Skeletal Muscle Relaxants

Question 1

Skeletal muscle relaxants will be working
on the

Answer 1

somatic nerves

Question 2

what is an issue due to the mechanism of action of certain skeletal muscle relaxants

Answer 2

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).

Question 3

Skeletal muscle relaxants fall into two different categories

Answer 3

• neuromuscular blockers
• spasmolytics and antispasmodics

Question 4

skeletal muscle relaxants will influence

Answer 4

the opening and closing of myoneural nicotinic receptors

Question 5

non-depolarizing skeletal muscle relaxants can be reversed by using

Answer 5

acetylcholinesterase inhibitor (AchEI)

Question 6

neuromuscular blockers

Answer 6

lack CNS activity due to the selectivity of the drugs to the myoneural nicotinic receptors used to produce muscle paralysis

Question 7

d-tubocurarine (curare)

Answer 7

non-depolarizing competitive inhibitor that blocks the myoneural nicotinic receptors so that Na+ does not gain entry into the skeletal muscle cell

Question 8

succinylcholine

Answer 8

depolarizing drug with two acetylcholine molecules linked END to END

Question 9

two different chemical classes for non-depolarizing drugs

Answer 9

• 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

Question 10

Potency of the benzylisoquinoline drugs is through the number of

Answer 10

methoxy groups (higher potency = higher amounts of methoxy groups)

Question 11

Atracurium (benzylisoquinoline) is no longer in widespread clinical use because it can breakdown into

Answer 11

laudanosine which is slowly metabolized by the liver and can cross the blood-brain-barrier (BBB) which may cause seizures.

Question 12

what is used instead of Atracurium

Answer 12

Cistracurium because it produces less laudanosine and histamine

Question 13

amino steroids are mainly eliminated by

Answer 13

the liver and through biliary excretion

Question 14

The benzylisoquinolines are mainly eliminated through

Answer 14

enzymatic hydrolysis of ester bonds and elimination by the kidneys

Question 15

For the neuromuscular blockers, the drug’s clearance is directly proportional to the

Answer 15

drug’s duration of action.

Question 16

when compared to acetylcholine, succinylcholine is

Answer 16

• More potent and prolonged binding at nicotinic receptor
• More resistant to degradation by acetylcholinesterases (AchE)

Question 17

For succinylcholine, it does not get inactivated by acetylcholinesterase within the synaptic cleft, but will be metabolized by

Answer 17

butyrylcholinesterase and pseudocholinestereasese in the liver and plasma, respectively.

Question 18

Of the nondepolarizing drugs, rocuronium has

Answer 18

the most rapid onset of action (60-120 seconds/ 1-2 minutes)

Question 19

Pancuronium and pipecuronium are

Answer 19

longer acting amino steroids

Question 20

adverse effects with succinylcholine

Answer 20

• 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.

Question 21

what are the adverse effects of depolarizing drugs on patients with burns, nerve damage, or neuromuscular disease

Answer 21

patients can develop proliferation of extra-junctional acetylcholine receptors which can cause hyperkalemia due to over release of K+ leading to cardiac arrest

Question 22

how can volatile anesthetics potentiate the neuromuscular block

Answer 22

• 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)

Question 23

how would antibiotics enhance the neuromuscular block

Answer 23

by blocking the release of acetylcholine
through inhibition of voltage-gated calcium channels on motor neuron

***aminoglycosides

Question 24

reversal agent approved for rapid reversal of amino steroid drugs

Answer 24

Sugammadex (Bridion®)

Question 25

Sugammadex (Bridion®) is a

Answer 25

modified gamma cyclodextrin molecule that binds tightly to rocuronium and vecuronium in a 1:1 ratio *** direct chemical antagonist

Question 26

Because Suggamadex binds to steroids, it can also bind to

Answer 26

progestins and estrogens in oral contraceptive pills.

Question 27

spasmolytics and antispasmodics

Answer 27

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

Question 28

Spasmolytic and antispasmodic drugs are used to treat

Answer 28

spasms from musculoskeletal conditions and spasticity from upper motor neuron lesions. - spinal injury, cerebral palsy, multiple sclerosis and stroke

Question 29

Mechanisms of action for the spasmolytic drugs

Answer 29

- 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

Question 30

Dantrolene

Answer 30

used to directly inhibit the skeletal muscle from contracting

Question 31

Benzodiazepines can facilitate the action of

Answer 31

GABA in the CNS **** (allosteric activators)

Question 32

flumazenil

Answer 32

reverses the effect of benzodiazepines

Question 33

Diazepam and Midazolam

Answer 33

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

Question 34

Baclofen

Answer 34

agonizes the GABA type B receptor and inhibits P-type calcium channels and opens K + channels to induce hyperpolarization (IPSPs)

Question 35

Baclofen may also reduce slow pain in patients by

Answer 35

inhibiting the release of substance P in the spinal cord.

Question 36

withdraw of Baclofen has to be done slowly due to

Answer 36

rebound effects which can include seizures

Question 37

Tizanidine

Answer 37

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+

Question 38

Cyclobenzaprine is used to treat

Answer 38

acute local muscle spasms associated with bruxism and TMJ due to its antimuscarinic effect

Question 39

Cyclobenzaprine is structurally related to the

Answer 39

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

Question 40

Botulinum toxin

Answer 40

inhibits the release of acetylcholine for generalized spastic disorders

Question 41

Dantrolene interferes with the

Answer 41

release of calcium (Ca²⁺) from the sarcoplasmic reticulum (SR) in muscle cells by inhibiting the ryanodine receptor (RyR1). * muscle weakness, sedation, hepatitis (rare)

Question 42

skeletal muscle motor units that contract rapidly are more sensitive to

Answer 42

dantrolene (fast-twitch fibers) *cardiac and smooth muscle not really affected

Question 43

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

Answer 43

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)

Question 44

why is Dantrolene used as a treatment for malignant hypothermia

Answer 44

Stops excessive calcium release, preventing sustained muscle contractions

Question 45

treatment for bruxism

Answer 45

- cyclobenzaprine can be given. - diazepam can also be utilized - botulinum toxin on the masticatory muscles can also be used

Question 46

Histamine can act through 4 different receptors and plays a major role in immediate hypersensitivity and allergic responses

Answer 46

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.