4-3

• clnically sick muscle
• neuromuscular disease
• autoimmune
• treatment related

• genetic testing available
• myasthenia gravis
• periodic paralyses
• endocrine myopathies

used for muscle fiber pathology nnuclei

surrounds each fasicle

multicucleated at the periphery

neuogenic dysfunction

dennervation as nuclear clumps

• large axonal neuropathy
• angular atrophy

NMJ

brown stain that measures integiry oof motor end plates

myosin loss PH stain

• normal muscle differentiation
• type I fibers slow twitch
• type II fibers fast twitch, glycogen rich

a fiber type atrophy

• dystrophin deficiency
• chromosome Xp21. weakness proximal to distal. failure to walk eventually

• clnical rash
• progressive pelvic/femoral weakmess
• chronic inflammation

• myofiber size
• round atrophy
• inflamation/myositis
• degenerating regenerating fibers

fibrosis, ragged red fibers

mitochonrdra

• NADH, SDH, COX 2
• NADH, succinate dehydrogenase reaction in ragged red myopathy

• alkaine phosphatase
• acid
• regeneration microvascular, lysosomes

low in dermatomysosis, connective tissue pathology

lysosomal activity, macrophages

inhalation anesthetics flurane, diethy; ether

concentration at which 50% of patients are unresponsive

anestheesia commences when a chemical substabce reaches a certain concnetration. Anesthetics disorder membrane lipids and increase membrane volume.

• major center of consciousness. When activity is depressed, ascending influences on limbic system are reduced.
• ALL agents block neuronal responses to sensory input

dorsal lamina of spinal cord

surgical anesthesia

medullary paraysis= death

alveoli>bld>brain. Parital pressure of each componenet gas is related to its concentration

anything that increases delivery of anesthesia will hasten

anything that enhances overall systemic uptake and removal of anesthetic from lungs will lower alveolar partial pressure and delay anesthesia.

higher concentration of nitrous oxide is taken up more rapidly

potent agents are delivered with nitrous oxide so increased amounts get to alveoli as NO get to pulmonary bld

low bld, tissue solubility, no biostransformation, no toxicity, nonirritating, highly potent can be given ample O2

no longer used because of CV depression, hypotension

not a true anesthetic

sedation, euphoria, nausea, chest wall, rep depresion

propofol

propofol with opiod

ketamine

Etomidate

functional depression in amine-dependent synaptic transmission

enhance monoamines and their metabolites(NE, dopa, serotinin)

• amine reuptake
• MOI inhibitors
• SSRIs
• tricyclics(non selective)

mixed NE and 5HT uptake inhibitors, dangerous in CV hen overdoes, low margin of safety

anticholergics, alcohol, CNS depressant, local anesthetics and vasoconstritors, use epinephrine carefully avoid levonoedefrin

used for atypical depression/panic disorder, clinical effect persists after drug discontinued, depressed REM sleep, correction of sleep disorder

• dry mouth
• headache
• CNS stim and depress

• hypertensice crisis
• alsohol CNS depressants
• opiods/meperidine

wider margin of safety, OCD and depression, anxiety

GI symptoms, contrandicated with MAOIs,

SSRI and MAOI fever agittaion can lead to seizure coma and death

non-lethal, but sedation, hypotension, dry mouth

Buproprion-ADHD smoking cessation

lithium salts decreases suicide risk and mood swings

overdose more common due to accmulation. Nausea trmor, diarreha, convulsions

anxiety, avoid dentist

• therapy
• SSRIs
• benzodiazepienes
• buspirone
• antihistamines
• beta blockers

diazepam

binding to benzodiazepine receptor on the GABA complex

antianxiety, CNS depression, anterograde amnesia, inhibition stage 4 sleep, respiratory depression, drowsiness

benzodiapeine antagonist used to treat ODs

zolpidem

• IV anesthtics that bind to receptors on the GABA to increase effects.
• Lower margin of safety than BZs
• Inhibite glutamate receptors

CNS depression, CV depression, anticonvulsant action

• decreased REM sleep
• liver
• teratogensis

first line agents in anti-axiety drugs

chloral hydrate

sedative GABA ergic, NMDA antagonism, low margin of safety. Acetaminophen interaction

linked to toxic metabolite, need to detox NAPQI y glutathione. NAPQI non-detoxed causes liver damamge. NAPQI productiion induced by ethanol

acetaldehyde

• deerly disordered thought
• organic-memory loss
• idiopathic-memory and orientation are in tact(Scitzo)

• Positive-hallucination, delusions
• negative symptoms- blunted affect, anhedonia, social withdrawl, aolition, alogia

block dopamine recceptors to reduce positive symtoms

block serotinin receptors

• phenothiazines
• thioxanthenes
• buterophenones

decrase emotional display, antiemitic effect, hypothalmic loss of thermoregu, increase appitite weight gain

EPS, dystonia, tremors

• postural hypotension
• reflex tachy

blurred vision, dry mouth, constipation, dyskinesia suppresion

neuroleptic exposure, risperidone

• improved negative symptoms
• reduced risk of TD, EPS

clozapine...no prolactin increase but seizure, tachy, constipation, agranulocutosis

anti-serotinin, antidopamine, antiNE, aticholergic, antihitsmin....LOSE libido, erection

• baribituates
• phenytonin
• used in bipolar disorder-carbamasepine

ligand gated vs G-protein linked

one receptor rule, nicotinic striated muscle

nicotinic antagonist, paralysis and flaccid muscles

• 70% before any effect
• 90% for full efcect

greatest in muscle od respiration, least in muscles face and eyes

• release histamine
• afffects muscarinic
• short duration

competitive antagonist for nicotinic, slow in onset

prolong depolarization to sustain the inactivation. These are AGONIST drugs...succinylcholine

rapid onset, short duration...needs continuous duration patients with congential deficiency of cholinesterases.

genetic diseasse after triggering agents,, alternered ryanoodine receptor magnifies Ca release

GABA activaton

old drugs...site dependent

most common at synovial joint, chrondyctes reside in launae in basophillic matrix, proteoglycans then collagen II further out

fibroblasts and chondroblasts. ABSENT at articular surfaces

• appositional- incorporation at perichondrium
• instersitial growth0 divison of chdrocytes within cartilage itseld

intersitial- chondrocytes within the cartilagde

less abindant matrix, elastic fibers,with type II

intervertbral discs, articular spaces, attach to bones. Perichrondrom absent, type I, aciophillic, collagen arrange din direction of tensile forces.

• flat bones-mesnechymal cells differentiate into osteoblsts
• produces islands of womven bone
• womven bone remodeled in to compact bone

periostem and primitive connective tissue

• long bone begin with template from cartiladge
• osteoblasts invade from perichondrom and secrete osteoid around catilage

osteoblasts

b/t metaphysis and epiphysis...cartiladge replaced with bone marrow except at articular

resting zone, proliferatin hypertrophic-degenrative, calcification.

this is where chondrocytes are replaced by bone!

drives chondrocyte prolif...Laron;s syndrome prevens GH binding dwarfism

GH overprodcution post/ppre epuusyseal plate closure

• chondrocytes ar epiphyseal plate inhibited
• common drawrfism- achondroplasia

• granulation tissue...soft callus
• then ossification to form woven bone"hard callus".
• Resolution woven bone reabsorbed

x-ray, collagen test, genetic test type I collagen mutation. too little and fragile bone, blue sclera

• dense bone architecturall unsound, bone marrow transplant
• compression of cranial nerve, reduced hematapoesis

• too much reansorption, porous bone
• aging has reduced osteoblast fnction

• increased bone remodeling, gain in bone massjigsaw, cotton wool
• increased circumference
• alkaline phosphatiase anf hydroxyproline

• PTH-hyper
• rickets

when serum Ca2+ is low

osteoblasts do not have them

tumor/hyperplasia

kidney failure low Ca2+

poorly mineralized bone matrix-ostepmalcia and rickets in children

closed, open, compression veterbra

clot-granualtion-procallus-callus

inflammation of bone, staph aureaus

• BRONJ, compromised bld supply
• inhibit bone remodeling via osetoclasts

benign lesion of membranous bone (head and neck) radioopaque

• malignant (knee area)
• RB genes mutated
• osteoblast malignant
• Codeman triange, indisticnt border

• common beningn tumor
• near metaphysis growth plate

developmental tuor like condition where bone is replaced by fibrous stoma

osteoclastoma

affect weight bearing joint, degeenration of articular cartillage

TNF-alpha inflammatory cells, immune complex, small joints

• hyperuricemia
• cytokine, inflammation chemotaxis tissue desctruction, uric acid depsotion in joint space,
• renal failure