Effect of atropine and glycopyrrolate in ameliorating the clinical signs associated with the inhibition of cholinesterase activity by imidocarb dipropionate in horses

Abstract

Equine piroplasmosis is a tick-transmitted disease caused by Theileria equi or Babesia caballi leading to haemolytic anaemia. Imidocarb is an effective treatment of piroplasmosis, but adverse clinical signs, including colic and diarrhoea, from cholinesterase inhibition are associated with its use. Atropine is advocated for the treatment of cholinesterase inhibiting compounds. Atropine is known to have a prolonged inhibitory effect on gastrointestinal motility. Glycopyrrolate is an anticholinergic drug that has similar effects to atropine on gastrointestinal motility, but with decreased penetration of blood-brain and blood-aqueous barrier. This study was performed to assess the adverse clinical effects of a therapeutic dose of imidocarb, the effect of this dose on gastrointestinal motility, and on cholinesterase activity. The ability of atropine or glycopyrrolate to ameliorate imidocarb’s adverse clinical signs, and the effect of the combination of atropine and imidocarb or glycopyrrolate and imidocarb on gastrointestinal motility was evaluated. A blinded crossover trial was performed in 8 horses. All horses were administered saline (CON), imidocarb 2.4 mg/kg im and saline iv (IMI), imidocarb 2.4mg/kg im and atropine 0.02 mg/kg iv (IMATROP) and imidocarb 2.4mg/kg im and glycopyrrolate 2.5 µg/kg iv (IMGLYCO), with a one week wash-out period between treatments. Butrylcholinesterase activity was measured in the CON and IMI group. Clinical signs, gastrointestinal motility and faecal production were assessed. Gastrointestinal motility was measured by abdominal auscultation and frequency of contractions in the duodenum, caecum and right dorsal colon visualized with transcutaneous abdominal ultrasound. Total faecal production, faecal dry matter, wet matter, faecal water percentage, frequency of defaecation and time to first defaecation was assessed. Abdominal pain and diarrhoea were observed in the IMI group. Borborygmi and frequency of intestinal contractions were not different in the IMI group compared to CON. Percentage water content, faecal production, faecal dry matter and frequency of defaecation were significantly increased in the IMI group. Butrylcholinesterase activity was not significantly decreased in the IMI group compared to CON. In the IMATROP group colic signs were observed, heart rate was significantly elevated and mydriasis was evident. Borborygmi and frequency of contractions in the right dorsal colon was significantly reduced in the IMATROP group. In the IMGLYCO group the incidence and severity of colic induced by imidocarb was reduced. Heart rate was significantly increased and borborygmi significantly decreased compared to CON. The effect of IMGLYCO on heart rate and borborygmi was significantly less than the effect of IMATROP. In the IMGLYCO group the frequency of ultrasound visualised intestinal contractions and faecal variables were not different from CON. Therapeutic doses of imidocarb are associated with clinical signs of muscarinic stimulation including colic and diarrhoea, and enhanced faecal production. Clinical signs of cholinesterase inhibition can be present without significant depression in plasma cholinesterase activity. Atropine prevents diarrhoea and normalises faecal water percentage but is not effective in decreasing incidence of abdominal pain, and causes a prolonged inhibition of gastrointestinal motility, which might make this drug undesirable to use as a pre-treatment to imidocarb in clinically affected horses. Glycopyrrolate only partially reduces gastrointestinal motility and decreases adverse signs and thus its use as a pre-treatment to imidocarb is preferred.