Antacids administered in a peptic ulcer regimen may decrease the AUC of a single dose of phenytoin. Patients should be cautioned against concomitant use of antacids and phenytoin. "Warfarin and trimethoprim increase serum phenytoin levels and prolong the serum half-life of phenytoin by inhibiting its metabolism. Consider using other options if possible. Pharmacology
Mechanism of action
Phenytoin is believed to protect against seizures by causing voltage-dependent block of voltage gated sodium channels. This blocks sustained high frequency repetitive firing of action potentials. This is accomplished by reducing the amplitude of sodium-dependent action potentials through enhancing steady-state inactivation. Sodium channels exist in three main conformations: the resting state, the open state, and the inactive state. Phenytoin binds preferentially to the inactive form of the sodium channel. Because it takes time for the bound drug to dissociate from the inactive channel, there is a time-dependent block of the channel. Since the fraction of inactive channels is increased by membrane depolarization as well as by repetitive firing, the binding to the inactive state by phenytoin sodium can produce voltage-dependent, use-dependent and time-dependent block of sodium-dependent action potentials.The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses which prevents cortical seizure foci from detonating adjacent cortical areas.
Hypersalivation, or ptyalism, also known as sialorrhea or hypersialosis is the excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva.Hypersalivation can contribute to drooling if there is an inability to keep the mouth closed or difficulty in swallowing (dysphagia) the excess saliva, which can lead to excessive spitting. Hypersalivation also often precedes emesis (vomiting), where it accompanies nausea (a feeling of needing to vomit). Causes
Excessive production
Conditions that can cause saliva overproduction include:
Rabies
Pellagra (niacin or Vitamin B3 deficiency)
Gastroesophageal reflux disease, in such cases specifically called a water brash (a loosely defined lay term), and is characterized by a sour fluid or almost tasteless saliva in the mouth
Gastroparesis (main symptoms are nausea, vomiting, and reflux)
Pregnancy
Fluoride therapy
Excessive starch intake
Anxiety (common sign of separation anxiety in dogs)
Pancreatitis
Liver disease
Serotonin syndrome
Mouth ulcers
Oral infections
Sjögren syndrome (an early symptom in some patients)Medications that can cause overproduction of saliva include:
aripiprazole
clozapine
pilocarpine
ketamine
potassium chlorate
risperidone
pyridostigmineSubstances that can cause hypersalivation include:
mercury
copper
organophosphates (insecticide)
arsenic
nicotine
thallium

Decreased clearance
Causes of decreased clearance of saliva include:
Infections such as tonsillitis, retropharyngeal and peritonsillar abscesses, epiglottitis and mumps. Problems with the jaw, e.g., fracture or dislocation
Radiation therapy
Neurologic disorders such as Amyotrophic lateral sclerosis, myasthenia gravis, Parkinsons disease, multiple system atrophy, rabies, bulbar paralysis, bilateral facial nerve palsy, and hypoglossal nerve palsy

Treatment
Hypersalivation is optimally treated by treating or avoiding the underlying cause.