Succinylcholine
depolarizing agents
non depolarizing agents
local anesthetics
Misc
NMBA
Somatic Nervous System
Malignant Hyperthermia
Reversal Agents
100
How is it eliminated?
-pseudocholinesterase
100
What is the only depolarizing agent that is used in the US and how does it work?
Succinylcholine
- Mimics ACh at the motor end plate. The process is prolonged because Suc is not broken down by acetylcholinesterase so it can act longer.
100
What is the MOA?
These agents compete with ACh for the same cholinergic receptors.
100
MOA of local anesthetics
L.A block Na channels from opening
100
anesthesia that is too light is hazardous to the ____, while anesthesia that is too heavy is hazardous to the _____. Therefore, we want _______ anesthesia.
Provider, patient, balanced
100
NMBAS consist of ______ and _______ agents.
depolarizing, non depolarizing
100
Controls this type of muscles on the body.
skeletal muscles
- voluntary skeletal muscle movement that is told what to do from the brain by efferent nerves.
sensory-> afferent nerves-> Brain-> efferent nerves-> skeletal muscles
100
What causes MH?
uncontrolled release of Ca2+ ions from the skeletal muscles.
100
Name the common reversal agents from highest potency to lowest potency.
- Edrophonium
- neostigmine
- pyridostigmine
200
Administration complications
- hyperkalemia
- Cardiac dysrhythmias
- Malignant hyperthermia
200
sustained opening of ion channels
depolarization and fasciculations occur during this phase
Phase 1
200
How would a TOF be different in a non depolarizing agent than a depolarizing agent?
In a non depolarizing agent there is a fade in impulses from the beginning and there is no other phases.
200
What two groups make up local anesthetics.
Amides and Esters
200
What type of procedures would use Regional anesthesia, what are the characteristics and what is the responsibility of the CRNA?
- superficial surgeries or invasive diagnostic procedures
- They would use a combination of oral and parenteral sedatives and local anesthetics
- our responsibility to maintain airway and patient response
200
What characteristics make up an ideal NMBA?
rapid onset, short duration, rapid rate of recovery, high specific potency for neuromuscular blockade, No CV side effects, no histamine release, no cumulative effects with repeated doses, inactive metabolites and pharmacologic reversibility.
200
How is the somatic nervous system different than the autonomic nervous system?
The somatic is a one neuron pathway that does not contain autonomic ganglions.
ACh is the only neurotransmitter that is used.
the pathway is completely myelinated.
200
True or False:
MH is a potentially life threatening event triggered by depolarizing NMBA and inhaled gases.
True
200
What is the MOA? How does the MOA explain why these agents do not work well on Succ, mivacurium and cis-atracurium?
- these agents increase the availability of ACh by blocking the break down of ACETYLCHOLINESTERASE, helping to increase competition at the acetylcholine receptor.
- The other medications mentioned are not broken down by acetylcholinesterase so therefore they are able to continue to work even after these reversal agents are given.
300
cardiac arrest from K+ to patients with:
- neuromuscular disease
- burns
- severe trauma
- nerve injury
300
This is the desensitization neuromuscular blockade
often occurs with large boluses or infusions (2-4 mg/kg IV) and abrupt transition
preceded by tachyphylaxis
Phase II Blockade
300
What are different long acting agents
Pancuronium (high HR and BP)
Doxacurium (longest acting, no CV effects)
Pipecuronium (no CV effects, caution in renal failure)
300
How does LAH+<-> LA + H+ work together to inhibit Na channels?
What happens when the pH increases?
- both are needed because the unionized molecules are used to cross the membrane while the ionized bind to the channel to block.
- Higher pH = more unionized molecules therefore quicker the block will be established.
300
What type of procedure would general anesthesia be used for? What type of medications would be used and what is the CRNA's responsibility?
- extensive surgery
- preoperative sedative, IV induction and IV/inhaled maintenance
- Provide complete anesthesia and extensive patient monitoring
300
Which neuromuscular pathway is manipulated in NMBAs?
The nicotinic cholinergic receptor
300
What type of receptors are used for triggering muscle action and what are the characteristics?
Nicotinic ACh receptors
- Quick, excitatory, ligand gated ion channels
300
What is the clinical presentation of MH
contracture / steel pipe rigidity of muscles and jaw
tachycardia
increased production of CO2
metabolic acidosis
heat production from skeletal muscles (late sign)
300
reliable signs of reversal
head lift x5 seconds
teeth clenching x5 seconds
- usually not difficult to reverse if 2 twitches are visible in TOF
400
Cardiovascular effects
What is the result of the mimicked activity of ACh at the M2 receptor of the SA node?
Who is more at risk? those with high sympathetic tone or low sympathetic tone?
- The result is bradycardia, junctional or sinus arrest
- pretreat with NDNMBA
- high sympathetic tone is more at risk (KIDS)
- pretreat with Atropine
400
What are fasciculations and how do you prevent them?
- muscle tremors caused by rapid depolarization of the muscle fibers (presynaptic receptors are blocked prior to postsynaptic receptors)
- prevented by pretreating with a non depolarizing agent.
400
Short acting agents
Mivacurium
- increased histamine release which may= tachycardia and bronchospasm (caution in asthma)
- metabolized primarily by pseudocholinesterase
400
What is Cm?
How does it differ in muscle fibers vs sensory fibers?
subarachnoid anesthesia vs. epidural anesthesia?
Cm is the minimum concentration required of L.A. to produce conduction blockade of nerve impulses.
muscle fibers need a higher minimum concentration than sensory fibers
Subarachnoid anesthesia needs a lower minimum concentration than epidural anesthesia
400
What characteristics make up the ideal agent?
Is there a single agent that can achieve all effects?
- to quickly, safely and reversibly achieve unconsciousness, amnesia, analgesia, inhibition of autonomic reflexes, skeletal relaxation.
- NO single agent can do all these things
400
What are the characteristics of the Nicotinic cholinergic receptor?
- membrane spanning, ligand - gated ion channel
- has 5 protein subunits around a central pore (2 alpha, 1 Beta, 1 Gamma, 1 Delta)
- ACh binds to the alpha sites to open the ion channel causing Na ions to come into the cell.
400
Cholinergic Toxidrome - Rebound cholinergic effects
Nicotinic Symptoms?
Nicotinic - M,T,W,T,F
muscle cramps, tachycardia, weakness, Twitching, Fasciculations
400
Treatment for MH
-Dantrolene
- O2
- cooling
400
Why is the administration of glycopyrrolate and atropine important when giving edrophonium, neostigmine or pyridostigmine?
Prevents:
Cardiac: hypotension and bradycardia
Pulmonary: bronchospasm, hypoxia, and increased secretions.
500
Why would we avoid giving Succ to patients that are already at risk of increased ICP?
(head trauma and and intracranial tumor patients)
- inconsistent finding of increased ICP and increase CBF have been observed due to the fasciculations.
500
How would a TOF be different in a depolarizing agent than a non depolarizing agent?
Depolarizing agents have two phases in the first phase there would be no fade in impulse. In the second phase you will start to see a fade.
500
intermediate agents
-Atracurium (ester hydrolysis and hofmann elimination, not for asthmatics d/t histamine release)
-Cis-atracurium (hofmann elimination, not for seizure people cleaner SE profile than atracurium)
-Vecuronium (no sig. CV effects seen, reduce dose in liver disease)
-Rocuronium (quickest onset, prolonged duration in hepatic disease pt.'s, used in RSI, duration is longer than SUCC with the same onset.)
500
What effect does epinephrine have on L.A.?
True or False:
epinephrine can be used in all body parts big or small.
Prolongs the effect from vasoconstriction. This decreases the rate of systemic absorption.
- False
- you would want to avoid giving epinephrine in places with poor blood flow, like ears, fingers, nose, and intracutaneous injection.
500
What are the different mechanisms of anesthetic agents?
and
True or False:
the mechanism behind anesthetic agents is basic and well understood by many pharmacists.
Neurons are affected pre and post synapticaly in the nerves and muscular junction. There is also inhibitory induction and excitatory inhibition taking place.
and
False
- The MOA is poorly understood and is very complex
500
What are different purposes of NMBA in anesthesia?
- skeletal muscle relaxation
- prevention of abdominal muscle spas
- facilitate intubation
- provide optimal surgical conditions
500
Cholinergic Toxidrome - Rebound cholinergic effects
Muscarinic Symtoms?
Muscarinic - SLUDGE
Salivation, Lacrimation, Urination, Defecation, GI cramping, Emesis
500
Dantrolene MOA
binds to the sarcoplasmic reticulum and reduces Ca2+ release.
500
How does sugammadex work as a reversal agent?
What agents is it FDA approved to reverse?
- forms a water soluble complex with steroidal NMBA
- rocuronium and vecuronium
600
Ophthalmic Effects and Intragastric pressure
Why do we avoid giving succ to open eye injury patients?
How does Succ effect intragastric pressures?
- Increased intra ocular pressure could cause extrusion of global contents.
- there are striated muscles of the eye that have several motor end plates
---------------------------------------------------------
Increased fasciculations = increase intragastric pressure
visible muscle contractions can lead to aspiration risk... may want to pretreat with NDNMBA
600
True or False:
Fasciculations can lead to myalgia.
- True
- myalgia - cause some damage to muscle fibers and can also cause pain postoperatively.
600
What is the benefit of a priming dose and how does it work?
used to speed the onset of NMBA
Theory - Enough receptors will be occupied that speed of onset will be increased significantly when the balance of the intubating dose is given.
600
Uses of regional anesthesia include:
- topical or surface
- local infiltration
- peripheral nerve block
- IV regional nerve block
- epidural
- spinal
600
What is the cause of Transient Neurologic Symptoms after intrathecal and how is it treated?
- cause: unequal distribution of nerve bundles usually caused by positioning (lithotomy position) especially when lidocaine is used.
Treated with opioids for pain full recovery expected in 1-7days
600
The prototype neuromuscular blocking agent
tubocurarine
600
For activation of various physiologic mechanisms like heart rate and mucous secretion we use MUSCARINIC ACh receptors which are:
- inhibitory mechanisms
- G protein coupled receptors
- action is slower metabolic response via second messenger
600
True or False:
Only a small amount of Dantrolene is needed to treat MH.
False
- Large volumes of Dantrolene is needed for treatment of MH
600
Sugammadex adverse reactions and interactions.
AE: hypotension, cough, nausea, vomiting, Headache, dry mouth, and anaphylaxis (rare).
interactions: birth control- equivalent to missing a day of birth control.
34% reduction in progesterone because the shape of progesterone is similar to rocuronium.
700
Why would patients that have muscular dystrophy and myopathies (like duchenne's muscular dystrophy), burn injury patients, skeletal muscle atrophy/ denervation, severe skeletal trauma in the last 72 hours, upper motor neuron lesions (like Guillain Barre), or prolonged immobilization NOT be candidates for Succinylcholine?
ALL these factors could cause hyperkalemia.
-burns
- susceptibility exists b/n 10-60 days post burn
- pretreatment does NOT inhibit this effect in burns
700
True or False:
Succinylcholine is the only depolarizing agent used in the US and its antidote is atropine.
False
- Succ is the only depolarizing agent used in the US but there is NO ANTIDOTE.
700
Who is most susceptible for adverse effects from a priming dose and what are the AE?
- patients with limited pulmonary reserve (COPD) and neuromuscular dysfunction (myasthenia gravis)
- AE include dyspnea, dysphagia and apnea
700
Warning signs of overdose in awake pt.s.
Early: oral numbness, tongue paresthesia (tingling), and dizziness
Sensory: tinnitus and blurred vision
Excitatory: restlessness agitation
700
Cauda Equina Syndrome causes? Symptoms?
Anterior Spinal Artery Syndrome causes? Symptoms?
CES- caused by non-homogenous distribution of LA on dependent stretched nerves. S: sensory anesthesia, bowel and bladder sphincter dysfunction, paraplesia
ASAS: caused by thrombosis or spasm of anterior spinal artery D/t hypotension or vasoconstrictor drugs. S: lower extremity paresis with a variable sensory deficit.
700
Nerve impulse travels down a nerve fiber to the terminal-> depolarization opens calcium channels in membrane causing calcium influx-> calcium promotes vesicles full of ACh into synaptic cleft-> ACh binds to cholinergic receptors and alters ion permeability of muscle fiber-> once action potential is reached it is passed into the surrounding cells
normal neuromuscular junction function
700
What does the parasympathetic system control?
involuntary movements/ glands
700
Why is conjunctive 100% oxygen at 10 mL/minute useful in treating MH?
- It will flush out volatile anesthetics and lower ETCO2
700
Which anticholinergics are recommended with which cholinesterase inhibitors?
Neostigmine and pyridostigmine = glycopyrrolate
edrophonium = atropine