Neuromuscular Blocking Agents and Fibromyalgia/Spasticity - Sweatman

Question 1

What are the isoquinolone derivatives used for neuromuscular blocking?

Answer 1

1) Atracurium
2) Cisatracurium

Question 2

What are the steroid derivatives used in neuromuscular blocking?

Answer 2

1) Pancuronium
2) Rocuronium
3) Vecuronium

Question 3

What is the only depolarizing agent used in neuromuscular blocking?

Answer 3

Succinylcholine

Question 4

What drugs are used to reverse neuromuscular blocking?

Answer 4

1) Edrophonium
2) Pyridostigmine
3) Neostigmine
4) Sugammedex (not approved in US yet)

Question 5

What receptor do the neuromuscular blocking agents act on?

Answer 5

Nicotinic M receptor –> found on skeletal muscle

Question 6

What is the physiological role of the nicotinic acetylcholine receptor?

Answer 6

Ligand-gated Na+ channel that opens during depolarization –> 2 Ach bind per receptor

Question 7

What is the mechanism of action of the non-depolarizing neuromuscular blockers?

Answer 7

Stabilize the closed conformation of the Nicotinic M receptor to prevent Na+ influx

Question 8

What is the mechanism of action of the depolarizing neuromuscular blocker?

Answer 8

Stabilizes the Nicotinic M channel in the open conformation –> blocks depolarization of the membrane

Question 9

What is unique about the inactivation of the isoquinolone drugs?

Answer 9

It undergoes hepatic metabolism and Hoffman elimination

Question 10

What advantage does cisatracurium have over atracurium?

Answer 10

Cisatracurium does no produce the toxic metabolite associated with seizures (laudanosine)

Question 11

How is succinylcholine metabolized?

Answer 11

Rapidly metabolized by cholinesterase’s in the plasma or liver (5-10 minute duration of action)

Question 12

What is the major “off target” action of pancuronium and rocuronium?

Answer 12

Cardiac M receptor blocking –> Pancuronium is worse Decreased rate and force of contraction

Question 13

What are the major adverse effects of succinylcholine?

Answer 13

1) Hyperkalemia
2) Malignant hyperthermia
3) Myoglobinuria

Question 14

What causes malignant hyperthermia when using neuromuscular blockers?

Answer 14

Uncontrolled release of Ca2+ from sarcoplasmic reticulum

Question 15

What is the treatment for malignant hyperthermia?

Answer 15

1) Dantrolene
2) Stop giving NM blocker
3) Correct hyperkalemia, acidosis, and cool core temp

Question 16

What are the major drug-drug interactions (3) of neuromuscular blockers?

Answer 16

1) Volatile anesthetics –> Malignant hyperthermia
2) Aminoglycosides –> Enhanced blockade
3) Local anesthetics –> block pre-junctional neural effect

Question 17

What are the three acetylcholinesterase inhibitors and their recommended anticholinergics?

Answer 17

1) Neostigmine –> Glycopyrolate
2) Edrophonium –> Atropine
3) Pyridostigmine –> Glycopyrolate

Question 18

What are acetylcholinesterase inhibitors used for?

Answer 18

To reverse non-depolarizing neuromuscular blockade

Question 19

What is the mechanism of action of Sugammadex?

Answer 19

Traps steroid-based neuromuscular blockers to stop their action

Question 20

What is the biggest difference between the non-depolarizing neuromuscular blockers and succinylcholine?

Answer 20

Non-depolarizing drugs have a longer duration of action and fewer adverse effects

Question 21

What are the drugs used to treat fibromyalgia?

Answer 21

1) Duloxetine (SNRI)
2) Milnacipran (SNRI)
3) Pregabalin (Ca2+ Channel Blocker)
4) Amitriptyline (tricyclic antidepressant)
5) Cyclobenzaprine (fucks you up; alcohol +++)
6) Fluoxetine (SSRI)

Question 22

What is the mechanism of action of duloxetine and milnacipran? What are their selectivities?

Answer 22

Both are serotonin-norepinephrine reuptake inhibitors; duloxetine is more selective for serotonin and milnacipran is more selective for norepinephrine

Question 23

How is duloxetine metabolized and why is that important?

Answer 23

Mainly Cyp2D6 and also mildly inhibits –> possible drug-drug interactions

Question 24

What are the cautions/contraindications of duloxetine and milnacipran?

Answer 24

1) Mild increase in HR and BP –> pre-existing CV issues
2) Uncontrolled closed angle glaucoma
3) Hyponatremia secondary to SIADH
4) BBW for suicide

Question 25

What is the mechanism of action of pregabalin?

Answer 25

Inhibit alpha-2-delta subunits of L-type Ca2+ channels in presynaptic nerves --\> inhibits excitatory transmission by glutamate

Question 26

How is pregabalin eliminated?

Answer 26

Renal elimination --\> reduce dose with renal dysfunction/failure

Question 27

What are the cautions and things that should be monitored with pregabalin?

Answer 27

1) Rebound symptoms with drug withdrawal 2) Potentially addictive 3) Depression/suicide risk 4) Monitor serum creatinine

Question 28

How do amitriptyline and fluoxetine help in fibromyalgia?

Answer 28

It is thought they restore the neurotransmitter imbalance --\> used off label

Question 29

What drugs are used as muscle relaxers?

Answer 29

1) Carisoprodol 2) Cyclobenzaprine 3) Methocarbamol 4) Tizanidine

Question 30

What is the mechanism of action of carisoprodol?

Answer 30

CNS action in reticular activating system and spinal cord leading to sedation and altered perception of pain --\> NO DIRECT EFFECT ON MUSCLES

Question 31

What are the cautions and monitoring parameters for carisoprodol?

Answer 31

1) Drowsiness/dizziness most common 2) Additive sedation with other drugs 3) Monitor serum creatinine and BUN

Question 32

What is the mechanism of action of cyclobenzaprine?

Answer 32

Similar to amitriptyline (sereotnin/norepi reuptake inhibitor) --\> central action possible at level of brain stem

Question 33

What are the cautions association with cyclobenzaprine?

Answer 33

1) Significant anti-cholinergic effects 2) Additive CNS depression with other drugs/alcohol (don't give to Kendall) 3) GI symptoms are MOST significant (paralytic ileum) 4) May increase QT interval

Question 34

What is the mechanism of action of methocarbamol?

Answer 34

Effects thought to be due to generalized sedative action --\> altered pain perception No direct action on muscles

Question 35

What is the elimination route for methocarbamol?

Answer 35

Hepatic dealkylation and hydroxylation with renal elimination --\> significant hepatic/renal dysfunction can cause toxicity

Question 36

What caution is associated with methocarbamol?

Answer 36

Additive CNS depression with other drugs and alcohol (sorry Kendall)

Question 37

What is the mechanism of action of tizanidine?

Answer 37

Agonist for pre-synaptic alpha-2 receptor --\> decreased activation of polysynaptic spinal cord motor neurons --\> reduced muscle tone but not strength

Question 38

What elimination problem is associated with tizanidine?

Answer 38

Decreased clearance in renal dysfunction and elderly --\> should titrate to effective dose

Question 39

What cautions and monitoring parameters are associated with tizanidine?

Answer 39

1) Hepatotoxicity --\> Monitor LFTs 2) Taper cessation to avoid rebound 3) Additive CNS depression

Question 40

What drugs are used to treat muscle spasticity?

Answer 40

1) Baclofen 2) Botulinum toxin 3) Dantrolene 4) Tizanidine

Question 41

What is the mechanism of action of Baclofen?

Answer 41

GABA_B agonist producing inhibitory or hyper polarizing signals which reduce excitatory polysynaptic pathways

Question 42

What elimination issue is associated with baclofen use?

Answer 42

Can't use in renal dysfunction --\> drug accumulation leads to encephalopathy , abdominal pain, seizures, respiratory depression

Question 43

What cautions are associated with baclofen use?

Answer 43

1) Abrupt discontinuation leads to rebound neural activity (confusion, seizures, psychiatric disturbances and spasticity occur) --\> taper over 2 weeks 2) Additive hypotension with antihypertensives and MAOIs 3) May increase blood glucose (fuckin diabetics)

Question 44

What is the mechanism of action of dantrolene?

Answer 44

Directly interferes with Ca2+ release from sarcoplasmic reticulum --\> blocks the ryanodine receptor

Question 45

What elimination issues are associated with dantrolene?

Answer 45

Crosses placenta causing "floppy baby syndrome" May cause hepatic dysfunction so monitor LFTs

Question 46

What cautions are associated with dantrolene?

Answer 46

1) Additive CNS depression 2) When given IV and combined with CCBs may cause Vfib and CV collapse