2002) Study 3Īnother controlled study was reported by Balali-Mood and Shariat. In particular, the factors needing control as described above were not controlled, and important design information was missing ( e.g., randomization procedures, patient weight used for dosing). However, these studies were flawed by methodological problems. Both of these studies concluded that 2-PAM was associated with a worse outcome, and they have been used to argue that the antidote should not be used. (2003) were able to find only 2 published, randomized controlled human trials of 2-PAM. These design flaws have made it difficult to draw any solid empirical conclusions on 2-PAM’s effectiveness. Unfortunately, they all suffer from methodological problems, as detailed below. Several attempts have been made to carry out controlled prospective human studies on the effectiveness of 2-PAM. For these substances, the time period for this aging to occur varies. (Karalliedde and Senanayake 1989 Eddleston, Szinicz et al. Some cholinesterase inhibitors undergo an “aging” process after which 2-PAM is no longer effective. 2002) So, for example, it is very effective with parathion, less effective with Dichlorvos, and had no apparent effect on dimethoate. (Xue, Ding et al. 2002) The specific cholinesterase inhibitor involvedĢ-PAM works with some but not others. 2002) The amount needed may vary depending on the specific cholinesterase inhibitor involved. If insufficient doses are used, 2-PAM’s effectiveness is compromised. (Johnson, Vale et al. Several factors need to controlled when assessing the effectiveness of cholinesterase-regenerating antidotes (oximes) such as 2-PAM. Studies with the cholinesterase inhibitor, paraoxon showed that a 20% reactivation of cholinesterase was achieved with a serum concentration of 10 µg/ml and 70% with 17 µg/ml. Recent in vitro studies suggest that a much higher level is actually needed.

(Wiener and Hoffman 2004)īalali-Mood and Shariat (1998) found that 2-PAM improved outcome and was not associated with serious side effects in eight patients treated with a loading dose of 30 mg/kg followed by a maintenance dose of 8 mg/kg/hr. Others point out that this does not take into account the dose and route of exposure. Some have argued that this has never been replicated with other cholinesterase inhibitors nor with other species. The dose recommendations listed above were designed to achieve a serum level of at least 4 µg/ml, a level that has been shown to provide protection from a sarin analogue in the cat model. (Howland 2002 Wiener and Hoffman 2004) (95% confidence limits)ģ9.4 (28.6-57.1) p<0.05 compared to no treatmentĤ60 (335.0-669.0) p< 0.05 compared to all other treatmentsĢ44 (180.0-339.0) p<0.05 compared to all othersĬurrently, despite manufacturer’s recommendations, there is controversy over the appropriate dosing of 2-PAM. 1989) Effectiveness of atropine and 2-PAM against carbaryl toxicity in rats Treatment (See table below abstracted from Harris et al.) (Harris, Talbot et al. (However, when atropine and 2-PAM were given together the protective ratio was 3.5). showed that the protective ratio (defined as the LD 50 with treatment/LD 50 without treatment) of 2-PAM alone for carbaryl was 0.6 as compared to a protective ratio of 6.6 from treatment with atropine alone. In this study it was found that carbaryl toxicity was worsened when treated with 2-PAM alone. This was apparently based on animal data from the study of a single carbamate, carbaryl, which was generalized to all carbamates. Published Attempts at Controlled Human Studies with 2-PAM (Optional Reading)Ģ-PAM was once thought to be contraindicated in carbamate toxicity.Factors Needing Control in Studies on 2-PAM (Optional Reading).Does 2-PAM Cross the Blood-Brain Barrier? (Optional Reading).Controversy Regarding What Receptor Sites are Affected by 2-PAM (Optional Reading.Reasons for Apparent Failure to Respond to 2-PAM.Controversy Regarding 2-PAM Dose (Optional Reading).How 2-PAM Works at the Molecular Level (Optional Reading).

How Cholinesterase Inhibitors Work: Aging (Optional Reading - continued).

How Cholinesterase Inhibitors Work (Optional Reading).

How Acetylcholinesterase Normally Works (Optional Reading).

2-PAM: Mechanism of Action (Optional Reading).

Reasons for Delayed Onset of Toxicity and Aging, and Need for Extended Treatment with 2-PAM.

How Long Does It Take for Aging to Occur?.

Atropine antidote for