Common Drugs Used for Neurologic Diseases
Karen Kline, DVM
The treatment of the neurologic patient is dependent upon findings a thorough owner history, thorough physical and neurologic examinations, and neurologicalization. The patient's neurologic condition is localized to either the brain, spinal cord or neuromuscular systems. This lecture will concentrate some of the diseases that affect each area of the nervous system and the drugs used to treat them.
The brain can be divided up into 3 components: the cerebral cortex (forebrain), which regulates intellect, behavior, and motor function; the brainstem, which is the relay pathway for consciousness, cranial nerve function motor and sensory function and the cerebellum, which controls fine motor movements. The most common dysfunction of the forebrain, (caused by a number of different etiologies - trauma, tumors, vascular accidents, metablic disease) is seizure activity, which can be generalized (tonic - colonic seizures), partial or focal in nature. The mainstays of seizure management are: establishing an underlying cause and terminating the spread of seizure activity. The main drugs used for immediate seizure control are: 1) Diazepam (Valium®) 2) Phenobarbital and 3) Phenobarbital. Diazepam is the drug of choice for the treatment of status epilepticus and cluster seizures. It is a benzodiazepine and although its mechanism of action is unknown, it is thought to antagonize serotonin release, increase GABA activity and decrease acetylcholine (ACh) release in the CNS (central nervous system). Best routes of administration are intravenous and per rectally at doses of 0.5-1.0 mg/kg and 0.25 to 0.5 mg/kg respectively. Valium should be administered slowly IV to prevent cardiotoxicity. It should be kept out of direct light and may absorb to IV solution plastic bags and infusion tubing, and is best given alone. The concentration of the injectable is 5 mg/ml. Phenobarbital is a barbiturate anesthetic that can be used if the status patient is refractory to Valium. It works by suppressing seizure spread, inhibiting the release of ACh, norepinephrine and glutamate and potentiating GABA. The dose is 2 to 8 mg/kg IV (50 mg/ml), to effect, and the patient must be monitored for respiratory depression, which is a main side effect of the drug.
Phenobarbital is one of the drugs of choice for the treatment of idiopathic epilepsy. It decreases seizure spread by affecting the chloride pump and also has similar properties as Pentobarbital. It can be given orally or IV and its half-life is 36-48 hours. It is metabolized by the liver. The drug is inexpensive and the oral maintenance dose is 3 mg/kg BID. Blood levels should be checked 3 weeks after initiating therapy and 2 weeks after changing therapy. Therapeutic levels are 15-45 Fg/ml. Side effects of this drug include polyuria, polyphagia, weight gain, and in some cases, hepatotoxicity and bone marrow suppression. Overall, however, it is an excellent drug for seizure therapy. It comes in 1/4 grain (15 mg), 1/2 grain (30 mg), 1 grain (60-65 mg) and 100 mg tablets as well as an elixir (20 mg/5 ml), and injectable (65 mg/ml). Remember, pentobarbital, phenobarbital, and diazepam are all controlled substances.
Potassium bromide (KBr) is fast becoming more popular as a maintenance anticonvulsant. Its mechanism of action is not known, but it is theorized to hyperpolarize the neuron cell membrane and make it less excitable. It can be used alone or with phenobarbital, and is not metabolized by the liver or any organ system, so it is helpful in animals who have liver disease and seizures. It is excreted by the kidneys. It is not commercially available, and must be compounded either into liquid for or capsules. The white powder can be a respiratory and/or skin irritant. Its half-life is 25 days. It can be given orally at a loading dose of 100 mg/kg BID x 2 days, then 10 mg/kg BID or can be given rectally at a dose of ??. Blood levels are attained 1 month after loading and are 1000-3000 Fg/ml. Side effects can include profound sedation, vomiting, and rarely pancreatitis.
The treatment of head trauma with corticosteroids is quite controversial, and the ABC's of emergency medicine as well as maintenance of blood pressure and fluid therapy are of utmost importance. If steroids are used, it is important that the patient is well-hydrated. Steroid of choice are short-acting preparations such as prednisolone sodium succinate (Solu delta Cortef®) and methylprednisolone sodium succinate at doses of 20 mg/kg and 15 mg/kg, respectively, IV. These drugs may also be used for the treatment of peritumoral, vasogenic edema caused by brain tumors. The same doses can be used IV; they should be given slowly over 10 minutes to prevent vomiting.
Mannitol is an osmotic diuretic that is also helpful to treat cerebral edema caused by brain tumors. It helps to draw fluid into the vascular space and can act quite quickly. It is given IV at a dose of .5 to 1 gram/kg (200 mg/ml vial) slowly over 20 minutes, and can be repeated twice. Pulse therapy is found to be more effective than constant rate infusion. It should be kept in an incubator or heated area so that it does not precipitate out of solution. Mannitol should be avoided in hypovolemic animals and those with heart disease. Furosemide (Lasix®) is also a diuretic that can be used for cerebral edema at a dose of 2-5 mg/kg IV and can be repeated; the patient should be adequately hydrated before using.
Spinal cord trauma can include intervertebral disk rupture, luxations, subluxations, fibrocartilagenous embolism or other blunt trauma. The drug of choice for acute spinal cord injury is methylprednisolone sodium succinate (Solumedrol®) at an initial dose of 30 mg/kg IV slow over 5-10 minutes, then repeated twice at 15 mg/kg at 2-4 hour intervals. This drug is best administered within 2 to 8 hours of the trauma and it theorized to inhibit lipid peroxidation and to scavenge free O2 radicals, although this is yet to be proven in the canine. Gastric protestant should be administered concurrently.
Neuromuscular disorders such as myasthenia gravis can be challenging to diagnose and treat. Two drugs that may be helpful are both acetycholinesterase inhibitors (then allow ACh to be available at the neuromuscular junction longer), one (edrophonium chloride (Tensilon®) is short-acting (intravenous) and the other pyridostigmine bromide, (Mestinon®), is long-acting and given orally. The Tensilon® dose is 1-5 mg IV maximum in the canine and 0.25-0.5 mg total IV in the feline. The Mestinon® dose is 1/8 to 3/4 of a 180 mg tablet in the canine BID to TID orally and 2.5 mg (syrup - 60 mg/5 ml) BID to TID in the cat. Side effects include salivation, lacrimination, urination, defecation
Drug used for the treatment of CNS and neuromuscular disorders can be beneficial, yet, have side effects that need to be recognized. When used properly, their advantages far outweigh their risks.