chronic disorders of brain function

7/30/2019 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


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


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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chronic disorders of brain function

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