Mssk Flashcards
Markers of inflammation
CRP ESR
-go up in anything with active disease activity not specific
ESR
Rises with age, higher in women, not specific
But good suspicion of active disease process
=polymyalgia wheumatica and giant cell arteritis
CRP
Synthesized in liver
Proinflammatory cytokines increase it
Can activate complement and promote phagocytosis
-assess disease activity >8 mg/l is inflammatory
Rises and falls quicker and falls quicker than ESR
Active inflammatory process
CRP and ESR
CRP falls faster and goes up faster than ESR
What else goes up with inflammation
Leukocytosis, thrombocytosis, ferritin, fibrinogen and complement increase
Rheumatoid factor
IgM antibody to IgG
Can be IgA, IgG and IgM but it is most common
Made by B cells in synovial joints of RA patients
Not pathonomunoic
In 70% and in other diseases
What is have nodular RA-bump on surface or ACL
They have rheumatoid factor 100% of the time
NODULAR
What percent of healthy patients have RF
4%
RA in other conditions
Sjorgen, cryoglobinemia, primary biliary cirrhosis, mixed connective tissue, endocarditis, SLE, sarcoidosis, malignancy, lung diseases, LUPUS
Associated with joint erosions-higher value more aggressive disease
What is a positive RF
45 IU/ml
What percent RA have no RF
20-30
But if positive higher the more aggressive the disease process
Anti citrullinated proteins anti CCP
Specific marker -more than RF
96% specific and 78% sensitivity
Associated with aggressive erosive disease
If get both positive CCP and RF
99.5% likelihood RA
More aggressive and erosive
Anti nuclear antibody
Not pathonumonic of anything can be in 20-30% of normal ppl don’t hang hat on one test
Homogenous pattern ANA
Histone antibody >95% drug induced lupus
Drugs
Rim pattern ANA
Anti DS DNA SLE
Speckled ANA
Anti SM lupus
Anti SSA SSB in sjorgen
Anticentromere antibody ANA
Scleroderma CREST/PSS
Anti scl-70
PSS/CREST
ACA
Scleroderma
Labs of lupus
Proteinuria>500 or >3 + or casts
Neurologic-seizures psychosis
Hematologists-hemolytic anemia with reticulocytosis, coombs test positive, leukopenia, lymphopenia, thrombocytopenia
-markers!!
Antibodies of lupus
Anti DNA Anti SM Syphilis Antiphospholipid antibodies based on IgG or IgM cardiolipin Positive lupus anticoagulant False RPR
ASO and anti DNAase B titers-reflective of streptococcal exposure
ASO and DNAase B titers
Group A strep causes strep throat and rheumatic fever
Can target kidney-glomerular problem
Heart-valvular problem
Bones-large joints and small joints polyarticular (more than 1)
-may cause post streptococcal reactive arthritis-small joints
46 yo male fatigue malaise, pain in both wrists and bl swelling over MCP (symmetry)
Decreased ins trength in both hands, swollen wrists, PIP, MCP nodule on extensor surface of left arm . What lab test think abnormal
Positive anti CCP elevated ESR and elevated RF
Joint fluid analysis normal
Clear viscous <200 cels
Non inflammatory joint analysis
200-2000 mononuclear cells
Inflammatory joint aspiration
2000-50000 cloudy inflammatory PMN
> 50000-septic(cloudy opaque)
Uric acid hyperuricemia
> 6.8
But not all get gout
20% america has high uric acid levels
DONT TREAT HYPERURICEMIA UNLESS REASON to treat, unless starting chemo-if starting chemo be ready to treat uric acid bc chemo can raise it pretty fast
Gout
Monosodium urate crystals in joint , 1MTP podagra nocturnal awakening
Lady-postmenopausal
What other joints with gout
Knee feet anky, hot swollen puffy and tender
Tophi-deposits under skin
Who gets gout
Men 40-60, post menopausal women
Alcohol
Treat gout
NSAIDS colchicine-GI toxicity, steroids
Xanthine oxidase inhibitor, uricouric drugs
Probenecid-block tubular resorption of urate and increased uric acid excretion
Radiography x ray
OK but not high degree sensitivity for erosions
Can show b/l of involvement but digital has higher resolution of spatial quality
Look fo b/l MCP, bone density, bone mass, and erosions (imply diseaseprocess active)
Not that great
US
Sensitive for soft tissue abnormalities (synovitis, tendinitis, bursitis) and erosions
Aid in injecting/aspirating joint
No radiation
Need if aspirate and inject joint
MRI
Good for ST and spine/SI joints, tenosynovial s, erosions, joint inflammation
Gadolinium contrast taken in inflamed synovial (thickened pannus) IV can cause nephrogenic systemic fibrosis in patient with kidney disease
CT
Best for bony abnormalities (trabecular, cortical bone), erosions, fractures, degenerative or inflammatory arthritis
CT good for bone erosions! Good image to use but
50 year old carpenter pain and swelling and decreased range of motion into e right elbow. The elbow is swollen and very tender. He hammers and lifts boards and sawing . What study . Fluid in it looks like fluid over that joint
Plain film-acute fall trauma
MRI-overkill
US-YES way to go bc noninvasive, fast for ST, if really want to confirm get MRI, but US best for St involvement particularly if fluid.
MRI ok but mroe expensive
CT-erosions
But now fluid from repetitive trauma US
If ESR high and factor sup
MRI but be cautious
Mono
One
Oligo
3 or less
Pauci
5 or less
Poly
Six or more
More migratory involvement
First MTP toe
Gout until proven otherwise
Could be pseudogout
Penis rash with arthritis
Reactive arthritis
Bowel arthritis
UC
Crohn more than US
Behcets-arthritis, ocular, genital , bowel symptoms diarrhea, bloody diarrhea
Reactive arthritis-bowel infection
Clubbing and arthritis
Intestinal lung disease until proven otherwise
Clubbing arthritis
HPO——-clubbing arthritis, and pulmonary
Nodules
RA/WG/paraneoplastic
Effusion
SLE/RA
Hilar nodes
Sarcoidosis RA, lymphoma
Infiltrates
Septic WG
Diabetes and arthritis
Charcots
Cheiroarthropathy
Thyroid and arthritis
Carpal/tarsal tunnel
Other endocrine and arthritis
Hyperparathyroidism-high Ca
Acromegaly-excess growth hormone and big bones high incidence of degenerative joint disease in hips and knees
Eye
RA, SLE, SS, PSS
RA is a disease of what
The synovial tissues it is inflammatory
Diartrhodial joints-easily movable ones and small joints over large joints
HLA RA-multigene
1/3 of patients have genetic susceptibility for developing RA
HLADRB4 allele increase susceptibility to develop. RA 60% chance of gettin RA
B cells make autoantibodies, cytokines THF a IL1 and IL6 cause synovial proliferation , increase synovial fluid and lead to pannus whic destroy cartilage and tissue in region
Pannus
RA
27 yo male pain in both feet and hands
L hand swollen warm and tender over PIP and MCP toes are sore on plantar flexion . Diagnosis and labs
RA
Reactive arthritis-predisposposition to larger joints
CRP, ESR, RF, ASO, ACA, ANA, CBC, uric acid
Could start out with plain films digital radiography but plain film so not super sensitive for erosions into joint
CT better for erosions
Treat
Steroid NSAID at first and DMARD
RA preg
Improved and flares 406 weeks post partum
Infections RA
Periodontal, EBV< paro virus, B19
Mortality of RA
Significant. Disables patiets and no perfect treatment
Mortality RA
Infection, renal disease, GI disease, HD< malignancy more so than general population for people with RA
Significant mortality
4 components of RA
Large glints, small joints, serology, symmetry, synovitis
At least one joint hot tender,
6/10 high probability RA
More points for small joints of inflammation
RA big or small joint
Small
C1-C2 RA
Has predisposition for RA but spares rest of cervical vertebra, thoracic and lumbar
RA and bone
Risk of OSTEOPOROSIS
If going ot surgery and general anesthetic tell them before bc sometimes C1-C2 vulnerable to flexion or hyperextension give heads up before intubation
Flexion contractures
RA
GEL
How long take to make joints loosen up bc worse in the morning with RA
Pyoderma gangrenosum
RA effect
Tender reddish purple papule that leads to necrotic, non healing ulcer
Lower extremity
Chancge from red to purple then to dark black necrotic on LE its nota venous stasis ulcer it is an inflammatory consequence of gangrenosum of the area
Rheumatoid vasculitis
Purpura and petechia at first then nail bed with splinter hemorrhages to digital infarct
Wha do
Check peripheral pulses on RA and look at feet and fingers
Heart RA
CAD , HF< pericarditis, CAD due to chronic endothelial inflammation
58 yo man cough and dyspnea on exertion medical history positive for RA for 10 years and smoking 1-2 ppd for 30 years . Chest x ray nodular opacity in both lungs and diffuse hyper lucency of lungs
Interstitial lung disease
Hyperlucency-dark COPD with smoking
Tests-chest x ray first then if abnormal CT, sputum culture for infection gram stain culture and sensitivity aerobic and anaerobic cultures, Tb test, PFt, bronchoscope with cytology and biopsy
Take home
Rheumatoid can have nodular disease in their lung dont know if all rheumatoid or other stuff
Caplan
RA nodule, pneumoconiosis with nodular opacities,
Silicosis
Lung RA
Pleuritis most common
Nodules
Caplan syndrome-nodular densities after exposure to coal or silica dust
Pulmonary fibrosis
Caplan seen in coal miners pneumoconiosis
36 dry mouth decreased testing and sandy feeling under eyelids, has bright light sensitivity and been treated her for RA for 5 years
SLE , HIV, Sjorgen-dry feeling YES , probably sjorgen from RA
Text
Ro-ssa, la-ssb, schirmers test, slit lamp test
Schrimers test
If lack of tears or dry eye put litmus paper under upper eyelid and close eyes for 5 min if see filter paper become wet then normal if filter paper not going down 10 mm that is positive lacrimal glands not working so has dry eye syndrome Sjorgen
Slit lamp
Make sure protect macula want to know
Treat sjorgen
Lube for eyes, oral hygiene encourage water
In 35% of RA autoimmune disorder with lacrimal and salivary dysfunction 90% of women
What eye part involved
Sclera is predisposed to vulnerability
Uveitis
Eye vulnerable to RA
Sjorgen
Dry eyes dry mouth
Felty
RA splenomegaly neutropenia fever anemia thrombocytopenia RF and aCCP
RA CA-C2
Subluxation due to erosion odontological process
__ single finding on PE or lab test is pathognomonic for RA
NO
Synovial flud of RA
2/3 PMN; wbc 5000-100000
Low blood glucose in RA
Idk
Treat RA bc its life long
Want remission rheumatologist, PT, OT, rest, Treat early to prevent irreversible cartilage and bone damage
Remission possible in 50% of patients
Treat
NSAIDS1
Glucocorticoids-low dose short time
Colchicine
Can use nsaids with dmards
Dmards-takes 2-5 months tow rok start within 2-3 months of disease MTX
Non biologics and biological DMAD
Start non biological-MTX then build from there
-always monitor for AE-look at white count, kidney, liver,
DMARDS
MTX< hydroxychloroquine, lufonemide, sulfasalazine
Hydroxychloroquiine-watch eye to protect macula of eyes can cause macular damage
Sulfa
Ok in preg
Biological
Work but toxic
Lower immunity and increase infection risk and toxicities -T, neoplasia, infection
TNF stoppers, etanercept, infliximab, adalimumab, rituximab they work
Seronegative spondyloarthropaties
Axial spine and SI joints!!! Fusion , rigidity/kyphosis
B27
Enthesitis-inflammation of insertion points of tendons and ligaments
Asymmetric peripheral arthritis
Ocular inflammation
Axial
Cranium and vertebral column
Enthesis
Site of ligamentous attachment to bone
Enthesitis
Inflammatory changes of the ligament, tendinous insertion into bone, or joint capsule
Oligoarticular
Few joints
Osteitis
Inflammation of bone
Periarticular
Around a joint
Spondylitis
Inflammation of vertebrae
Spondylolithesis
ANTERIOR DISPLACEMENT OF VERTEBRAL BODY RELATIVE TO ADJACENT
SPONDOLOLYSIS
DEFEC OF PARS OF VERTEBRA
Which arthritis is more female
RA
Seronegative
Mostly males
Ankylosing spondylitis
Axial
Symmetrical
Maybe eye
Enteropathy arthritis
Axial and peripheral
Symmetrical
Psoriatic arthritis
Axial and asymmetrical and peripheral
Asymmetrical
Course non marginal
Psoriasis
Reactive
Axial and symmetrical peripheral
Asymmetrical
Iritis and conjunctivitis, keratoderma
B27
Not positive 90% AS 80%REA ENTEROPATHIC SPONDYLITIS 75% Psoriatic spondylitis 50%
Not all are positive with it
28 yo male presents with a history of low back pain for 4 months, denies trauma, heavy lifting or unusual activity. He indicates the lower portion of the back over the lumbar-SI region, right side worse than left. He admit to morning stiffness. 9 lb weight loss, What should we ask
- Constitutional symptoms, anything help, exercise improve?(ank get better with activity)
- Plain fils of Ls and pelvis, if not supportive jump to CT of back, MRI is really good for SI joints and back, get B27, CRP, ESR
Ankylosing spondylitis
B27 cant diagnose, but can provide infor
Most common inflammatory disorder of axial skeleton* SI joints involvement **
905 have b27
Males more
20% have affected family member B27
2-3rd decade
Symptoms ank
Low back pain in morning stiffness and get better with activity
Fatigue, weight loss, fever
Symmetrical SI joint pain loss of mobility/flexibility; arthritis of hips
Tendinitis, plantar fasciitis(Achilles-heel pin)/enthesitis
Achilles tendinitis
Ankylosis spondylitis asymmetric in heels erosion of calcaneous from inflammatory component
Extra ocular ank
Scleritis , iritis, uveitis, photophobia
PE ank
Restriction to flexion of back with SCHOBER test stand up and drop down 5 cm below and 10 cm above and LS junctionask to bend over and measure distance between those if hasn’t changed Korea’s than 4 cm then restriction in bending
Fabere test-measure chest circumference inhale and see if change in that
Lab ank
ESR CRP
B27
Anemia
RF ACCO ANA NEGATIVE
SI joint x ray ank
Whitening sclerosis
More dense more hard
Syndesmophoytes
Bridging of vertebra causing ankylosis
Straightening of vertebra with white density
Yes
Tests
CT for erosions
MRI inflammation before changes seen on C ray and CT
Ank differential DISH
Diffuse idiopathic skeletal hyperosteosis-calcification of ligaments from one vertebra cause restriction motion in back but SI joints are ok
Calcification of 4 continuous vertebrae
Osteitis condensans illi and not ank
Young middle age females
Normal si joints x ray shows sclerosis on iliac side of SI joint
Cause equina from ank
Late complication, bowels bladder and low back pain and host of other bowel related issues, paresthesia, cant feel when have a bowel movement, bladder dont know start or stop or empty.
Kyphosis
Ank
Loss lumbar lordosis, flexion knees, severe kyphosis
Ank
Young men, insidious onset, hurting for months, morning stiffness better with activity and positive family history , better with activity, osteoarthritis does not
Treat ank
Stay mobile, PT, swim, NSAIDS< TNF inhibitors, non biologics DMARDS/
NSAID help ain but not process
26 yo male with pain swelling and warmth in right knee. Onset 2 weeks prior to office visit. Pain in ACL tendon and sore soles and sore soles of feet, tendons hurt feet hurt and knee hurt. No eye pain, rash, or urethral discharge
Aks-when worse better, trauma, sexual history, GU GI tract, oral ulcers, penile rash, IV drug, venereal disease, enteric pathogens (can cause reactive arthritis),
Reactive arthritis
REA
Autoimmune disease; asymmetric monoarthritis or oligoarthritis in lower extremities
Infection from GI/GU
Salmonella, shigella, yersinia, campylobacter jejuni, chlamydia (this one GU)
B27 in 75% of ReA and IBD
Reactive
Arthritis-asymmetrical, oligoarthritis, lower extremities
Enthesitis-Achilles tendon/plantar
Dactylitis-sausage fingers
Asymmetrical SI
Reiters triad
Urethritis, arthritis, conjunctivitis/uveitis
Can have sores in mouth circulate balantitis on penis, keratoderma blennorhagicum-painless eruption on palms and soles pustular
Lacs ReA
Same AS
WBC 2000-50000 PMN
Imaging-SI asymmetric
Differential for ReA
GC Sepsis ReA HIV Endocarditis Viral infections -parvo
Reactive arthritis
Fever, fatigue, anorexia, asymmetric, inflammation toes fingers dacytlitis, low back pain, skin lesions, ocular, nonspecific inflammatory markers
Treat ReA
Resolve in a few months
NDSAID steroids, supportive, if chronic use DMARD
Urethritis-chlamydia, azithromycin Or doxycycline
Psoriatic arthritis
5-205
20-50% B27
Associated with SI and axial involvement
DIP, PIP, MCP, MTP also large joint,
Pitting nails, dactylitis, enthesitis, C1-C2
PSORIAtIC SKIN lesions
Pencil in cup
DIP narrowed joint space and condylar erosions
Reactive sub periosteal new bone
Pencil in cup appearance
Ankylosis if SLE joint space
Treat
NSAID pain
Dmards
Biologics
ENTEROPATHIC arthritis
1:1 male female
UC CD
Axial involvement like as but asymmetric SI joint
Parallels activity IBD, if arthritis acting up so is IBD
Large joints lower ex, small joints upper extremity
Extramanifestations more common in crohns than UC
Cutaneous
Pyoderma gangrenosum, erythema nodosum, uveitis,
Treat
Manage inflamed bowel and steroids, DMARDS, tnf alpha
Problem not a lot are handed well orally so try
Gout
Uric acid crystals engulfed and attached to synvium macrophage and inflammatory cascade and underlying etiology of all of these components to cause inflammation in joint
Acute gout
Hope red warm tender swollen
Red meat, sea food, purine, alcohol, trauma, seasonal weather extremes, dehydration, excessive exercise
Chronic ethicists
Tophi (ears, forearms, Achilles’ tendon
Renal insuffiency , radiolucent
Kidney stones gout
Uric acid
Treat gout
No best
Do not treat asymptomatic hyperuricemia
Exception-about to receive cytotoxic therapy for neoplasm
Chemo
Lysecells and increase uric acid
Drugs
Allopurinol
Uric acid inhibitor
As ingest purine get hypoxanthine
Uric acid deposited in joint or excreted in urine
Probenecid
Increase excretion
Colchicine Or NSAIDS
Inflammation inhibited
Acute treatment
NSAIDS, naproxen/indomethacin
Inc risk GI bleed/ulcer/renal disease/fluid retention/interfere with anticoagulant/HF/HT
Watch gi and kidney of nsaids
Steroids-reasonable , safe effective anti inflammatory and taper
Colchicine
Effective GI AE, liver an renal
Effective if given in first 24 hours
GI SIDE EFFECTS but worlds
Biologics
Inhibitors Il-1B antagonists anakinra for acute gout!
When put on uricosuric agents
Kidney stones, cutaneous tophi
Xanthine oxidase inhibtiors, uricouric acids (probenacid)
Pseudogout
Calcium pyrophosphate
Large joints, older, polyarticular,
Chondroma Lino’s is-calcium deposits in articular cartilage
CPPD crystals
Short blunt rods, rhomboid/cuboid
Weak positive birefringence by polarizing microscopy
associated with aging
Younger-primary hyperparathyroidism, hemochromatosis, hypomagnesemia, chronic gout, gitelman syndrome
Needle
Gout
Rhomboid/cuboidal
Pseudogout
Treat
NSAID steroid colchinie
Same treatment
Most common arthritis
OA prevelance our obesity and aging
Most common cause of disability to LE world wide
OA
OA improves with
Rest
Worse with activity and repetitive motion
Hurts a the end of the day
Destroying hyaline articular cartilage type II collagen and getting sclerosis at the joint and hardness and areas of granulation tissue
IB and TNFa that drive tissue destruction
Enurbation bone on bone joint mice no cartilage to cushion
Joints of OA
CMC 1st, DIP PIP, knees hips spine
Older
Spondylosis OA
Spine can lead to spinal stenosis
Crepitus
Decreased rang of motio effusion
COOL EFFUSION!!!!!!!
Cool to touch
OA
Effusion
OA
Bony outgrowth over DIP areas
Lose joint space and bone on bone
OA
Bone spur
OA
Most common OA
Cervical, lumbar spine, 1st cmc, pip, dip, hip, knee, 1st MTP
Labs OA
ESR up but WBC<2000 nothing diagnostic
Radiographically hallmarks OA
Asymmetry, narrow joint space, subchondral sclerosis-thickening, osteophytes and marginal lipping, bone cysts, joint mice
Joint mice
Gritty sensation
Most common OA
Idiopathic primary cause
Erosive OA
DIP and PIP more pain than typical hand of OA
PAIN
Women
Central erosions seen on radiography with seagull appearance in fingers
Pain out of proportion
Secondary OA
Underlying disorder
Trauma, infection, hemochromatosis, congenital joints like hip dysplasia
Charcot joints
Diabetics lose architectural function of joints. Joints are distorted and abnormal and lose pain sensation and position sense and really disfiguring architectural distortion
Osteonecrosis
Avascular necrosis blood supply gone -steroids cause this
Manage OA
Start immediately
Lose weight
Oral, NSAIDS< steroids, analgesics , surgery
Glucosamine and chondroitin failed to show efficacy for pain relief
Indications for an EDX consultation
Motor neuron, nerve root, plexus, peripheral nerve, neuromuscular junction
Symptoms of neuromuscular
Numbness or tingling, decreased sensation, pain, cramping or spasm
What is EMG
Test integrity of PNS
NCS-nerve conduction studies
EMG electromyography
How do NCS
Peripheral nerve stimulated with electrical stimulus and responses are recorded
Compound motor action potential (CMAP)
Sensory nerve action potential (SNAP)
F wave
H reflex
Three things measure emg
Latency, size of response, speed with which travels
Motor latency
Measure of conduction time from stimulations cross a nerve segment through the neuromuscular junction to initial activation of msucle fibers
Motor amplitude
Measure of the number of activated msucle fibers
Sensory latency
Measure of conduction time of action potential from stimulations cross a nerve segment
Sensory amplitude
Measure of the number of activated sensory axons
Conduction velocity
Measure of the velocity of the fastest conducting axons (motor and sensory)
Guillane
Loss myelin focal
Can see change in amplitude or configuration of amplitude of conduction block
Needle electromyography
Needle electrode inserted into msucle
Multiple msucles are accessible for exam
Combination of msucles tested which is dependent on clincal question
Level of discomfort is mild
C6-deltoid, brachioradialis and biceps
Study msucle at rest then have patient activate it a bit then exert full strength
Look at pattern
Needle electromyography
What evaluate with needle
Insertional activity
Spontaneous activity
Motor unit configuration
Motor unit recruitment
Interference pattern
Insertional activity
As soon as put in injur and see and hear burst of activity soon goes away then see nothing
Spontaneous activity
Fibrillation, positive sharp waves, fasciculations
Interruption in nerve supple to msucle that is not insertional
C6-see deltoid, biceps and brachioradialis see breaks
Hallmark of issue
Abnormal spontaneous
Positive sharp wave and fibrillation
1-4
0-no fib
+/1 fibs/PSW not persistent
1 persistent Fibs.PSE in at least 2 areas
2…….
Motor unit configuration
Muscle is volitionally activated at different force levels
Single motor
Then whole motor
Decreased recruitment
One unit recruited
Increased amplitude
Ok
Increased duration
Most short can be long
Polyphasic
Many turns in a motor unit
What is reduced recruitment, increased amplitude, increased duration, polyphasia
Insult and healed!
Anterior horn cell disease (motor neuron disease. Tell me about anterior horn
C6-several motor neurons contribute to that nerve
Dirosder of degeneration of motor neurons in spinal cords with or without lesions in lower brain and long tracts
Characterization anterior horn disease
Progressive wasting and weakness of the affected muscles without accompanying sensory, cerebellar or mental changes
Sensory cerebellar or metal changes with motor neuron
NO just msucle
Idiopathic mTOR neuron disease
Adult and child
ALS
Causes other
Toxins like heavy metals, polio, west Nile, HIV, a glucosidase defiency, remote effect of cancer, thyroid, POMPES disease
Amyotrophic lateral sclerosis
Most common
Progressive bulbar palsy
1/3
Progressive spinal muscular atrophy
5-10
Primary lateral sclerosis
<5%
Variant rare motor neuron disease
Brachial amyotrophic diplopia Leg amyotrophic diplopia Isolated bulbar ALS Monomelic amyotrophy Hirayama’s disease Familial or associated with other neurodegenerative disorders
Amylotrophic lateral sclerosis
A-without Myo-muscle Tropic-nourishment Lateral-side Sclerosis-hardening or scarring
Nerve gives neourishmet
Who gets ALS
Males
Signs ALS
Mixed upper (spasticity, hyperflexia, babinski sign)and lower motor neuron signs (atrophy, fasciculations)
May also be bulbar involvement of the upper or lower motor neuron type
MIXED SIGNS-
Risk factors ALS
Nope
Fasciculations
Muscle twitch
ALS is espicially in _____
The same limb with mixed upper and motor neuron signs
Arm patchy msucle atrophy and fasciculations and check reflexes and hyperreflexive which dont go together
Pathophysiology ALS
Degeneration of beta, lower brainstem, descending Corticospinal tracts, and anterior horn cells
Etiology unknown -cause
Enterovirus D68 myositis flaccid in kids
Clincal picture ALS
> 50 hand clumsiness or impaired dexterity with mild wasting/weakness hand writing worse,
Spread to other limbs and leg involvement
Bulbar sucks involved
Atrophic hands, atrophic tongue tongue fasciculations
Anterior horn cells white
Sclerosed
Diagnose ALS
Spinal fluid normal
EMG-enervation and reinnervation widespread*****
Urine for heavy metals serum but not now unless reason for it
CPK normal or up
Imaging-brain , spine-normal
HIV
Muscle biopsy-only needle in confusing cases
Pertinent negatives
No story issue Normal mentally No extraocular muscle involvement Bowel or bladder symptoms not prominent Decubitus rare Fasciculations rarely the presenting symptoms
Prognosis ALS
No remission, progressive, death from respiratory failure, 4 years symptoms, dead 2-5 years, s
Treat ALS
Supportive
Rilutek-somewhat helpful in ppl with a lot of bulbar, a glutamate inhibitor EXPENSIVE
Progressive bulbar palsy
Presenting symtpoms in 20% of MND
Selective involvement of the motor nuclei of the lower cranial nerves
Tongue, swallowing, respiratory
Symptoms progressive bulbar palsy
Dysarthria, dysphagia, dysphagia, chewing difficulty, drooling respiratory difficulty
Usually progress to ALS but better life span
Progressive spinal muscular atrophy
5-10%
Males
64
Lower motor neuron deficits predominate from degeneration of anterior horn
No upper motor neuron invovne t
Symmetric upper extremity involvement
Weakness, atrophy, respiratory
Can become ALS but longer live
Live 15 years
Primary lateral sclerosis
2-4%
50-55
Upper motor neuron Corticospinal tract
Spasticity, hyperreflexia, babinski,
Slow progression but can become ALS
Survival better than als
Acquires MND
Polio, West Nile virus, HIV, post polio, Hopkins syndrome (follows asthma attack, usually one limb), heavy metals lead mercury, enterovirus D8 acute flaccid myelitis in kids
Associated with other neurodegenerative disorders
Familial western pacific(dementia-ALS compelx of Guan) blah blah
Infantile spinal muscular atrophy
Hypotonic, arreflexia, poor suck, breathing difficult, death in 6-12 months
Intermediate spinal muscular atrophy
Ok
Juvenile muscular atrophy
Milder than werdnig Hoffman
Peripheral neuropathy
Common
Diabetics-numbness tingling in feel
Carpal tunnel
Pinched nerve radiculopathy in back
Epinephrine perineureum endoneureum
Out ot in
Blood supply to nerve
Vaso vasorum
Where injure nerve
Cell Boyd, nerve root, plexus, peripheral nerve
Wallerian degeneration
Severed distal goes away
Segmental demyelination
Gillian demyelinating not uniform different never different places
Axonal degeneration
Nutrients/
Radiculopathy
Root where exits spinal cord
Single spinal nerve innervates
Dermatome
Myotome (group of muscles-C6 deltoid, biceps and brachioradialis)
Sclerotome-area of bone supplied by a single spinal root
L5
Head of femur
L4
Across knee
Radiculopathy
Nerve root dysfunction from structural or not (DM infections)
C5-C6
C6 nerve root compression
C6-C7
C7 nerve root compression
L4-L5
L5 nerve root compression
L5-S1
S1 nerve root compression
C5
Scapula shoulder pain
Lateral arm sensory
Weak shoulder abd
Lose biceps DTR
C6
Pain-scapula shoudler
Sensory 1st and 2nd digit lateral arm
Shoulder abd and elbow flexion weak
Lose biceps DTR
Cy
Pain-scapula shoulder arm elbow forearm
3rd digit sensory
Weak elbow ext and wrist ext
Triceps DTR loss
C6
Deep pain in forearm
C8
Pain-scapula shoudler arm medial forearm
4th 5th digit sensory
Weak finger abd and flex
DTR loss finger flexors
C7
Feel tight band around elbow
L4
Pain anteriolateral thigh knee and medial calf
Sensory medial calf
Weak hip flexion,
Loss patella DTR
L5
Pain dorsal thigh and lateral calf
Sensory lateral calf and dorsum of foot
Weakness hamstring, foot forsiflecion, inversion, eversion
No DTR loss
S1
Loss posterior thigh and calf
Sensory postlateral calf
Last foot
Weak hamstrings and foot plantarflex
Achilles reflex loss
L4
Pain band around knee
C6
Thumb index finger
C7
Middle finger
C8
Fourth fifth
T1
Medial forearm
T4
Nipple line
T10
Umbilicus
L1
Inguinal
L4
Medial calf
L5
Lateral calf
Brachial plexopathy
Routine nerve conduction not adequate to make diagnosis
paraspinal msucles must be examined
Sensory are abnormal
Rhomboids and serrated anterior may identify proximal lesions
SNAPS abnormal plexopathy
Vs radiculopathy
Bc peripheral nerve!
Brachial plexopathy
Compression or stretch injury
Inflammatory/idiopathic
Radiation injury
Neoplastic
Traumatic injury
Ischemia
Radiation injury
Upper trunk, lateral cord, painless
Neoplastic
Medial cord painful (breast lun tumor)
Traumatic injury
Traction, laceration missile
Ischemia
Diabetic usually lumbar
Parsonage turner
Unknown etiology, probably autoimmune as it often follows infections, vaccinations, surgery
Clincila parsonage turner
Severe pain in shoudler area followed within a few days by weakness and atrophy (as the pain subsides) usually involving msucles of the shoulder girdle
Course of parsonage turner
Spontaneous recovery in 6-18 months; steroids are helpful
Peripheral neuropathy
Mononeuropathy, polyneuropathy, mononeuropathy multiplex
Mononeuropathy
Single nerve
Polyneuropathy
Diffuse, symmetrical, motor and sensory
Mononeuropathy multiplex
Several single mononeuropathy
DM
Symptoms peripheral neuropathy
Loss of sensation
Paresthesia-secondary to large myelinated fiber disease “pin needle:
Pain from small unmyelinated fiber
-burning
Dysestheia
Hyperalgesia
Hyperpathia
Motor signs peripheral nerve
Weak, atrophy, crampons, fasciculations, decreased DTR, reduced tone
Large fiber
Decrease vibration and joint position sense, areflexia, ataxia, hypotonic
Tingling pin needle numbness
Small fiber
Decrease pain and temp
Burning jabbing
Autonomic
Hypotension decreased sweat, impotence, urinary retention, constipathion
Hyperhydrosis, urinary frequency
Large myelinated fibers
Light touch cotton swab
Two point discrimation
Vibration*
Joint position sense*
Small unmyelinated
Temperature perception
Pain perception with pin prick
Motor test
Atrophy weakness, depressed DTR, cramps, fasciculations
Upper motor neuron
Spastic, normal bulk, weakness atrophy , hyperactive DTR, babinski sign
No fasciculations
Lower motor
Hypoactive, hypotonis decreased reflexes
Distal Flacco’s atrophic fasciculations
No sensation whole right side
Upper motor
Mononeuropathies
Dermatomes ,
Or skin look at for innervated by a peripheral nerve
Nerve root peripheral nerve
Nerve root dont split digits peripheral nerve do
Median nerve pierces ____
Pronator teres can pinch there
Median nerve and brachial artery pass below what in 20%
Ligamentum struthers can get pinched if have
Pronator syndrome
Insidious onset of diffuse/dull ache about the proximal forearm
Pain with forced forearm pronation
Easy fatigue o the forearm muscles
Diffuse numbness of hand mostly involving the 2nd and 3rd fingers
Absence of nocturnal awakening bc of pain or numbness
-wrist down in pain sensory weakness
Anterior interosseous syndrome
To long finger flexors
Ok sign
Can’t flex distal phalanxes
Now ensory loss
Ulnar
Axilla elbow-between medial epicondyle and olecranon
Cubical tubule-between tendinous arch of FCU
Wrist-guyon canal
Ulnar elbow EMG
Abnormalities in 1st dorsal interosseous Abductor digiti minimi Adductor polices Flexor carpi ulnaris Flexor digitorum profundus
Transition around elbow disturbed
Froment sign
Can’t adduct thumb it is an ulnar neuropathy cant grab sheet of paper end up using distal thumb to pinch paper
Radial mononeuropathy
Axilla-crutch palsy
Saturday night palsy
Supination
Wrist
Edx features Saturday night palsy
Radial motor and sensory studies often normal
EMG findings in extensors of wrist and digits and perhaps brachioradialis
Perineal
Fibular neck
Leg crossing , squatting
Foot drop weak evertors, sensory loss in dorsum of foot
Sciatic
Sciatic notch, hip , piriformis muscle
Pain down lateral thigh, footdrop absent ankle jerk
Mainly L5-but L5 weak inversion and eversion! Distinguishing
Posterior tibial
Medial amlleolus
Muscle edema
Ankle fracture, tenosymovitis
Sensory loss sole of foot
Last fem cutaneous
Inguinal ligament
Tight clothing weight gain
Sensory loss in lateral thigh
Just sensory pinch over pelvic brim with belt
Peroneal mononeuropathy
Stimulation at ankle toe twitch
Below knee same
Above knee-drop in amplitude
Needle-abnormalities in Tb ant, EHL, EDB, PL, TBI post and SHBF are normal
Peripheral neuropathy
Usually symmetric, may be motor, sensory, autonomic or combination
Progressice, but not always
Acquired or inherited
Motor peripheral
Weak, atrophy, hypo arreflexia, cramps, fasciculations
Sensory
Large-position vibratory
Small-pain/temp sense
Distribution peripheral neuropathy
Stalking destruction
Pain sensory loss weakness symmetrical and most usually distal portions of limbs
Legs affected first and more severely that arms
STOCKING GLOVE
Causes peripheral neuropathy
MANY
Hereditary, metabolic and endocrine, infections, immune, defiency, toxins, drugs, vasculitis paraneoplastic, idiopathic
Metabolic/endocrine
DM, thyroid uremia, porphyria
Defiency
B1, 6, 12, E, copper
Toxins
Alcohol metals, n-hexane, organophosphate
Drug
Vinca alkaloids, phenytoin, isoniazid, amiodarone
Cisplastin, nitrofurantoin and a host of others
Vincristine
Peripheral neuropathy
B12 defiency
Combined systems degeneration
Dorsal column, Corticospinal tracts (lateral and ventral)
Neuropathy, babinski
Lose reflexes, babinski is from Corticospinal tract dysfunction,
Depressed reflexes but babinski!
How test b12
Romberg
For position sense
Vasculitis peripheral neuropathy
RA, SLE, polyarthritis nodosa
Paraneoplastic peripheral neuropathy
Before, during after tumor
Pure sensory (dorsal ganglionopathy)
Check for antibodies
Pure sensory polyneuropathy
Rare-considered sensory ganglionopathy
- paraneoplastic
- toxins(platinum Cisplastin)
Small fiber polyneuropathy
Pain burning dysesthesias, paresthesia, temp sensation prob
Decreased pin prick and temp sensation
Dysesthesias to light touch
Normal strength reflexes, proporioception, vibratory sensation
EMG/nvc normal
Diabetes
Most common cause neuropathy
-distal sensorimotor neuropathy stocking glove
But can cause cranial nerves-III most common but VI)
Nerves not operating optimally bc of DM and glucose metabolic abnormalities any little disruption may be magnified -carpal tunnel and facial neuropathies
Lumbo-sacral, radiculopathy
Hereditary neuropathies Charcot Marie tooth neuropathies
Type I and II
HMSN1
Most common demyelinating
HMSNII
Axonal
HMSNIII
Hm
HMSN(
AD 10-20 with difficult walking or running just clumsy
Distal symmetric atrophy legs>arm
Arreflexia
Mild sensory loss
Skeletal deformities (high arch hammer toe scoliosis)
EMG uniform slowing of Moro’s nerve conduction (demyelination )
HIGH ARCH HAMMER TOE
HMSN II
AD adulthood Distal symmetric atrophy Motor nerve legs>arms Arreflexia Axonal not myelin EMG is normal or nearly normal
Fairy
A galactosidase defiency
Kidney problems
Hereditary polyneuropathies
Metachomiatc leukodystrohy
Arylsulfatase a defiency
Polyneuropathy
Refusumdisease
Big orange tonsils
Phytanic acid storage disease
Tangier disease
Defiency in HDL hereditary polyneuropathies
Acquired demyelinating polyneuropathies
Acute-Gillian barre
Chronic-inflammatory demyelination polyneuropathy
Gillian barre
Acute/subacute ascending paralysis
Antecedent illness, surgery, immunization
EBV, mycopalsma, campylobacter
HIV hodgkin can mimic
GB onset
Low back pain radiating down legs
Ascending from feet
Hypo or absent DTR
Minimal sensory signs
Possible respiratory failure, autonomic involvement
Nadir-4-6 weeks improves over weeks
Big problem GB
Respiratory insuffiency
Lab GB
Spinal fluid increase protein normal cell and glucose
NCV-slow conduction velocity, focal conduction block, prolonged F waves
Issue GB
Support and pay attention to swallowing, respiration, CVD, infection, DVT
Treat GB
IVIg
Prognosis GB
90% recover weeks to months
Some die, disables, lots have persistant fatigue with extremes of acute tivity
If emg shows axon involvement those areas get poor prognosis
Miller fisher
GB
Kids
Ophthalmoplegia, ataxia, areflexia,
Facial weakness, dysarthria, dysphagia also possible, GQub and GT1a antibodies
Acute motor axonal neuropathy
GM1, GM1b, GD1a antibodies
Acute motor and sensory
GM1, GM1b, GM1a
GB antibodies
None associated but variants do
Chronic inflammatory demyelinating polyneuropathy
Similar to GB but slower and more persistent >2 months
Progressive or relapsing
IgM Ir IgG
Treat with IVIg, steroids, plasma exchange, immunosuppression
May occur de novo or as sequelae of GBS
Multifocal motor neuropathy
Mimics peripehral but different
Slowly progressive distal weak
No UMN or sensory
GM-1 antibody ad emg show conduction block or focal demyelinating features!!!!
IVIg
HIV neuropathies
Distal symmetrical polyneuropathy
Blood tests
CBC, chemistry panel, fasting blood glucose, ESR< ANA, RF< thyroid function
Basophils stippling, IEP, B12 folate
Systemic vasculitis
AANCA
MGUS
Anti MAG
Multifocal motor neuropathy
Anti GM1
Heavy metal
History of exposure
Skin biopsy
Small fiber neuropathy
EMG.ncv
Rarely specifi except GBS, CMT1, MMN
Presynaptic
Lambert eating Botulism Steroids Mg Black widow Congenital myasthenic Aminoglucosides Tetanus Tick paralysis A aminopyridine
Synaptic
Oraganophosphates
Edrophonium
Neostigmine
Congenital
Post synaptic
Myasthenia
Myasthenia
Defect in neuromuscular transmission antibody to Ach receptor on membrane
Etiology myasthenia
Not sure most sporadic but high frequency of HLA haplotypes B8 DR3
Seen with other autoimmune SLE RA thyroid
Incidence
All age group but young women old men
Characteristics myasthenia gravis
Fluctuating weakness-ptosis, dyplopia
Clinical response to cholinergic drugs
*my eyelids droop when I’m driving and squinting then in shade see droopy and i see double later in the day
Achietylcholinesterase
Clincial history and exam myasthenia gravis
Acetylcholine receptor antibodies
-MUSK antibodies
EMG myasthenia gravis
Decremental response on repetitive stimulation increased jitter on single fiber EMG
Tension
Edrophonium test
Positive in >90% of patients
Side effects edrophonium
Bradycardia, ventricular arrhythmias,
Antibody negative myasthenia
Many will have MUSK antibodies
Normal have antibodies to achR
EMG myasthenia
3 shocks per second see normal reproducible responses look identical even
Myasthenia each shock get decrease in force of contraction and bigggest between 1st and 2nd
DECREMENTAL RESPONSE
Give tensiolon
The ptosis is gone! That’s the tension tests
Lasts 10 minutes then ptosis comes back but can run into problem ith ventricular arrhythmias
Treat myasthenia gravis
Acetylcholinesterase inhibitors (mestinon)
Prednisone
Immunosuppressive agents
Plasma exchange/IVIg
Thymectomy probably helpful but without thymoma not indicated
What drugs exacerbate or unmask myasthenia gravis
Neuromuscular blockers-succinylcholine, pancuronium
Excessive anticholinesterase medication
Corticosteroids and ACTH-usually with high initial dose
Thyroid supplements
Mg salts-
Antiarrhythmic-lidocaine, quinine, procainamide, verampamil, b blockers
Antibiotics-aminoglycosides
D penicillamine-may cause antibodies and stop antibodies go away and so does MG! Can get antibodies produced but not have myasthenia gravis
Antibody myasthenia
10% no anti AcHR
40% MUSK
MUSK
Occulopharyngeal weak
Neck shoulder respiratory weakness
Indistinguishable from antibody from positive MG
Treat myasthenia gravis
Poor response to anticholinesterase medications
Lambert Eaton
Autoimmune to voltage gated
SCC, breast ovarian
Clincila lambert eaton
Proximal weakness, loss of deep tendon reflexes, myalgia, dry mouth, impotence,
Oropharyngeal and ocular muscles may be mildly affected but not to the degree in MG
Strength improve after exercise
May see slight response to tensilon
Bulbar and ocular
MG
Office test MG
Eye lids droop
Hold arms out and have them look up at finger do it for a minute
When minute it up i want you to keep arms up and shift eyes to finger
MG-they will gradually sag as msucles fatigue see ptosis !
Antibodies lambert
VGCC antibodies in most
EMG lambert
Low amplitude response increase with brief exercise
Incremental response on fast repetitive stimulation
20 shocks per second lambert 50
BUILD UP!
Treat lambert eaton
First look for malignancy
Acetylcholinesterase inhibitors-mestinon
Amifampridine
3-4 diaminopyridine helps most but AE
Guanosine hydrochloride helps LEMS but AE
Immunosuppression
IVIg
Botulism
Blocks presynaptic Ach release
Mg to lambert eaton? NO Mg is +2 and Ca is +2 so Mg interfere with Ca influx at presynaptic terminal and make worse
Clincial botulism
Dry, sore mouth , blurred vision, diplopia, nausea, vomiting hydros is, total external ophthalmoplegia, facial oropharyngeal limb and respiratory paralysis
Treat botox
ICU monitoring with respiratory support and general medical care
-antitoxin (horse serum product which may cause serum sickness or anaphylaxis)
Guanidine hydrochloride (AE bone marrow suppression)
Nerve gases
Organophosphate terrorist
Easily vaporized
Block acetlycholineesterase and overstimulation of end organ-cholinergic crisis can be to vapor or liquid
Onset is fast
Miosis, increase secretions, bronchospasm, abdominal cramps, NV, diarrhea, HR, BP,
Death by respiratory failure
Treat nerve gas
Decontamination-remove clothiers, clears skin with water and Nahypochlorite
Respiratory support
Atropine
Seizures
Connective tissue disorders
Ok
22 yo arthralgia ANA 1:160 titer with a homogenous diffuse staining pattern
She might have an autoimmune process as the etiology for her symptoms
ANA
Non specific
1:160 ratio ANA
High so probably autoimmune process going on
Homogenous diffuse staining pattern ANA
Everywhere
7 yo female spot on face been there for a couple of weeks
Localized scleroderma
Discoid lupus what look like
Ring worm
Got centralized area nothing going on raised ring
What is this localized lesion called
Morphia-benign localized area of fibrosis wont progress or get worse typically in kids
55 yo increased dry eyes, bl facial swelling, dry mouth, what most likely at risk of developing
Oral candidiasis
Sjorgen
Libyan sacs
Lupus
Esophageal adenocarcinoma
Diffuse sclerosis can lead to GERD-barret-esophageal adenocarcinoma
Gastric antral vascular ecstasia
Diffuse scleroderma
Pulmonary artery HTN
Limited scleroderma
Intestinal lung disease
Diffuse scleroderma
50 yo caucasion with malaise severe neck and bl shoulder stiffness and pain all day long but more in morning, weaker and cant comb hair, 7lb weight loss past 3 months, ESR up, CK normal
Temporal arteritis
Polymyalgia rheumatica
Polymyalgia rheumatica
Pain makes them feel weak
*normal msucle strength but feels weak be of all the pain
Smoking history
RA
Thromboangiotis obliterrans
Primary raynaud syndrome
Hyperresponse to emotion, cold no underlying pathology
BENIGN
Secondary raynaud
Secondary to scleroderma of CT process
Hep B
Polyarthritis nodosum
DVT
Factor V Leiden
Antiphospholipid
Lupus
Berchets-oral genital ulcer uveitis DVT!
25 yo joint pains med student 3rd year had positive PPD and quantiferon gold put on isoniazid and B6. What serology seen
Histon Ab- she has drug induced lupus from isoniazid
DsDNA
Lupus
Anti Sm
Lupus
Centromere
Limited scleroderma
Scl70
Diffuse scleroderma
37 black chest pain worse on respiration, left leg swollen , tired and 10 lb weight loss, history and psychotic episode, red hot swollen red lower extremity, bicytopenia, anemia and thrombocytopenia, DVT . ECG sinus tachycardia
Lupus-bc cotton wool spots, thrombocytopenia, neuropsych manifestations, african American, no insurance, DVT-antiphospholipid antibody
VDRL
Chest pan in lupus-
PE orpleuritis
If lupus heart pain change position and ECG diffuse St segment changes
Pericarditis
Sinus tachycardia
PE
Ecgcyclic citrulinated
RA
Topoisomerase I Ab
Diffuse scleroderma
Histone ab
Drug induced lupus
Centromere
Limited scleroderma
VDLR
Lupus
Best management plan for her Lupus DVT
Hydrocychloroquine (mainstay treatment for lupus) and warfarin (for the DVT)
When give warfarin
Bridge with enoxaparin (a low molecular wight heparin) until warfin is in therapeutic range
Warfin on own-prothrombotic
Amlodipine
Ca channel blocker
Raynaud
Omperazole
GERD from diffuse scleroderma
IVIG and high dose Asprin (ASA)
Kalasaki
Stop smoking
RA
Bergers (thromboangitis obliterrans)
50 year old african American hashimoto thyroiditis, ANA and ds DNA , abdominal pain
SLE
Interstitial lung disease
RA, diffuse scleroderma(cause of mortality!)
Pulmonary artery HTN
Limited scleroderma (cause of mortality)
Intestinal angina
Post or dial intermittent abdominal pain
Lupus but not cause of death
Seizure disorder
Lupus but not cause of death
Atherosclerosis
Cause of death SLE-HIGH RISK HEART ATTACK SO MODIFY ALL RISKS FOR ATHEROSCLEROSIS!!! Blood lipids, exercise program,
45 yo white female facial numb right sided weakness ischemic stroke, no meds, vitals normal, serology and Smith, dsDNA and antiphospholipid
RRR murmur, valve thickening and Cerritos valvular
Libyan sacks endocarditisfrom lupus
Normal lipids and vitals bc ischemic stroke is usually froma. Vascular disease of atherosclerosis in HTN hyperlipidemia
Infectious endocarditis
Blood cultures
Murmur stroke valve lesion
Libyan sacks
What murmur libman
Mitral regurgitation
Pericarditis
Lupus with positional changes and ECG elevated st
Rheumatic heart disease
Can cause endocarditis mitral valve
No recent sick so not it
Need receipt strep
Persistent a fibrillation
Can cause stroke
Which h/o bipolar disorder joint pain episodic chest pain and speckled pattern ANA and malar rash which serologic test correlated with disease state
Anti dsDNA -is what monitor for disease process and treat work
Sm and dsDNA both go with lupus
CK up
Dermatomyositis polymyositis
IgA deposition
Henoch s purpura
Best preventative manage lupus
Ok
Is my hydroxychloroquine working
Use dsDNA
Dentist
Sjorgen risk infection and carries
Set up EGD appointment (endoscopy)
Scleroderma
CREST=carcinom is raynaudys esophagility dysmotility sclarodactyly and telangiectasia ESOPHAGEAL can lead to gerd and stuff
EDG diffuse scleroderma
GERD barrett to adenocarcinoma
Gastric antral vascular ectasia if irony efiency anemia!!! EGD
Order PFT
Diffuse scleroderma bc has interstitial lung disease
Schedule an echo or influenza vaccine for SLE
Influenza *** vaccinate, stay away from sun, regular cancer screening
Echo-pericarditis->tamponade or effusion or show libann before manifest -need something to order echo BUT echo can be preventative
Echo preventative in which scleroderma
Limited bc of pulmonary artery HTN and if echo PFT no good right heart cath
43 yo african American female no insurance fibrosis and necrosis several fingers sometimes food catches in throat
CREST
Dilation of small vessels causing focal red lesions
Strawberry tongue
Kawasaki
Purple red rash on eyelids
Heliotrope rash with dermatomyositis
Proximal muscle weakness
Polymyositis, dermatoymositis, polymyalgia rheumatica (not true weakness)
Parotid gland big
Sjogrens mumps infection
Crest
Limited scleroderma
29 yo Hispanic female arthralgias and depression C3 and C4 low and ds DNA and renal insuffiency
Type III hypersensitivity
Lupus
Hep B
Hep B with polyarthritis nodosa
Screen for cervical cancer
HPV , dermatomyositis typically look for occult malignancy if present dermatomyositis
Ovarian, cervical bc age , any cancer starting with age and risk factors
Tanning bed treatment
No lupus decrease sun exposure
Heliotropes rash
Dermatomyositis
45 yo white female finger stiffness hard white nodules at times go blue slight perioral furrowing with red spots aon lips and tongue -telangiectasia
Esophageal dysmotility
Crest limited scleroderma
Pericarditis
Lupus
Malt lymphoma
Sjorgen! Dry mouth dry wyes MALT lymphoma
Temporal arteritis/ giant cell arteritis
Polymyalgia rheumatica
DIAGNOSE WITH BIOPSY OF TEMPORAL ARTERY
Parotid gland
Sjorgen
DIAGNOSE WITH LIP BIOPSY
43 yo females dyspnea SOB GERD, raynaud, carpal tunnel, restrictive PFT, mediastinal LAD an honeycombing, topoisomeraseI ab positive, EF 50% and pulmonary artery pressure 20
Interstitial lung disease
Mediastinal lymphadenopathy
Sarcoidosis
Honeycombing dry Velcro crackles
Wet crackles-CHF
Topoisomerase antibody
Diffuse scleroderma
EF50
Normal
PAP 20
High but not too high
> 40
Asthma
Allergies, excema
Eosinophilic granulomatosis
Emphysema
A1- antitrypsin
Or a lot of smoking
CHF
Systolic low EF
Diastolic-cant relax
Polyarthritis nodosa
50 yo caucasion male bl weakness having trouble getting out of bathtub and up out of a chair cant bend fingers symptoms gradual over last year. ESR CRP CK normal
Endomysial inflammation rimmed vacuoles on H and E cNIA antibodies
Supportive-he has inclusion body myositis , usually serology normal finger flexors serology and biopsy inclusion body
Doesn’t respond to anything but supportive
MALES
39 yo female from India uncontrolled HTN taking 4 antihypertensive meds, fundoscopic shows copper wiring (retinal infarcts), radial and pedal pulse 1/4, narrowing renal arteries, highest risk of getting which of the following
Aorta rupture
Takiasku narrowing renal artery-renal artery stenosis on many anti HTN secondary cause of renal artery stenosis
Large vessel vasculitis, aorta, pulseless disease, lot of collaterals form so limb ischemia rare,
Coronary artery aneurysm
Small vessel
-talk about later
PE
Lupus, antiphospholipid bechet
MI
Atherosclerosis, lupus
Aortic suture
Large vessel
Takiatsu
55 yo Turkish mouth and genital sores h/o DVT< HLAb51 present pustilat site of lab draw
Bechet
Mouth, genital sore, eye inflammation
Pustule is called pathergy
30 yo african American male, stiffness weakness arthralgias, carpal tunnel confusion bp 212/109 , granular casts, anti centromere ab neg, RNA polymerase I and III abs are positive . What is diagnosis
Scleroderma renal crisis
Diffuse scleroderma
Renal crisis-predominance for males, lupus has a lot of renal studs but nocrisis like scleroderma
Gave
Diffuse scleroderma
Granulomatosis with polyangitis
Wegners-Upper rep and lung
Polyarthritis nodosa
Vasculitis in men associated with hep B effects kidney but not in this way
RNA p I and III ab
Diffuse scleroderma
45 yo female HA wont go away with Tylenol, blurry vision for 3 days, lost 10 lb over month, painful to chew food, smoker, ESR up, temporal arteries
- Temporal arteritis perform a biopsy
1. BUT IF DELAY CORTICOSTEROIDS THEY WILL GO BLIND FOR
Polyarthritis nodosa
HBC
41 yo F weakness everyone in family healthy, weak in arms and legs, diffuse itchy skin, violacious periorbital macular erythema, papules over the dorsal MCP joints with a shawl sign noted what additional work up
Dermatomyositis
Heliotrope rash
Mammogram !!!!!!!!!!!!!! Look for occult malignancy
Hep b
Polyarthritis odosum
Lip biops
Sjorgen
Right heart cath
Limited scleroderma look for pulmonary arter HTN
PFT
Diffuse scleroderma for interesting lung disease
41 yo elevated CK msucle weak last 3 weeks, muscle biopsy endomysial inflammation with invasion of non necrotic muscle fibers. PE normal 4.5 muscle strength of bl UE and LE anti jo ab on serology
Polymyositis
Polymyalgia rheumatica
Polyarthritis
Inclusion body myositis
Different muscle biopsy. More common in males and we may try steroids and immunosuppression but treatments fail and doesnt mean we should have tried them
SUPPORTIVE CARE is what we rely on heavily for inclusion body
Giant cell arteritis
Persistent HA, vision changes, temporal artery biopsy showing granulomas and multinucleated giant cells
30 yo female concerns raised rash worsen over last month tingling in arms and legs MPO ANCA positive and eosinophilia
Palpable purpura
(Henoch is also palpable)
Thrombocytopenia purpura not palpable
Eosinophilic granulomatosis with polyanitis (vasculitis and asthma, allergies and peripheral eosinophilia) ASTHMAAAAAAA!!!! History
Hep B
Polyarthritis nodosa
Polymyalgia
Terms art
Occult malignancy
Dermatomyositis
Primary biliary cirrhosis
Potential manifestation from diffuse scleroderma
35 yo male chronic hep b and HTN
Has concern of fatigue and myalgia. Concerned abut numbness in hands and feet. Right foot drapes when he walks. Skin changes. What organs are effects
Diagnosis-polyarthritis nodosa
Hep B! Can have HTN due to renal manifestations , fatigue, myalgia, neuropathy, vasculitis neuropathy (foot drop)
Cardiac-CHF, HTN, MI , GI-intestinal postprandial abdominal pain , skin -albino reticularis skin remodeling , ulcers nodules gangrene, renal-infarcts as HTN
Pulmonary spared
4 yo Asian female present with diffuse LDA. Fever 102 last 2 days, palmar erythema rapid strep negative, congestive eyes, and tongue papilla. What is cause of mortality in late disease
Kawasaki-mucucutaneous lymph node sydnrome
Childhood can resemble scarlet fever or toxic shock, strawberry tongue is the papilla , vasculitis an lead to limb ischemia as opposed to takiatsu which is collaterals, but not cause of mortality
CORONARYA RTERY ANEURYSMM (smaller vessel as opposed to tak)-causes death
Aortic rupture
Takiastu
PE
Bechet and antiphospholipid
CHF
Polyarthritis nodosa
50 yo WF with rashon ankles, chronic sinusitis, lung nodule on lung show necrotizing granuloma, heme analysis shows hematuria. What is also found on PE
Wegners(granulomatosis with polyangiitis_ Upper resp, lower resp, kidney and skin , renal manifestations, lung nodule is necrotizing granuloma and sinus disease
SADDLE NOSE
Strawberry tong
Kawasaki or strep pharyngitis
Malar rash
Lupus
Got torn
Dermatomyositis
Saddle nose
Wegners!!!!! Destruction and collapse of nasal bridge bc of process
25 yo male finger ulcer worsening and another starting. Dad died of colon cancer, smokes a pack per day, rarely drinks alcohol, all labs are normal, most likely cause of finger ulcer
Bergers (thromboangiitis obliterans)
Smoking young males start losing fingers and extremities no internal organ involvement
STOP smoking or will continue to lose digits
Type II hypersentivity
Lupus
IgA
Henoch
Basement membrane antibody
Good pastures
Kruse skeletal msucle relaxants
Ok
Two categories of skeletal muscle relaxants
Neuromuscular blockers-interfere with transmissiona t the neuromuscular end plate and lack CNS activity
Used as adjunct during anesthesia
No known effects on consciousness or pain threshold
Spasmolytic agents-often called centrally acting muscle relaxants
-used to reduce spasticity in a variety of neurologic conditions (chronic back pain, fibromyalgia, muscle spasm)
Neuromuscular blockers
a) Nondepolarizing
i) Isoquinoline derivatives
(1) Atracurium (2) Cisatracurium (3) Doxacurium (4) Mivacurium (5) Tubocurarine
ii) Steroid derivatives (1) Pancuronium (2) Pipercuronium (3) Rocuronium (4) Vecuronium
b) Depolarizing
i) Succinylcholine
Acetylcholinesterase inhibitors
a) Ambenonium b) Donepezil
c) Echothiophate d) Edrophonium e) Galantamine f) Neostigmine g) Physostigmine h) Pyridostigmine i) Rivastigmine
j) Tacrine
Muscle relaxants spasmolytics (central and non central)
Central-baclofen, carisprodol, cyclobenzaprine, diazepam, tizanidine
Non centrally-dantrolene, botulinum toxin
Antimuscarinic compounds
Atropine, glycopyrrolate
Cholinesterase reactivators
Pralidixime
How block end plate function
Nondepolarizing neuromuscular blocking agents
(1) Act as antagonists of the nicotinic acetylcholine receptor (nAChR)
(2) Prototype: d-tubocurarine
ii) Depolarizing neuromuscular blocking agents
(1) Blockade can be produced by the excess of a depolarizing agonist (e.g., excess acetylcholine (ACh), see below)
(2) Prototype: succinylcholine
Atracurium
Isoquinoline
Eliminated by hydrolysis by plasma esterases
2-4 min onset
Works 30-60 min
Cisatracurium
Isoquinoline
Spontaneous elimination
204 min onset
25-45 min duration (intermediate)
Doxacurium
Isoquinoline
Renal elimation
4-6 min onset
90-120 min action (long action)
Mivacurium
Isoquinoline
Plasma cholinesterase
Time 2-4 min
10-20 min action (short)
Pancuronium
Steroid
Renal
4-5 min onset
120-180 long actin
Pipecuronium
Steroid
Renal and hepatic excretion
204 min onset
80-100 long action
Rocuronium
Steroid
Hepatic elimination
1-2 min onset
20-35 intermediate
Vecuronium
Steroid
Renal and hepatic elimination
2-4 min onset
20-35 min intermediate
Succinylcholine
Plasma cholinesterase
1-2 min onset
Ultra short duration 5-8 min
Non depolarizing neuromuscular blocking agent pharmacokinetics
a) Pharmacokinetics
i) Highly polar; must be administered parenterally
Nondepolarizing neuromuscular blocking agents pharmacodynamics
Pharmacodynamics
i) MOA: competitive antagonists at the nAChR
ii) As a general rule, larger muscles (abdominal, trunk, paraspinous, diaphragm) are more
resistant to blockade and recover more rapidly (the diaphragm is usually the last muscle to
be paralyzed and the quickest to recover
Reversal of neuromuscular blockade with non depolarizing neuromuscular blocking agents
Reversalofneuromuscularblockade
i) Effects of nondepolarizing neuromuscular blocking agents are reversed upon the addition of acetylcholine using an acetylcholine esterase (AChE) inhibitor (larger doses of nondepolarizing agents diminish the antagonizing effects of cholinesterase inhibitors due to blockade of channel pore, which occurs at higher doses)
ii) Anticholinergic agents (e.g., atropine, glycopyrrolate) are coadministered with AChE inhibitors to minimize adverse cholinergic effects (bradycardia, bronchoconstriction, salivation, nausea, vomiting) at muscarinic AChRs
Adverse effects of nondepolarizing agents
) Adverse effects of nondepolarizing agents
i) Some nondepolarizing agents produce histamine release, which can cause histamine-like
wheals to appear, bronchospasm, hypotension, and bronchial and salivary secretion
(premedication with an antihistaminic compound can attenuate these effects)
ii) At large doses, tubocurarine can produce acetylcholine receptor blockade at autonomic
ganglia and at the adrenal medulla, which can result in a fall in blood pressure and
tachycardia
iii) d-tubocurarine causes significant histamine release and has a very long duration of action,
its clinical use has declined in favor of more specific, shorter-acting neuromuscular blockers
Nondepolarizing neuromuscular blocking agents AE
i) Some nondepolarizing agents produce histamine release, which can cause histamine-like
wheals to appear, bronchospasm, hypotension, and bronchial and salivary secretion
(premedication with an antihistaminic compound can attenuate these effects)
ii) At large doses, tubocurarine can produce acetylcholine receptor blockade at autonomic
ganglia and at the adrenal medulla, which can result in a fall in blood pressure and
tachycardia
iii) d-tubocurarine causes significant histamine release and has a very long duration of action,
its clinical use has declined in favor of more specific, shorter-acting neuromuscular blockers
Drug drug interactions non depolarizing neuromuscular blocking
Drug-drug interactions
i) Anesthetics
(1) Inhaled anesthetics potentiate the neuromuscular blockade produced by
nondepolarizing muscle relaxants in a dose-dependent fashion
(2) Isoflurane»_space; sevoflurane = desflurane = enflurane = halothane > nitrous oxide
ii) Antibiotics
(1) Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin,
kanamycin, paromomycin, netilmicin, spectinomycin) have been shown to enhance
neuromuscular blockade
(2) Some antibiotics reduce the release of ACh in the prejunctional neuron, likely due to
blockade of specific P-type calcium channels
iii) Other agents that block signaling at the NMJ (e.g., tetrodotoxin, local anesthetics,
botulinum toxin) enhance the actions of nondepolarizing agents
Nondepolarizing neuromuscular blocking agent effects of disease and aging on neuromuscular response
Prolonged duration of action from nondepolarizing relaxants occurs in elderly patients with reduced hepatic and renal function
ii) Neuromuscular blockade by nondepolarizing muscle relaxants is enhanced in patients with myasthenia gravis
iii) Patients with severe burns and those with upper motor neuron disease are resistant to nondepolarizing muscle relaxants (likely due to increased expression of nAChRs, which requires an increase in dose
Nondepolarizing neuromuscular blocking agents : atracurium
Atracurium (isoquinoline derivative, intermediate acting)
(1) Inactivated by a form of spontaneous breakdown known as Hofmann elimination
(2) Less histamine release than other nondepolarizing agents
ii) Cisatracurium (isoquinoline derivative, intermediate acting
NDM cisatracurium
) Cisatracurium (isoquinoline derivative, intermediate acting)
(1) Stereoisomer of atracurium with fewer side effects (less laudanosine, histamine release)
(2) Can be used even with significant renal and hepatic impairment; devoid of CV effects
iii) Doxacurium (isoquinoline derivative, long-acting
doxacurium
iii) Doxacurium (isoquinoline derivative, long-acting)
(1) Not often used because of the long-lasting effects as well as high degree of elimination by the kidney (not used in patients with renal failure); devoid of CV effec
Mivacurium
v) Mivacurium (isoquinoline derivative, short acting)
(1) Large doses can be associated with histamine release and subsequent CV effects (2) Metabolism by plasma cholinesterase
Steroid derivatives
v) Steroid derivatives
(1) Intermediate-acting steroid muscle relaxants (vecuronium, rocuronium) tend to be
more dependent on biliary excretion or hepatic metabolism for their elimination and are more likely to be used clinically than long-acting steroid relaxants (pancuronium, pipecuronium
The __ neuromuscular blocking agents have the least tendency to cause histamine release
Steroidal
Rocurinium
(3) Rocuronium
(a) Rocuronium has the most rapid time of onset (60-120 seconds) (b) Alternative to succinylcholine
Succinylcholine
a) Succinylcholine is the only depolarizing blocking drug used clinically
Pharmacokinetics succinylcholine
Ultra-short duration of action is due to rapid hydrolysis and inactivation by butyrylcholinesterase and pseudocholinesterase in the liver and plasma, respectively
ii) Prolonged neuromuscular blockade can occur in patients with a genetically abnormal
variant of plasma cholinesterase after a dose of succinylcholine
iii) Not effectively metabolized at the synapse by acetylcholinesterase
Pharmacokinetics succinylcholine
E ffects of succinylcholine are similar to ACh (i.e., succinylcholine is a nAChR agonist), but
with longer duration of action compared to ACh
Succinylcholine phase I block
Phase I block (depolarizing): after activating the nAChR, depolarization of the motor end
plate spreads to adjacent membranes causing muscle contraction; the depolarized membranes remain depolarized and unresponsive to subsequent impulses (i.e., a state of depolarizing blockade); because excitation-contraction coupling requires end plate repolarization and repetitive firing to maintain muscle tension, flaccid paralysis results; phase I depolarizing block is augmented, not reversed, by cholinesterase inhibitors
Succinylcholine phase II block
Phase II block (desensitizing): continued exposure to succinylcholine causes the initial end plate depolarization to decrease and the membrane becomes repolarized; the membrane is unable to be depolarized because the receptor is desensitized; although this mechanism is unclear, the channels behave as if they are in a prolonged closed state similar to nondepolarizing block; phase II desensitizing block is reversed by acetylcholinesterase inhibitors (increase in ACh at the NMJ
Effect succinylcholine
iv) A standard pharmacological dose of intravenous succinylcholine causes transient muscle fasciculations (twitches) over the chest and abdomen within 30 sec; paralysis develops rapidly (<90 sec) in arm, neck, and leg muscles initially followed by respiratory muscles
Clincial succinylcholine
) Succinylcholine is often used for rapid sequence induction (e.g., during emergency surgery when the objective is to secure the airway rapidly and prevent soiling of the lungs with gastric contents) and for quick surgical procedures where an ultrashort acting neuromuscular blocker is practical
Reversal of neuromuscular blockade
Time due to cholinesterase degradation
AE and contraindications succinylcholine
Cardiovascular effects
(1) Cardiac arrhythmias when administered during halothane anesthesia
(2) Stimulation of nAChRs and mAChRs produces negative inotropic (cardiac muscle
contraction strength) and chronotropic (heart rate) effects, which may be attenuated by
administration of an anticholinergic drug (atropine)
(3) Large doses can cause positive inotropic and chronotropic effects
ii) Hyperkalemia – patients with burns, nerve damage or neuromuscular disease, closed head injury, and other trauma can respond to succinylcholine by releasing potassium into the blood, which, on rare occasions, can cause cardiac arrest
iii) Increased intraocular pressure, increased intragastric pressure, muscle pain
iv) Contraindications include personal or familial history of malignant hyperthermia;
myopathies associated with elevated serum creatine phosphokinase (CPK) values; acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle or upper motor neuron injury
v) BLACKBOXWARNING(cardiacarrestrisk):rarely,acuterhabdomyolysiswith hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death can occur after administration to apparently healthy children with an undiagnosed skeletal muscle myopathy (usually males <8 y/o but also reported in adolescents
Black box succinylcholine
BLACKBOXWARNING(cardiacarrestrisk):rarely,acuterhabdomyolysiswith hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death can occur after administration to apparently healthy children with an undiagnosed skeletal muscle myopathy (usually males <8 y/o but also reported in adolescents
Drug drug interactions succinylcholine
i) Anesthetics
(1) The combination of succinylcholine and volatile anesthetics can result in malignant hyperthermia (rare)
(2) Malignant hyperthermia is caused by abnormal release of calcium from stores in skeletal muscle and is treated with dantrolene (see below)
ii) Antibiotics: See above for drug-drug interactions for nondepolarizing agents
iii) Local anesthetics and antiarrhythmic drugs (minor
Uses of neuromuscular blocking drugs
) Surgical relaxation
b) Tracheal intubation
c) Controlofventilation:providesadequategasexchangeandpreventsatelectasisinpatients
who have ventilatory failure; neuromuscular blocking drugs reduce chest wall resistance and
improve thoracic compliance
d) Treatment of convulsions: attenuates the peripheral motor manifestations of convulsions
associated with status epilepticus or local anesthetic toxicity; no effect on the CNS because neuromuscular blocking agents do not cross the blood-brain barrier
AchE inhibitors : subgroups
Subgroups
i) Alcohols: contain an alcohol group, positively charged; reversible (example: edrophonium)
ii) Carbamic acid esters: can be positively charged or neutral and are reversible (example:
neostigmine, pyridostigmine, physostigmine)
iii) Organophosphates: organic derivatives of phosphoric acid; neutral, highly lipid-soluble;
irreversible (examples: echothiophate, parathion, malathion, sarin, soman
Pharmacokinetics AchE inhibtors
Quaternary and charged AChE inhibitors: relatively insoluble (parenteral administration), no CNS distribution (examples: neostigmine, pyridostigmine, edrophonium, echothiophate)
ii) Tertiary and uncharged AChE inhibitors: well absorbed from all sites, CNS distribution (examples: physostigmine, donepezil, tacrine, rivastigmine, galantamine)
iii) Organophosphates: lipid-soluble and readily absorbed from the skin, lung, gut, and conjunctiva, CNS distribution (except for echothiophate, which is charged); since the interaction between organophosphates and AChE is covalent and irreversible, there is virtually little metabolism and excretion via common biotransformation pathways; regeneration of AChE is required in order to reestablish the termination of ACh signaling at the neuromuscular junction (pralidoxime, see below
MOA ache inhibtiors
Inhibiton of AChE
Duration AchE inhibitors
Duration of action: alcohols bind weakly and reversibly resulting in short duration of action (2-
10 minutes); carbamic acid esters bind reversibly but with longer duration of (30 minutes to 8- hour duration of action); organophosphates bind covalently and reversal of binding requires rapid administration of pralidoxime to regenerate the activity of AChE
Organ system effects ache inhibtiors
) Organ system effects: depending on the site of action, AChE inhibitors have the ability to
(1) stimulate mAChRs at autonomic effector organs and (2) stimulate, followed by
depression or paralysis, all autonomic ganglia and skeletal muscle (nAChRs
CNS ache inhibitos
i) CNS: low concentrations: diffuse activation on EEG and a subjective altering response; high concentrations: generalized convulsions due to neuronal hyperstimulation (may be
followed by coma and respiratory arrest
NMJ ache inhibitos
i) NMJ: therapeutic concentrations of AChE inhibitors prolong and intensify the actions of
ACh, which increases the strength of contraction; fibrillation of muscle fibers and fasciculations result with high concentrations; continued inhibition of AChE results in the progression of depolarizing neuromuscular blockade to nondepolarizing blockade (as seen with succinylcholine); some quaternary carbamate AChE inhibitors have additional direct nicotinic agonist effects at the NMJ (e.g., neostigmine
AchE inhibitors eye
Sphinctermuscleofiris Contraction (miosis) Ciliarymuscle Contraction for near vision (accommodation
Heart ache inhibitors
Sinoatrialnode
Decrease in rate (negative chronotropy)
Atria
Decrease in contractile strength (negative inotropy). Decrease in refractory period
Atrioventricularnode
Decrease in conduction velocity (negative dromotropy). Increase in refractory period
Ventricles
Small decrease in contractile strength
Blood vessels ache inhibitors
Arteries,veins
Dilation (via EDRF). Constriction (high-dose direct effect)
Lung
Bronchialmuscle
Contraction (bronchoconstriction)
Bronchialglands
Secretion
GI ache inhibitors
Motility
Increase
Sphincters
Relaxation
Secretion
Stimulation
Urinary bladder ache inhibitos
Detrusor
Contraction
Trigoneandsphincter
Relaxation
Glands Ache inhibitors
Sweat,salivary,lacrimal,nasopharyngeal
Secretion
Clinical ache inhibitors
he major therapeutic uses of agents that stimulate AChRs (direct acting or indirect acting) are for diseases of the eye (glaucoma, accommodative esotropia), GI and urinary tracts (postoperative atony, neurogenic bladder), NMJ (myasthenia gravis, curare-induced neuromuscular paralysis), heart (rarely for certain atrial arrhythmias), and Alzheimer disease
Treat myasthenia gravis
Myasthenia gravis: pyridostigmine, neostigmine, and ambenonium are the standard AChE inhibitors used in the symptomatic treatment of myasthenia gravis (do not cross the blood- brain barrier); due to the relatively short duration of action of these agents, repeated dosing is required every 2-8 hours depending upon agent, dose, and clinical response
i) Edrophonium test: the short-acting agent edrophonium had been used as a diagnostic agent for myasthenia gravis (edrophonium test); replaced by ice pack test and immunologic and/or electrophysiologic testing
ii) Myasthenic vs. cholinergic crisis
(1) Myasthenic crisis is a life-threatening condition defined as weakness from acquired
myasthenia gravis that is severe enough to necessitate intubation
(2) Cholinergic crisis is a potential major side effect of excessive AChE inhibitors; the main
symptom is muscle weakness, similar to myasthenic crisis
(3) To distinguish, an AChE inhibitor (edrophonium) may delineate the cause of symptoms
(a) If the patient is in myasthenic crisis the symptoms will improve
(b) If the condition is cholinergic crisis, the symptoms will remain unchanged or worsen
Reversal of pharmacological paralysis
Reversalofpharmacologicparalysis:neostigmineiscommonlyusedtoreverse
neuromuscular blocking drug-induced paralysis; AChE inhibitors may be used to treat paralytic
ileus, atony of the urinary bladder, and congenital megacolon
Glaucoma
Glaucoma: AChE inhibitors reduce intraocular pressure by stimulating mAChRs of the ciliary
body and causing contraction, which facilitates outflow of aqueous humor; replaced by topical
β-blockers and prostaglandin derivatives
Dementia
e) Dementia: patients with progressive dementia of the Alzheimer type have a deficiency of intact
cholinergic neurons; tacrine was approved in 1993, but due to the high incidence of hepatotoxicity newer agents are preferred (donepezil, rivastigmine, galantamine, physostigmine); patients with dementia associated with Parkinson disease also benefit
Antidote
) Antidote: over 600 compounds have anticholinergic properties (e.g., anticholinergic agents (atropine), antihistamines, tricyclic antidepressants, sleep aids, cold preparations); intoxication due to anticholinergic agents can produce cutaneous vasodilation, anhidrosis, anhydrotic hyperthermia, nonreactive mydriasis, delirium, hallucinations, and a reduction or elimination of the desire to urinate, which are generally the result of reduced or blocked mAChR stimulation; physostigmine is preferred because it crosses the blood-brain barrier
Drug drug interactions
a) Nondepolarizing neuromuscular blocking agents: AChE inhibitors diminish NMJ blockade
i) Exception: mivacurium (metabolized by plasma AChE), AChE inhibitors prolong blockade
b) Succinylcholine: AChE inhibitors will enhance phase 1 block and antagonize phase 2 block
c) Cholinergicagonists(direct-acting):AChEinhibitorsenhanceeffectsofcholinergicagonists
d) Beta-blockers: AChE inhibitors may enhance the bradycardic effects
Acute intoxication
The dominant initial signs of AChE intoxication are those of mAChR stimulation: miosis, salivation, sweating, bronchial constriction, vomiting, and diarrhea
ii) The route of administration dictate which symptoms are noted initially
(1) After ingestion, GI symptoms occur earliest
(2) Percutaneous absorption results in early symptoms of localized sweating and muscle
fasciculations in the immediate vicinity
iii) With poisoning from lipid-soluble agents, CNS involvement follows rapidly (confusion,
ataxia, generalized convulsions, coma, and respiratory paralysis)
iv) Time of death after a single acute exposure may range 5 minutes to 24 hours and is
caused primarily by respiratory failure
Treatment toxicity
i) Atropine in combination with maintenance of vital signs (respiration) and decontamination
ii) Atropine is ineffective against the peripheral neuromuscular stimulation (nAChRs)
iii) To regenerate AChE at the NMJ, cholinesterase regenerators can be administered
Cholinesterase regenerator
Cholinesterase reactivators (pralidoxime) are capable of regenerating active AChE enzyme
by removal of the phosphorous group from the active site of the enzyme
ii) Restores the response to stimulation of the motor nerve within minutes
iii) Must be given soon after AChE inhibitor exposure
iv) Atropine, pralidoxime, and a benzodiazepine (anticonvulsant) are typically combined
Skeletal msucle relaxants
Spasticity (muscle twitch) is characterized by an increase in tonic stretch reflexes and flexor muscle spasms (i.e., increased basal muscle tone) together with muscle weakness
b) Spasticity is associated with spinal injury, cerebral palsy, multiple sclerosis, and stroke
c) Spasmolytic agents may improve some of the symptoms of spasticity by modifying the stretch
reflex arc or by interfering directly with skeletal muscle (i.e., excitation-contraction coupling)
d) Currently available drugs can provide significant relief from painful muscle spasms, but they
are less effective in improving meaningful function (e.g., mobility, return to work
Baclofen
i) Baclofen
(1) MOA: agonist at GABAB receptors; results in hyperpolarization (due to increased K+
conductance) and inhibition of excitatory neurotransmitter release in the brain and
spinal cord
(2) As effective as diazepam in reducing spasticity and causes less sedation; does not
reduce overall muscle strength as much as dantrolene
(3) Adverse effects include drowsiness and increased seizure activity in epileptic patients
(withdrawal must be done slowly); vertigo, dizziness, psychiatric disturbances,
insomnia, slurred speech, ataxia, hypotonia, and muscle weakness
Carisprodol
(1) Precise mechanism of action unclear; acts as CNS depressant
(2) Schedule IV controlled substance due to addictive potential (use only short term)
(3) Adverse effects include dizziness and drowsiness
(4) Metabolized by CYP2C19; use with caution when coadministered with CYP inhibitors
(5) Metabolized to meprobamate, which has anxiolytic and sedative effects (used to
manage anxiety disorders)
iii) Chlorzoxazone
(1) MOA: Acts on the spinal cord and subcortical levels by depressing polysynaptic reflexes
Cyclobenzaprine
1) Exact mechanism of action unclear; reduces tonic somatic motor activity by influencing both alpha and gamma motor neurons
(2) Structurally related to tricyclic antidepressants and produces antimuscarinic side effects (may cause significant sedation, confusion, and transient visual hallucinations)
(3) Metabolized by CYP450s; use with caution when coadministered with CYP inhibitors
(4) Adverse effects include drowsiness, dizziness, and xerostomia
Diazepam
(1) Long-acting benzodiazepine; produces sedation at the doses for spasticity
(2) MOA: promote the binding of the major inhibitory neurotransmitter in the CNS - aminobutyric acid (GABA) to the GABAA receptor, enhancing GABA-induced ion currents (increase frequency of channel openings); leads to increased inhibitory
transmission and a reduction in spasticity
(3) Causes sedation, muscle relaxation, anxiolytic and anticonvulsant effects
(4) Schedule IV controlled substance
Tizanidine
(1) MOA: alpha2-adrenergic agonist (similar to clonidine); decreases excitatory input to
alpha motor neurons
(2) Causes drowsiness, hypotension, dry mouth, asthenia/muscle weakness
Dantrolene
(1) In contrast to the centrally acting drugs, dantrolene reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers
(2) MOA: causes inhibition of the ryanodine receptor (RyR); blocks the release of calcium through the sarcoplasmic reticulum and muscle contraction is impaired
(3) Cardiac and smooth muscle are unaffected due to a different RyR channel subtype
(4) Side effects include generalized muscle weakness, sedation, and occasionally hepatitis
(5) Used to treat spasticity associated with upper motor neuron disorders (e.g., spinal cord
injury, stroke, cerebral palsy, or multiple sclerosis) and malignant hyperthermia
Botulism toxin
(1) MOA: cleaves components of the core SNARE complex involved in exocytosis, preventing the release of ACh
(2) Many clinical uses: strabismus and blepharospasm associated with dystonia; cervical dystonia; temporary improvement in the appearance of lines/wrinkles of the face; severe primary axillary hyperhidrosis; focal spasticity; prophylaxis of chronic migraine
(3) Adverse effects include focal muscle weakness in the area of injection, which may last up to several months
Glucocorticoids for MS
c) Glucocorticoids
i) Monthly bolus IV glucocorticoids (typically 1000 mg of methylprednisolone) are used for
treatment of primary or secondary progressive MS alone or in combination with other
immunomodulatory or immunosuppressive medications d)
Glatiramer acetate
e) Glatiramer acetate i) MOA
(1) A mixture of random polymers of four amino acids (L-alanine, L-glutamic acid, L-lysine, and L-tyrosine) that is antigenically similar to myelin basic protein, which is an important component of the myelin sheath of nerves
(2) Thought to induce and activate T-lymphocyte suppressor cells specific for a myelin antigen; also proposed to interfere with the antigen-presenting function of certain immune cells opposing pathogenic T-cell function
Interferons
i) Interferon-beta-1a and interferon-beta-1b
ii) MOA: Acts on blood-brain barrier by interfering with T-cell adhesion to the endothelium by
binding VLA-4 on T cells or by inhibiting the T-cell expression of MMP
iii) Results in a reduction of relapses by one-third, a reduction of new MRI T2 lesions and the
volume of enlarging T2 lesions, a reduction in the number and volume of Gd-enhancing
lesions, and a slowing of brain atrophy
Mitoxantrone
i) Antineoplastic agent used to treat MS, acute myeloid leukemia, and advanced, hormone- refractory prostate cancer
ii) MOA: intercalates into DNA resulting in cross-links and strand breaks (related to anthracycline antibiotics
Methotrexate
Biological DMARD, also administered systemically to treat other autoimmune diseases such as psoriasis
Vemurafenib
Inhibits the mutatedBRAF V600D MAP kinase found in 60% of melanomas
Apremilast
Orally active phosphodiesterase type IV inhibitor that inhibits numerous pro inflammatory mediators, used in moderate to severe plaque psoriasis and psoriatic arthritis; severe diarrhea is AE
Miconazole
Amongthe imidazole drugs commonly used to treat vulvovaginal candidiasis
Amphotericin B
Antifungal agent with topical effects limited to candida infections, may temporarily stain the skin yellow (also given IV for ther fungal infections as well including aspergillus and endemic mycosis)
C diffe
Common cause of diarrhea due to antibiotic associated colitis, well known example where handwashing. With soap and water is superior to alcohol based gels
Okspironolactone
Oral contreptives
Canbe effective treatment for acne in women
Biofilms?
Form on surfaces, very hard to kill bc resident microbes of different species help each other survive
Polymixin B
Peptide antibiotic with efficacy against gram negative bacteria including pseudomonas, has a detergent like effect that damages the bacterial cell membrane
Tetracyclines
Drug class useful for systemic treatment of acne, photosensitivity, GI distress and contraindication in pregnancy and young children due to gray discoloration of permanent teeth are noteworthy adverse effects
Neomycin
Aminoglycosides antibioticof neosporin with activity against gram negative bacteria
Benozyl peroxide
Topical antimicrobial agent commonlyused to treat acne; local skin irritate and may bleach hair or clothing
Type IV hypersensitivity
Delayed hypersensitivity reaction that can be caused by substances such as latex and drugs such as neomycin and bacitracin; sometimes induced as treatment of skin disorder (psoriasis, alopecia)
Inadequate oxygenation
Local vasoconstriction due to blood volume deficit, unrelieved pain, hypothermia, can impair wound healing due to an inadequate amount of this in the tissue
Becaplermin
Platelet derived growth factor that promotes the cell proliferation and angiogenesis needed for diabetic ulcer repair, but must use cautiously as too much increases risk of malignancy
Emollients
Refers to substance in moisturizers that form an oily layer to trap water in the skin; petrolatum, lanolin and mineral oil are among common examples
Glycemic control
Control that is now considered a priority for optimal wound closure
Naphazoline, tetrahydrozoline, phenylephrine, and oxymetazoline
Alpha adrenergic agonist in visine known for its ability to get the red out
Chlorhexidine
Broad spectrum antimicrobial agent widely used in homes and hospitals due to efficacy on skin and oral mucosa with low irritability
Clindamycin
Antibiotic that works similar to macrolides, kills anaerobes, useful for range of infections including topical treatment. Of acne and for osteomyelitis; associated with increased risk of c diffe
Calcineurin inhibitos
Cyclosporine and tacrolimus are among these agents that revolutionizes transplantation therapy (didn’t cause bone marrow suppression), among theses agents that revolutionized transplantation therapy (didn’t;t cause bone marrow suppression) among other uses includes topical or systemic administration for psoriasis and topical administration for anogenital pruritis
Moisturizers
Very important component of skin care for health care providers
Tar
Very old remedy for psoriasis; works but color and smell create a challenge
NYSTATIN
When sued to treat thrush it is held on the mouth before swallowing (has negligible GI absorption)
Debridement
Important component of wound healing it conserves the local resources by limiting the need to synthesize proteases; stage when hydrogens are good wound covering
Hand hygiene
Most important component of infection control
Bacitracin
Peptide antibiotic with activity against gram positive organisms and some anaerobes; only applied topically to limit systemic toxicity, often causes contact dermatitis
Ciclopirox
Prescription synthetic topical antimycotic agent with broad spectrum of activity against fungal skin infections such as ringworm, athletes foot, tinea versicolor, dandruff
Azaleicacid
Component of plant defenses against bacteria, active against P acne
Moist
To heal best, wounds should be kept clean and -_-
Isotret
Retinoid administration orally for treatment of severe acne, powerful teratogen that mandates participation by young females in the iPledge program
Horny substances (keratin softeners)
Urea, alpha-hydroxyl acids and allantoin are among the agents found in moisturizers to soften this and give skin a smoother feeling
Physical interventions
Sometimes need to resort to things such as unna boots in the category to try to break the itch scratch cycle
Uva
Radiation that may not cause erythema and sunburn but neverthe less still contribute to akin aging and phtocarcinogenesis
Aprepitant
Substance P antagonist used to treat nausea and vomiting of chemotherapy also useful to treat intense itching of cutaneous T cell lymphomas (sezary syndrome)
Anogenital pruritus
Itching here is far less funny than it sounds, topical calcineurin inhibitors such as tacrolimus can help treat
5-fu topical
Effective topical therapy for actinic keratosis, causes fast proliferating dysplastic cells to die a thymidine-less death; necrosis/erosion gives way to re-epithelization over several weeks (no hyphen)
Minocycline
Tetracycline used to treat acne, noteworthy for its ability to cause dark pigmentation in skin and sclera
Ketoconazole
Imidazole antifungal drug applied topically for range of fungal infections, also noteworthy as a classic inhibitor of cytochrome P450
Impede
Agents such as iodine, chorhexidine and hydrogen peroxide and potentially do this to wound healing
Creams
50% water and 50% oil with a emulsifier, base that is useful for covering large and.or wet areas with a drug but preservatives, can cause allergic reactions
Local anesthetics
Can be useful therapies for neuropathic pruritus
Dacarbazine
FDA approved conventional therapy for malenoma
Gabapentin
Antiepileptic drug used to treat neuropathic pain and itching
Ingenolmebutate
Treatmentfor actinic keratosis, derived from euphorbia peplus sap, causes chemoablation with neutrophil-mediated antibody dependent cellular cytotoxicity eliminating remaining tumor cells
Erythromycin
Macrolides antibiotic, among uses is for topical or systemic treatment of acne among the well known cytochrome P450 inhibtiors to remember
Ivermectin
Orally administered insecticides to treat ectoparasites, binds glutamate activated Cl channels to hyprepolarize the nerve and muscle cells
Humectants
Refers to agents such as glycerin, lecithin and propylene glycol found in moisturizers to draw water into the outer layer of skin
Ustekinumab
Monoclonal antibody against IL12 and IL23 a biologics agent used to treat psoriasis
Butorphanol
Opioid receptor agonist.a-opioid receptor antagonist administered intranasally to treat intractable.nocturnal pruritis
Antihistamines
Drug class that may or may not stop itch, but associated drowsiness may help one deal with it
Finasteride
Blocks the conversion of testosterone to more potent androgen dihydrotestosterone, among its uses is to treat male pattern baldness in men and second line agent in women
Permethrin
Synthetic insecticide similar to that of chrysanthemums, ectoparasite therapy that binds to insect Na channels and prevents membrane repolarization
Azithromycin
Macrolides among the systemic therapies used to treat acne; noteworthy bc it is not a cytochrome P450 inhibitor, has unusual pharmacokinetics in that it is taken up in phagocytes and released by them at sites of infection
Imidazole
Class of antifungal drugs with a wide range of activity , blocks ergosterol synthesis
Imiquimod
Topical immune response modifier used to treat actinic keratosis and basal or squamous cell carcinoma or genital warts
Tretinoin
Topical retinoid administrated for the treatment of acne, alter gene expression to normalize keratinization, decrease keratinocytes cohesiveness and reduce microcomedone formation
Griseofulvin
Can be given systemically to treat tinea capitis (ringworm in scalp)
Dpcp
Treatment for alopecia, it is a contact allergen applied to cause dermatitis which can be followed by hair growth
Tolnaftate
Among OTC drugs (tinactin) used to treat jock itch and athletes foot; like terbutaline, inactive against yeasts
Ointment
Comprised of 20% water and 80% oils, best for dry skin, stay on the surface of skin and are not well absorbed , permit mor ecomplete drug absorption and less likely tocause allergic reaction skin no preservatives
Efinaconazole
Antifungal applied topically that penetrates into nails to treat fungal infection
Reservoir
The formation of one of thesefor a drug in the skin may prolong its half life and permit 1.day dosing
Fluconazole
Example of a systemic imidazole therapy to treat tinea versicolor
Naltrexone
Opoid receptor antagonist that can treat the pruritus associated with chronic kidney disease and cholestasis
Flutamide
Prototypical non steroid androgen antagonist, uses besides prostate cancer include treatment of male baldness in women
Minoxidil
Potent vasodilator due to hyperpolarization via activation of K channels applied topically to grow hair
Ph
Lower closer to that of skin is why synthetic detergents minimize skin irritation during home skin care
Alpha
Class of adrenergic agonistsadministered topically to treat rosacea or red eyes
Newman
Ok
Failed screen
Simply an indication for a more thorough evaluation
Why developmental screen
Sooner identify delays better
Four domains of development
Gross motor
Fine motor
Language
Cognitive/social emotional and behavioral
Gross motor
Movements using large msucles
Fine motor
Movements using hands and smaller msucles often involving daily living skills
Language
Receptive and expressive communication, speech anal nonverbal communication
Cognitive/social emotional and behavioral
Attachment, self regulation and interaction with others
Myopathy domain
Gross motor
6 months
Babbles and sits momentarily
9 months
Momma/daddy
Pulls up
Cruises
Sits well without support
1 year
Stands momentarily
2 years
Walk up stairs
Kicks ball forward
3 years
Tricycle
4 year
Balance on one foot
Hop on one foot
6 years
Skip
Myopathies
Muscle
-muscular dystrophy, metabolic myopathies, congenital, central core
Acquired myopathy
Infections, inflammatory processes , systemic diseases, toxic myopathy
Inherited myopathy
Muscular dystrophy, congenital, metabolic, mitochondrial
How do most myopathies present
Weakness in the proximal msucles
Acquired muscle
Juvenile dermatomyositis
Statin induced myopathy
What causes dystrophy
Abnormalities in dystrophin associated protein complex but not all do this
Duchene and Becker
Proximal weakness
Shawl and thighs
DTR will be present
FaCIOSCAPULOHUMERAL
Just proximal shawl and face
Emery dreyfus
Proximal could ESR and lateral ankles and feet
Duchene becker fascioscapulohumeral and emery Dreyfus
Duchene 1/3500 male
Becker 1/1845
Rare rare
Duchene
Proximal weakness
Most severe childhood form
Onset early, weakness more severe
Cardiomyopathy and frameshift mutation
Inheritance duchene
X linked recessive
Prob with duchenne
Out of frame mutation so nothing correct and absent of muscle dystrophin
Why boys duchene
X recessive
X recessive inheritance
Carrier mom unaffected dad
Unaffected son, unaffected daughter, carrier daughter, and affected son
Chance male offspring effected
50%
Becker
Older presentation
X recessive
Less msucle damage
Can walk independently longer
Shorter lifespan 40-60
Respiratory and cardiac
Preschool weak toe walking difficulty walking falls get what
CK
Family history
Involvement on moms side dystrophinopathy most common
Baby hypotonic in nursery
Do a cpk get good family history and genetic testing
Mitochondrial
MELAS
Mitochondrial encephalomyelitis with lactic acidosis and stroke like symptoms
Pompe
Glycogen storage type II
AR
Weakness, hypotonia, build up of glycogen in lysosomes in cell
Can give enzymes that can help
Juvenile dermatomyositis
Most common idiopathic inflammatory myopathy in kids
7 years
Red or purplish heliotrope rash over eyelids
Gottron papules
Thrombi or hemorrhage in peri ungual capillary beds
Acquired
Statin induced myopathy
Can cause necrotizing and inflammatory myopathy
-msucle weakness pain tenderness
Why look for myoglobin in the urine
Break down msucle if have heme positive urine and no blood cells look for myoglobin if muscular symtpoms it is so hard on kidney
GGT
Gamma glutamyl transferase can help determine if the liver is involved
-if elevated think liver
If normal think muscle
