administration of plasmid DNA complexed with polyethylene glycol-grafted polyethylenimine led to prolonged transgene expression in the spinal cord. Gene Then, 10(14), 1179-1188. 

Although benzyl alcohol is listed as an approved antimicrobial under the FDA guide, there are many factors that should be considered before including it in an oral solution formulation. There are numerous reports of adverse reactions to benzyl alcohol following IV and intrathecal administration and it is not recommended for use in premature infants. Benzyl alcohol is incompatible with methylcellulose and is also known to be incompatible with a number of container types. For example, a 2% aqueous solution in a polyethylene container, stored at 20°C, may lose up to 15% of its benzyl alcohol content in 13 weeks. However, it is only slowly sorbed by closures composed of natural rubber or neoprene. 

Dosages and routes of administration Morphine is available in different salt forms but the hydrochloride and sulfate (Vermeire and Remon, 1999) are used preferentially. The compound can be administered by the oral, parenteral or intraspinal route. Oral application is preferred for chronic pain treatment and various slow release forms have been developed to reduce the administration frequency to 2-3 times per day (Bourke et al., 2000). Parenteral morphine is used in intravenous or intramuscular doses of 10 mg, mostly for postoperative pain and self-administration devices are available for patient-controlled analgesia (PCA). Morphine is additionally used for intraspinal (epidural or intrathecal) administration. Morphine is absorbed reasonably well in the lower gastrointestinal tract and can be given as suppositories. 

Penn, R.D. and Paice, J.A. Adverse effects associated with the intrathecal administration of Ziconotide, Pain 2000, 85, 291-296. 

Fisher, K., Fundytus, M. E., Cahill, C. M., Coderre, T. J. Intrathecal administration of the mGluR compound, (S)-4CPG, attenuates hyperalgesia and allodynia associated with sciatic nerve constriction injury in rats, Pain 1998, 77, 59-66. 

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