Muscle Relaxants

Front 1

Why might we need muscle relaxation in medicine?

Back 1

1. To offset muscle hypertonicity, often due to analgesics such as Ketamine, BZPs & alpha2 agonists.

2. To relieve muscle spasm (BZPs)

3. To facilitate smooth induction of anesthesia in large animals (GGE)

4. To improve surgical conditions

Front 2

How do we produce adequate muscle relaxation for surgery?

Back 2

1. Deep general anesthesia - side effects associated...

2. Local anesthesia - blocks to nerves in specific area

3. Centrally acting muscle relaxants

4. Neuromuscular blocking drugs

Front 3

Where do muscle relaxants act within the Neuromuscular Junction?

Back 3

Act by blocking actions at three potential locations depending on the drug used:

1. Interfering with post-synaptic action of acetylcholine within the NM synapse by NMBs drugs (Depolarizing or Non-depolarizing)

2. APs blocked from entering the NM junction by Local Anesthetics (most nerves resistant to this)

3. Blocking of Ca2+ channels by Mg ions & aminoglycosides (don't fully block NM Junction so not useful clinically, but keep in mind wrt side effects)

4. Other means of blocking:

- Inhibiting acetylcholine synthesis & release (e.g. botox)

Front 4

_________________ are used in the case of reversing muscle relaxant action of NON-DEPOLARIZING NMBs by blocking acetylcholinesterase.

Back 4

ANTICHOLINESTERASES

Front 5

_______________ work by interfering with post synaptic action of acetylcholine.

Back 5

NEUROMUSCULAR BLOCKING DRUGS

Non-depolarizing:

- Tubocurarine, Gallamine, Pancuronium, Vecuronium, Atracurium, & Rocuronium

Depolarizing:

- Suxamethonium

Front 6

List the main non-depolarizing NMB drugs:

Back 6

1. Tubocurarine

2. Gallamine

3. Pancuronium

4. Vecuronium

5. Atracurium

6. Rocuronium

Front 7

Depolarizing NMB drugs:

Back 7

SUXAMETHONIUM

Front 8

Mechanism of action of NON-DEPOLARIZING NeuroMuscular Blocking drugs:

Back 8

COMPETITIVE ANTAGONIST at the Nicotinic ACh receptor

Front 9

Describe the pharmacological characteristics of Non-Depolarizing NMB drugs.

Back 9

1. RIgid, bulky molecules which compete & block receptors

- Need to block 80% of receptor sites to exhibit effects

- Degree of blockade relates to proportion of fiber blocked

2. Some may block ion channels

3. Reversed by anticholinesterases

4. Muscle can still respond to K+ or direct electrical stimulation; drugs simply block the transmission pathway

Front 10

Effects of Non-Depolarizing NMB drugs? Unwanted effects?

Back 10

EFFECTS:

- Flaccid motor paralysis

- Respiratory muscles are last to be effected and first to recover

* Consciousness & perception of pain still present so MUST USE WITH SEDATION, ANALGESIC & ANESTHESIA.

UNWANTED EFFECTS:

- Fall in BP = ganglion block/histamine release

- Tachycardia = muscarinic receptor block

Front 11

Pharmacokinetics of Non-Depolarizing NMB drugs?

Back 11

1. Mostly quaternary ammonium compounds

2. Administered IV

3. Rate of onset & duration vary

4. Generally, metabolized by the liver or excreted unchanged by the kidney

5. Doesn't cross BBB or placenta = safe to use in Caesarians

6. Not absorbed by GIT

Front 12

Mechanism of action of DEPOLARIZING NMBs?

Back 12

AGONIST at NICOTINIC ACh receptor

- Enhanced by anticholinesterases

- Leads to loss of electrical excitability of muscle cells (unlike the non-depolarizing NMBs)

- Beware = metabolized slowly, and persistent stimulation of receptor causes it to switch itself off = no longer stimulated

Front 13

Effects of Depolarizing NMBs?

Back 13

Initial fasciculation (muscle rippling/twitch), which eventually fades & muscle becomes relaxed.

Front 14

Depolarizing NMBs can be reversed with anticholinesterases.

True or False?

Back 14

FALSE

- NON-DEPOLARIZING NMBs can be reversed with anticholinesterases, but not depolarizing NMBs.

Front 15

What are the two main groups of Non-Depolarizing NMBs?

Back 15

1. AMINOSTEROIDS (suffix '-onium')

- Vecuronium, Rocuronium, Pancuronium

- More CV-stable!

2. BENZYLISOQUINOLINES

- Atracurium, cisatracurium, mivacurium

- Histamine release!

Front 16

List the three main NON-DEPOLARIZING NMBs and the most important feature of each.

Back 16

1. VECURONIUM = aminosteroid ('-onium')

- NO of CV side effects.

2. ROCURONIUM = aminosteroid

- Fastes onset of any non-depolarizing agent (<2mins)

3. ATRACURIUM = benzylisoquinoline

- Hofman elimination = spontaneous degradation at physiological pH & temp = not relying on organs for elimination from body

Front 17

Muscle Relaxants are only administered IV.

True or False?

Back 17

TRUE

Front 18

Muscle relaxants rarely induce apnea.

True or False?

Back 18

FALSE - Muscle relaxants WILL induce apnea & so patients must be mechanically ventilated.

Front 19

Muscle relaxants only administered to anesthetized patients.

True or False

Back 19

TRUE

Front 20

Muscle relaxants have no anesthetic or analgesic effects..

True or False?

Back 20

TRUE

Front 21

______________ relaxants can be 'topped up' or given additional IV infusion for as long as required.

Back 21

NON-DEPOLARIZING

Front 22

All muscles are equally sensitive to relaxants.

True or False?

Back 22

FALSE

- Diaphragm & intercostal mm most resistant = last to become affected & first to start working again

- Muscles of pharyngeal area are highly SENSITIVE

* Significant to remember because during recovery, an animal's diaphragm and intercostals may start working again well before the pharyngeal area & so should not remove endotracheal tube until you know the pharynx is completely normal.

Front 23

No relaxants are licensed for animal use.

True or False?

Back 23

TRUE

Front 24

Which muscle relaxant would you choose for the following pre-existing pathologies?

1. Cardiostability

2. Renal/hepatic disease

3. Rapid onset

Back 24

1. Cardiostability = VECURONIUM

2. Renal/hepatic disease = ATRACURIUM

3. Rapid onset = ROCURONIUM

* Although, choice often down to personal preference.

Front 25

SUXAMETHONIUM

Back 25

DEPOLARIZING NMB RELAXANT

- Not used commonly in vet med... more so in humans where rapid endotracheal intubation is required

- Fastest onset time of any relaxant

- Lots of potential side effects (muscle pain/damage, cardiac arrhythmias) = why it's not used in animals so much.

- Can't be topped up or reversed!_

Front 26

_________________ NMBs are the only ones really used clinically in animals.

Back 26

NON-DEPOLARIZING NMBs

Front 27

Clinical uses for NMBs.

Back 27

1. Facilitate fast endotracheal intubation (e.g. animals at high risk for regurgitation/aspiration = full stomachs, megaesophaguses, particularly cats)

2. Relax skeletal muscle for easier surgical access

3. Control ventilation during anesthesia

4. Opthalmic surgery - impossible to perform without NMBs because of opthalmic reflexes

Front 28

Describe the recovery process from NMBs.

Back 28

Occurs Spontaneously:

- As plasma concentration of relaxant declines, drug moves downs concentration gradient from NMJ into plasma

- Eventually, sufficient relaxant will have left to restore NM Transmission

- Can be hastened with NON-DEPOLARIZING RELAXANTS by administering anticholinesterases

Front 29

The recovery process from NMBs can be hastened with NON-DEPOLARIZING RELAXANTS by administering anticholinesterases (neostigmine, edrophonium). How does this work?

Back 29

- Non-depolarizing relaxants are competitive with ACh and so if ACh concentrations increased to a sufficient level at the NMJ, transmission would be restored.

- ACh is broken down by acetycholinesterase, so if this enzyme is inhibited, ACh levels will increase

Front 30

What are the two main types of anticholinesterases?

Back 30

1. NEOSTIGMINE

2. EDROPHONIUM

* Only effective against NON-DEPOLARIZING NMBs

Front 31

Side effects of Anticholinesterases, aside from reversal of NON-DEPOLARIZING NMB drugs?

Back 31

- Bradycardia

- Salivation

- Bronchoconstriction

- Urination & defecation

* All muscarinic effects, and so they are usually combined with antimuscarinic drugs (anticholinergics), such as atropine & glycopyrrolate.

Front 32

SUGAMMADEX?

Back 32

Novel antagonist to Rocuronium/Vecuronium

- Cyclodextrin molecule, which surrounds relaxant, rendering it inactive

= No crazy muscarinic effects (bradycardia, salivation, bronchoconstriction, urination/defecation)

= Expensive!

Front 33

Factors effecting NeuroMuscular Junction blockades by muscle relaxants?

Back 33

1. Other drugs used (anesthetics, antibiotics, anticholinesterases)

* Can cause paralysis in horses if muscle relaxants combined with certain antibiotics...

2. Pathophysiological conditions:

* Hepatic/renal impairment

* Age

* Temp - hypothermic animals recover slower

* Acid-base balance

* Electrolyte disturbances

* Myasthenia gravis

Front 34

Centrally-acting Muscle relaxants?

Back 34

1. Benzodiazepines (BZPs)

- Diazepam, midazolam

2. Guaifenesin = GGE = Glycerol gualacolate

- Blocks impulse of transmission at internuncial neurones within spinal chord and brain stem

- Relaxes limb > respiratory muscle

- Mild sedation but no analgesia

Front 35

Mechanism of action of GGE (Guaifenesin)?

Back 35

CENTRALLY ACTING MUSCLE RELAXANT:

- Blocks impulse of transmission at internuncial neurones within spinal chord and brain stem

- Relaxes limb > respiratory muscle

- Mild sedation but no analgesia

Front 36

Clinical uses of Guanifenesin (GGE)?

Back 36

CENTRALLY ACTING MUSCLE RELAXANT:

- Commonly used for smooth induction of anesthesia in horses (MYORELAX licensed) & cattle = avoids rearing up

- Administered via IV catheter until animal shows signs of ataxia, immediately followed by IV anesthetic agent

* IV catheter mandatory (irritant)

* Cattle sensitive to hemolysis with GGE solutions so usually used as homemade 5% solution in this species

Front 37

Difference between centrally acting muscle relaxants and those that act at the periphery?

Back 37

CENTRALLY ACTING MUSCLE RELAXANTS:
- General anesthetics & muscle relaxers which block the transmission of signals at internuncial neurones within the spinal chord & brain stem

PERIPHERY MUSCLE RELAXANTS:

- Act at NMJ (NM blocking drugs)

Front 38

Differences between the pharmacological actions of the depolarizing (suxamethonium) & Non-depolarizing agents (atracurium, vecuronium, rocuronium)?

Back 38

** DEPOLARIZING AGENTS:

- AGONISTS at NICOTINIC ACh receptor

- Enhanced by anticholinesterases

- Leads to loss of electrical excitability of muscle cells (unlike the non-depolarizing NMBs)

** NON-DEPOLARIZING AGENTS (most imp):

- COMPETITIVE ANTAGONIST at the Nicotinic ACh receptor

- Reversed by anticholinesterases

- Muscle can still respond to K+ or direct electrical stimulation; drugs simply block the transmission pathway

Front 39

Why do Non-depolarizing NMB agents tend to be used more clinically in vet med?

Back 39

DEPOLARIZING NMBs not ideal because:

- Lots of potential side effects (muscle pain/damage, cardiac arrhythmias) = why it's not used in animals so much.

- Can't be topped up or reversed!

Front 40

Why/when is Guaifenesin (GGE) used most commonly in vet med?

Back 40

Used pre-induction in horses to avoid them rearing of up and taking off as they commonly do when anesthesia kicks in.

- Administered via IV catheter until animal shows signs of ataxia, immediately followed by IV anesthetic agent

* IV catheter mandatory (irritant)

* Cattle sensitive to hemolysis with GGE solutions so usually used as homemade 5% solution in this species

Front 41

MYORELAX?

Back 41

Licensed GGE, centrally acting muscle relaxant for HORSES.

- Used for smooth induction of horses.