Skeletal Muscle Relaxants Flashcards
Skeletal muscle relaxants will be working
on the
somatic nerves
what is an issue due to the mechanism of action of certain skeletal muscle relaxants
adverse or off-target effects that can influence muscarinic receptors and ganglionic nicotinic
receptors which means that it could have vagolytic actions on the heart (i.e.,tachycardia) or block the release of catecholamines from the adrenals or postganglionic neurons (i.e., hypotension).
Skeletal muscle relaxants fall into two different categories
- neuromuscular blockers
- spasmolytics and antispasmodics
skeletal muscle relaxants will influence
the opening and closing of myoneural nicotinic receptors
non-depolarizing skeletal muscle relaxants can be reversed by using
acetylcholinesterase inhibitor (AchEI)
neuromuscular blockers
lack CNS activity due to the selectivity of the drugs to the myoneural nicotinic receptors used to produce muscle paralysis
d-tubocurarine (curare)
non-depolarizing competitive inhibitor that blocks the myoneural nicotinic receptors so that Na+ does not gain entry into the skeletal muscle cell
succinylcholine
depolarizing drug with two acetylcholine molecules linked END to END
two different chemical classes for non-depolarizing drugs
- amino steroid drugs: steroid structure in the middle of the drug structure
- benzylisoquinoline drugs: d-tubocurarine chemical class have quinoline groups that have methoxy- residues
- MOA is still the same
Potency of the benzylisoquinoline drugs is through the number of
methoxy groups (higher potency = higher amounts of methoxy groups)
Atracurium (benzylisoquinoline) is no longer in widespread clinical use because it can breakdown into
laudanosine which is slowly metabolized by the liver and can cross the blood-brain-barrier (BBB) which may cause seizures.
what is used instead of Atracurium
Cistracurium because it produces less laudanosine and histamine
amino steroids are mainly eliminated by
the liver and through biliary excretion
The benzylisoquinolines are mainly eliminated through
enzymatic hydrolysis of ester bonds and elimination by the kidneys
For the neuromuscular blockers, the drug’s clearance is directly proportional to the
drug’s duration of action.
when compared to acetylcholine, succinylcholine is
- More potent and prolonged binding at nicotinic receptor
- More resistant to degradation by acetylcholinesterases (AchE)
For succinylcholine, it does not get inactivated by acetylcholinesterase within the synaptic cleft, but will be metabolized by
butyrylcholinesterase and pseudocholinestereasese in the liver and plasma, respectively.
Of the nondepolarizing drugs, rocuronium has
the most rapid onset of action (60-120 seconds/ 1-2 minutes)
Pancuronium and pipecuronium are
longer acting amino steroids
adverse effects with succinylcholine
- due to the initial stimulatory nature of succinylcholine, the drug can cause cardiac arrhythmias, especially if given with halothane for anesthesia
- can also bind to muscarinic receptors within the SA node to induce transient bradycardia.
what are the adverse effects of depolarizing drugs on patients with burns, nerve damage, or neuromuscular disease
patients can develop proliferation of extra-junctional acetylcholine receptors which can cause hyperkalemia due to over release of K+ leading to cardiac arrest
how can volatile anesthetics potentiate the neuromuscular block
- decrease sensitivity of motor nerve to depolarization causing less Ach release
- increase blood flow to the NMJ to allow more the skeletal muscle relaxant to reach site of action
- decrease CNS activity which can depress the function of the somatic motor nerve.
**isoflurane (most) nitrous oxide (least)
how would antibiotics enhance the neuromuscular block
by blocking the release of acetylcholine
through inhibition of voltage-gated calcium channels on motor neuron
***aminoglycosides
reversal agent approved for rapid reversal of amino steroid drugs
Sugammadex (Bridion®)
Sugammadex (Bridion®) is a
modified gamma cyclodextrin molecule that binds tightly to rocuronium and vecuronium in a 1:1 ratio
*** direct chemical antagonist
Because Suggamadex binds to steroids, it can also bind to
progestins and estrogens in oral contraceptive pills.
spasmolytics and antispasmodics
primarily called “ central-acting” muscle relaxants because they block at the level of the spinal cord and are used to reduce muscle spasticity in a variety of painful conditions
Spasmolytic and antispasmodic drugs are used to treat
spasms from musculoskeletal conditions and spasticity from upper motor neuron lesions.
- spinal injury, cerebral palsy, multiple sclerosis and stroke
Mechanisms of action for the spasmolytic drugs
- block afferents coming from sensory or corticospinal pathway or activate an inhibitory neuron within this circuit
- inhibit the alpha-motor neuron to prevent the generation of the action potential
Dantrolene
used to directly inhibit the skeletal muscle from contracting
Benzodiazepines can facilitate the action of
GABA in the CNS
** (allosteric activators)
flumazenil
reverses the effect of benzodiazepines
Diazepam and Midazolam
enhances the effects of GABA at GABA-A receptors, increases chloride (Cl⁻) influx, leading to hyperpolarization of neurons (IPSPs)
- schedule IV drug (addiction potential)
- sedatives
Baclofen
agonizes the GABA type B receptor and inhibits P-type calcium channels and opens K + channels to induce hyperpolarization (IPSPs)
Baclofen may also reduce slow pain in patients by
inhibiting the release of substance P in the spinal cord.
withdraw of Baclofen has to be done slowly due to
rebound effects which can include seizures
Tizanidine
alpha,2-adrenergic agonist that can reduce CNS activity by inhibit the release of neurotransmitters like glutamate and aspartate through a Gi mechanism causing a ↓ in intracellular Ca2+
Cyclobenzaprine is used to treat
acute local muscle spasms associated with bruxism and TMJ due to its antimuscarinic effect
Cyclobenzaprine is structurally related to the
tricyclic antidepressants (TCAs) which acts on inhibition of locus coeruleus and reticulospinal pathways within the brain stem and inhibit both the alpha- and
gamma motor neurons
Botulinum toxin
inhibits the release of acetylcholine for generalized spastic disorders
Dantrolene interferes with the
release of calcium (Ca²⁺) from the sarcoplasmic reticulum (SR) in muscle cells by inhibiting the ryanodine receptor (RyR1).
* muscle weakness, sedation, hepatitis (rare)
skeletal muscle motor units that contract rapidly are more sensitive to
dantrolene (fast-twitch fibers)
*cardiac and smooth muscle not really affected
Malignant Hyperthermia (MH) is a genetic disorder caused by mutations in the ryanodine receptor (RyR1) in skeletal muscle where a life-threatening reaction can be triggered
by anesthetics like succinylcholine leading to symptoms including metabolic acidosis (due to excessive muscle activity), hyperthermia (due to increased heat production) and hyperkalemia (due to muscle breakdown)
why is Dantrolene used as a treatment for malignant hypothermia
Stops excessive calcium release, preventing sustained muscle contractions
treatment for bruxism
- cyclobenzaprine can be given.
- diazepam can also be utilized
- botulinum toxin on the masticatory muscles can also be used
Histamine can act through 4 different receptors and plays a major role in immediate hypersensitivity and allergic responses
H1: activates Gq pathways to increase IP3 and DAG. Increases in intracellular calcium can cause neuroexcitation, smooth muscle contraction, and increase in nitric oxide (NO) release from endothelial cells.
H2: increase adenylyl cyclase to promote gastric acid secretion and smooth muscle relaxation
H3: autoreceptors found on histaminergic neurons to inhibit histamine synthesis and release through Gi signaling.
H4: inhibitory and are involved in mast cell chemotaxis and eosinophil shape.
