Smooth m relaxants--Agents that act on the NMJ Flashcards
1
Q
Neuromuscular blocking drugs
A
Nondepolarizing- Isoquinoline derivatives, Steroid derivatives
-Depolarizing- Succinylcholine
2
Q
Isoquinoline derivatives
A
-Atracurium
-Cisatracurium
-Doxacurium
-Metocurine
-Mivacurium
-Tubocurarine
CURIUM
3
Q
Steroid derivatives
A
-Pancuronium
-Pipercuronium
-Rocuronium
-Vecuronium
CURONIUM- PPRV
4
Q
M relaxants (spasmolytics)
A
- Dantrolene
- Botulinum toxin
5
Q
Acetycholinesterase inhibitors
A
- Ambeonium
- Donepezil
- Echothiophate
- Edrophonium
- Galantamine
- Neostigmine
- Physostigmine
- Pyridostigmine
- Rivastigmine
- Tacrine
6
Q
Antimuscarinic compounds
A
- atropine
- glycopyrrolate
7
Q
Cholinesterase reactivators
A
-Pralidoxime
8
Q
neuromuscular blocking drugs- 2 mech’s
A
- Nondepoliarizing- antagonists at nAChR (d-tubocurarine- prototype)
- Depolarizing- excess of a depolarizing agonist (prototype- succinylcholine)
9
Q
Nondepolarizing neuromuscular blocking agents- moa, pharmacodynamics
A
- competitive antagonist at nAChR
- large doses- can enter the pore of nAChR- diminish the ability of ACHase inhibitors to antagonist their effects
- larger m’s- more resistant to blockade and recover more rapidly (diaphragm- last m to be paralyzed, quickest to recover)
10
Q
Reversal of neuromuscular blockade
A
- ACH (nAChR agonist) or succinylcholine (rarely used)
- Neostigmine and pyridostigmine (cholinesterase inhibitors)- inc availability of ACH at motor end plate AND inc release of NT from motor n terminal
- Edrophonium- purely a cholinesterase inhibitor
- Anticholinergic agents (coadmin w cholinesterase inhibitors)- minimize adverse cholinergic effects
11
Q
Nondepolarizing agents- adverse effects
A
- produce histamine release- wheals, bronchospasm, hypotension, bronchial and salivary secretion
- at large doses- hypotension and tachycardia
- d-tubocurarine causes significant histamine release; very long duration of action- not used as much clinically
12
Q
Nondepolarizing agents- drug-drug interactions
A
- Anesthetics- (inhaled)- potentiate the neuromuscular blockade - Isoflurane»_space; sevoflurane = desflurane = enflurane = halothane > NO
- aminoglycosides enhance blockade; some reduce the release of ACH in prejunctonal neuron
13
Q
Nondepolarizing agents- effects of dz and aging on neuromuscular response
A
- prolonged duration of action- in elderly pts w reduced hepatic and renal fxn
- enhanced in pts w MG
- severe burns and UMN dz- resistant to nondepolarizing agents!!
14
Q
Atracurium
A
- intermediate-acting
- inact by Hofmann elimination
- breakdown products- Laudanosine
- Laudanosine- slowly metabolized in liver- crosses BBB- can cause seizures- only a problem for pts w prolonged infusions of atracurium!!!
15
Q
Neuromuscular blockers- short duration of action
A
- Mivacurium
- Succinylcholine!!
16
Q
Neuromuscular blockers- intermediate duration of action
A
-atracurium
-cisatracurium
-rocuronium
-vecuronium
(ACRV)
17
Q
Neuromuscular blockers- long duration of action
A
-Doxacurium
-Pancuronium
-Pipecuronium
(DPP)
18
Q
Mivacurium
A
- shortest duration of action; onset of action is slower than succinylcholine
- larger dose used to speed onset- assoc w profound histamine release and CV effects
- metabolism by plasma cholinesterase (pts w renal failure have dec levels)
19
Q
Steroid derivatives
A
-intermediate-acting (vecuronium, rocuronium) - hepatic metabolism- more likely to be used clinically than long-acting (pancuronium, pipecuronium)
20
Q
Steroid derivatives- metabolites
A
- 3-hydroxy metabolites
- if a pt has given a steroidal nondepolarizing agent for several days in a ICU setting, the 3-hydroxy metabolite can cause prolonged paralysis b/c it has a longer half-life
21
Q
Rocuronium
A
- most rapid time of onset, intermediate duration, lower potency
- rapid onset- used as an alternative to succinylcholine in rapid-induction anesthesia and in relaxing the laryngeal and jaw m’s to facilitate tracheal intubation
22
Q
Succinylcholine- pharcokinetics
A
- only depolarizing blocking drug!!
- ultra-short duration of action
- plasma cholinesterase hydrolyzes succinylcholine- onal a small percentage of dose reaches the NMJ
- pts with genetically abnormal variant of plasma cholinesterase- can have prolonged blockade!!
23
Q
Succinylcholine- phases
A
- phase I block (depolarizing)- depolarization of motor end plate spreads to adj membranes causing m contraction- m’s remain depolarized, unresponsive to subsequent impulses- flaccid paralysis occurs; augmented by cholinesterase inhibitors
- phase II block (desensitizing)- continued exposure to succinylcholine causes the initial end plate depolarization to dec and memb becomes repolarized- memb is unable to be depolarized b/c the R is desensitized; reversed by acetylcholinesterase inhibitors
24
Q
Succinylcholine- effects
A
- transient m twitches over chest and abdomen (30 s)
- paralysis (<90s) in arm, neck, leg m’s, followed by resp m’s
- used for rapid sequence induction (secure airway rapidly), and for quick surgical procedures
25
succinylcholine- reversal
-plasma cholinesterases
26
succinylcholine- adverse effects
CV
-cardiac arrhythmias- when admin during halothane anesthesia
-negative inotropic and chronotropic effects- can be attenuated by admin of an anticholinergic drug
-large doses can have + inotropic and chronotropic effects
Hyperkalemia- in pts w burns, n damage, or neuromuscular dz, closed head injury- release K into blood- can cause cardiac arrest
inc intraocular P
inc intragastric P
m pain
slight histamine release
27
succinylcholine- contraindications
- malignant hyperthermia hx
- myopathies assoc w elevated CPK
- acute phase of injury after major burns, mult trauma, extensive denervation of skeletal m or UMN injury
- black box warning- cardiac arrest risk!!!- after admin to healthy children w an undiagnosed skeletal m myopathy!!
28
succinylcholine- drug-drug interactions
- Anesthetics- can cause malignant hyperthermia
- Antibiotics
- local anesthetics and antiarrhythmic drugs (minor)
29
neuromuscular blocking drugs- uses
- surgical relaxation
- tracheal intubation
- control of ventilation- in pts who have ventilatory failure; neuromuscular blockind rugs reduce chest wall resistance and improve thoracic compliance
- tx of convulsions
30
Spasmolytic agents- drugs
- dantrolene
| - botulinum toxin
31
Dantrolene- moa
- causes inhibition of RyR (ryanodine R) Ca channel- blocks release of Ca thru the SR and m contraction is impaired
- cardiac and smooth m are unaffected (diff RyR subtype)
- SEs- m weakness, sedation, hepatitis
32
Dantrolene- used for?
- tx spasticity assoc w UPMN disorders
| - malignant hyperthermia!!!!!
33
Botulinum toxin- moa
- cleaves the SNARE complex and blocks release of ACh by preventing vesicle exocytosis
- tx- generalized spastic disorders
