Drugs- Agents that act on the NMJ (Linger) Flashcards
Cisatracurium
Isoquinolone derivative (nondepolarizing) NMJ blocking drug
spontaneous elimination
2-3 min onset
25-45 min duration of action
tubocurarine
Isoquinolone derivative (nondepolarizing) NMJ blocking drug
6 min onset
80 min duration of action
Pancuronium
steroid derivative non depolarizing NMJ blocking drug
steroid
renal elimination
60-100 min duration of action
Rocuronium
steroid derivative non depolarizing NMJ blocking drug
hepatic elimination
LEAST potent
1-2 min onset
20-35 min duration of action
Vecuronium
steroid derivative non depolarizing NMJ blocking drug
succinylcholine
depolarizing NMJ blocking drug
eliminated by plasma cholinesterases
time of onset 1-1.8 min
duration of action 5-8 min
Dantrolene
Muscle relaxant (sapsmolytic)
echothiophate
AChE inhibitor
edrophonium
AChE inhibitor
alcohol type
binding to AChE is noncovalent and reversible
quaternary and charged
Neostigmine
AChE inhibitor
(1) Carbamic acid esters of alcohols bearing quaternary or tertiary ammonium groups (positively charged or neutral)
quaternary and charged
Physostigmine
AChE inhibitor
(1) Carbamic acid esters of alcohols bearing quaternary or tertiary ammonium groups (positively charged or neutral)
tertiary and uncharged
-CNS distribution
pyridostigmine
AChE inhibitor
quaternary and charged
(1) Carbamic acid esters of alcohols bearing quaternary or tertiary ammonium groups (positively charged or neutral)
Atropine
Antimuscarinic compound
Pralidoxime
Cholinesterase reactivator
what is the role of neuromuscular blockers
i) Interfere with transmission at the neuromuscular end plate and lack CNS activity
ii) Used primarily as adjuncts during general anesthesia to achieve adequate muscle relaxation without the cardiorespiratory depressant effects produced by deep anesthesia
iii) One of the most commonly used classes of drugs in the operating room
iv) No known effect on consciousness or pain threshold
what is the function of spasmolytics
i) Used to reduce spasticity in a variety of neurologic conditions (e.g., chronic back pain, fibromyalgia, and muscle spasms)
ii) Traditionally have been called “centrally acting” muscle relaxants
iii) Due to their actions within the CNS, most spasmolytic agents will be covered in the Neuroscience System II course
what is the protoype of the nondepolarizing NMJ blocking drugs
d-tubocurarine
antagonist at the nicotinic acetylcholine receptor
prototype depolarizing NMJ blocking agents
succinylcholine
what limits the CNS entry of NMJ blocking drugs
the presence of one or two quaternary nitrogens makes them poorly lipid soluble and limits CNS entry
why must you administer NMJ blocking drugs parenterally
d) All of the neuromuscular blocking drugs are highly polar and inactive orally, so they MUST be administered parenterally
how do NMJ blockers that are eliminated via liver compare in their duration of action to those that are renally eliminated ?
d) All of the neuromuscular blocking drugs are highly polar and inactive orally, so they MUST be administered parenterally
MOA of nondepolarizing NMJ blocking agents
competitive antagonists at the nACHR
iii) In large doses, nondepolarizing muscle relaxants can enter the pore of the nAChR to produce a more intense motor blockade and diminish the ability of acetylcholinesterase inhibitors to antagonize their effects
iv) Can block prejunctional nAChRs and interfere with the mobilization of acetylcholine at the nerve ending
v) 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)
how do you reverse the affects of non depolarizing neuromuscular blocking agetns
add ACh or succinylcholine
ii) To increase the concentration of ACh at the NMJ, a cholinesterase inhibitor may be given (larger doses of nondepolarizing agents diminish the antagonizing effects of cholinesterase inhibitors because the channel pore is blocked, see above)
atropine is coadminstered with cholinesterase inhibitors to minimize adverse cholinergic effects (bradycardia, bronchoconstriction, salivation, n/v)
what are the ADR’s of nondepolarizing NMJ blockers
- histamine release- bronchospasm, hypotension, bronchial and salivary secretion
- large doses –> tubocurarine and metocurine – > can produce ACh receptor blockade at autonomic ganglia and at adrenal medulla–> fall in blood pressure and tachy
iii) Because 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 of neuromucular blockers and 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
drug drug interactions of antibiotics and neuromuscular blockers
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
phenytoin and carbamazepine effects on neuromuscular blocker drugs
Conversely, phenytoin and carbamazepine significantly increase the requirement for nondepolarizing NMBAs by an unknown mechanism
which patients are resistant to nondepolarizing muscle relaxants
severe burns
upper motor neuron disease
likely due to increased expression of nAChRs, which requires an increase in dose)
myasthenia gravis and NMJ blockers
ii) Neuromuscular blockade by nondepolarizing muscle relaxants is enhanced in patients with myasthenia gravis
aging and NMJ nondepolarizing blockers
i) Prolonged duration of action from nondepolarizing relaxants occurs in elderly patients with reduced hepatic and renal function; reduce dose in patients > 70 y/o
atracurium
duration?
Hofmann elimination?
(1) Intermediate-acting neuromuscular blocker
(2) Inactivated by a form of spontaneous breakdown known as Hofmann elimination
(a) The main breakdown products are laudanosine and a related quarternary acid, neither of which possess any neuromuscular blocking properties
can be used in hepatic and/or renal insufficiency
less histamine release than other nondepolarizing agents
laudanosine
breakdown product of atracurium
(b) Laudanosine is slowly metabolized by the liver, has a long half-life (150 min), readily crosses the blood-brain barrier, and in high concentrations can cause seizures and an increase in the volatile anesthetic requirement
(c) Increased laudanosine concentrations is only a problem for patients with prolonged infusions of atracurium (e.g., ICU)
(d) Due to the short-term use of atracurium in the OR, however, accumulation of laudanosine with resultant seizure activity is not a concern, even in patients with end-stage renal or hepatic failure
what are the 3-hydroxy metabolites
these are the metabolites of steroidal muscle relaxants
(c) Under normal circumstances this is not an issue, but if a patient has been given a steroidal nondepolarizing agent for several days in an ICU setting, the 3-hydroxy metabolite can cause prolonged paralysis because it has a longer half-life than the parent compound
the steroidal neuromuscular blocking agents have the least tendency to cause what?
histamine release
Pancuronium
agent of choice for what patients?
onset
duration
potency
intermediate onset (3-4 min)
long acting
high potency
agent of choice for pt’s with normal renal and hepatic function requiring paralysis for more than 1 hour
(c) Adverse effects include moderate risk of tachycardia, hypertension, and increased cardiac output due to vagal blockade; but these can be minimized by smaller doses permitted by high potency
Rocuronium
clinical use of this drug?
onset
duration
potency
most rapid time of onset (60-120 sec)
intermediate duration
lower potency
(b) The rapid onset allows it to be used as an alternative to succinylcholine in rapid-induction anesthesia and in relaxing the laryngeal and jaw muscles to facilitate tracheal intubation
(c) Virtually devoid of cardiovascular effects
vecuronium
onset
duration
potency
slower onset of onset (2-4 min)
intermediate duration
high potency
(b) It is an acceptable alternative competitive nondepolarizing blocker to rocuronium for rapid sequence intubation; it is also commonly used in critically ill patients for > 24 hours
(c) Virtually devoid of cardiovascular effects
why is succinylcholine ultra short acting
i) Ultra-short duration of action is due to rapid hydrolysis and inactivation by butyrylcholinesterase (aka, pseudocholinesterase or plasma cholinesterase) in the liver and plasma
ii) Plasma cholinesterase has a high capacity to hydrolyze succinylcholine and only a small percentage of the original IV dose reaches the neuromuscular junction
what is the mechanism of action of succinylcholine
depolarizing neuromuscular blocker
ii) Phase I block (depolarizing)
(1) After activating the nAChR, depolarization of the motor end plate spreads to adjacent membranes causing muscle contraction
(2) The depolarized membranes remain depolarized and unresponsive to subsequent impulses (i.e., a state of depolarizing blockade)
(3) Because excitation-contraction coupling requires end plate repolarization and repetitive firing to maintain muscle tension, flaccid paralysis results
(4) Phase I depolarizing block is augmented, not reversed, by cholinesterase inhibitors
phase II of succinylcholine actions
desensitizing
(1) Continued exposure to succinylcholine causes the initial end plate depolarization to decrease and the membrane becomes repolarized
(2) The membrane is unable to be depolarized again because the receptor is desensitized
(3) Although the mechanism of desensitization is unclear, the channels behave as if they are in a prolonged closed state similar to nondepolarizing block
(4) Phase II desensitizing block is reversed by AChE inhibitors (increase in ACh at the NMJ
what happens to a patient after a standard pharmacological dose of IV succinylcholine
iv) A standard pharmacological dose of intravenous succinylcholine causes transient muscle fasciculations (twitches) over the chest and abdomen within 30 sec
v) Paralysis develops rapidly (<90 sec); initially in arm, neck, and leg muscles followed by respiratory muscles
in what clinical scenarios is succ used?
vi) 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
how is succ degraded
by plasma cholinesterase
ADR’s of succinylcholine
CV
- arrythmias
- (2) Stimulation of nAChRs (ganglionic) and mAChRs (cardiac) 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
Hyperkalemia- most common***
- can cause cardiac arrest
- especially occurs in burns, nerve damage, closed head injury, trauma
Increased intraocular pressure
Increased intragastric pressure
- could cause regurgitation and aspiration
- highest risk in pt’s with delayed gastric emptying (diabetics), traumatic injury, esophageal dysfunction and morbid obesity
muscle pain
histamine release
what are the contraindications for using succinylcholine
vii) 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
what is the black box warning for succinylcholine
cardiac arrest risk):
rarely, acute rhabdomyolysis with 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)
what are the drug drug interactions of succinylcholine
anesthetics
- malignant hyperthermia
- treat with dantrolene
what are the uses of neuromuscular blocking drugs?
surgical relaxation
endotracheal intubation (succ is first choice, followed by rocuronium or vecuronium)
control of ventilation
- NM blocking drugs reduce chest wall resistance and improve thoracic compliance
- permits adequate gas exchange and prevents atelectasis in pt’s who have ventilatory failure
-pancuronium and vecuronium are the most commonly prescribed agents for use >24 hours
dantrolene MOA
spasmolytic agents
causes inhibition of the ryanodine receptor (RyR) calcium channel; blocks the release of calcium through the sarcoplasmic reticulum and muscle contraction is impaired
cardiac and smooth muscle are unaffected due to different RyR channel subtype
what are the side effects of dantrolene (spasmolytic agent)
iv) Side effects include generalized muscle weakness, sedation, and occasionally hepatitis (oral administration is contraindicated in patients with hepatitis)
what are the uses of dantrolene
treatment of spasticity associated with upper motor neuron disorders (spinal cord injury, stroke, cerebral palsy, or MS)
management of malignant hyperthermia
malignant hyperthermia
(1) A rare heritable disorder that can be triggered by a variety of stimuli, including the combination of general anesthetics and succinylcholine
(2) Patients at risk for this condition have a hereditary mutations in the RyR receptor gene, which permits excessive calcium release from the sarcoplasmic reticulum in the presence of certain triggering agents
(3) After administration of a triggering agent, a sudden and prolonged release of calcium causes massive muscle contraction, lactic acid production, and increased body temperature
(4) Reduction of calcium is accomplished with administration of IV dantrolene
effects of botulinum toxin (MOA)
i) MOA: cleaves the SNARE complex and blocks the release of ACh by preventing vesicle exocytosis
what are the uses of botulinum toxin?
ii) Local injection of botulinum toxin has become a useful treatment for generalized spastic disorders, such as cervical dystonia and blepharospasm
AChE inhibitors
i) Produce their primary effects by inhibiting acetylcholinesterase (AChE)
ii) Inhibition of AChE increases the endogenous ACh concentration in the synapse, which increases stimulation of nAChRs and mAChRs (amplify endogenous ACh effects)
iii) Some indirect-acting cholinomimetics have a modest direct action on nAChRs as well (e.g., neostigmine)
iv) The chief differences between members of this group are chemical and pharmacokinetic (their pharmacodynamic properties are almost identical)
what occurs with organophosphate poisoning ?
(1) Lipid-soluble and readily absorbed from the skin, lung, gut, and conjunctiva, which make them particularly dangerous to humans and highly effective as insecticides
(2) Distributed to all parts of the body including the CNS
(3) Organophosphate poisoning includes CNS toxicity
MOA of AChE inhibitors
a) Mechanism of action
i) Inhibition of AChE (BuChE is also inhibited)
ii) ACh accumulates throughout the body, which results in activation of nAChRs and mAChRs
iii) Consequences may be deleterious or beneficial
duration of action of alcohol type AChE inhibitors
(1) Bind reversibly through electrostatic interactions and hydrogen bonding at the binding site for ACh
(2) These relatively weak interactions are short-lived and result in short duration of action (2-10 minutes)
carbamic acid esters type AChE inhibitors duration of action
(1) Undergo a two-step hydrolysis sequence analogous to ACh
(2) The second step involves the formation of a covalent bond between the enzyme and the carbamic acid group of the inhibitor that requires 30 minutes to 6 hours to hydrolyze
Quaternary AChE inhibitors systemic effects?
i) Quaternary AChE inhibitors are absorbed poorly from the GI tract or across the skin, are excluded from the CNS by the blood-brain barrier (at moderate doses), act preferentially at the NMJ of skeletal muscle, and have less effect at autonomic effector sites and ganglia
depending on the site of action, AChE inhibitors have the ability to ….
iv) Depending on the site of action, AChE inhibitors have the ability to:
(1) Stimulate mAChRs at autonomic effector organs
(2) Stimulate, followed by depression or paralysis, all autonomic ganglia and skeletal muscle (nAChRs)
(3) Stimulate, with occasional subsequent depression, cholinergic receptor sites in the CNS
CNS effects of AChE inhibitors
(1) Low concentrations: diffuse activation on the electroencephalogram and a subjective altering response
(2) High concentrations: generalized convulsions due to neuronal hyperstimulation (may be followed by coma and respiratory arrest)
AChE inhibitors effects on the eye
contraction (miosis)
contraction for near vision
AChE inhibitors effects on CV system
(1) AChE inhibitors can increase the activity of both sympathetic and parasympathetic ganglia supplying the heart and at mAChRs on cardiac cells
(2) Parasympathetic tone dominates and cardiac output decreases
(3) The net cardiovascular effects of moderate doses of AChE inhibitors is modest bradycardia, a fall in cardiac output (due to bradycardia, decreased atrial contractility, and some reduction in ventricular contractility), and either no change or a modest increase in blood pressure (due to increased vascular resistance initiated at sympathetic ganglia)
(4) Toxic doses of AChE inhibitors cause more marked bradycardia, occasionally tachycardia, and hypotension
what are the AChE inhibitors effects on the NMJ
(1) Therapeutic concentrations of AChE inhibitors prolong and intensify the actions of ACh, which increases the strength of contraction
(2) Fibrillation of muscle fibers and fasciculations result with high concentrations
(3) Continued inhibition of AChE results in the progression of depolarizing neuromuscular blockade to nondepolarizing blockade (as seen with succinylcholine)
(4) Some quaternary carbamate AChE inhibitors have additional direct nicotinic agonist effects at the NMJ (e.g., neostigmine)
GI tract effects of AChE inhibitors
increase motility
relax sphincters
stimulate secretions
urinary bladder effects of AChE inhibitors
contraction of detrusor
trigone and bladder relaxation
what are the standard AChE inhibitors for myasthenia gravis
pyridostigmine
neostigmine
ambenoium
(these do not cross the BBB)
what is the edrophonium test ?
(1) The short-acting agent edrophonium had been used as a diagnostic agent for myasthenia gravis (edrophonium test)
(2) In patients thought to have myasthenia gravis, administration of edrophonium can temporarily relieve the ptosis, difficulty speaking and swallowing, and extremity weakness associated with the disease
(3) Due to the dangers associated with edrophonium administration (increased muscarinic effects of ACh, including bradycardia and bronchospasm) and variations in physician interpretation of test results, this test has been phased out of use in favor of the ice pack test (ice pack on eyelid for 2-3 minutes, which temporarily inhibits cholinesterase enzyme activity, and check for eyelid droopiness) and immunologic and/or electrophysiologic testing
what is a myasthenic crisis
(1) Myasthenic crisis is a life-threatening condition defined as weakness from acquired myasthenia gravis that is severe enough to necessitate intubation (essentially severe myasthenia)
what is a cholinergic crisis
(2) Cholinergic crisis is a potential major side effect of excessive AChE inhibitors
(3) The main symptom of cholinergic crisis is muscle weakness, which can be difficult to distinguish from myasthenic crisis
how do you tell apart a myasthenic crisis versus a cholinergic crisis ?
(4) To distinguish between the two, the edrophonium test 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
(5) Due to the rarity of cholinergic crisis, current opinion is as follows: it should be assumed that patients with myasthenia gravis in crisis are in myasthenic crisis unless it is known that the doses of AChE inhibitors exceed the daily allowable limits (appropriate treatment consists of additional AChE inhibitors)
AChE inhibitors effects on the GI system
ii) AChE inhibitors may be used to treat paralytic ileus (atony or paralysis of the stomach or bowel following surgical manipulation), atony of the urinary bladder, and congenital megacolon
how are AChE inhibitors used to treat glaucoma
i) Characterized by increased intraocular pressure
ii) AChE inhibitors reduce intraocular pressure by stimulating mAChRs of the ciliary body and causing contraction, which facilitates outflow of aqueous humor
iii) Therapy with AChE inhibitors has largely been replaced by topical β-blockers and prostaglandin derivatives (these agents will be covered in more detail during the NSII course)
how can AChE inhibitors used to treat dementia
i) Patients with progressive dementia of the Alzheimer type are found to have a deficiency of intact cholinergic neurons
ii) Tacrine was approved to treat this condition in 1993, but due to the high incidence of hepatotoxicity newer agents are preferred (donepezil, rivastigmine, galantamine, and physostigmine)
iii) Patients with dementia associated with Parkinson disease also benefit from AChE inhibitors
how are AChE inhibitors used as an antidote for antimuscarinics
i) Over 600 compounds have anticholinergic properties (e.g., anticholinergic agents (atropine), antihistamines, tricyclic antidepressants, sleep aids, cold preparations)
ii) 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
iii) Physostigmine can reverse the above mentioned anticholinergic effects and is preferred because it crosses the blood-brain barrier
a) Nondepolarizing neuromuscular blocking agents combination with AChE inhibitors
will diminish neuromuscular blockade
ii) One exception is mivacurium (metabolized by plasma AChE), where neuromuscular blockade is prolonged
succinylcholine and AChE inhibitors
will enhance phase 1 block and antagonize phase 2 block
drug drug interactions cholinergic agonists (direct acting) and AChE inhibitors
c) Cholinergic agonists (direct-acting)
i) Direct-acting agents act predominantly on mAChRs
ii) Combination with AChE inhibitors will enhance the effects of cholinergic agonists
Beta blockers + AChE inhibitors
i) Combination with AChE inhibitors may enhance the bradycardic effects
systemic corticosteroids + AChE inhibitors
i) Coadministration with AChE inhibitors may enhance muscle weakness seen in patients with myasthenia gravis
what are the initial signs of ACHe inhibitor intoxication
are those of mAChR stimulation: miosis, salivation, sweating, bronchial constriction, vomiting, and diarrhea
(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
what is the antidote recommended for cholinergic poisoning
iii) The mAChR antagonist atropine is the antidote recommended for cholinergic poisoning in combination with maintenance of vital signs (respiration in particular) and decontamination (removal of clothing and washing of the skin in cases of exposure to dust and spray pesticides)
iv) Atropine is ineffective against the peripheral neuromuscular stimulation (nAChRs)
vi) Therapy often also includes benzodiazepines for seizures
cholinesterase regenerators
i) Cholinesterase reactivators (e.g., pralidoxime) are capable of regenerating active enzyme from the organophosphorus-cholinesterase complex via removal of the phosphorous group from the active site of the enzyme (the oxime group, NOH, has a high affinity for the phosphorus atom)
ii) Can restore the response to stimulation of the motor nerve within a few minutes following a dose of an organophosphorus compound that produces total blockade of transmission
iii) Must be given before aging has occurred between the organophosphate and cholinesterase (the time-dependent process of aging further strengthens the phosphorus-enzyme bond, making the complex even more difficult to break)
what do cholinesterase regenerators NOT do
iv) Does not reverse central effects of organophosphate poisoning because pralidoxime does not enter the CNS
what is the current antidotal therapy for organophosphate exposure from warfare, terrorism or other sources
parenteral atropine, an oxime (pralidoxime), and a benzodiazepine as an anticonvulsant
what is the prophylaxis in AChE inhibitor poisoning
common side effects of this
i) Studies with animals have shown that pretreatment with pyridostigmine reduces the incapacitation and mortality associated with nerve agent poisoning, especially with agents such as soman that show rapid aging
iii) The approved dose is much lower than amounts used in patients with myasthenia gravis (30 mg every 8 hours vs. an average of 100 mg every 4 hours)
iv) Pyridostigmine should be discontinued at the first sign of nerve gas exposure and the above-mentioned treatment regimen should begin
v) Common side effects include stomach cramps, diarrhea, nausea, frequent urination, headaches, dizziness, shortness of breath, worsening of peptic ulcer, blurred vision, and watery eyes
what can penicillamine induce
production of autoimmune antibodies (myasthenia gravis type disease)
aminocylgoside toxicity
nephrotoxicity
ototoxicity
neuromuscular blockade
if they have myasthenia gravis DO NOT use aminoglycoside
in myasthenia gravis patients, what other disease must you check for !!
thymoma
what enzyme associated with ACh may be reduced in pt’s with Alzheimers
ChAT (choline acetyltransferase)
enzyme that combines acetyl coenzyme A and choline to form ACh
nAChR’s
Activated by ACh (binds alpha subunits) and nicotine
Ligand-gated ion channel (Na+)
Pre- and postjunctional
NMJ: Na+ increase causes muscle action potential
located in skeletal muscle function is contraction
somatic motor nerves !
Nm- found only at NMJ
Nn- found in CNS, autonomic ganglia, adrenal medulla
mAChR’s
Activated by ACh and muscarine
G-protein coupled receptor
Pre- and postjunctional
NOT located at skeletal NMJ
location
-smooth muscle - contraction
-cardiac muscle - SA node, AV node, Atrium, Ventricles
Decrease HR, conduction velocity, contraction
VAGUS nerve
what is the difference b/w pre-junctional activation of nAChR and mAChR
nAChR
Mobilization of additional ACh for subsequent release
ACh vesicles move toward the synaptic membrane
mAChR activation results in ACh-mediated inhibition of further ACh release
what re the differences is presenting symptoms of parasympathetic versus sympathetic tone
Parasympathetic Cholinergic Salivation, lacrimation Pupil constriction (myosis) Decrease in HR Increased secretion and motility Urination, defecation
Sympathetic Adrenergic (anticholinergic) Cutaneous vasodilation Pupil dilation (mydriasis) Increase in HR Decreased secretion and motility Reduction/elimination of the desire to urinate
which two neuromuscular blocking drugs are used when a patient has renal or hepatic insufficiency
atracurium
cisatracurium
what are the classic signs of malignant hyperthermia
Classic signs are hypermetabolic Hyperthermia, tachycardia, tachypnea Increased CO2 production, acidosis Increased O2 consumption Muscle rigidity ATP depletion leads to compromised muscle membrane integrity, causing hyperkalemia and rhabdomyolysis Typically rapid onset
