chronic disorders of brain function
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Chronic Disorders of Brain FunctionNUR 235
Seizure Disorders
Seizure:o Sudden, explosive, disorderly discharge of cerebral neurons.
Characteristics:o Transient alt in brain function, involves motor, sensory, autonomic (involuntary
control, psych/behavioral clinical manifestationso Altered level of arousal (temporary)
Seizure:o Seizures are component of many disease processeso Can be known or unknown causeo Anyone can have seizure under the right circumstances
Epilepsy (chronic/unknown)o Phenomenon of recurrent seizures; etiology unknown; no underlying correctable
cause identified.
Convulsion: Not everyone with seizures have this jerky movement Etiology of seizures;
o d/o that alters neuronal environment1. Acquired: cerebral trauma, cerebral lesions2. Metabolic/Nutritional: electrolytes, water, O2, withdrawal, toxins (water
toxicity)3. Idiopathic: epilepsy
a. No idea whats causing it Precipitating Events:
o Hypoglycemiao Fatigueo Lack of sleepo Emotional/physical stresso
Febrile illnesso Stimulant drugso Toxinso Etoh withdrawalo Withdrawal from depressant drugso Hyperventilationo Sensory Stimuli
Triggering that causes them to have seizureso Ingesting large amounts H20o Inadequate nutritiono Menseso lights, menstruation, high temp
Transmission of a Nerve Impulseo more Na outside cell, K inside cello depolarization repolarizationo hyperpolarization?
Pathophysiologyo Alteration in membrane potential: specific neurons become abnormally
hyperactive & hypersensitive to changes in their environment Cell membrane has been altered somehow
Genetic mutation
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Disrupts normal functiono Epileptogenic focus: abnormal neurons from this-are in brain where sz originates
Local area, hyperactive, where seizures originateo Area focuses autonomouslyo Recruits neurons in adjacent and synaptically related areas of braino miserly likes company gets other cells involvedo depending on Epileptogenic Focus determines Clinical Manifestationso Clinical Manifestations: develop when sufficient # of neurons are
excited/threshold reached
o O2 consumption o O2 & glucose rapidly depletedo Lactate accumulates in brain
In right pH standard lactic acidosis cause breakdown of brain,damage
Lactic: normal build up of cellular metabolism Too much is not good
o If sz activity continued: progressive, irreversible brain damage can occur.o >15 mins: status epilepticuso
** O2 is needed to produce ATP
Types of Seizures
Box 45-1 Generalized sz
o Whole brain surface affected Partial/focal sz
o Located one hemisphere/part of brain surface Mixed
o Starts off as partial then becomes generalized Hardest to treat
Aura/Prodrama
Prodromao Subjective sense that a seizure is about to occuro Beginning of seizure
Headache/tired Early clinical manifestations
Aurao Actually beginning of seizureo Subjectiveo Visual, auditoryo funny feeling im having
Generalized Seizures
Entire brain involved from onset Occurs in children Mild/motion less Sitting there motionless 2-10 seconds unaware of their environment full disoriented & tired even ater a few hours. Max seizure = 2 mins past 5 mins = concern!
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1. Absense (Petit mal)2. Atypical absence
a. Accompanies the myoclonici. One or more jerks within one muscle
ii. Automatism: lip smacking3. Myoclonic muscle jerking4. Atonic
a. Without tone fall to the ground drop attacksi. Sudden complete loss of muscle control
1. No content5. Clonic, tonic, toni-clonic (grand mall)
a. Jerking and stiffening at the same timeb. Chornic: muscle groups jerkingc. Tonic: stiffening (loss of control of bladder and bowl)d. Tonic clonic: some people stop breathing
6. Status epilepticusa. Can lead to irreversible brain damage
Partial/Focal Seizures Activity restricted to one brain hemisphere1. Simple partial
a. LOC does not change = * hall mark (diff to complex)i. Motor, sensory or both
ii. Motor: shakes; sensory: tinglingiii. Respiratory changes: tachypnea, slow breathing, sweating aotiv. Diaphoresis
2. Complex partiala. Drowsyb. Alt. to LOCc. Exhibit aggressive behaviord. Automatism; lip smacking; repetitive movements
3. Partial generalized (mixeda. Can start off as simple/complex full blown generalized tonic/clonic seizures
Diagnosis and Management
Patient history, phycsical/neuro exam EEG
o Electrodes on head May look normal between seizures Tell us the focus of epileptogenic focus
Labso Basic metabolic panel (BNP); glucose, calcium levels, protein, BUN & creatinine,
urine (meds/drugs infections) (change in pH) o Find the cause
Surgeryo Management
Monitoring Acute management: Maintain airway and protect from injury (concerned about) Chronic: manage source, medication, risk reduction
o Teach patient about meds and potential side effectso If pt. were eating prior do a mouth sweep
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Goal: reduce # of seizures monitor drug levelsAction of Antiepileptics
Suppress discharge of neurons within seizure focus Suppress spread of seizure activity to recruitment of other parts of brain Four major actions of antiepileptics
o Suppress sodium influxo Suppress calcium influxo Antagonize glutamate (excitatory AA)o Potentiate gaba
Neurotransmitter Monitor
Pharmacological management
Medications: antiepileptic drugs Traditional1. Phenytoin: most widely used2. Carbamazepine3. Valproic Acid4. Ethosuximide: absence sz5. Phenobarbital: older agent; not widely used
a. Depression, learning impairment6. Dilantin
a. Get to know its therapeutic rangeb. 10 20
Newer antiepileptic drugs Acute management meds
Newer Antiepileptics
Oxcarbazepine (trileptal)
Lamotrigine (Lamictal) Gabapentin (neurontin) Pregbalin (lyrica) Topiramate (topamex) Zonisamide (zonegram) Felbamate (Felbatol) Vigabatrin (Sabril)
*less risk to fetus E drug interactions
Cognitive and Motor Disorders
Aspects of Cognitive Function
Attention Executive Function
o Any problems pt. will go through inability to sustain attention, unable to setgoals and recognize when they meet their goals
o Vigilance Awareness of surroundings
o Detection Distinguish between important/unimportant
o Working memory
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Using what is happening to move forwardo Memory
Pattern recognition Put data into a sequence category count to 7 backwards
Semantic processing The part of memory that leads to understanding or giving
meaning to what just occurred
Data Processing Deficits
Agnosiao Defective pattern recognition
Doesnt recognize shape, sounds, smells that they used to know Dysphasia/Aphasia
o Inability to swallow/severe form of dysphasia Dont remember how to swallow
o Expressive (Broca)o Receptive (Wernickle)o Anomia
A problem with recalling words one of thoseo Neologism
New word Come up with new words that only have meaning to them
Memoryo Retrograde amnesia
Amnesia of the past Cant remember things from long time ago (DOB x)
o Antegrade amnesia No new memories going forward
Dyspraxia
Difficulty with actions Inability to perform skilled motor acts (speech, gait, dressing) Activity requires1. Develop idea (cortical injury)2. Formulate execution plan (temporal)3. Motor performance (pre-motor area) Left and right cortical connection interrupted Problem planning what to do and how to do it
o ex. Getting dressed, walking, chewing, swallowingo Alzheimers some Parkinsons
Can get it from Birth (Developmental Dyspraxia) not from wound Can happen to stroke patients
Aspects of Motor FunctionFLASH CARDS
Cognitive Dysfunction
Acute Confusional States
Global cerebral dysfunction
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o Drug/ETOH intoxication or witdrawalo Metabolic disordero Nervous system disease
Polypharmacy Febrile illness Infection Systemic disease (HF) Head injury Anesthesia Sudden (days) vs. gradual (week): needs to be rulled ouf for other issues
o Confused with dementia Underlying infections can cause delirium
Delirium
not a disease clinical symptom
Pathophysiology:
1. Injury to nervous tissue2. Toxin/chemical affect on neuronal tissue3. Overactivity of previously depressed brain
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Clinical Manifestations (develop abruptly 2-3 days)
Inattentive (absolute) Altered perceptions
o Misperception/misinterpretation Hallucinations Emotional liability/incoherence Incoherent Tremor-restless-violent Disrupted sleep/wake cycles (symptoms inc at night) Dilated pupils Flushed Tachycardia, hypertension, hyperventilation, elevated temperature Diaphoretic
DEMENTIA(not a disease but a) Syndrome associated with many pathologic processesProgressive deterioration of memory and cognition accompanied by behavioral changes
Orientationo No clue where they are e
Recent memoryo Cant remember what they ate 5 minutes ago
Remote memoryo past
Languageo Neologism
Executive attentional networko Vigilance
Working memory (naming things)Classifications of Dementia
Primary (no well defined cause) Secondary (well-defined etiology and co-morbidity) Degeneration
o Genetic (inheriting certain gene)o infection
Compression (2nd) Atherosclerosis (2nd) Trauma Disease: Alzheimer and vascular most commonly Not right of passage of getting old Alcoholism can cause dementia ^ wernickes syndrome Mad Cow Disease lead to dementia Vascular atherosclerosis and dementia
Dementia Epidemiology
4th leading cause of death in US 30-50% >85 years old (onset > 65) W > M 60-70% Alzheimer
o Most common cause of severe cognitive dysfunction in elders
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o Familial Alzheimer dementia (FAD) [early onset] Before 69 years old familial risk genes
o Nonhereditary (sporadic) late-onset AD (70%) 75- 80 years old
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Risk factors for all forms of Dementia
HTN PVD Lower Education Lower estrogen levels History of traumatic brain injury Elevated serum homocysteine
o AA in body, build up puts person at risk Exercised mind = good mind Vascular Dementia risk CVA, HTN BMI, diabetes
Alzheimer Disease
Ageo 65 years old
Family Historyo First degree relative 4x risk
Genetic mutationso Early onset (before 60): mutations of chromosomes
Presenilin 2 Presenilin 1 Amyloid precurser protein
Presence of apolipoprotein E4o Late onset: chromosome 19
Alzheimer Dementia
Cause genetic component, ? inflamm/oxidative influence, changes in cell Ca balance?o Damage to nerve cell communication metabolism, and repairo Characteristics: neurofibrillary tangles and amyloid plaques
When tangles & plaques occur, degeneration of cholinergic nerve endings dont produceacetylcholine
What are tangles and plaques?
Tangles: neural thread protein normally helps to stabilize central nervous system cells. InAlzheimer dz, they change structure/build up
Plaques: amyloid normally stabilizes neural cell membranes. In Alzheimer dz, it isformed improperly and builds up
This is concentrated in the cerebrum where our cognitive function takes placeo This is why the person has cognitive syndromes
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shows how brain size changes
Pathologic Changes: Alzheimers- causes disease progressive deterioration of brain
Alzheimer Pathophysiology
amyloid deposition early on terminal axons degenerate around amyloid core senile plaques disrupt nerve-
impulse transmission
tau protein becomes tangled and twisted, adds to plaques inflammatory response in response abnormalities in cholinergic system
o destruction in neurons that secrete acetylcholine neuron degeneration excess glutamate
Clinical Manifestations
early insidious (forgetfulness, emotion, illness blmed) progressively more forgetful eventual confusion, disorientation unable to concentrate deterioration in abstraction, problem solving, judgment, calculation, visual-spatial,
language
dyspraxia
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o forget to do things they used to (button shirt) behavior change (restless, irritable, agitated, hostile anxiety) difficulty communicating Late: difficulty eating, swallowing, bowel control, loss of ability to ambulate: rigidity,
flexion posturing (at risk for pneumonia)
Corticalo Agnosia dont understand patterno Apraxia dont remember things tot doo Semanticso Receptive aphasiao Loss of recent, remote memoryo Decreased computation and visual-spatial ability
Subcorticalo Forgetfulo Apathyo Depressiono Slow thoughto Personality changeo Accident proneo Loss of motor function shuffling gait, muscle rigidityo Incontinence
Diagnosis
Preclinical diagnosis Mild cognitive impairment due to Alzheimers disease Dementia due to Alzheimers disease
Adjunct Medications for Alzheimers/Dementia
Antidepressantso
SSRIs Anxiolytics Antipsychotics: (for aggressive behavior)
o Risperidone (Risperidal)o Qutipine (Seroquel)o Olanzapine (Zyprexa)
Target subcortical Vitamin E and selegiline: Antioxidant NSAIDs (only delays) (does not prevent) Estrogen (doesnt help! In this disease) Gingko Biloba: Stabilize/improve cognition
o Just eat/sleep rightDelirium vs. Dementia Delirium Dementia
Onset Acute: hrs days Insidious: most-yrsAcuity Acute emergency Chronic progressiveCourse Lucid confused/day
confused at night
Stable
Duration Hrs wks tx improves Progressive- irreversible death
Aware, Attn, alertness Reduced, distracted, short Unaffected
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attention spanOrientation Disoriented time/place Progressive impairment. Cant
recognize adl objectsMemory Impaired short-term Impaired recent unconcernedThoughtSpeech
DisorganizedInchorent
Word finding problems,Concrete, confabulations
(stretching the truth ifmemory is not good/theymake it up)
Sleep-wake Disturbed hour-hour Day/night reversalParkinsons Disease
Degenerative disorder of basal ganglia
Familial pattern 1% of population > 50 years old Primary
o Degeneration in blood ganglia Secondary parkinsonism caused by other disorders or medications
o Infection*o Intoxication*o Traumao Drug side effectso * can be reversible
men > women any damage to substantia nigra antipsychotics
Pathophysiology
basal ganglia disorder degeneration of dopamine-producing cells in substantia nigra depletion of dopamine & receptors in basal ganglia overabundance of Ach (excitatory) loss of inhibitory influence of dopamine in basal ganglia, instability of feedback circuit manifested as hypertonia, akinesis Lewy body formation (alpha synudein)
o Alpha-synudein protein and its build up leads to the Lewy body formationo Sets person up for developing dementia
Hyperkinesia tremors while movingDopamine Pathway in brainDopamine affects niagra stratum
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There needs to be an equal amount of acetylcholine and dopamine for a flow in movement
Clinical Manifestations
Insidious (early: dec. flexibility, aching, fatigue) Initially: unilateral progressing to bilateral 1st signal that prompts treatment: resting tremor Other early: bradykinesia, loss of facial expression, rigidity, hypokinesia Progression: Micrographia: small writing Dysarthria unable to speak soft talking are accompanied by drooling Akinesis: swallowing function, inability to initiate movement Postural abnormality (forward flexion) with instability Gait disturbance Weakness Dysphagia Semiflexed position Every patient will have different sets of symptoms
o Progression occurs in stagesClinical Manifestations: Parkinsons
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-fall risk
Symptoms dont show up until 50% of cells (that produce dopamine) are destroyed
Pharmacological Management:
Goal: restore functional balance between dopamine and acetylcholine Dopaminergic agents
o Levadopa-carbidopao Dopamine agonistso COMT inhibitorso MAO-B inhibitor
Anticholinergico Decrease acetylcholine
Parkinson: acetylcholine dopamine
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Multiple SclerosisPrimary demyelinization disorder of CNS
Acquired, autoimmune component 400,000 cases in US, 10,000 new cases dx/year 2.5 million worldwide 10-50 yo F>M (3:1)
o Men: more progressive Familial disease
Race: White, Northern European ancestry Range: Mild disability with exacerbations to progressive loss of function (20+ years) Only lower motor neuron is affected
Worldwide distribution MS
Further away from equator > MS risk
Pathophysiology
Genetically susceptible individual (+) Viral infection (+) Abnormal immune response T-cells autoreactive to myelin
o Destroy myelin protein ? Glutamate, ? Proinflammatory cytokins
o secreted by inflammatory cells to cause MORE damage causes neurotoxicity
Reccuring inflammatory reaction causes Plaque and lesion development (white matter)
o Can show up in gray matter too Demyelination Reversible conduction block in partially demyelinated axons
o Going thru relapse and remission Gliosis chronic stage
o No myelino Scarring = gliosis
Corticospinal Tract
affect brain & spinal cord
Destroys myelinPrimary motor cortex (start)
Brain stemMRI: MS
spots = MS
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Classifications:Relapsing remitting: Most common 85%
Be fine then exacerbationPrimary progressive: 10%
From beginning of disease processo Slow continuous progression of disease
Secondary progressive: common before meds developedo Steady worsening w/ or w/out remission
Progressive-relapsing 5%o Steady disease w/ relapses
Multiple Sclerosis
Precipitating factors onset/exacerbationo Heat
o Temp of body riseso Causes electrical activity too Electricity leaks to neurons causes symptoms
o Infectiono
Traumao Stress (post-partum, fatigue?)
Clinical ManifestationsMotor, sensory, cerebellar, emotionalSymptoms depend on the location that is affected
o Early cognitive changes (poor judgment)o Neurologic deficits short lived
o Temporary: weakness of limbso Paroxysmal attacks sensory/motor (can occur daily) [numbness in some part of body or
vertigo]o Paresthesias lack of balanceo Dysarthria inability to speako Ataxia tingling or numbnesso Tonic head-turningo Vertigo dizziness
o Weakness limbs, trunk, heado Spasticityo Visual disturbance, diplopia, blurred, acuityo Paralysis (late disease)
Lhermitte sign: shock like sensation trunk with neck flexionNot only in MS pts. But known for MS pts.
o Shock like sensation going down patients backAdditional System manifestations:
o Fatigue (muscle weakness)o GU dysfunctiono GIo Paino Tremoro Depression, emotional liabilityo Heat intoleranceo Sexual dysfunction
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o Memory and cognitive impairmento Incontinenceo Bowel/bladder incontinenceo Important to understand how far they are into their diseaseo Problem with lower motor neuron
o Cause muscle weakness in the bladderDiagnosis (Know what to check)CNS functionAt least two attacks or slow progression
MRI:Demyelination plaques
Lab Testing:
Lymphocytosis ( in lymphocytes)Elevated serum proteinCSF IgG elevated (60%)Oligoclonal IgG on electrophoresis (90%)
Treatment
Pharmacologic managemento Delay progression
o Antiinflammatories/Steroids (Solumedrol)o Immune-modulating medicationso Immunosuppresants
o Symptom managemento Antispasmodicso Anticholinergicso Antidepressantso Antimicrobials
o Avoid complications--- not discussed in class ---Symptom Management
o Bladder dysfunction:o Tolterodine (Detrol)o Solifenacin (Vesicare)o Tamsulosin (Flomax)o Terazosin (Hytrin)
o Bowel dysfunctiono Psyllium (Metamucil)o Docusate (colace)
o Fatigueo Amantadine (symmetrel)o Metylphenidate (Ritalin)o SSRIs
o Depression:o SSRIso Tricyclics
o Spasticity:o Baclofen (Lioresal)o Tizamidine (Zanaflex)
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o Neuropathic pain:o Carbazepine (tegretol)o Gabapentin (Neurontin)o Oxcarbazepine (trileptal)o Amitriptyline (Wellbutrin)
o Ataxia/Tremor:o Clonazepam (Klonopin)o Propanolol (inderal)
o Cognitive Dysfunction:o Donepezil (Aricept)o Memantine (Namenda)
o Dizziness/Vetigo:o Meclizine (Antivert,Dramamine)o Odansetron (Zofran)
------------Amyotrophic Lateral Sclerosis (ALS)
o no muscle wastingo muscle is progressively wasting and scarring of cortical spinal tract
oupper and lower motor neuron
Diffuse degenerative disorder of upper and lower motor neurons
o Lou Gehrig disease classic ALSo 30,000 people living with diseaseo 5,600 new cases per year (15/day)o 40-60 yo
o M > F (20% more common in men)o Genetic predisposition (5-10% familial)o Risk factors: Smoking, environmental,
genetic, agricultural, glutamate intakeo Debilitating disease
Pathophysiology:
o Genetic defect #21 in familial form free radicals
o 90% dont have the defect(Family)
o Free radicals cause oxidativestress
Dysfunctionmitochondria NO ATP NO ENERGY
o Altered glutamate metabolism andtoxicity
o Premature upper and lower motorneuron death and deeneration (cortex, brainstem, SC)
o Secondary demyelination, glialformation & sclerosis
o Supportive to the neurons Hold neurons together Help stabilize them
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o Too much nerve glue causes sclerosiso Denervation (interruption of nerve connection) of motor units lower motor neurons
o Interruption of the impulse to the motor units in the lower motor neuronso Compensatory enlargement of functional motor unito Non-inflammatory
o b/c it is caused by oxidative stress and free radicals
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motor unit
Clinical Manifestations
o diffuse muscle weakness, twitching, cramping, stiffnesso overreactive twitches, reactions
spastico hyperreflexia/spasticityo flaccid muscles and spastic paralysiso progressive atrophy
o cognitive status intact (1-2 years) become paralyzed and have trouble speaking & swallowing
o 2-3 years respiratory gets paralyzedo Average life expectancy after diagnosis/onset of symptoms = 3 -5 years
o But actually 2-5 yearso Rare but people can live for 10 years
Diagnostic and Treatmento Diagnosis and Treatment
o (H&P)o EMG
o Electromyelography (test muscles) checking lower neuronso NO treatmento Riluzole (Rilutek): Glutamate antagonist
o Prolongs life and gives more time before ventilationo Has SE
Cause asthenia = strengh, NVDo Rule out lyme disease, MS, spinal/brain tumors, HIV
Myasthenia GravisDecrease muscle strength
PNS degenerative disorder affecting neuromuscular junctiono Autoimmuneo Correlated with changes in thymuso Associated with other autoimmune diseaseo Classfications:
o Neonatal, congenital, juvenileo Ocular, generalized autoimmune
Attainable to treatment
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Weakness of eyelidsEpidemiology: Myasthenia Gravis
o Onseto Females 20-30 years oldo Males > 50o F>M
o Occurs in Malse < Femaleso Inherited vs. Spontaneous
o Tumors onset MGPathophysiology:
o Defective nerve impulse transmission at junctiono Auto-antibodies against acetylcholine receptorso Acetylcholine binding blockedo Receptor destructiono Decreased transmission and depolarization
Clinical Manifestationso Insidiouso Exacerbated by pregnancy, anesthesiao Muscle fatigue and weaknesso URIo Facial muscle weaknesso Diplopia (double vision), ptosis (drooping of eyelids), ocular palsy (weakness of eye
muscles)o Difficulty swallowing, chewingo Change in voiceo Respiratory muscle weakness, impaired ventilation
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Lab test:Tensilon testAntiacetylcholine (anti-AchR) receptor
Antibody titers
- good h&P- rule out the diseases- injection given:
o if immediate improvement then its MGo or remained week (NOT MG)
- MRI rule out thymus tumorsPharmacology
Anticholinesterase drugs (Neostigmine, Ambenonium, Pyridostigmine)o Prevents ACh inactivation
Steroids suppress inflammation Immunosuppressants Cytoxan
o Cancer drugo Chemo drug
Myasthenia crisis: (can be life-threatening)
Quadriplegia d/t weakness, resp distress-arrest
Stimulated by infections, surgery, child-birth & as we are tapering them off steroidso Too little acetylcholine availableo Cant move arms & legso Resp. muscles dont work
Needs to be ventilatedCholinergic crisis:Anticholinesterase toxicity risk resp arrest
Too much acetylcholineo Become toxico risk for respiratory crisis
pupil constrict salivating perspirating (sweating profusely) bradycardia
o check if pulse falls below 60
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