Methylxanthines

Source Xanthines e.g. theophylline are used as bronchodilators (and very rarely for its positive inotropic effects on the cardiac muscle). Also have the methylxanthines e.g. theobromine (in chocolate) and caffeine. All xanthines are phosphodiesterase inhibitors i.e. will increase the levels of cylcic AMP and are also adenosine receptor antagonists.

The most common form of xanthine toxicity is theobromine (found in chocolate, cocoa, soft drinks and tea)

Clinical signs -Increased urination -Vomiting -Diarrhoea -Tachycardia -Arrhythmias -Restlessness -Ataxia -Seizures

Toxicity Lethal range in dogs = 100-250mg/kg LD50 of caffeine and theobromine = 100-200mg/kg LD50 of theophylline = 300mg/kg dogs, 700mg/kg cats

The highest concentration of theobromine is found in unsweetened baking chocolate and dark chocolate.

Mechanism of action By preventing the inactivation of cAMP there is an increase in intracellular calcium and also a decrease in calcium sequestration. Hence, it acts to stimulate the CNS and cardiac tissue, causing increased myocardial contractility.

Diagnosis Clinical signs and history of exposure

Treatment -There is no specific antidote -Attempt gastric decontamination:

       - Emesis, gastric lavage if a small dog
       - Activated charcoal
       - Cathartics 

-Supportive therapy and reduction of side effects:

       - Respiratory
       - Cardiovascular --> need to control arrhythmias and correct any acid/base or electrolyte abnormalities.
       - CNS --> may need to control any excitement or seizures using diazepam.