MSK Exam 2 Flashcards
1
Q
axonal peripheral nerve disease characteristics
A
lower density of axons
degeneration of axons
regeneration/sprouting
2
Q
demyelination peripheral nerve disease characteristics
A
axons without myelin
evidence of remyelination
3
Q
inflammatory peripheral nerve disease characteristics
A
inflammatory cells
demyelination>axonal degeneration
ascending paralysis
often recovery w support
-conditions: Geuillian Barre, CIPD
4
Q
infection peripheral nerve disease characteristics
A
acid fast bacilli
granulomas (occassional)
symmetric polyneuropathy (worse in extremities and face due to temperature
-infections: leprosy, herpes simplex, varicella zoster
5
Q
metabolic peripheral nerve disease characteristics
A
axonal degeneration and/or demyelination
thickened blood vessels
-conditions: diabetes
6
Q
toxic peripheral nerve disease characteristics
A
axonal degeneration and/or demyelination
few with characteristic findings
history often vital
-causes: alcohol, toxins
7
Q
vascular peripheral nerve disease characteristics
A
inflammation or blood vessels with/without necrosis
systemic conditions that affect the nerves
-conditions: vasculitis
8
Q
genertic peripheral nerve disease characteristics
A
hypertrophic nerves with onion bulbs, leads to palpable nerves
-conditions: charcot marie tooth, dejerine sottas
9
Q
conduction velocity tests for neuromuscular diseases
A
slower conduction = demyelination
weaker stimulation = axonal degeneration
10
Q
skeletal muscle structures
A
sarcolemma
T tubules
sarcoplasmic reticulum
mitochondria
myofibrils
11
Q
1 muscle fiber innervated by what
A
1 alpha motor neuron
12
Q
1 motor neuron does what and innervates how many muscle fibers
A
branches and innervates several fibers
13
Q
motor unit
A
all the muscle fibers innervated by branches of the same motor neuron
14
Q
muscle tension strength increased by what
A
recruitment of additional motor units
15
Q
timing and sequence of motor unit recruitment controlled from what
A
cerebral motor cortex
16
Q
secretion of ACh steps
A
action potential causes opening of voltage gated Ca channels which lets Ca enter the presynaptic terminal causing release of ACh
17
Q
ACh receptor channels located where
A
top of subneural cleft
18
Q
voltage gated Na channes where
A
along the sarcolemma incuding the T tubules
19
Q
post synaptic ACh receptors
A
nicotinic ACh receptors allow passage of NA and K
driving force of Na influx creates end plate potential (EPP)
usually EPP reaches threshold and initiates an AP that spreads through sarcolemma
20
Q
ACh removed how
A
- acetylcholinesterase
- diffuse out of synaptic space and no longer available to act on the muscle fiber
21
Q
what carries the AP to the sarcoplasmic reticulum
A
t tubules
22
Q
what happens when the AP reaches the sarcoplasmic reticulum
A
AP reaches t tubule
depolarization activates Dihydropyridine receptors (DHP)
DHP triggers opening of mechanically linked ryanodine receptors on SR
ryanodine receptor opening allows Ca out
23
Q
thin filaments
A
actin, tropomyosin, troponin
24
Q
actin structure
A
backbone is double stranded F actin
each F is composed of G actin
each G actin has myosin head binding sites
25
tropomyosin structure
regulatory protein
blocks myosin binding sites on actin
26
troponin
regulatory protein
t - bind tropomyosin
c - bind calcium
i - bind actin and inhibit contraction
27
thick filament
myosin
28
myosin structure
heavy chains : 2, wrap spirally around each other, rod/hinge/head, head has binding site for actin and binding site for ATP (myosin ATP ase)
light chains : 4, stabilizes myosin head, regulate ATPase activity
29
what role does calcium play in sliding filament theory
troponin must bind calcium to induce conformation change of tropomyosin to reveal binding sites for mysoin heads
once attached myosin does the power stroke, pulling actin along (sliding)
30
sarcomere structure
nebulin - aligns thin filaments
titin - helps thick filament return to original position after contraction
z disk - where thin filaments attach (seperates sarcomeres)
i band - contains only thin filaments
a band - contains all the thick filament
h band - only the thick filament in the center
m line - attachment for thick filament
31
how many thin filaments are each thick filament surrounded by
6
32
how many thick filaments are each thin filament surrounded by
3
33
what happens to the components of the sarcomere in contraction
z disks move toward one another
I band shortens
H band shortens
A band remains unchanged
34
contraction cycle
ATP binds myosin (causing it to release actin)
APT immediately hydrolyzes ATP into ADP and Pi
conformational change in myosin rotates the head (waiting for calcium release)
Ca binds troponin tropomysin complex letting myosin firmly bind and power stroke occurs (head rotates pulling actin with it)
once head tilts ADP is released and binding of ATP releases actin
35
power stroke
during contraction while one myosin head dissociating another head is performing the powerstroke so actin doesnt slip
36
the greater number of cross bridges in contact with actin
the stronger the force of contraction
37
rigor mortis
no ATP to bind myosin and release actin
38
lambert eaton myasthenic syndrome
autoimmune atttack against voltage gated calcium channels on presynapic terminal
weak end plate potential
39
myasthenia gravis
autoimmune disease characterized by presence of antibodies against nicotinic ACh receptor
weak end plate potentials
40
botulism
botulinum toxin decreases release of ACh by cleaving proteins in the vesicle
41
muscular dystrophy
duchenne - absent or tuncated dystrophin
becker - dystrophin present but less functional
42
malignant hyperthermia
constant leak of SR Ca through ryanodine receptor
triggered by anesthetics
complications - rhabdomyolysis and hyperkalemia
treatment - cooling and dantrolene (ryanodine receptor antagonist)
43
relaxation phase of skeletal muscle contraction
voltage change closes DHP receptors closing ryanodine receptors
Ca pumped back into SR using Ca ATPase (SERCA)
as Ca decreases more dissociates from troponin C, tropomyosin slides back to block myosin
crossbridges break and myosin returns to relaxed position (with help of titin)
44
isometric contraction
length remains unchanges but tension increases
stretching of elastic elements in tendons
45
isotonic contraction
one point of muscle fixed and other has load added
shortening of the muscle if tension greater than the load
elastic elements are already stretched so sarcomere shortens
concentric - muscle shortens reducing angle
eccentric - muscle lengthens while contracting
46
muscle contracts rapidly when
against no load
47
muscle contracts slowly when
against large load
48
power equals what
load x velocity
49
if a second stimulus occurs during a twitch what happens
another contraction occurs before the first contraction is finished
50
summation of contractions
force of contration increases with summation
51
tetanus
muscle stimulated repeatedly so muscle doesnt relax
52
force summation
frequency - increase the frequency a single fiber contracts
multiple fiber - increase the number of motor units contracting
53
size principle
progressive recruitment of first small then large fibers
54
slow oxidative (type I) fibers
low myosin ATPase activity, high oxidative capacity
dark red
smaller fibers innervated by smaller nerves
increased mitochondria
lots of myoglobin
fatigue resistant
back muscles/marathon running
55
fast oxidative glycolytic (type 2A) fibers
high myosin ATPase activity with high oxidative capacity and intermediate glycolytic capacity
fatigue resistant
moderate myoglobin
red muscle
abundant glycogen and mitochondria
standing/walking
56
fast glycolytic (type 2X) fibers
high myosin ATPase activity with high glycolytic capacity
rapid forceful movements
fewer mitochondria
low myoglobin
white muscle
easily fatigues
jumping/sprinting/weightlifting
57
muscle plasticity
exercise training or changes in patterns of neuronal stimulation can cause changes in proportion of slow vs fast twitch muscle fibers
58
smooth muscle unitary structural organization
sheets of electrically coupled cells
gap juncts for communication
cels contract together - syncytium
59
smooth muscle multiunit structural organization
each cell receives seperate input
each can contract independently
no gap juncts
60
tonic smooth muscle
usually contracted
sphincters
61
phasic smooth muscle
normally relaxed and undergoes rhythmic changes in contractile state
stomach and bladder
62
smooth muscle key characteristics
contraction initiated by electrical, chemical, and mechanical input
ANS release NT through varicosities
Ca from ECF and sarcoplasmic reticulum
myosin ATPase only active when phosphorylated
63
spontaneous electrical initiation of smooth muscle contraction
pacemaker activity from channels that spontaneously increase depolarizing currents
interstitial cells of cajal in digestive system
64
hormones and paracrine signals of smooth muscle contraction
vasopressin and angiotensin II (vasoconstrictor)
NE (vasoconstrictor and vasodilator)
histamine (constrict airway)
nitric oxide (relax smooth muscle of vessels)
65
how does smooth muscle increase Ca
L type voltage gated calcium channels
calcium induced calcium release from SR
chemically stimulated IP3 (agonist binding GPCR leads to formation IP3)
store operated channels (depletion SR Ca cause aggregation STIM 1 which activates orai channels allowing Ca entry)
66
what allows myosin to bind actin
phosphorylation by myosin light chain kinase
67
MLCK stimulated by what
Ca dependent calmodulin
68
what dephosphorylates myosin and promotes relaxation
myosin light chain phosphorylase
69
smooth muscle contraction stages
increased cytosolic calcium
Ca binds calmodulin
Ca calmodulin activates myosin light chain kinase
phosphorylated MLC triggers conformational change that allows attachment myosin head
70
smooth muscle relaxation
decreased cytosolic calcium (decreased activation MLCK)
refilling of SR stores w SERCA
sodium calcium exchangers
plasma membrane calcium ATPase
71
what second messenger inhibits MLCK
cAMP
72
what second messenger inhibits MLCP
rhokinase
73
cyclic nucleotides favor what
vasodilation
NO increases cGMP
cGMP increases MLCP activity
prostoglandins increase cAMP
cAMP inhibit MLCK
74
Ca favors what
constriction
Gq IP3 induced Ca release by endothelin and thromboxane
extracellular calcium influx
75
vasoconstriction does what
increase BP
decrease perfusion
76
vasodilation does what
decrease BP
increase perfusion
77
airway smooth muscle changes
cyclic nucleotides favor relaxation
Ca favors constriction
bronchodilators increase cAMP levels and decrease G mediated Ca increase
78
cardiac muscle contraction
Ca is a mediator and an activator
Ca binds troponin revealing binding site
Ca influx to cardiomyocytes trigger SR Ca release
79
cardiac muscle relaxation
calcium reuptake into the SR by Ca ATPase (SERCA2)
SERCA2 regulated by phospholambin which is regulated by phosphorylation
Na Ca exchanger
80
how does cardiac muscle avoid tetanus
duration AP = period of contraction and relaxation
81
increasing endurance capacity
increase type 1 fibers
greater oxidative capacity
increase oxygen delivery
increase capillary supply
increase mitochondria content
increase glycogen storage
82
strength training
strength of muscle determined by size
increase in contractile proteins
resistance training amplifies type 2 fibers (rapid forceful movements but fatigue quickly)
83
immediate energy sources for muscles
ATP (1-2s)
phosphocreatine (3-5s)
84
nonoxidative/anaerobic glycolysis for muscle energy
1 - 2 minutes
uses muscle glucose and glycogen
85
aerobic oxidation for muscle energy
plasma glucose, muscle glycogen, liver glucagon, plasma free fatty acids, adipose triglycerides
86
sustained activity of moderate intensity
use mainly fatty acids and glucose oxidation provides the remainder of the energy
87
in the absence of glucose or triglycerides
proteins utilized for energy for muscles
88
breaking down of proteins promoted by what
glucocorticoids
89
types of muscle fatigue
central
peripheral
lactic acid accumulation
glycogen depletion
90
central fatigue
changes in CNS
reduce excitatory input
91
peripheral fatigue
impaired initiation or propogation of AP (impaired membrane excitability or depleted ACh)
impaired Ca release
accumulation byproducts
92
lactic acid accumulation
decreases pH
reduce myosin ATPase activity
93
glycogen depletion
no glycogen for energy
carb loading can prevent hitting the wall by increasing resting glycogen stores
94
muscle building
active myocytes promote vasodilation, secrete growth factors (IGF 1/2, FGF), promote satellite cell activation
stress of exercise induce sympathetic nervous system and increases cardiac output
95
hypertrophy
caused by near maximal force development
increase in myofibrils
96
lengthening
occurs when muscles are stretched
new sarcomeres added
increase shortening capacity
increase contraction velocity
97
hyperplasia
formation new muscle fibers
caused by endurance training
98
causes of muscle atrophy
denervation/neuropathy, tenotomy, sedentary life style, cast, space flight
99
effects of muscle atrophy
degeneration of contractile proteins
decreased max force of contraction
decreased velocity of contraction
100
effects of loss of innervation on muscle
2 months - degenerative changes occur
(if returned rapidly full function can return in 3 months w electrical stimulation)
1-2 years muscle fibers are lost and replaced with fibrous and fatty tissue
contracture - fibrous tissue replacing muscle fibers shorten
101
depletion of muscle and liver glycogen
increase in muscle catabolism
stimulated by glucocorticoids
102
testosterone
protein synthesis via direct and powerful transcriptional effects
-loss of muscle with aging
103
estrogen
increased protein assembly via metabolic pathways
-loss of muscle post menopause
104
increased glucocorticoids/cortisol
response to stress
elevated in many pathologies (cushing syndrome)
increased muscle catabolism
105
growth hormone effect on muscle
stimulates IGF release which promotes hypertrophy
106
thyroid hormone effect on muscle
increase muscle contractility, glycolytic capacity, myofibril assembly
107
steps of O2 uptake and consumption
1. uptake of O2 by lungs depends on pulmonary ventilation (VO2 max is point transport system can no longer keep up with demand, O2 uptake plateus)
2. O2 delivery to muscles depends on blood flow and O2 content (increase alveolar ventilation to maintain PO2 levels, increase cardiac output to ensure high flow of blood)
3. extraction of O2 from blood depends on O2 delivery and pressure gradient between blood and mitochondria (training can augment maximal cardiac output)
108
pH 4.6 staining
type 1 dark
type 2a pale
type 2b intermediate
109
pH 9.4 staining
type 1 light
type 2a dark
type 2b dark
110
nadh staining
type 1 dark
type 2 light
111
succinate dehydrogenase staining
type 1 dark
type 2 light
112
COX staining
type 1 darker
type 2 lighter
113
neurogenic muscle disease characteristics
distal>proximal weakness
atrophic fibers (denervated) and type grouping
114
myopathic muscle disease characteristics
increased internal nuclei
degenerating/regenerating fibers
proximal>distal weakness
115
types of neuromuscular diseases
myasthenia gravis
lambert eaton syndrome
116
myasthenia gravis
antibodies again post synaptic ACh receptors with loss of receptors
increased weakness with repetitive stimulation
can occur w thymomas
117
lambert eaton syndrome
antibodies again presynaptic voltage gated calcium channels
increased strength with nerve stimulation
can be paraneoplastic
118
types of myogenic muscular diseases
inflammatory (polymyositis, dermatomyositis, inclusion body myositis)
dystrophic (dystrophinopathy, limb girdle, myotonic dystrophy)
metabolic (McArdle, lipid myopathies, mitochondrial myopathies)
congenital (floppy babby)
drug/toxic (corticosteroids, statins)
systemic disease
119
inflammatory muscle disease characteristics
internal nuclei, inflammation, myophagocytosis, degenerating and regenerating fibers
antibodies (anti-Jo-1) may be present
120
polymyositis
wide spread changes throughout the involved muscle
responds to steroids
increased serum creatine kinase
121
dermatomyositis
inflammation (perivascular), perifasicular atrophy, skin changes
responsive to steroids
122
inclusion body myositis
cytoplasmic inclusions, rimmed vacuoles
not responsive to steroids
123
dystrophic muscle disease characteristics
can be genetic
wide spread variation in fiber size including hypertrophic fibers
124
dystrophinopathy
absence (duchene) or irregular (becker) staining for dystrophin
X linked
produces cardiac manifestations
hypertrophy of calf muscles secondary to fatty replacement of fibers
125
limb girdle
autosomal inheritance
prob with dystrophic associated proteins
similarities w muscular dystrophy
126
myotonic dystrophy
CTG repeats
large increased internal nuclei
muscles inable to relax
cataracts, baldness, gonadal atrophy
127
metabolic muscle disease characteristics
secondary to enzyme/genetic issue
often related to energy stores
128
McArdle
deficiency of phosphorylase
difficult cleaving glucose molecules from glycogen
difficulty w exercise
129
lipid myopathies
accumulation lipids
130
mitochondrial myopathies
abnormal mitochondria
abnormal staining mitochondrial enzymes
include MELAS, Kearns Sayre, MERRF
131
congenital muscle disease (floppy baby)
nemaline rod (accumulation z band material)
centronuclear
central core myopathies
132
corticosteroid muscle disease
type 2 fiber atrophy
133
statins muscle disease
myalgia, mitosis, rhabdomyolosis, vacuolization
134
skeletal muscle nuclei
in peripheral
135
cardiac muscle nuclei
central
136
smooth muscle nuclei
random
137
what percentage of internal nuclei are typically seen in normal muscle
4%
138
hemiplegic gate
loss of normal arm swing
139
diplegic gait
spasticity in lower extremities worse than upper extremities
140
neuropathic (steppage) gait
patients with foot drop
141
myopathic (waddling) gait
hip girdle weakness
drop in pelvis on contralateral side of pelvis while walking (trendelenburg)
142
choreiform gait (hyperkinetic)
irregular, jerky, incoluntary movements in all extremities
143
ataxic gait
staggering movements with wide based gait
144
parkinsonian gair
slow little steps
145
spurlings test
extend neck and sidebend head toward affected side, place axial pressure
positive is radicular arm pain reproduced
cervical radiculopathy
146
bakodys sign
externally rotate and abduct ipsilateral arm and shoulder above patients head
relief of pain is positive
cervical radiculopathy
147
hoffmans sign
flick tip of middle fingernail
positive is thumb flexion
spinal cord lesion/pathology of neck region
148
babinski reflex
trace curve of sole of foot
positive is hallux extension
spinal cord lesion
149
supracondylar humerus fracture
type 1 - fracture but no gaps in bone
type 2 - fracture and some gapping/displacement
type 3 - complete split of bone and kinked brachial artery
fail to treat correctly can lead to volkmanns ischemic contracture
150
in toeing
metatarsal adductus, internal tibial torsion
anteversion of humeral head
PT, serial casting, shoes/braces, sx
151
kocher criteria
for child with painful hip (non weight bearing on affected side, ESR >40 mm/hr, WBC >12000, fever)
4/4 99% chance septic arthritis
3/4 93% chance septic arthritis
2/4 40% chance septic arthritis
1/4 3% chance septic arthritis
152
congenital hip dislocation
barlow - dislocates
ortolani - lying in dislocated position and can be manually reduced
use brace
153
club foot (talipes equino varus)
tx - manipulation, serial casting, posteomedial release
154
congenital scoliosis
embryologic complications
renal/cardiac issues
155
neuromuscular scoliosis
caused by upper or lower motor neuron lesion during growth
can be long c shape
156
degenerative scoliosis
common in elderly
loss of disc and joint integrity may lead to loss of disc height asymmetrically and result in loss of coronal and sagital balance
157
idiopathic scoliosis
infantile <3 years
juvenile 3-10 years
adolescent 10-18 years
usually family history, more girls than boys
<30 degrees at maturity rarely progress significantly
>80 degrees increase risk of shortness of breath
curve between 25-40 degrees (reisser 2 or less) can brace
>45 degrees can do surgery
158
reisser classification
assess bone maturity by looking at ossification of iliac crest
0 - no ossification
5 - complete ossification
(curve >30 before peak growth or while at reisser 0 will most likely need surgery)
159
cobb angle
used to determine degree of scoliosis curve
draw line from most tilted superior vertebra and most tilted inferior vertebra, perpendicular lines drawn from both of these creating the cobb angle
160
septic arthritis
most <5 yrs
infants - hip most common
other joints - knees, ankles, elbows, shoulders, wrist
radiographic findings normal early in the course of the disease
161
slipped capital femoral epiphysis
adolescent, more often male and obese
usually unilateral
mechanical and hormone related
AP and lateral films (step off seen on affected hip)
immediate non weight bearing and surgery to insert a screw
162
spiral/toddlers fracture
usually <11 years
distal 2/3 of tibia
closed reduction and short leg casting for 4-6 weeks
163
osteosarcoma
most common primary bone tumor <40 years
occur at onset of puberty
in long bones of lower extremities
pain with activity
surgery, chemo, radiation
164
legg calve perthes
ischemic necrosis, collapse, and repair of femoral head
caused by disruption of blood flow to femoral head
4-8 years and usually boys
thigh, hip, or knee pain
decreased hip abduction, internal rotation, slight leg length discrepancy
braces/surgery, ROM therapy
165
compartment syndrome
increased pressure in limited space compromises circulation and function of muscles and nerves
causes - fracture, reperfusion injury, crush injury, animal bites, trauma
symps - sever pain and tense swollen compartments
increased serum creatine kinase and motor deficits indicate irreversible damage
children - analgesia, anxiety, agitation
adults - pain, palor, paresthesia, pulselessness, paralysis
remove restrictive casts, place limb at heart level, surgical fasciotomy
166
polymyalgia rheumatica
muscle inflammatory condition
>50 years
bilateral shoulder pain and stiffness, pelvic girdle pain
onset acute and symptoms worse in morning
association with giant cell arteritis
elevated ESR and CRP
tx - steroids
167
fibromyalgia
chronic pain disorder w widespread musculoskeletal pain, fatigue, sleep disturbances, headaches, cognitive/mood disturbances
usually starts after a stressor
initially pain isolated to shoulder
no cure, use antidepressants, anti seizure drugs, therapy, aerobic activity, OMT
168
glucocorticoid
any substance, usually a steroid, that activates a glucocorticoid receptor
169
where are natural glucocorticoids made
adrenal glands
170
what controls the release of glucocorticoids
HPA axis (hypothalamus anterior pituitary)
171
effects of glucocorticoids
stimulate gluconeogenesis, decrease utilization glucose, elevate blood glucose
reduce cellular protein, liver protein enhanced, increase blood AAs
metabolize fatty acids from adipose, excess causes fat redistribution
172
short acting glucocorticoids
hydrocortisone
cortisone
173
intermediate acting glucocorticoids
prednisone
prednisolone
methylprednisolone
triamcinolone
174
long acting glucocorticoids
paramethasone
betamethasone
dexamethasone
175
use of glucocorticoids
reduce inflammation
suppress immune response
reduce nausea and vomiting
reduce terminal pain
replacement therapy
176
replacement therapy
same as biological dose
hydrocortisone, prednisone, prednisolone
177
anti inflammatory
4x replacement dose
prednisone, prednisolone
178
inhibit immune response
16x replacement dose
prednisone, prednisolone
179
antiinflammatory action of glucocorticoids
modulate inflammatory response by suppressing expression of proinflammatory cytokines
repress expression adhesion molecules
induce expression of annexin 1 (promotes neutrophil detachment and apoptosis)
switch resident macrophage gene expression to anti inflammatory (increase phagocytic activity)
act on t cells blocking th1 and th2 cytokine production and induce cell death
180
glucocorticoid effects on gene transcription
bind and block promoter sites of inflammatory genes (IL1, IL1 beta)
activate anti inflammatory genes (IkappaBalpha, IL1receptor2, lipocortin 1, annexin 1, IL10)
inhibit synthesis of cytookines (NF kB, AP1)
181
glucocorticoid side effects
rise in blood neutrophils
cushing syndrome
thin skin
osteoporosis
immune suppression
hyperglycemia
182
kinetics of glucocorticoids
90% bound in blood
transport into cells
bind glucocorticoid receptor
active transport of dimer to nucleus
activating gene sequences
increase or decrease transcription
183
glucocorticoid resistance
HPA axis
receptor downregulation
heat shock protein complex redesign
Co Activators
184
glucocorticoid contraindications
peptic ulcers, hypertension and diabetes, viral and fungal infections, tuberculosis, osteoporosis, epilepsy and psychosis, CHF and renal failure
185
DMARDs definition
disease modifying antirheumatic drugs
186
conventional synthetic dmards
methotrexate
hydroxychloroquine
sulfasalazine
leflunomide
azathioprine
187
biologic dmards
anti TNF alpha - etanercept, adalimumab, certolizumab pegol, goligumab, inflixumab
immune cell targets - abatacept, rituximab
IL receptor antagonists - tocilizumab, sarilumab, anakinra
188
targeted synthetic DMARDs
JAK inhibitors - tofacitinib, baricitinib
189
bridge therapies
used in conjunction w dmards
use while waiting for dmard to become effective or experiencing flares
NSAIDS - mild to moderate flares
corticosteroids - moderate to severe flares
190
mild to moderate RA
csDMARDs
191
moderate to severe RA
csDMARDs or bDMARDS or csDMARDs+bDMARDs
192
methotrexate
first line, unless low disease activity
inhibit AICART which increases adenosine
inhibit proliferation and stimulates apoptosis of immune inflammatory cells
inhibit proinflammatory cytokines
-contraindications: pregnancy, hepatic/renal impairment, bone marrow suppression/aplastic anemia/GI toxicity
-adverse effects: nausea, mouth/mucosal ulcers, leukopenia, anemia, ulcerative stomatitis, GI ulceration, alopecia (leucovorin decrease GI side effects)
193
dmard naive with low disease activity
hydroxychloroquine then sulfasalazine then methotrexate then leflunomide
194
uncontrolled disease management
increase dose or switch to another class
195
pretreatment testing
CBC, ESR, CRP, LFT, BUN, creatinine, hep b/c
hydroxychloroquine - routine eye exams
biologics/jak inhibitors - TB screen
JAK inhibitors - lipid panel
196
hydroxychloroquine
stabilize lysosome enzymes, inhibit leukocyte chemotaxis, inhibit rna/dna synth
contraindications - cardiomyopathy and QT interval prolongation, cimetidine
197
sulfasalazine
suppress t cell response and inhibit b cell proliferation
inhibit release inflammatory cytokines (IL1, IL6, IL12, TNF alpha)
198
leflunomide
pyrimidine antagonist (block DNA synthesis and cell cycling) so arrest lymphocytes in G1
inhibit DHOD
inhibit t cell proliferation
adverse effects - diarrhea, increased liver enzymes, alopecia, weight gain, contraindicated in pregnancy
199
azathioprine
immunosuppressive antimetabolite
SEVERE RA
do not use in pregnancy
200
what do they mean?
momab - mouse
ximab - chimera
zumab - humanized
umab - human
201
Anti TNF alpha antibodies MOA
neutralize sTNF, neutralize tmTNF
bind tmTNF expressing immune cells and induce apoptosis
complement dependent cytotoxicity
202
adverse reactions anti TNF
neutropenia, infections, heart failure, cutaneous reactions
203
infliximab
bind to s and tm TNF
downregulation macrophage and t cell function
IV infusion
increased risk inefction with anakinra or abatacept
204
adalimumab
complexes s TNF and down regulates macrophage and t cell function
clearance decreased with methotrexate
205
certolizumab pegol
no fc region, does not fix complement
sub q
moderate to severe RA w methotrexate
206
golimumab
bind s and tm TNF
moderate to severe RA with methotrexate
sub q
207
etanercept
binds TNF
sub Q
do not start in active infection
hep b virus for reactivation
208
abatacept
inhibits t cell activation
decrease t cell proliferation and inhibit production of cytokines TNF alpha, interferon and interlukin 2
moderate to severe RA
increased risk of infection
209
ritixumab
targets CD20 b lymphocytes
moderate to severe RA
fatal infusion reaction
210
tocilizumab/sarilumab
bind IL6 receptors and inhibit IL6 mediated signaling\adverse effects - upper respiratory infections, headaches, injection site reactions, hypertension, nasopharyngitis, increased ALT, neutropenia, reduced platelets, lipid abnormalities
211
anakinra
bind and inhibit IL1 receptor
treat RA pts who have failed 1 or more DMARDs
sub Q
serious infections can occur
212
tofacitinib/baricitinib
target JAK inhibitor
influence transcription of genes that are crucial for differentiation, proliferation, function NK cells and T and B lymphocytes
in RA as monotherapy or in combination with methotrexate
adverse effects - increased risk of infection, thrombosis, CV death , MI, elevated liver enzymes, GI perforation
213
lateral epicondylitis
pain with wrist or finger extension
extensor carpi radialis brevis
pain with passive wrist flexion
tx - support straps and PT/OT
214
medial epicondylitis
pain with wrist flexion with elbow extended
pain with passive wrist extension
over head thrower medial ulnar collateral ligament injury should be ruled out
flexor pronator strain can be culprit
tx - rest, ice, PT, NSAIDs
215
olecranon bursitis
swelling bursa over olecranon usually after trauma, arthritis, or infection
common site for rheumatoid nodules or tophi from gout
tx - ice, anti inlammatory meds, aspiration/compression
216
nursemaids elbow
children 1-4 years
must rule out fracture
anular ligament is interposed into radiocapitellar joind
reduction with flexion, supination (palpable clunk)
217
cubital tunnel
compressive mononeuropathy, often trauma or prolonged elbow flexion
numbness/paresthesia of ulnar nerve
tinel test over ulnar groove, nerve conduction studies for definitive diagnosis
can result in claw hand
tx- splints, avoid provocation, sx
218
carpal tunnel
physical test (durkens compression, phalens, reverse phalens, tinel)
nerve conduction studies/electromyelogram for difinitive diagnosis
numbness/tingling in lateral hand
can result in thenar atrophy
219
dequervains tenosynovitis
entrapment of abductor pollicis longus and extensor pollicis brevis tendons at radial styloid
not inflammatory
secondary to chronic overuse of wrist
finkelsteins test
tx - splint, injection
220
triangular fibrocartilage complex
meniscus of wrist
injured in ulnar deviation and wrist extension
lunate is susceptible to ulnar abutment (can have chronic pain and instability)
pinpoint tenderness of ulnar fovea
MR arthrogram and wrist arthroscopy to diagnose
221
dupuytrens contracture
fibrosis of palmar fascia due to fibrobastic proliferation and collagen deposition
nodules form and lead to contractures
tx - collagenase injections, sx
222
trigger finger
stenosing flexor tenosynovitis
snapping or catching of finger in flexion
discomfort in finger but stenosing occurs more proximally
tx - injections, sx, consider getting A1c, DO NOT SPLINT
223
scaphoid fracture
FOOSH
pain over anatomical snuffbox
x ray (if initially negative brace and reevaluate in 2 weeks), if pain persists and xray negative consult ortho
wrist fusion is unacceptable
224
complex regional pain syndrome
reflex sympathetic dystrophy
pain in distal limbs
pain, swelling, skin changes
often after trauma to extremity
increased sensitivity
3 phase bone scan to detect metabolic changes
tx - NSAIDs, anticonvulsants, antidepressants, regional nerve blocks
225
avascular necrosis of hip
osteonecrosis/aseptic necrosis
compromise of vasculature to bone
pain in groin, but, thigh (worse w weight bearing)
radiograph shows classic crescent sign
tx - conservative care and sx
226
meralgia paresthetica
lateral femoral cutaneous nerve entrapment as it passes under inguinal ligament
obesity, pregnancy, diabetes
burning pain, tingling, deminished sensation on lateral thigh
tx - avoid constrictive clothing, weight loss, OMT, PT, NSAIDs (refreactory cases can use anticonvulsants)
227
snapping hip syndrome
snap with mvmt of hip with or without pain
common in athletes
external most common (mvmt glut max tendon, tensor fascia latae, IT band
internal usually w flexion abduction and external rotation
tx- OMT, PT
could be labral tear of hip
228
trochanteric bursitis
pain over lateral hip over greater trochanter
pain when laying on side of bursitis and with activity
resist abduction
can have antalgic gate
tx - NSAIDs, activity moification and exercises, steroid injection
could also be IT band syndrome, lumbar radiculopathy, hip nail could cause bursitis
229
piriformis syndrome
entrapment of sciatic nerve
often in sprinters and runners
buttock pain that increases with sitting (wallet sign), can have paresthesias
frieberg test, pace test
tx - OMT, PT, steroid injection
230
psoas syndrome
lower back and pelvic girdle pain, difficulty sitting up straight
often in runners, jumpers, or sitting for long periods of time
dx - thomas test
tx - OMT, PT
231
impingement syndrome
pain w overhead motion, pain at night sleeping on shoulder, pain on internal rotation
common after 40 due to partial rotator cuff tear
compression of subacromial bursa or rotator cuff tendons
neer and hawkins test
tx - PT, modify activity, injections, OMT
232
rotator cuff disorders
usually supraspinatus
weakness in internal and external rotation
empty can test
xray to rule out other issues, MRI to confirm tear
partial tear - OMT/PT
full tear - PT/Sx in most young active pts
233
adhesive capsulitis (frozen shoulder)
constant, deep, poorly localized shoulder pain w worsening pain with motion, often worse at night
commonly in diabetics
conservative therapy, can do sx
234
labrum tear
acute, history of dislocation, chronic overhead throwing
SLAP
deep pain in joint, catching and locking of joint
obriens test
MRI to confirm
tx - rest, NSAIDs, PT, OMT, sx
235
biceps tendonitis
inflammed long head of biceps tendon, usually caused by overuse
anterior shoulder pain radiating down biceps
speed and yergasons test
tx - steroid injection, NSAIDs, omt, sx for distal tears
236
AC joint instability/separation
graded 1-6
crossover test
tx - conservative tx with sling vs sx
237
patellofemoral pain syndrome
runners knee
undersurface of patella pain
patella not ride in femoral groove
patellar apprehension test, j sign
tx - ice, NSAIDs, strengthen and stretch, brace, OMT, sx as last resort
238
neuromuscular blocking drugs
interfere with transmission at neuromuscular end plate without affecting CNS
nondepolarizing - long acting (tubocurarine, pancuronium), intermediate acting (vecuronium, rocuronium, atrocurium, cisatrocurium), short acting (mivacurium)
depolarizing blockers - succinylcholine
excreted by kidney = longer half life
eliminated by liver = shorter half life (also most of the intermediate acting)
239
spasmolytic drugs
reduce abnormally elevated muscle tone without paralysis, reduce spasticity in neurologic conditions
cns action - baclofen, tizanidine, gabapentine, diazepam
acute local spasms - cyclobenzaprine, metaxalone, methocarbamol, carisoprodol, orphenarine
muscle action - dantrolene, batulinum toxin
240
nondepolarizing blockade
prevent acetylcholine access to receptor and prevent depolarization and cause neuromuscular paralysis
like tubocurarine
241
tubocurarine
prototype receptor blocker
side effects - hypotension
reversible blockade accomplished w use of AChE inhibitors (neostigmine)
242
depolarizing blockade
succinylcholine
persistent depolarization of endplate so much so that it can no longer depolarize and contract
243
succinylcholine
2 ACh molecules bound together
diffuses and metabolized by plasma
short duration of action
used to initiate relaxation and other muscle relaxants used to maintain relaxation
adverse effects - hyperalemia, increased gastric and intraocular pressure
244
cisatracurium/atracurium
no ganglion blockade, no cardiac M2 receptor activity, no histamine release
intermediate acting nondepolarizing muscle relaxant
245
mivucurium
shortest duration
profound histamine release
cleared by plasma cholinesterase
duration prolonged in renal impairment
246
vecuronium/rocuronium
rocurmonium most used
steroid derivates can produce tachycardia causing arrythmias
247
baclofen
orally active GABA mimetic agent
reduce spasticity with less sedation than BZD
adverse effect is drowsiness
248
tizanidine
alpha 2 adrenoreceptor agonist
used for spasticity, muscle cramps, muscle tightness
drowsiness, hypotension
contraindicated with ciprofloxacin and fluvoxamine
249
gabapentin
centrally active gaba
antispasmolytic with multiple sclerosis
250
diazepam
facilitate GABA
muscle relaxation and reduce muscle spasms
251
dantrolene
interferes with excitation coupling in muscle fibers (inhibits release of calcium by binding ryanodine receptor)
can treat malignant hyperthermia
252
botulinum toxin
prevent ACh release
253
methocarbamol
skeletal muscle relaxation via general CNS depression
254
cyclobenzaprine
reduce tonic somatic motor activity
anticholinergic effects
255
metaxalone
disrupt spasm pain spasm cycle
256
carisoprodol
central depressant
257
