Neuromuscular Blocking Drugs

Question 1

What is the purpose of neuromuscular blocking drugs

Answer 1

Temporary paralysis of skeletal m. and m. relaxation
Prevent interaction between ACh and Nicotinic receptors
Act as nicotinic acetylcholine receptor Nm

Question 2

MOA of competitive (non-polarizing) neuromuscular blocking drugs

Answer 2

Competitive ACh antagonism –> ACh can’t act –> Repolarized plate –> relaxation
NO DEPOLARIZATION (contraction)

Question 3

How is the block relieved?

Answer 3

By increasing ACh levels at the synaptic cleft (Ach competing with the drugs)
Ex: use cholinesterase inhibitors

Question 4

MOA of depolarizing neuromuscular blocking drugs

Answer 4

Sustained repolarization and later block –> ACh cannot act –> depolarization plate
CONSTANT DEPOLIZATION in 2 phases

Question 5

Phases of depolarizing neuromuscular blocking

Answer 5

1. Agents activate Nicotinic ACh receptor –> channels open –> endplate membrane potential to -55 mv —> flaccid paralysis due to continued activation
2. Membrane repolarizes but receptor desensitized to ACh

Question 6

Centrally acting neuromuscular blockers

Answer 6

Dantrolene sodium and Quinine

Question 7

Peripherally acting neuromuscular blockers

Answer 7

Depolarizing blockers (non competitive)
Non-depolarizing blockers (competitive)

Question 8

Depolarizing blockers

Answer 8

Succinylcholine and Decamethonium

Question 9

Long acting non depolarizing blockers

Answer 9

D-tubocurarine, Gallamine, pancuronium, doxacurarium, pipercuronium

Question 10

Intermediate acting non depolarizing blockers

Answer 10

Vecuronium, atracirum, roccuronium

Question 11

Short acting non depolarizing blocker

Answer 11

Mivacirum

Question 12

Non-depolarizing neuromuscular blockers pharmokinetics

Answer 12

Poor oral absorption (IV)
Poor membrane permeability (doesn’t cross BBB)
Generally excreted unchanged (not metabolized)
Low metabolism

Question 13

Pancuronium

Answer 13

Not metabolized (long acting, depolarizing blocker)
Excreted through the kidney
Duration of action is 2-3 hours
Onset of action: 2-6 minutes

Question 14

Vecuronium and roccuronium pharmokinetics

Answer 14

Liver metabolism
DOA increases in the liver
Duration of action is 30-40 minutes
Onset of action: 2-6 minutes

Question 15

Non depolarizing blockers therapeutic uses

Answer 15

In general anesthesia: facilitate tracheal intubation
Induce muscle relaxation
Make orthopedic surgery east
Reduce dose of anesthetics
(descending paralysis)

Question 16

Non depolarizing blockers adverse affects

Answer 16

Hypotension, increased respiratory secretion, bronchospasms
Hyperkalemia
Increased intraocular pressure

Question 17

Which NDMB drugs prolong the action of NDMB?

Answer 17

Aminoglycosides antibiotics (streptomycin)
Calcium channel blockers (Verpamil)
Halogenated anesthetics (Isoflurane)

Question 18

Cholinesterase inhibitors (NDMB)

Answer 18

Neostigme- decreases the effectiveness of NDMB

Question 19

Calcium channel blockers

Answer 19

Verpamil- prolongs the action of NDMB

Question 20

Halogenated anesthetics

Answer 20

Isoflurane will prolong

Question 21

Depolarizing muscle blockers uses

Answer 21

Adjuvant drugs in surgical anesthesia
Effects similar in action to ACh, but longer acting

Question 22

Succinylcholine uses

Answer 22

Only depolarizing drug in clinical use
Use muscle relaxant for passing endotracheal tube

Question 23

DMB interactions

Answer 23

Halothane with DMB produces malignant hyperthermia in some
Tx: rapid cooling of the body and dantrolene

Question 24

____________ augment DMB effects

Answer 24

AChE inhibitors

Question 25

How does age prolong the neuromuscular blockade?

Answer 25

Neonates or old age

Question 26

How does disease prolong the neuromuscular blockade?

Answer 26

Obesity, hepatic disease, renal disease, neuromuscular disease

Question 27

How does drugs prolong the neuromuscular blockade?

Answer 27

Inhalational agents will prolong the blockade of depolarizes and NDMB Antibiotics(dantrolene, tetracyclines)

Question 28

How does electrolytes prolong the neuromuscular blockade?

Answer 28

Hypokalemia, hypermagnesia, hypocalcemia, hypothermia and metabolic acidosis

Question 29

Drug that antagonize NMB

Answer 29

Cholinesterase inhibitors Calcium Phenytoin Carbamazepine Azathioprine Steroids

Question 30

Paralysis in humans

Answer 30

Competitive: Flaccid Depolarizing: Fasciculation resulting in flaccidity

Question 31

Paralysis in chicks

Answer 31

Competitive: Flaccid Depolarizing: Splastic

Question 32

Species sensitivity

Answer 32

Competitive: Rat> rabbit > cat Depolarizing: cat

Question 33

Neostigmine

Answer 33

Competitive: Antagonism block Depolarizing: no effect

Question 34

Inhalation anesthetic (ether)

Answer 34

Competitive: Synergist Depolarizing: no effect

Question 35

Order of paralysis

Answer 35

Competitive: fingers --> eyes --> limbs --> neck --> face --> trunk --> intercostal muscles Depolarizing: neck --> limbs --> jaw --> eyes --> pharynx --> trunk --> intercostal muscles

Question 36

Central and direct muscle relaxants

Answer 36

1. Doesn't affect neuromuscular transmission of EPP 2. Depolarization triggered release of calcium ion from sarcoplasmic reticulum reduced 3. Fast contracting twitch muscles 4. Reduce muscle tone by a selective action in cerebrospinal axis without altering consciousness 5. No effect on neuromuscular transmission 6. Reduces rigidity, spasticity and hyperreflexia

Question 37

Centrally acting muscle reactants

Answer 37

Muscle tone decreased No reduction in voluntary movements Postsynap. relfexes in CNS inhibited CNS depression Administered orally/ parentally Value in the treatment of spastic muscle spasms, tetanus

Question 38

Peripherally acting muscle relaxants

Answer 38

Muscle paralysis Voluntary movements are lost Neuromuscular transmission is blocked CNS effect no significant Administed IV Used for short procedures

Question 39

Dantrolene (central muscle relaxant)

Answer 39

Absorbed orally Penetrated BBB and produces sedation Metabolized by liver, excreted by kidney Malignant Hyperthermia

Question 40

Adverse effects of dantroene

Answer 40

Muscle weakness, sedation, malaise, light headedness

Question 41

Other central muscle relaxants

Answer 41

Mephenesin group: mephenesin, carisoprodol, chlorzoxazone Benzodiazepines (diazepam) GABA derivatives: baclofen

Question 42

Clinical uses to centrally acting muscle relaxants

Answer 42

Acute muscle spasms, tension, torticollis, lumbago, neuralgia, anxiety, tetanus