Pentetic 1571 Thalassaemia. Iron overload in patients with thalassaemia Treatment may be monitored by the determination of (p. 1124.1) is usually treated with desferrioxamine, but blood-cholinesterase concentrations and clinical symptoms. auditory toxicity can result. Calcium pentetic acid has Other oximes with cholinesterase-reactivating properties been used as an alternative. A studyr in 5 patients in that have been used similarly include asoxime chloride whom desferrioxarnine had to be withdrawn because of (p. 1541.1). obidoxime chloride (p. 1566.3), and high-tone deafness found tbat the pentetate was as effec­ trimedoxime bromide (p. 1579.1). tive as desferrioxamine and hearing improved during treatment. Oral zinc supplements were necessary to main­ Administration in children. Pralidoxime chloride is used in tain adequate plasma-zinc concentrations. children as an adjunct to atropine jn the treatment of l. Wanke B, et al. Reversal of desferrioxamine induced auditory organophosphorus poisoning; the BNFC recommends the neurotoxicity during treatment with Ca-DTPA. Arch Dis Child 1989; 64: same dose as that recommended by the BNF for adults, see 77-82. above. Adverse Effects and Precautions Pharmacopoeias. In It. Carbamate poisoning.The use of pralidoxime for poison­ Adverse effects that have been reported with calcium or zinc ing due to carbamate insecticides is controversial. Licensed trisodium pentetate include headache and lightheadedness. Uses and Administration product information states that pralidoxime should not be Pentetates chelate trace metals and supplements may be used to treat poisoning by carbamate pesticides as it may Pralidoxime is a cholinesterase reactivator. It is used as an needed with long-term use. Trace metals and serum­ increase toxicity, and it has been suggested that as carba­ adjunct to, but not as a substitute for, atropine in the electrolytes should be monitored during use. mate-induced cholinesterase inhibition is spontaneously treatment of poisoning by certain cholinesterase inhibitors. Other adverse effects reported with calcium trisodium reversible, oxime therapy is not necessary. However, there Its main indication is in poisoning due to organophosphorus pentetate include nausea and diarrhoea, injection-site are reports of successful use of pralidoxime in carbamate insecticides or related compounds (see p. 2158.3). These reactions, chest pain, allergic reactions, dermatitis, and a poisoning, and it is suggested, with atropine, as a treat­ compounds phosphorylate and consequently inactivate t-"3 metallic taste. Bronchospasm has occurred after inhalation. ment option by some authorities. cholinesterase, causing acetylcholine accumulation and It should be used with caution in patients with severe 1. Burgess JL, et al. Aldicarb poisoning: a case report with prolonged muscle paralysis. Pralidoxirne reactivates cholinesterase, haemochromatosis since fatalities have been reported when cholinesterase inhibition and improvement after pralidoxime therapy. restoring the enzymatic destruction of acetylcholine at the Arch InternMed 1994; 154: 221-4. high doses were used. neuromuscular junction and relieving muscle paralysis. Use 2. Tracqui A, et al. Repeated measurements of aldicarb in blood and urine 20: with atropine is required to counteract the adverse effects of in a case of nonfatal poisoning. Hum Exp Toxicol 2001; 657-60. 3. Hoffman RS, et al. Use of pralidoxime without atropine in rivastigmine Pharmacokinetics acetylcholine accumulation, particularly at the respiratory (carbamate) toxicity. Hum Exp Toxicol 2009; 28: 599-602. Pentetates are rapidly distributed throughout the extra­ centre. Its ability to antagonise different organophosphorus anticholinesterases varies, as reactivation is dependent on cellular space and eliminated by glomerular filtration, with Organophosphorus poisoning. Oximes such as pralid­ the nature of the phosphoryl group and the rate at which most of a dose excreted in the urine within 24 hours. Only a oxime are widely used in poisoning with organophosphate inhibition becomes irreversible. It is not effective in the small amount (less than 3%) is excreted in the faeces. pesticides. Although benefit has been shown in animal stu­ treatment of poisoning due to phosphorus, inorganic dies, reviewsU have pointed out that there is little good phosphates, or organophosphates without anticholinester­ evidence from human studies to support their use and ase activity. Its use in the treatment of poisoning by that randomised controlled studies are needed to confirm Proprietary Preparations (details are given in Volume B) carbamate insecticides (p. 2150.1) is controversial, see their efficacy and safety, as well as the optimum regimens Carbamate Poisoning, below. In some countries pralidoxime Single-ingredient Preparations. Cz.: Ditripentat; Ger.: Ditripen­ to use. A randomised study3 in patients with moderately is used for the treatment of overdosage by anticholinester­ tat-Heyl; Israel: DTPA; Frosstimage Kit (DTPA). severe poisoning with organophosphorus pesticides found ase drugs used to treat myasthenia gravis such as that a continuous infusion of pralidoxime iodide I g/hour neostigmine, pyridostigmine, and ambenonium, although for 48 hours was more effective than a dose of 1 g every 4 caution is advised when using pralidoxime in patients with hours. However, another controlled study4 found that the (BAN, r/NNM) myasthenia gravis, see Precautions, below. Pralidoxime WHO-recommended regimen of pralidoxime chloride 2 g . Pralidoxime is usually given as the chloride but the 2'PAM; Pra i pl( iimi; Prati oksyn?;.,f>ra!l<;lossl ;• Prali�oxl ; as a loading dose, followed by constant infusion of l d � d nr� d-t mesilate, iodide, and metilsulfate salts have also been used. 500 mg/hour, was of no benefit in patients self-poisoned Pra!idoxima; Pralidoximum; !lpam1,(\0KCI1W� In severe poisoning pralidoxime is usually given as an . with organophosphorus insecticides, despite clear evidence ;1-H)!dto)l;yiminomethyH·met .hytpyridiniut'Tt intravenous infusion over 15 to 30 minutes, or as a slow of reactivation of red cell acetylcholinesterase. C"H9N20437,2 intravenous injection over at least 5 minutes if infusion is Cholinesterase reactivators such as the oximes have also CAS -'- 6735·59·7,' 495-94�3. not practicable or there is pulmonary oedema. Alterna · been used for poisoning with organophosphate nerve agents. A TC. V03A BM tively, for less severe toxicity or when the intravenous route Studies in animals have suggested that the efficacy of the � is not feasible, pralidoxime can be given by intramuscular or :,AfCVe t :- Q\i03Aey(J4, different oximes depends on the organophosphate involved; subcutaneous injection; it has also been given orally. UNit ·"- PlMU9UTF'52: asoxime (p. 1541.1) and HLo-7 may be more effective than In the treatment of organophosphorus poisoning pralidoxime or obidoxime for poisoning with nerve agents, pralidoxime should be given as soon as possible. After about (BANM. USAN, riNNMJ particularly for soman poisoning. 5 Pralidoxime Chloride 36 hours it becomes less effective since cholinesterase l. Eyer P. The role of oximes in the management of organophosphorus Formyl-1 • eth)i!pyri(ji!'llum Chloride ime: inactivation usually becomes irreversible after this time; 22: 2 m . 2-PA�I; 2". pesticide poisoning. Toxicol Rev 2003; 165-90. � Pralldoxlma however, patients with severe poisoning may occasionally et al. PAM Cnlpride: 2-PAMc!; Pra!idoxirn nlorld; : 2. Buckley NA, Oximes for acute organophosphate pesticide q respond up to 48 hours or longer after exposure, depending poisoning. Available in The Cochrane Database of Systematic Reviews; slon.Jro de;pralidoxime, Chlorure.de: .PraH oJ<lfX\i 1 qntoridufX\: on the organophosphate involved. Injections of atropine Issue 2. Chichester: John Wiley; 2011 (accessed 01103111). 2-Pyridinc:. Aldoxime · Methoch!oride; llpan�o�.QoKCVIJI!a 3. Pawar KS, etal. Continuous pralidoxime infusion versus repeated bolus should be given intravenously or intramuscularly and injection to treat organophosphorus pesticide poisoning: a randomised repeated as necessary until muscarinic effects disappear or controlled trial. Lancet 2006; 368: 2136-41. signs of atropine toxicity are seen; atropinisation should 4. Eddleston M, et al. Pralidoxime in acute organophosphorus insecticide then be maintained for 48 hours or more. Large amounts of poisoning-a randomised controlled trial. PLoS Med 2009; 6: el000104. Available at: http://www.plosmedicine.org/article/ atropine may be required. See under Atropine Sulfate, fetchObjectAttachment.action?uri=info% 3Adoi %2F 10.1371 %2Fj our­ p. 1311.3, for details of dosages. As soon as the effects of nal.pmed. 1000104&representation=PDF (accessed 18/12/09) atropine become apparent. I to 2 g of pralidoxime chloride 5. Kassa J. Review of oximes in the antidotal treatment of poisoning by should be given intravenously and repeated after 1 hour organophosphorus nerve agents. J Toxicol Clin Toxico/ 2002; 40: 803-16. and then every 10 to 12 hours if necessary. Alternatively, the BNFrecommends pralidoxime chloride in an initial dose Adverse Effects of 30 mg/kg given by intravenous infusion or injection; the initial dose is then followed by intravenous infusion at a rate Use of pralidoxime may be associated with drowsiness, of 8 mg/kg per hour to a usual maximum dose of 12 g in 24 dizziness, disturbances of vision, nausea, hypertension, hours. Pralidoxime treatment is continued until the patient tachycardia, headache, hyperventilation,