Pharmacology I - Muscle Relaxants

Front 1

Does ketamine need to be used in combination with another drug with muscle relaxant properties?

Back 1

Yes

Front 2

amino-steroids end with?

Back 2

amino-steroids end with -curonium?

Front 3

benzylquinloium end with?

Back 3

benzylquinloiums end with -curium

atracurium, mivacurium

Front 4

What type of receptor is located at neuromuscular junction?

Back 4

nicotinic

Front 5

What are the three essential prerequisites to using muscle relaxant drugs?

Back 5

Animal must be unconscious
Ensure adequate analgesia
there must be a means of supporting ventilation

Front 6

4 classes of drugs used for muscle relaxant:

Back 6

1. Depolarising (non-competitive) muscle relaxants
2. Non-depolarising (competitive)
3. Centrally acting
4. Drugs with muscle relaxant properties (but not)

Front 7

Name only Depolarizing muscle relaxant/blocker learned about in Pharm.; produces a non-competitive block at the neuromuscular junction

Back 7

Succinylcholine <- depolarizing

* simply two acetyl choline molecules linked through the acetate methyl groups
* not used anymore in clinics, but often appears on PAVE

Front 8

Disadvantages of succinylcholine use: (name five)

What is myalgia?

Back 8

* Sux is associated w/painful muscle fasciculations (twitch) b/c muscle is depolarized, recover with muscle soreness (myalgia)
* also induction of hyperkalaemia and arrhythmias associated with initial fasciculations
* anaphylactic reactions
* muscarinic cardiac effects (bradycardia, salivation).
* cited as a trigger for malignant hyperthermia

Front 9

What does ACh bind to on muscle cells?

Back 9

Nicotinic receptors

Front 10

When do we use nuromuscular blocking drugs?

Back 10

Intra-ocular surgery
Intracranial surgery
Deep laparotomy

Front 11

What are some depolarizing (non-competitive) muscle relaxants?

Back 11

Suxamethonium (Succinyl choline)

Front 12

What are some Non-depolarizing (competitive) muscle relaxants?

Back 12

Vecuronium
Atracurium
Rocuronium
Cis-atracurium

Hint: VARC

Front 13

What are some centrally acting muscle relaxants?

Do they work at neuromuscular junction?

Back 13

Gualfenesin

No; centrally acting

Front 14

What are some drugs that are not NMBs but have muscle relaxing properties?

What is they're mech. of action?

Back 14

Benzodiazepines
alpha2 agonists

* centrally acting (on CNS), not at NM junction

Front 15

In what two species are neuromuscular blocking drugs most commonly used?

Back 15

Dogs
Horses

Front 16

atracurium most often used in ____?

Back 16

horses

Front 17

Which animals are very sensitive to NMBs?

Back 17

Sheep

Front 18

Guaifenesin is most commonly used in ____?

Back 18

in horses, cattle, and pigs

Front 19

Neuromuscular blocking drugs are most commonly used in dogs?

Back 19

vecuronium, rocuronium,
atracurium, mivacurium

VRAM

Front 20

In the past what was suxamethonium used for?

Back 20

Facilitate intubation of cats or pigs

Front 21

Two types Non-depolarizing (competitive) neuromuscular blocking drugs

Back 21

1. Amino steroidal compounds
2. Benzylisoquinolium compounds

Front 22

Which NMBs lack histamine release when injected, are generally not extensively metabolized in the liver, and has a high potency?

Back 22

Amino steroidal compounds (Vecuronium and Rocuronium)

Front 23

Name benzylquinloium compounds:

Back 23

Benzylisoquinolium -> atracurium, mivacurium

BAM!

Front 24

What is the delay to onset of paralysis of non-depolarizing neuromuscular blocking drugs?
Why?

Back 24

Time taken for drug to occupy at least 70% of receptors

Competitive, so must be higher conc. than ACh., otherwise animals recovers

Front 25

What is the speed of onset of a NMB influenced by? (give 5)

CPPMD

Back 25

Cardiac output (higher CO, faster onset)
Muscle blood flow (same)
Potency (inversely proportional)
Dose of relaxant (size of dose)
...and as always pharmacokinetics

Front 26

What drug mimics the action of ACh, remains bound to POST-junctional receptors, and the muscle first conTRacts followed by relaxation?

Back 26

Suxamethonium (Succinyl Choline)

Front 27

Relationship between Potency and onset?

Back 27

Potency is inversely related to onset time - more potent the drug slower the onset

Front 28

Which NMB is considered the cleanest of the currently available NMBs?

Hint: Minor hepatic metabolim - depends on biliary excretion for termination of effect

Back 28

Vecuronium

no histamine release
very cardiostable
renal disease - little effect on clearance
Minor hepatic metabolim - depends on biliary excretion for termination of effect
Duration of action is prolonged in hepatic disease

Front 29

Size of dose affects ?

Back 29

onset time (delay) and duration of action

Front 30

Which drug is considered to have the fastest onset of the non-depolarizing agents?

Back 30

Rocuronium

Front 31

Vecuronium and Rocuronium are ___?

How are they metabolized?

Back 31

amino-steroids = Vecuronium, Rocuronium

metabolised in the liver; ‘not extensively’
some drugs are only minimally metabolised

(vecuronium recovery determined. mostly by bilary excretion)

Front 32

what proportion of benzylquinloium compounds (atracurium, mivacurium) are eliminated unchanged?

Back 32

< 10%

BAM!

Front 33

What are some possible side effects of non-depolarizing neuromuscuar blocking drugs?

Back 33

Drug interactions
Residual paralysis
Autonomic reactions
Histamine release
Allergic/anaphylactic reactions

Front 34

What drug interactions may produce resistance to the effects of neuromuscular relaxants?

Back 34

Anticonvulsant agents such as carbamazepine and phenytoin

Front 35

In the US, what is used for Reversal of non-depolarizing agents?

Back 35

In the US, use anticholinesterase combined with an antimuscarinic

-> want to make sure ACh builds up in periphery/plasma (not in CNS), ACh must have higher conc. than drug to beat it out

Front 36

2 anticholinesterase agents are commonly used

Back 36

-neostigmine
-edrophonium

Front 37

Which REVERSAL agent of neuromuscular blocks is the most potent and may cause cardiac arrhythmia esp. if animal is hypercapnic (high CO2 in blood)?

Back 37

Neostigmine

very potent, but too many side effects

Front 38

What is the neuromuscular block REVERSAL agent of choice?

Back 38

Edrophonium

Front 39

Which drug degradation produces laudanosine, which has been shown to be an epileptiform?

Back 39

Atracurium - has special mechanism for metabolism

Front 40

How are negative effects of anticholinesterase prevented (bradycardia, increased secretions, and increased smooth muscle activity) ?

Examples?

Back 40

Background: Increased concentrations of ACh (result of anticholinesterases) cause muscarinic side-effects

By co-administering antimuscarinic agents such as atropine and glycopyrrolate (w/anticholinesterase) reduce these risks
:

Front 41

Which muscle relaxant is a spinal acting muscle relaxant, does NOT act on muscles of respiration or CVS, and there is no antidote?

Back 41

Guaifenesin (GGE)

"just makes animals lie down"

Front 42

What are the solution percentages of guaifenesin in horses?

Back 42

5-10%, never greater than 10%, because can damage RBC's

Front 43

Cows should be administered what percent of guaifenesin?

Back 43

5%, prone to GGE-induced haemolysis, can damage RBC's

Front 44

What are some negative effects of guaifenesin?

Back 44

* Extremely irritating if injected peri-vascularly
* Will cause thrombophlebitis unless catheters are flushed before removal
(inflammation of vein due to clot)

Front 45

The ideal muscle relaxant drug is ____.

Back 45

* non-depolarising
* rapid onset
* intermediate duration...huh?
* free of ganglion blocking, antimuscarinic or histamine-releasing side effects

Front 46

Are NMBAs anesthetics?

Back 46

NO, they do not affect conscientiousness

Front 47

Which muscles are affected first?

Back 47

smaller muscles

Front 48

How do monitor action of NMBA's?

Back 48

* peripheral nerve stimulators on distal limb or facial muscles,
* monitor response to stim., these are tiny muscles so if respond - animal has recovered

Front 49

True or False:
Suxamethonium is non-competitive?

Back 49

True; it does not prevent ACh from binding

Front 50

True or False:
Suxamethonium (aka succinyl- choline) mimics action of ACh at NM junction?

Back 50

True; which is why causes muscle contraction like ACh, but stays bound (non-competitively);
After Ach leaves (confirm this), and you get muscle relaxation

Front 51

Is succinylcholine fast or slow onset?

Is short long acting or short acting?

Back 51

Extremely fast onset

Short acting

Front 52

True or False:
Sux recovery is spontaneous without need for reversal agent?

Back 52

True

Front 53

How is Suxamethonium metabolized?

Back 53

metabolized by cholinesterases produced in liver

Front 54

Which muscle relaxant causes histamine release as side effect?

Back 54

Benzylquinloium compounds (atracurium, mivacurium)

(check on mivacurium - if it is one of the benz's)

Front 55

True or False:
Atracurium & cis-atracurium cause bradycardia.

Back 55

FALSE!
Benzylquinloium compounds Atracurium & cis-atracurium have Minimal CVS effects

Front 56

True or False:
There is very marked individual variation in the response to a specific dose of NM blockers.

Back 56

True

Front 57

Do Non-depolarizing (competitive) muscle relaxants cross BBB?

Back 57

No; that would kill animal b/c would shut down all nicotinic receptors in CNS
-> only act as NMBA

Cannot cross b/c these are very large molecules

Front 58

Which drugs are partially degraded spontaneously by Hoffman degradation and is often used in patients with liver and renal disease?
Why is it used with liver/renal diseased patients?

Back 58

Benzylisoquinolium (Atracurium and Cis-atracurium)

Atracurium is very unique b/c doesn't rely on liver for metabolism - this spontaneous Hoffman degradation occurs in plasma

Front 59

What type of NMBs are classified into or include Amino steroidal compounds and Benzylisoquinolium compounds?

Back 59

Non-depolarizing (competitive) neuromuscular blocking drugs

Front 60

Only time TOTAL muscle relaxation absolutely essential?

Back 60

Total muscle relaxation is NOT essential in any of these cases, with the possible exception of intra-ocular surgery

Front 61

curariform is another name for?

example?

Back 61

(curariform) = Benzylquinolium derivatives

atracurium