Week 2 Flashcards
What are 8 mechanisms that cause CNS degenerative disorders?
Hypoxia
Excitatory amino acids
Ion fluxes
Free radicals
Immune responses
Infections
Apoptosis
Protein aggregation
What is hypoxia?
Region of body is deprived of adequate oxygen (linked to cardiovascular system)
What are some excitatory amino acids that are associated with CNS degenerative disorders?
Glutamate and its receptors AMPA/kainate and NMDA
What ion fluxes can be disturbed to cause CNS degenerative disorders?
Calcium and magnesium from extra/intracellular
True or false… too much glutamate is damaging and it is involved with apoptosis
True
True or false… viruses can activate apoptotic mechanisms which can lead to degenerative diseases
True
What are Lewy bodies?
Found in dopamine neurons in parkinsons patients
Lewy bodies are areas of protein accumulation. Spherical inclusions are seen in the melanin-containing neruons of Parkinson’s disease (substantia nigra)
True or false.. inflammation can make proteins “sticky” which can lead to accumulation and degenerative disease
True
What are the clinical manifestations of Parkinson’s disease?
Tremors
Rigidity
Bradykinesia (slow moment)
Abnormal posture
Slow and monotonous speech
Shuffled gait
True or false… trauma to the head can lead to inflammation increasing the chances of parkinsons
True
Parkinsons patients are often prescribed anticholinergic drugs. What does this do to salivation?
Saliva secretions decrease, but since they swallow less it leads to drooling. Bottom line is that salivation isn’t managed well.
What are some late symptoms of Parkinson’s disease?
Depression
Immobile
Constipation (loss of bowel control leads to less efficient bowel movements)
Why is hygiene extremely important for parkinsons patients?
It is difficult for them to brush so extra time and effort is needed to brush
Since their salivation isn’t managed well, oral hygiene is critical
Early onset parkinsons is __ caused whereas late onset parkinsons is __ caused.
Genetically
Environmentally
Briefly describe the 5 stages of parkinsons
1 (mild/early) - one side of body is affected with minimal functional impairment
2 - goes bilateral. Posture and balance remains normal
3 (moderate disease) - both sides of body affected. Mild imbalance when standing/walking. Patient remains independent
4 (advanced disease) - both sides affected. Instability while standing/walking. Patient requires substantial help and cannot live alone.
5 (severe) - fully developed disease. Pt is restricted to bed or wheel chair
__% of all people will eventually develop parkinsons
0.5%
True or false… parkinsons is an age independent disease
False. It is age dependent
After the age of 85 about __% of people have parkinsons
25%
Most cases of parkinsons occur after the age of 60. Early onset parkinsons occurs between ages ___ and ___
20-50
___% of dopamine pathway must be diminished before parkinsons symptoms are manifested
70%
Why is it that everyone would eventually develop parkinsons if they were able to live long enough?
The dopamine pathway is diminishing for everyone throughout life. If you live long enough you will eventually reach the 70% threshold.
Which gender is parkinsons mostly found in? Why?
Males>females 1.5>1
Men are typically exposed to more toxins and head trauma
How many new cases of Parkinson’s disease are reported in the US every year?
60,000
What causes the substantia nigra in the brain to be darker pigmentation?
DA has a darker pigment. DA neuronal cell bodies are found in the substantia nigra
Parkinson’s disease is associated with the degeneration of the ___ in the brain due to…
Substantia nigra
Death of cell bodies
True or false.. in Parkinson’s disease, oxygen consumption goes down causing a decreased activity of the striatum
True
Both genetics and the environment play roles in the development of parkinsons. What are some environmental factors that may cause parkinsons?
Mg and Hg
Pesticides
Trauma
Dopamine itself
How does dopamine itself play a role in the development of Parkinson’s disease?
DA has two hydroxyl groups which get oxidized easily. If exposed to oxygen, DA becomes reactive. The neurons try to keep dopamine in a safe place , not exposed to oxygen (vesicles), when DA concentrations get too high it may kill the neuron
What are two genes associated with Parkinson’s disease? Describe them
Larkin
Alpha synuclein - trafficking protein which shows up in Lewy bodies. It is important in vesicles contains DA
What is the underlying etiology of Parkinson’s?
DA is decreased so cholinergic activity goes up to compensate
What are the two broad approaches for treating parkinsons?
Increase DA or decrease ACh side of balance
How is L-DOPA used to treat parkinsons? Why is it necessary to take ____ with it?
L-DOPA is a precursor to DA. However, L-DOPA is easily metabolized in the blood stream before it can cross the BBB.
Carbidopa is necessary to take with L-DOPA because it inhibits the metabolism of L-DOPA in the periphery so it can cross the BBB.
What is an effective diagnostic tool to determine if the pt has parkinsons?
Give the patient L-DOPA + carbidopa. If the tremors stop, they have parkinsons. This medication is very effective.
How can parkinsons treatment affect dental treatment?
L-dopa can be metabolized in the periphery to NE. So you must be careful with using epinephrine
What is levodopa?
L-DOPA
What is Azilect? What is entacopone? How do they work?
These are Parkinson’s medications.
Azilect: inhibits dopamine breakdown
Entacapone: improves effects of carbidopa-levodopa. It is an inhibitor of catechol methyl transferase (extracellular enzyme that breaks down monoamines such as DA)
What is trihexylphenedate?
Anticholenergic drug used to treat symptoms of parkinsons. It is only a temporary fix
What is selegelein?
Monoamine oxidase inhibitor used to slow down the progression of parkinsons
What is pramipexole?
Dopamine agonist used to treat early onset Parkinson’s disease
True or false… benztropine is an anticholenergic drug used to treat parkinsons
True
Describe the surgical procedure that can be done to treat parkinsons
Deep brain stimulation. An electrode is placed into the brain to stimulate the substantia nigra to diminish tremors. Typically used for younger parkinsons patients.
Patient flips a switch to turn up the dopamine
True or false… levodopa causes adverse Orofacial reactions
True. It can cause movement of the tongue and orofacial distortions and strange movements.
It may also cause darkening of the saliva
What are some dental implications for treating parkinsons patients?
Do major dental interventions early in PD course.
Keep appointments short
Limit anesthetic use to three carps (LDOPA->NE)
Give excellent oral hygiene techniques
Describe the pathway that is involved with huntingtons disease
Affects GABA neurons. (AMPA and NMDA receptors are altered) input from DA and ACh neurons are diminished.
How is huntingtons disease obtained?
It is 100% hereditary from an autosomal dominant gene. No environmental influence
When is the onset of huntingtons disease typically occur?
Relatively early onset (30-40 years old)
What are the clinical manifestations of huntingtons disease?
Abnormal moves - chorea form - sudden jerky movements like ticks involving the whole body.
Progressive intellectual dysfunction
Auditory projections
Facial grimaces
Cognitive systems deteriorate
How are huntingtons disease and Parkinson’s disease kind of the opposite?
Parkinson’s disease - too little DA
Huntingtons disease - too much DA
Describe the progressive intellectual dysfunction involved with huntingtons disease
Occurs early onset
Pt has severe withdrawal and depression
Pt develops full blown schizophrenia
Pt becomes compulsive due to DA dominant behavior
Approximately ___% of people in the US have huntingtons disease
0.01% (its very rare)
What is the timeline from diagnosis of huntingtons disease to death?
5-10 years
Which receptors are altered in huntingtons disease? Describe how this causes huntingtons.
NMDA/AMPA glutamate receptors (on GABA neurons) are mutated and let calcium pour into the cell. This damages the cell and kills the GABA neurons
In huntingtons disease, there is too much __ and __ activity in the striatum, but too little ___ activity in the substantia nigra
DA
ACh
GABA
Why do Huntington disease patients have enlarged ventricles in their brain?
Ventricles are enlarged due to loss of caudate neurons
What do you do for the diagnosis and treatment of huntingtons disease?
Do genetic screening
What are the pharmacological treatments for huntingtons disease?
DA antagonists (antipsychotics) (especially D2 antagonists) (may also be used tor hallucination/delusions
DA depletion for choreiform movement (reserpine)
DA agonists - for bradykinesia and rgidity (may lessen movements but increase psychotic behaviors)
SSRIs for depression
True or false.. SSRIs are used to treat the degeneration of huntingtons disease
False. Seratonin targetd drugs are used to help with depression associated with huntingtons disease but it doesn’t actually affect the underlying cause of HD
What is haldol (haloperidol)?
DA antagonist (D2). Blocks DA from binding to DA receptors. This drug will result in symptoms mimicking parkinsons. Used to treat huntingtons disease
What is olanzepine?
An atypical antipsychotic. It has antiserotonin properties and has less side effects than some other huntingtons disease drugs
What is the most common degenerative brain disease? About how many people in the US have it?
Alzheimer’s disease
3-4 million people in the US have it.
Once diagnosed with Alzheimer’s disease, how long does the patient have to live?
5-20 years
What are the three categories/stages of Alzheimer’s disease? Describe them.
Early - short term memory goes first. Still functional and aware that the memory is slipping. Don’t like change. Can still remember very important short term memories
Moderate - function begins to be compromises. Often stops working. Needs assistance and support. Do not follow routine
Late - motor functions deteriorate. Pt has no judgment. Can stop eating and become immobile.
True or false… Alzheimer’s has a genetic and environmental factor
True. It is also considered an inflammatory disease
ACh neurons have cell bodies in the ___ and its projections reach to the ___ which is associated with memory. Both of these locations are effected in Alzheimer’s as well as the ___
Nucleus basilis
Hippocampus
Cortex
What are senile plaques?
Associated with Alzheimer’s disease. They have beta amyloid in them.
Amyloid is normally found in the brain, but it accumulates as you grow older. Beta amyloid is sticky and forms excessive plaques
What are neurofibulary tangles?
Made up of tau protein which is a microtubule protein involved in transport. Tau protein aggregates in cells which makes it difficult for them to function.
What is the protein precursor for beta amyloid?
APP (amyloid precursor protein)
This is abnormally formed due to genetics. It makes the amyloid sticky so it aggregates.
Beta amyloid accumulation causes a decrease in ___ activity in the nucleus basilis and hippocampus. ___ may help fix this.
ACh
AChE inhibitors
What genes may predispose you for Alzheimer’s disease?
Apolipoprotein which turns to APP which turns to beta amyloid.
Problems with apolipoprotein is the genetic cause of Alzheimer’s
What is the only way to have a definitive diagnosis of Alzheimer’s?
Autopsy
What drug is an AChE used to treat Alzheimer’s? Studies say that it can improve function by 5-10%
Donepezil
What are the clinical manifestations of MS (multiple sclerosis)?
Diverse manifestations. Depending on the site affected, the manifestations may affect…
Senses
Autonomics
Cognition
Mood
True or false… MS affects the entire body
False. It is site specific, so only part of the nervous system are affected, however it can spread to more parts of the body
What is multiple sclerosis?
A degenerative disease in which demyelination of axons occur, which affects the ability for the signal to travel
What population of people are more prone to MS?
Scandinavians have a higher prevalence (northern states)
Asians have a very low incidence
Is MS more prevalent in females or males?
Females. 2:1
How many people in the US have MS? Is it typically found in younger or older individuals?
300,000 people in the US
1/1000 people
Found in younger individuals
What is an initiating factor for MS?
Virus infection causes an autoimmune reaction
Describe the different classifications of the progression of MS.
Progression is variable.
1) benign - asymptomatic
2) relapsing remission - on/off but no progression or worsening
3) relapsing progressive - on/off but severity worsens
4) chronic progression - constantly “on” and progressively worsens. This is the worst case scenario and is fatal
What percent of people with MS have chronic progression?
~10%
How do you definitively diagnose MS? What are some other diagnostic tools?
Autopsy. So instead you must use an MRI. Radiopacities + symptoms = MS.
What drug do you use to manage MS relapses?
Prednisone - steroids for antiifnlammation (limiting autoimmunity)
What are some symptoms of prednisone?
Lots of symptoms including moon face and buffalo hump shoulder
In order to treat severe MS, you must treat the symptoms individually. What drugs do you use to treat the following symptoms?
Bladder dysfunctions Bowel dysfunction Depression Fatigue Pain Tremors
Bladder dysfunctions - tamsulosin (flomax)
Bowel dysfunction - Metamucil (psyllium)
Depression - prozac
Fatigue - modafinil
Neuropathic pain - gabapentin (neurontin) (this is also an antiseizure medication)
Tremors - clonazepam (klonopin)
True or false… there are nociceptors in brain tissue
False
Define pain
Unpleasant sensor and emotional experience associated with actual or potential tissue damage
Where are the three sites in which pain is processed?
Where it occurs
Where it is transmitted
Where it is interpreted
What are the three elements to pain?
Sensory discriminative component
Cognitive component
Emotional/affective component
Define nociception
The physiological process by which information on actual/potential tissue damage is conveyed to the CNS
Define nociceptors
Specialized ion channels on sensory nerve endings that respond to noxious stimuli (ion channel receptors )
Define nociceptors pain
Pain resulting from activation of nociceptors as a result of actual or potential tissue damage and processing by the CNS
-somatic/visceral/inflammatory
True or false… if inflammation is present it dulls the pain
False.. if inflammation is present it is easier to sense pain
Define neuropathic/neurogenic pain.
A pathophysiological process resulting from abnormal sensory processing, which does not signal actual or potential tissue damage, does not promote healing or repair, and may be considered a disease.
(No nociceptors are stimulated)
What is the difference between somatic and visceral pain?
Somatic: pain associated with musculoskeletal system and skin. Well defined.
Visceral: pain associated with internal organs and associated tissues. Dull, burning, poorly defined.
What is the difference between analgesia and anesthesia?
Analgesia: selective reduction of pain perception without affecting other sensory modalities.
Anesthesia: absence of ANY sensation due to suppression of CNS function. (Tend to be sodium channel blockers)
What are the four basic processes in nociception?
Transduction - occurs at nerve terminal. Transfers one form of energy into a neuronal message
Transmission - Action potential itself
Modulation - first point of synaptic connection in the dorsal horn of spinal cord. (Remember that once it synapses here, the next neuron crosses over to contralateral side) (descending neurons form brain can modulate this synapse)
Perception - after the signal goes through the thalamus into the cortex, specific parts of brain assess the intensity of the pain.
What are the four different types of sensation that nociceptors can sense through their variety of channels?
Mechanical
Chemical
Thermal
Polymodal
Name some examples of mechanical ion channels nociceptors
TRPA1
P2X/P2Y
Name some examples of chemical nociceptors
ASIC
TRPV1
Remember that chemical nociceptors bind H+
Name two types of thermal nociceptors
TRPV1
TRPM8
What does TRP and P stand for regarding nociceptors?
TRP - transient receptor potential
P - prostaglandin/purino - and pyramidine - receptors type
Capsaicin activates the ___ nociceptors: __
Polymodal
TPRV1
This is because capsaicin causes the release of substance P from the tissue which is a chemical mediator that sends the pain message.
Describe the secondary activation of nociceptor nerves. Action potential propagate toward cell body in ___ and then enter the ___.
Surrounding tissues (and nociceptor nerve endings) release secondary mediators such as substance P and bradykinin that cranks up the sensitive of nociceptors (positive feedback).This is the body’s way of protecting an area that is already damaged.
Dorsal root ganglion
Spinal cord
What is sensitization? What is the difference between hyperalgesia and allodynia? What is the purpose of these responses?
Sensitization: increased sensitive and response to stimuli in and near the injured area.
Hyperalgesia: increased perception of pain in response to painful stimuli
Allodynia: pain evoked by normally non painful stimuli
This may be important for protection of damaged area and promote healing
Name two major candidates for sensitization and where they come from.
Substance P (from nerve endings)
Prostaglandins (from damaged cells)
Prostaglandins are derived from ___ and converted by ___.
Aracadonic acid
Cycloxygenase
Note that COX inhibitors are often used to prevent this conversion of arachadonic acid to prostaglandins
How do prostaglandins cause sensitization of nociceptors?
They activate specific sodium channels, making the nociceptive nerve endings more excitable.
Which, Cox 1 or Cox 2 is constitutive? What does that mean?
Cox 1 is constitutive, meaning it is always found in many tissues. So if you inhibit Cox-1 you are likely to have some adverse side effects.
What are some functions of COX-1? (4)
GI cytoprotection
Platelet aggregation
Renal electrolyte homeostasis
Renal blood flow maintenance
True or false.. Cox 2 is constitutive like Cox 1
False. It is induced by hormones, growth factors, and inflammatory mediators
What are the constitutive and inducible effects of cox 2?
Constitutive: renal electrolyte homeostasis. Renal blood flow maintenance. Cardiovascular protection.
Inducible: pain. Fever. Inflammation
Cox 2 is inhibited by classic NSAIDs and by selective Cox 2 inhibitors such as ___
Celebrex (celecoxib)
Describe the mechanisms of anti-nociceptive action of NSAIDs
NSAIDs inhibit synthesis of prostaglandins that are involved in sensitizing the nociceptor nerve endings. This will limit and focus what the nociceptors sense.
NSAIDs are good for somatic pain, but not visceral pain
Nociceptors in the viscera are normally activated by ___ stimulation. Visceral pain may be referred to somatic sites.
Mechanical
Describe the signal carried by A-delta axons.
Small, myelinated, fast conducting
Associated with mechanical and thermal nociceptors
First, or fast pain
Describe the signal carried by C axons.
Small, unmyelinated, slow conducting
Associated with polymodal nociceptors
Slow, or second pain
The plexus of nerves in the tooth is called the ___ or ___.
Sub-odontoblastic plexus
Plexus of raschkow
The plexus of nerves in the tooth consists of _ afferents of the ___ nerve and sympathetic branches from the ___ ___ __.
Sensory
Trigeminal
Superior cervical ganglions
What are the two types of nerve fibers in teeth?
A-delta fibers: myelinated. Fast. Diameter 1-6um. Sharp, localized, fast pain.
C-fibers: unmyelinated. Slow conducting. Diameter 2um. Dull diffuse pain.
Nociceptive fibers synaps with ___ neurons in the ___.
Projection
Dorsal horn
What are is the NT for C fibers? What is the NT for A-delta fibers?
C fibers: substance P
A-delta: glutamate
Describe the ascending pain pathway
Projection neurons send axons across midline (decussate)
Ascend contralaterally in spinothalamic tract; thalamus as major somatosensory relay
The trigeminal nucleus inputs to the ___. The __- to somatosensory cortex __ and __ and __ areas.
Thalamus
Thalamus
1 and 2
Limbic
Nociceptive input is heavily modulated at the ___ horn. Both ___ and ___ influences
Dorsal
Facilitatory
Inhibitory
Define central sensitization.
Dorsal horn projection neurons also become sensitized and hyper-responsive to nociceptive input, which contributes to hyperalgesia, and to touch input which contributes to allodynia
What is central sensitization?
Top down sensitization.
Prostaglandins released from descending neurons or glia in dorsal horn (in response to neural input and inflammatory mediators) are probably involved in central sensitization.
True or false.. the dorsal horn is a major site of action for analgesic drugs
True
True or false.. a second mechanism for the anti-nociceptive action of NSAIDs is inhibition of synthesis of prostaglandins in dorsal horn that participate in central sensitization. The dorsal horn is also a major site of action of opioids.
True
What is “gate control”?
Inhibition of pain by touch. Sometimes, strong touch stimulation can inhibit nociception.
Note convergence of inputs from A-beta and A-delta fibers
Referred pain is when visceral afferent nociceptors converge on the same pain-projection neurons as the afferents from the ____ sturctures in which the pain is perceived. The brain cant distinguish the origin
Somatic
Free radicals such as ____ and ___ may cause degenerative disorders. The free radicals may cause cross-linking, or activate oxygen species. The oxygen species may be neutralized by reducing enzymes such as ___.
Catecholamines and glutamate
Catalase
True or false… Parkinson’s disease pateints have tachykinesia
False.. they have bradykinesia
What are the autonomic and neuroendocrine clinical manifestations of parkinsons?
Increased salivation
Dysphasia (difficulty swallowing)
Name 5 late symptoms of parkinsons patients
Slurred speech
Depression
Immobile
Constipations
Low of bowel control
The average parkinsons patient has how many root canals?
7
What is amyotrophic lateral sclerosis (ALS) (Lou Gehrig’s disease)?
Progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, namely motor neurons. Affected areas lead to scarring/hardening.
Voluntary muscle action is reduced
What is Myasthenia Gravis?
Chronic autoimmune neuromuscular disease causing weakness in the skeletal muscles. Muscle weakness worsens after activity and improves after rest.
Due to an error in the transmission of nerve impulses to muscles.
Antibodies block, alter, or destroy the receptors for ACh at the neuromuscular junction.
Treatment includes use of AChE inhibitors such as prostigmine or neostigmine
What is Guillain-Barré syndrome?
Disorder in which the body’s immune system attaches part of the peripheral nervous system.
Weakness or tingling sensations in legs is first sign, then spreads to upper body.
Increases in severity until near paralysis.
Occurs after a respiratory or GI viral infection.
What are extrapyarmidal disorders?
Includes any group of clinical disorders marked by abnormal involuntary movements, alterations in muscle tone, and postural disturbances. This includes… Parkinsonism, chorea, athetosis.
It’s a functional, rather than anatomical, unit comprising the nuclei and fibers in motor activities.
How much money is spent per year due to pain?
Over 500 billion
