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Pharmacological Mgmt of Nervous System Disorders (part 1)
Terms in this set (82)
_____ sudden involuntary muscular contractions & relaxations
____ abnormal CNS electrical activity
______ a group of recurrent disorders of cerebral function characterized by both seizures & convulsions
What is the primary etiology of epilepsy?
How is an EEG set up?
- 1-300 electrode array
- Reference electrode for movement
What are the 2 main ways to treat epilepsy?
1. identify underlying cause
____% of patients have their seizures controlled by medication
What is the main goal of treatment of epilepsy?
- main goal is to decrease neuronal activity
1. Inhibition of excitatory transmission
2. enhancement of the inhibitory transmission
Medications for epilepsy target what channels on the neuron/ postsynaptic neuron that inhibit excitatory transmission?
1. Voltage gated Na+ channels
2. L-type Ca2+ channels
4. NMDA receptor
5. AMPA & Kainate receptors
Medications for epilepsy target what channels on the neuron/ postsynaptic neuron that enhance inhibitory transmission?
2. Cl- channels
What are examples of Na+ channel blockers to treat epilepsy?
- Phenytoin (Dilantin)
- Carbamazepine (Tegretol)
What is the first choice of medication for partial and generalized tonic-clonic seizures?
Na+ channel blockers
(Phenytoin & Carbamzepine)
What is the DDI for Na+ channel blockers?
decreases blood levels of many medications
What are the adverse effects of phenytoin?
- hirsutism & coarsening of facial features
- gingival hyperplasia
- decreased serum concentrations of folic acid, thyroxine, & vitamin K with long term use
What is the primary reason for not prescribing phenytoin in children?
Is gingival hyperplasia from phenytoin reversible?
What are examples of Calcium channel blockers?
What is the MOA of CCB?
- originally designed to be a centrally acting GABA agonist
- selective inhibition of voltage gated Ca2+ channels
What are the adverse effects of Gabapentin?
- weight gain (5%) with ankle edema
- behavioral problems in children (6%)
- has been associated with movement disorders
____ is primary inhibitory transmitter in CNS
What are the 2 types of GABA receptors?
GABA-A: ionotropic receptor
GABA-B: metabotropic receptor
____ receptors are widely distributed throughout the brain
What happens when GABA A receptors are activated?
1. Cl- ion channel opens
2. membrane hyper-polarization & inhibition of neuronal firing
T/F: GABA is an agonist that only needs 1 molecule to open the channel
FALSE; needs 2 molecules to open channel
what is the MOA of BZDs & barbituates?
- Potent antiepileptic (sedative & anxiolytic) drugs.
- Bind to an allosteric site on GABAA receptor.
- inhibits neuronal firing
What are the indications of BZDs?
-commonly prescribed anxiolytics (i.e valium)
- sedatives for sleep disorders
- used to treat epilepsy
Which has a greater risk of overdose, BZDs or barbitautes?
BZDs << barbituates
What are the s/e of BZDs?
they are dose dependent!!
What are the dental mgmt considerations for pt's with epilepsy?
• Epilepsy patients may experience a seizure in your dental practice (Clear all instruments & protect patient from injury).
• Gingival overgrowth and oral ulcerations are common with phenytoin
• Benzodiazepines and Barbiturates may cause sedation
• Drug interactions (pharmacokinetics)
Signs of Alzheimer's dx are first noticed in the ___ (part of brain)
What is the first sign of AD?
AD spreads throughout the brain and extensive damage to cerebral cortex leads to (signs):
- language problems & behavioral abnormalities (agitation, wandering)
What type of long term memory is the hippocampus responsible for?
- semantic & episodic
The hippocampus is required for the _____ of memory
(i.e. turning immediate experiences into long-term memory)
What is the difference between retrograde & anterograde amnesia?
retro= inability to recollect OLD memories
antero= inability to acquire NEW memories
What is the tx for alzheimer's dx?
- there is no cure
- tx typically focuses on managing symptoms (far from adequate)
What is the signal-noise hypothesis?
- Under normal situations, you have normal activity going on in the brain "noise"
- but you have signals that can overcome the noise, and get an AP
What is the pathological signal-noise hypothesis?
you have increased "noise" in the brain, and the signals you recieve are not large enough to overcome the noise
What are the potential therapeutics for Alzheimers?
NMDA receptor antagonists (MK-801)
- at rest, you have no activity in this receptor
- in the pathology, you have activity in this receptor (which we don't want)
What is the issue of NMDA antagonists?
What are the s/e?
blocking activity in the NMDA receptor IS what we want, HOWEVER NMDA also sends the signal, so now we have also blocked the signal which we don't want.
What is Memantine? Why is it good for Alzheimers?
NMDA receptor antagonist
- the low affinity & rapid off-rate kinetics of memantine preserves physiological function of the receptor
- only binds when the cell is hyperpolarized!!! so blocks pathology, but leaves normal function in tact
What are the FDA approved drugs to treat AD?
1. Memantine (NMDA antagonist)
2. Galantamine (AChE Inhibitor)
3. Rivastigmine (AChE Inhibitor)
4. Donepezil (AChE Inhibitor)
How is acetylcholine inactivated?
Ach is hydrolyzed by enzyme acetylcholinesterase (AChE) in the synaptic cleft to form choline
- choline is recycled (i.e. taken up by nerve terminal for Ach synthesis) --> rate limiting
How are AChE Inhibitors used to tx AD? what are the s/e?
- Symptoms of AD may be associated with loss of cholinergic transmission
- AChE inhibitors (Tacrine, donepezil, rivastigmine, and galantamine) are used to restore loss of function
- Treat symptoms and do not alter progression of disease
- Side effects are mainly GI
Donepezil increases (sympathetic/ parasympathetic) function
parasympathetic (nausea, diarrhea, frequent urination, etc)
What are the dental mgmt considerations for pt's with alzheimers?
• Patient with dementia may forget how to brush his or her teeth or forget why it's important.
• Communicating with patients with AD can be challenging, and oral health professionals need to demonstrate patience and empathy.
• Xerostomia is common complaint in AD patients (due to other medications)
____ is a Chronic autoimmune disease in which the body's immune system attacks its own tissues (myelin)
What are the symptoms of MS?
Signs and symptoms differ greatly from person to person and over the course of the disease depending on the location of affected nerve fiber:
- Numbness or weakness
- Electric-shock sensations
- Tremor, lack of coordination or unsteady gait
- Vision problems are also common
What is the tx for MS?
- There is no cure for multiple sclerosis.
- Treatment typically focuses on recovery from attacks, slowing the progression of the disease and managing symptoms.
- Primarily anti-inflammatory therapeutics
What are the FDA approved disease modifying therapies used to tx MS?
Anti-CD20 therapies (ritixumab)
- Those who receive this treatment are slightly less likely to progress than those who are untreated
- B cells bind to a 'foreign' antigen and initiate an antibody response
What is the most common tx of MS?
what are the dental mgmt considerations for MS?
- MS symptoms can make it difficult to adequately care for the teeth (hand numbness, pain, spasticity, etc.)
- Basic periodontal treatment that removes supragingival and subgingival biofilm and calculus can reduce the inflammatory response in the entire body.
- Xerostomia is common complaint in MS patients (due to other medications)
___ Progressive fatal neurodegenerative disorder
Comparison between ALS & MS (chart)
What is the only drug used to tx the symptoms of ALS?
Riluzole (glutamate inhibitor) delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months.
What are the dental mgmt considerations for ALS?
- ALS symptoms can make it difficult to adequately care for the teeth (decreased upper limb mobility)
- High occurrence of dysphagia (swallowing problems) in individuals with ALS, modification of patient treatment in the dental chair is often necessary
- Shorter appointments, or appointments with built in breaks, due to tiredness from keeping mouth open
What are the symptoms of Parkinson's disease?
What is the etiology of parkinson's?
A loss of dopamine neurons in substantia nigra pars compacta
How is Parkinson's treated?
< Preventive/Disease modifying treatment >
- No definitive treatment available
- Neurotrophic factors
** Treatment typically aimed at increasing dopamine levels in the brain.
What is the MOA of carbidopa (peripheral decarboxylase inhibitor) with L-dopa?
- Decreases adverse reactions from peripheral formation of catecholamines
- Increases L-dopa into brain
Explain the pharmacokinetics of L-dopa
- L dopa is readily absorbed from GI tract
- usually large doses must be given, since ~1% cross the BBB & due to first pass effect
- L dopa is metabolized by dopa decarboxylase in liver & periphery to dopamine
- secreted in urine unchanged or conjugated with glucoronyl sulfate
- most of L dopa converted in periphery to NE & EPI
What are the dental management considerations for Parkinson's disease?
- PD-related rigidity, tremor and dyskinesia can make it hard to brush one's teeth.
- Scheduling short morning appointments that begin 90 minutes after administration of PD medication enhances the patient's ability to cooperate with care.
- Many drugs (COMT/MAO inhibitors) may interact with epinephrine administered via local anesthetic. As such, epinephrine should be limited to concentrations of 1:100,000 in these patients and no more than 2-3 carpules of anesthetic should be administered
what is the gold standard therapy for parkinsons?
carbidopa with l-dopa
what is the age of onset for HD?
The age of onset can range from age two to over age 80 (typically between 35 & 45).
How do patients die from HD?
The patient eventually succumbs to complications such as heart failure or aspiration pneumonia.
what are the primary characteristics of HD?
How is HD acquired?
- Autosomal dominant
- For an affected parent, 50% probability that a child is affected
- Can be caused by genetic mutation
# of CAG repeats correlates (directly/inversely) with age of onset in HD
What does chorea mean?
- Chorea (Greek word for dance, dance-like involuntary movements).
- "excessive, spontaneous movements, irregularly timed, randomly distributed, and abrupt"
What are the chorea movements in the early phases of HD?
- slight, uncontrollable movements
- stumbling and clumsiness
What are the chorea movements in the late phases of HD?
1. Bradykinesia (slowness of voluntary movement)
2. Akinesia (difficulty initiating movement)
3. Rigidity, especially in the late stages of the disease
4. Dysphagia (difficulty swallowing)
5. Dysarthria (slurred speech)
T/F: Dementia in pt's with HD is always the same level across all patients
Intellectual impairments in all cases; varies with severity.
What are the symptoms of sub-cortical dementia seen in HD pts?
- decrease in planning & organization
- decrease in memory
- decrease in the recall of old familiar things
-No cortical dementia, no aphasia (loss of speech/language) no agnosia (loss of ability to recognize objects/persons/smell)
What pathology do you see in HD?
- The most striking neuropathology in HD occurs within the neostriatum,
- gross atrophy of the caudate nucleus and putamen
- accompanied by selective (GABAergic) neuronal loss and astrogliosis.
- Later stages, large ventricles and cortical atrophy
What pathology do you see in the basal ganglia of HD patients?
- Loss of striatal medium spiny projection neurons
- Those projecting to GPe are first to degenerate
- Loss leads to increased motor output due to thalamic disinhibition
- Dramatic loss of striatal medium spiny projection neurons
- Loss leads to decreased motor output (bradykinesia, akinesia)
What drugs are used to treat the symptoms of HD?
- Monoamine-depleting agents (reserpine, tetrabenazine) (PD side-effects)
- Sedatives; benzo's (diazepam)
- Neuroleptics (DA antagonists: haloperidol)
- antidepressants: fluoxetine
- mood stabilizers: lithium
HD vs PD (chart)
what are the similarities between HD & PD?
- Late-stage HD (rigidity and bradykinesia)
- Associated with depression & dementia
What are the dental mgmt considerations for HD?
- Huntington's Disease (HD) can often make dental care difficult for patients.
- Involuntary movements can lead to recurrent lip trauma, bruxism
- Xerostomia has also been a reported as a side-effect of tetrabenazine (monoamine depleting agent)
What drugs are used to treat epilepsy?
- Na+ channel blockers (Phenytoin & Carbamzepine)
- Ca+ channel blockers (gabapentin)
What drugs are used to treat AD?
- NMDA antagonist (memantine)
- AChE inhibitors (Galantamine, Rivastigmine, Donepezil)
What drugs are used to treat MS?
- CD20 antagonist
What drugs are used to treat ALS?
Na+ channels inhibitors
What drugs are used to treat parkinson's disease?
-dopamine agonists (direct/indirect)
- Carbidopa with L-dopa
What drugs are used to treat HD?
Dopamine antagonists (direct/indirect)
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