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MSK II Exam I > Drugs- Agents that act on the NMJ (Linger) > Flashcards

Drugs- Agents that act on the NMJ (Linger) Flashcards

1
Q

Cisatracurium

A

Isoquinolone derivative (nondepolarizing) NMJ blocking drug

spontaneous elimination

2-3 min onset
25-45 min duration of action

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2
Q

tubocurarine

A

Isoquinolone derivative (nondepolarizing) NMJ blocking drug

6 min onset

80 min duration of action

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3
Q

Pancuronium

A

steroid derivative non depolarizing NMJ blocking drug

steroid

renal elimination

60-100 min duration of action

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4
Q

Rocuronium

A

steroid derivative non depolarizing NMJ blocking drug

hepatic elimination

LEAST potent

1-2 min onset

20-35 min duration of action

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5
Q

Vecuronium

A

steroid derivative non depolarizing NMJ blocking drug

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6
Q

succinylcholine

A

depolarizing NMJ blocking drug

eliminated by plasma cholinesterases

time of onset 1-1.8 min

duration of action 5-8 min

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7
Q

Dantrolene

A

Muscle relaxant (sapsmolytic)

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8
Q

echothiophate

A

AChE inhibitor

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9
Q

edrophonium

A

AChE inhibitor

alcohol type

binding to AChE is noncovalent and reversible

quaternary and charged

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10
Q

Neostigmine

A

AChE inhibitor

(1) Carbamic acid esters of alcohols bearing quaternary or tertiary ammonium groups (positively charged or neutral)

quaternary and charged

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11
Q

Physostigmine

A

AChE inhibitor

(1) Carbamic acid esters of alcohols bearing quaternary or tertiary ammonium groups (positively charged or neutral)

tertiary and uncharged

-CNS distribution

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12
Q

pyridostigmine

A

AChE inhibitor

quaternary and charged

(1) Carbamic acid esters of alcohols bearing quaternary or tertiary ammonium groups (positively charged or neutral)

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13
Q

Atropine

A

Antimuscarinic compound

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14
Q

Pralidoxime

A

Cholinesterase reactivator

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15
Q

what is the role of neuromuscular blockers

A

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

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16
Q

what is the function of spasmolytics

A

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

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17
Q

what is the protoype of the nondepolarizing NMJ blocking drugs

A

d-tubocurarine

antagonist at the nicotinic acetylcholine receptor

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18
Q

prototype depolarizing NMJ blocking agents

A

succinylcholine

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19
Q

what limits the CNS entry of NMJ blocking drugs

A

the presence of one or two quaternary nitrogens makes them poorly lipid soluble and limits CNS entry

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20
Q

why must you administer NMJ blocking drugs parenterally

A

d) All of the neuromuscular blocking drugs are highly polar and inactive orally, so they MUST be administered parenterally

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21
Q

how do NMJ blockers that are eliminated via liver compare in their duration of action to those that are renally eliminated ?

A

d) All of the neuromuscular blocking drugs are highly polar and inactive orally, so they MUST be administered parenterally

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22
Q

MOA of nondepolarizing NMJ blocking agents

A

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)

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23
Q

how do you reverse the affects of non depolarizing neuromuscular blocking agetns

A

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)

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24
Q

what are the ADR’s of nondepolarizing NMJ blockers

A
  • 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
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25
Q

drug drug interactions of neuromucular blockers and anesthetics

A

(1) Inhaled anesthetics potentiate the neuromuscular blockade produced by nondepolarizing muscle relaxants in a dose-dependent fashion
(2) Isoflurane&raquo_space; sevoflurane = desflurane = enflurane = halothane > nitrous oxide

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26
Q

drug drug interactions of antibiotics and neuromuscular blockers

A

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

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27
Q

phenytoin and carbamazepine effects on neuromuscular blocker drugs

A

Conversely, phenytoin and carbamazepine significantly increase the requirement for nondepolarizing NMBAs by an unknown mechanism

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28
Q

which patients are resistant to nondepolarizing muscle relaxants

A

severe burns

upper motor neuron disease

likely due to increased expression of nAChRs, which requires an increase in dose)

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29
Q

myasthenia gravis and NMJ blockers

A

ii) Neuromuscular blockade by nondepolarizing muscle relaxants is enhanced in patients with myasthenia gravis

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30
Q

aging and NMJ nondepolarizing blockers

A

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

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31
Q

atracurium

duration?
Hofmann elimination?

A

(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

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32
Q

laudanosine

A

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

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33
Q

what are the 3-hydroxy metabolites

A

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

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34
Q

the steroidal neuromuscular blocking agents have the least tendency to cause what?

A

histamine release

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35
Q

Pancuronium

agent of choice for what patients?

onset
duration
potency

A

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

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36
Q

Rocuronium

clinical use of this drug?

onset
duration
potency

A

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

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37
Q

vecuronium

onset
duration
potency

A

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

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38
Q

why is succinylcholine ultra short acting

A

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

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39
Q

what is the mechanism of action of succinylcholine

A

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

40
Q

phase II of succinylcholine actions

A

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

41
Q

what happens to a patient after a standard pharmacological dose of IV succinylcholine

A

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

42
Q

in what clinical scenarios is succ used?

A

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

43
Q

how is succ degraded

A

by plasma cholinesterase

44
Q

ADR’s of succinylcholine

A

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

45
Q

what are the contraindications for using succinylcholine

A

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

46
Q

what is the black box warning for succinylcholine

A

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)

47
Q

what are the drug drug interactions of succinylcholine

A

anesthetics

  • malignant hyperthermia
  • treat with dantrolene
48
Q

what are the uses of neuromuscular blocking drugs?

A

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

49
Q

dantrolene MOA

A

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

50
Q

what are the side effects of dantrolene (spasmolytic agent)

A

iv) Side effects include generalized muscle weakness, sedation, and occasionally hepatitis (oral administration is contraindicated in patients with hepatitis)

51
Q

what are the uses of dantrolene

A

treatment of spasticity associated with upper motor neuron disorders (spinal cord injury, stroke, cerebral palsy, or MS)

management of malignant hyperthermia

52
Q

malignant hyperthermia

A

(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

53
Q

effects of botulinum toxin (MOA)

A

i) MOA: cleaves the SNARE complex and blocks the release of ACh by preventing vesicle exocytosis

54
Q

what are the uses of botulinum toxin?

A

ii) Local injection of botulinum toxin has become a useful treatment for generalized spastic disorders, such as cervical dystonia and blepharospasm

55
Q

AChE inhibitors

A

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)

56
Q

what occurs with organophosphate poisoning ?

A

(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

57
Q

MOA of AChE inhibitors

A

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

58
Q

duration of action of alcohol type AChE inhibitors

A

(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)

59
Q

carbamic acid esters type AChE inhibitors duration of action

A

(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

60
Q

Quaternary AChE inhibitors systemic effects?

A

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

61
Q

depending on the site of action, AChE inhibitors have the ability to ….

A

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

62
Q

CNS effects of AChE inhibitors

A

(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)

63
Q

AChE inhibitors effects on the eye

A

contraction (miosis)

contraction for near vision

64
Q

AChE inhibitors effects on CV system

A

(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

65
Q

what are the AChE inhibitors effects on the NMJ

A

(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)

66
Q

GI tract effects of AChE inhibitors

A

increase motility
relax sphincters
stimulate secretions

67
Q

urinary bladder effects of AChE inhibitors

A

contraction of detrusor

trigone and bladder relaxation

68
Q

what are the standard AChE inhibitors for myasthenia gravis

A

pyridostigmine
neostigmine
ambenoium

(these do not cross the BBB)

69
Q

what is the edrophonium test ?

A

(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

70
Q

what is a myasthenic crisis

A

(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)

71
Q

what is a cholinergic crisis

A

(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

72
Q

how do you tell apart a myasthenic crisis versus a cholinergic crisis ?

A

(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)

73
Q

AChE inhibitors effects on the GI system

A

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

74
Q

how are AChE inhibitors used to treat glaucoma

A

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)

75
Q

how can AChE inhibitors used to treat dementia

A

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

76
Q

how are AChE inhibitors used as an antidote for antimuscarinics

A

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

77
Q

a) Nondepolarizing neuromuscular blocking agents combination with AChE inhibitors

A

will diminish neuromuscular blockade

ii) One exception is mivacurium (metabolized by plasma AChE), where neuromuscular blockade is prolonged

78
Q

succinylcholine and AChE inhibitors

A

will enhance phase 1 block and antagonize phase 2 block

79
Q

drug drug interactions cholinergic agonists (direct acting) and AChE inhibitors

A

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

80
Q

Beta blockers + AChE inhibitors

A

i) Combination with AChE inhibitors may enhance the bradycardic effects

81
Q

systemic corticosteroids + AChE inhibitors

A

i) Coadministration with AChE inhibitors may enhance muscle weakness seen in patients with myasthenia gravis

82
Q

what are the initial signs of ACHe inhibitor intoxication

A

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

83
Q

what is the antidote recommended for cholinergic poisoning

A

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

84
Q

cholinesterase regenerators

A

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)

85
Q

what do cholinesterase regenerators NOT do

A

iv) Does not reverse central effects of organophosphate poisoning because pralidoxime does not enter the CNS

86
Q

what is the current antidotal therapy for organophosphate exposure from warfare, terrorism or other sources

A

parenteral atropine, an oxime (pralidoxime), and a benzodiazepine as an anticonvulsant

87
Q

what is the prophylaxis in AChE inhibitor poisoning

common side effects of this

A

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

88
Q

what can penicillamine induce

A

production of autoimmune antibodies (myasthenia gravis type disease)

89
Q

aminocylgoside toxicity

A

nephrotoxicity
ototoxicity

neuromuscular blockade

if they have myasthenia gravis DO NOT use aminoglycoside

90
Q

in myasthenia gravis patients, what other disease must you check for !!

A

thymoma

91
Q

what enzyme associated with ACh may be reduced in pt’s with Alzheimers

A

ChAT (choline acetyltransferase)

enzyme that combines acetyl coenzyme A and choline to form ACh

92
Q

nAChR’s

A

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

93
Q

mAChR’s

A

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

94
Q

what is the difference b/w pre-junctional activation of nAChR and mAChR

A

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

95
Q

what re the differences is presenting symptoms of parasympathetic versus sympathetic tone

A 
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
96
Q

which two neuromuscular blocking drugs are used when a patient has renal or hepatic insufficiency

A

atracurium

cisatracurium

97
Q

what are the classic signs of malignant hyperthermia

A 
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

MSK II Exam I (6 decks)

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