Post on 04-Jan-2016
Epilepsy
Parkinsonism
Neurological Diseases
Epilepsy
Seizures that occur on a chronic, recurrent basis
Thought to be caused by damage to the network of cortical neurons that have become capable of sustaining an excessive discharge pattern for several seconds
The results of this excessive discharge pattern is a seizure
Question
If the damage to the cortical neurons is permanent, why don’t seizures occur all the time?
Answer
There is an interplay between environmental and internal brain factors
The normal neuronal control mechanisms that contain and control abnormal neuronal firing are overcome
Sometimes fatigue and sleep loss can trigger a seizure
Normally impossible to determine what sets off seizures in most patients with epilepsy
Non-Epilepsy Seizures
Isolated seizures caused by a number of potentially reversible problems CNS trauma, infection, or stroke
Blunt force trauma to the brain, concussions, damage to parts of brain, patients who had strokes
Hyponatremia and hypoglycemia Hypoxia Alcohol withdrawal Fever (mainly in children)
If underlying causes of seizures are not corrected, may lead to the development of recurrent seizures or epilepsy
Etiology
The cause of 80% of the seizures in patients with epilepsy are unknown
The most common causes of epilepsy include head trauma and stroke
CNS tumors and infections are also common causes
Epidemiology
2 million in US are afflicted Incidence is between 35-75 cases/100,000
persons About 8% of population will experience a
seizure during their lifetime New onset seizures occurs most frequently
in infants <1 month of age and in adults >55 years old More chances in very young and very old
Classification of Seizures
Partial seizures Simple partial seizures Complex partial seizures Secondary generalized
Generalized seizures
Simple Partial Seizures
Caused by a group of hyperactive neurons confined to a single locus in brain
Patient experiences abnormal sensations or uncontrolled muscle movements in a portion of their body
Patient does not lose consciousness
Complex Partial Seizures
Also caused by a group of hyperactive neurons confined to a single locus in brain
Patient may experience sensory hallucinations and mental distortions
Abnormal muscle movements may include chewing movements and loss of bowel or urine control
Patient may lose consciousness
Secondary Generalized
Generalized seizures that begin as simple or complex partial seizure and spread to involve the entire brain
Many patients complain of a “aura” Aura may be the beginning of the seizure
Generalized Seizures
Entire cortex is involved from the onset of the seizure Tonic-clonic seizures Absence seizures Myoclonic seizures Atonic seizures
Tonic-Clonic Seizures
Sudden loss of consciousness accompanied by tonic extension and rhythmic clonic contractions of all major muscle groups.
The duration of the seizure is usually 1 to 3 minutes.
This type of seizures are often called grand mal
Absence Seizures
Sudden and brief loss of consciousness without muscle movements.
These seizures are often described as daydreaming or blanking out episodes
Seizures often called petit mal
Myoclonic Seizures
Single and very brief jerks of all major muscle groups lasting 3-4 seconds
Patients with these may not lose consciousness
Patients describe seizures as shoulder shrugs or spinal chills.
May cluster and build into a generalized tonic-clonic seizures.
Atonic Seizures
The patient loses consciousness and muscle tone.
No muscle movements are typically noted
Patient falls if not sitting or lying down Often described as “falling out”
Overview of Treatment
Selecting appropriate therapy is dependent upon identifying and understanding the different seizure types
Selecting appropriate therapy is dependent mechanism of action, effectiveness, adverse effects, and potential for drug interactions
Doses must be individualized using titration to minimize adverse effects and maximize therapeutic benefits
Selecting appropriate therapy is based upon some knowledge, experience, luck and “black magic”
In many cases, no logical approach “black magic?” – wagner calls it this because in some cases there is
no logical approach to tx or seizures
Mechanisms of Action Glutamate is the major excitatory neurotransmitter in
the cerebral cortex Glutamate is released from presynaptic neurons and
attaches to cetain receptor sites on postsynaptic neurons.
This results in a opening of membrane channels allowing calcium or sodium to flow into the postsynaptic neurons thus depolarizing it and transmitting an excitatory signal
Phenytoin, carbamazepine, and lamotrigine interfere with this mechanism (interfere w/stimulatory mech)
Mechanisms of Action
GABA is the major inhibitory neurotransmitter in the cerebral cortex
GABA attaches to neuronal membranes and opens chloride channels
When chloride flows into the neuron, it becomes less excitable.
Mechanism causes seizure activity to be “shut off” by controlling excessive neuronal firing.
Benzodiazepines work by enhancing action of GABA
Approach to Treatment
Type of seizures must be determined Determine if there is an underlying cause Risk of subsequent should be determined If it is determined that the patient has “real”
seizures and if there is a risk of subsequent seizures, drugs are given
Approach to Treatment
In the design of pharmacological plan, the patient Must be willing to take the medication Must be willing to monitor seizure
frequency Most be willing to monitor adverse
reactions
Selection of Treatment
Proper identification of seizure type is helpful in selecting appropriate therapy
Adverse reaction patterns and economic factors should be considered
Follow consensus recommendations for treatment by American Academy of Neurology
Effectiveness of Treatment
50% of patients with epilepsy can be completely controlled
Of the remaining 50% 25% have meaningful improvement with
treatment 25% of patients do not respond well
Generic Name Brand Name
Dose related Side Effects Idiosyncratic Side Effects
Divalproex sodium Depakote Drowsiness, nausea, tremor Hepatotoxicity
Lamotrigine Lamaictal Drowsiness, headache Rash
Levetiracetam Keppra Drowsiness, dizziness Depression
Phenytoin Dilantin Drowsiness, diplopia, ataxia Rash, others
Topiramate Topamax Drowsiness, ataxia, dizziness acute myopia and glaucoma
Carbamazepine Tegretol Drowsiness, nausea, diplopia Aplastic anemia
Oxycarbazepine Trileptal Drowsiness, diplopia Hyponatremia
Gabapentin Neurontin Drowsiness Edema
Pregabalin Lyrica Drowsiness, ataxia, diplopia Edema
General Consultation Take medication with a glass of water. Follow the directions on the prescription label. Take your doses at
regular intervals about the same time every day Do not take your medicine more often than directed. If you miss a dose, take it as soon as you can. If it is almost time for
your next dose, take only that dose. Do not take double or extra doses.
Visit your doctor or health care professional for a regular check on your progress.
Do not change brands or dosage forms of this medicine without discussing the change with your doctor
If you are taking this medicine for epilepsy do not stop taking it suddenly
Consultation
You should keep a record at home of how you feel and how your condition is responding to treatment
You should share this information with your doctor or health care professional at each visit.
You should contact your doctor or health care professional if your seizures get worse or if you have any new types of seizures
Many Problems
Many, many adverse effects Adverse frequently cause drug to be
discontinued Dose related Idiosyncratic
Many drug interactions
Generic Name Brand Name
Dose related Side Effects Idiosyncratic Side Effects
Divalproex sodium Depakote Drowsiness, nausea, tremor Hepatotoxicity
Lamotrigine Lamictal Drowsiness, headache Rash
Levetiracetam Keppra Drowsiness, dizziness Depression
Phenytoin Dilantin Drowsiness, diplopia, ataxia Rash, others
Topiramate Topamax Drowsiness, ataxia, dizziness acute myopia and glaucoma
Carbamazepine Tegretol Drowsiness, nausea, diplopia Aplastic anemia
Oxcarbazepine Trileptal Drowsiness, diplopia Hyponatremia
Gabapentin Neurontin Drowsiness Edema
Pregabalin Lyrica Drowsiness, ataxia, diplopia Edema
Idiosyncratic Side Effects
Rash including Stevens-Johnson Syndrome
Hepatotoxicity Bone marrow toxicity These side effects are potentially life-
threatening
Drugs Associated with most Idiosyncratic Reactions
Carbamezepine Phenytoin Valproate Lamotrigine
Parkinson’s Disease (PD)
Overview
Patients display motor and non-motor symptoms
The most useful diagnostic tool is the clinical history
Therapy is begun when the disease affects quality of life
Disease is progressive Late stages of the disease may be associated
with dementia
Epidemiology
Affects 1 million Americans Average age of onset is >60 years old Genetics may play a role in that 15%
of patients with PD have a first-degree relative with the disease
Etiology
Cause is unknown Deterioration and eventual death of nerve cells in the substantia nigra Neurotransmitters needed for normal fx
are reduced
Motor Symptoms – “TRAP”
T = Tremor at rest ("pill rolling") R = Rigidity A = Akinesia or bradykinesia P = Postural instability and gate
abnormalities
Non-Motor Symptoms – “SOAP”
S = Sleep disturbances insomnia, rapid eye movement sleep behavioral disorder, restless legs syndrome
0 = Other miscellaneous symptoms nausea
fatigue, speech, pain, dysesthesias, vision, seborrhea A = Autonomic symptoms drooling, constipation, sexual
dysfunction, urinary problems, sweating, orthostatic
hypotension, dysphagia P = Psychological symptoms anxiety, psychosis, cognitive
impairment, depression Psychological impairment Cognitive impairment, depression,
dimensia
Response Fluctuations - MAD
M= Motor fluctuations A = Akathisia D = Dyskinesias
Approach to Treatment Three phases
Lifestyle changes, nutrition, exercise Helps in early stages
Pharmacological treatment with drugs that enhance dopamine concentrations Want to decrease progression of disease, but majority of the
time it’s not possible
Surgical treatment take pt, do NOT anesthetize open up patient’s skull(do
use SOME anesthetic) expose the brain(brain has no pain receptors)
Take electrodes and put on parts of brain that theoretically is controlling abnormal movements Apply electrical stimulation to those areas, if you hit electrical impulses,
everything stops
Classification of Drugs
2 types of drugs for tx:1. Drugs which increase dopamine
concentration or activity
2. Drugs which block acetylcholine1. Theoretically better, but in reality are A LOT
less effective, used as an adjunct (NOT as primary tx)
Levodopa DOPA is metabolic precursor to dopamine Restores dopamine levels in substantia
nigra Levodopa must be converted to dopamine in dopamanergic neurons
As disease progresses(more dopramanergic neurons are destroyed in brain) response to L-Dopa declines less dopamanergic neurons are present to convert DOPA to dopamine
Results of Treatment with L-DOPA
Must use high doses Causes significant nausea and vomiting Causes significant orthostatic hypotension (especially in
elderly)– most of time elderly has it)
With chronic treatment, patients often complain that drug effects wears off resulting in development of motor fluctuation
Relief provided by levodopa is only symptomatic and temporary Does not halt progression of disease
Carbidopa
Carbidopa is a dopa decarboxylase inhibitor Decreases metabolism of levodopa in GI tract
and peripheral tissues Used in combination with levodopa (Sinemet
combo of L-dopa and carbidopa) Can use a lot less L-dopa
Increases available of levodopa in CNS May decrease dose of levodopa five-fold and
thus decrease incidence of side effects
Consultation Take orally with water at least 30 minutes before
eating or 1 hour after meals to maximize absorption May be taken with a small non-protein snack, such as fruit
or a cracker, to avoid nausea. Administering with food may decrease absorption.
***Causes orthostatic hypotension **Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells Good advice for any pt that causes orthostatic
hypotension
Consultation
Visit your doctor or health care professional for regular checks on your progress.
It may be several months before you feel the full benefits of this medicine.
Continue to take your medicine on a regular schedule You may experience a wearing of effect of this medication You may also experience an on-off effect where the medicine
apparently stops working Tell your doctor or health care professional if any of these
symptoms happen to you. Your dose may need to be changed.
Psychiatric disturbances
Psychiatric disturbances can occur including agitation, anxiety, confusion, dizziness, headache, euphoria, insomnia, memory loss, nightmares, toxic delirium, hallucinations, paranoid delusion, psychosis, and hypomania and depression
Sinemet’s psychiatric effects tend to be progressive and frequently a compromise must be reached between psychiatric effects and control of parkinson symptoms.
Dopamine Agonists
Pramipexole Mirapex Ropinirole Requip Directly stimulate dopamine receptor
sites in brain Actions similar to levodopa Severe side effects limit usefulness
Consultation
Take this medicine with a glass of water. Take it with or without food but if it upsets
your stomach, take it with food. Do not stop taking this medicine except on
your doctor's advice. Do not stand or sit up quickly, especially if
you are an older patient. This reduces the risk of dizzy or fainting spells. (orthostatic hypotension)
Antimuscarinic Drugs
Much less effective that other drugs Used as an adjunct to
levodopa/carbidopa Adverse effects similar to high doses
of atropine Benztropine Cogentin
(on top 200)
Consultation
May be administered without regard to meals Your mouth may get dry. Chewing sugarless gum or sucking
hard candy, and drinking plenty of water may help This medicine may cause dry eyes and blurred vision. If you
wear contact lenses you may feel some discomfort. Lubricating drops may help.
You may sweat less than usual while you are taking this medicine. As a result your body temperature could rise to a dangerous level.
Be careful not to get overheated during exercise or in hot weather. You could get heat stroke.
Avoid taking hot baths and using hot tubs and saunas.