Mm Relaxants

Front 1

Neuromuscular Blocking Agents:
Nondepolarizing (Competitive) Blockers

Back 1

Tubocurarine (generic)
Atracurium (Tracrium)
Mivacurium (Mivacron)
Pancuronium (generic, Pavulon)
Rocuronium (Zemuron)
Pipecuronium (Arduan)

Front 2

Neuromuscular Blocking Agents:Depolarizing Blocker

Back 2

Succinylcholine (Anectine: others)

Front 3

Spamolytic Drugs:

Back 3

Benzodiazepines: Diazepam (Valium)
Baclofen (generic, Lioresal)
Tazanidine (Zanaflex)

Front 4

Drugs Act Directly at Skeletal Muscle

Back 4

Dantrolene (Dantrium)
Botulinium Toxin Type A (Botox

Front 5

Drugs Used For Acute Local Muscle Spasm:

Back 5

Cyclobenzapine (generic, Flexeril)
Carisoprodol (generic, Soma)

Front 6

Neuromuscular blocking agents
What are they?
What do they do?

Back 6

are drugs used during surgical procedures to cause muscle PARALYSIS-- interfere with transmission at the neuromuscular junction WITHOUT CNS activity.

Front 7

“Curare”

Back 7

a generic term for various South American arrow poisons discovered centuries ago. Tubocurarine was the active alkaloid in curare; curare was first used for promoting muscle relaxation with general anesthesia in the 1940’s

Front 8

NEUROMUSCULAR BLOCKING AGENTS fall into 2 classes

Back 8

1. Nondepolarizing (competitive)
2. Depolarizing

Front 9

Nondepolarizing (competitive)Blockers

Back 9

tubocurarine--ISOQUINOLINE
mivacurium (Mivacron)
atracurium (Tracrium)
pancuronium (generic, Pavulon)--STEROID
rocuronium (Zemuron)
pipecuronium (Arduan)

Front 10

Mechanism of action of Nondepolarizing (competitive)Blockers

Back 10

Blocks N-R competitively-- INHIBITS Na- CHANNEL & EPP
REVERSIBLE; SURMOUNTABLE

Front 11

Nondepolarizing (competitive)Blockers: Effects on skeletal muscle

Back 11

Muscle paralysis

Front 12

Sequence of paralysis:

Back 12

Small, rapidly moving muscles are affected earliest – fingers, toes, jaws, eyes, etc.

Next, the muscles of the limbs, neck, trunk.

Last to be affected are the intercostal muscles and, finally, the diaphragm – death.

Recovery of muscles usually occurs in reverse order:
Diaphragm>limbs,trunks> fingers, toes, eyes

Front 13

______________ can antagonize the effects of tubocurarine and other nondepolarizing NM blocking agents:

i.e., the block is “surmountable”-- increase ACH

Back 13

Anticholinesterase drugs, e.g., neostigmine,edrophonium

Front 14

Cardiovascular effects of Nondepolarizing (competitive)Blockers

Back 14

With the exception of pipecuronium, & rocuronium, all nondepolarizing muscle relaxants produce some CV effects.

Front 15

Tubocurarine can result in what CV event

Back 15

PRONOUNCED HYPOTENSION due largely to histamine release and sympathetic ganglionic blockade.-- REFLEX TACHYCARDIA

Front 16

Pancuronium can cause what CV complications

Back 16

increase heart rate & BP --vagolytic.

Front 17

mivacurium causes a moderate amount of ________ release

Back 17

histamine

Front 18

tubocurarine causes a moderate amount of ________ release and is a _________ of autonomic ganglia

Back 18

histamine
weak block

Front 19

Pancuronium is a ___________ of the cardiac muscarinic receptors

Back 19

moderate blocker

Front 20

Succinylcholine is a _________ of autonomic ganglia and a ___________ of the cardiac muscarinic receptors

Back 20

stimulator
stimulator

Front 21

Pharmacokinetics of nondepolarizing (competitive) neuromuscular blocking agents

Back 21

Quaternary ammonium compounds-poorly absorbed from GI tract; I.V. (preferred) or I.M.

Following I.V. administration, get rapid redistribution phase followed by slower elimination phase.

Undergo varying degrees of liver metabolism; others are excreted in the urine.

Front 22

Mivacurium duration of action

and degradation

Back 22

Short-acting

plasma choninesterases

Front 23

Vecuronium, atracurium duration of action

Back 23

Intermediate-acting

Front 24

Atracurium:
degredation & duration of action

Back 24

degraded spontaneously

intermediate

Front 25

Tubocurarine: duration of action

Back 25

long acting

Front 26

pancuronium: duration of action

Back 26

long acting

Front 27

pipercuronium: duration of action

Back 27

long acting

Front 28

rocuronium: duration of action

Back 28

intermediate acting

Front 29

vecuronium: duration of action

Back 29

intermediate acting

Front 30

Succinylcholine: duration of action

degredation

Back 30

very short acting

plasma cholinesterases

Front 31

Clinical uses of Nondepolarizing (Competitive) Blockers

Back 31

Adjuncts to general anesthetics during surgery.

Controlled mechanical ventilation--COPD

Prevent trauma during convulsions

Front 32

Nondepolarizing (Competitive) Blockers used during short surgical procedures

Back 32

atracurium, mivacurium

Front 33

Nondepolarizing (Competitive) Blockers used during Endotracheal intubation

Back 33

rocuronium

Front 34

Adverse reactions: Nondepolarizing (Competitive) Blockers

antagonized by

Back 34

Prolonged apnea

cholinesterase inhibitors (e.g. neostigmine(Prostigmin))

Front 35

Cautions, drug interactions:
Nondepolarizing (Competitive) Blockers

Back 35

Respiratory depression
Myasthenia gravis
Renal impairment
Liver or CV impairment

Front 36

drugs can enhance the effects of NM blocking agents

Back 36

Inhalation anesthetics e.g. halothane

Antibiotics, esp. aminoglycosides - ?
↓ ACH RELEASE

Calcium channel blockers-?
↓ CA INFLUX

Antiarrhythmic agents (e.g., quinidine)-
BLOCKS Na-CHANNELS

Local anesthetics-?

Front 37

Depolarizing Neuromuscular blocking drugs: MOA

Back 37

Depolarization block-- FLACCID PARALYSIS Can be divided into two phases.

1) Phase I block: Depolarization, fasciculations, unresponsiveness with continued depolarization.

Potentiated by cholinesterase inhibitors -- increase ACh

2)Phase II block-“desensitization”: With continued exposure to succinylcholine, repolarization occurs but the membrane is NOT easily depolarized again.

Closely resembles a nondepolarizing block.(= CURARE)REVERSED BY AChE INHIBITORS

Front 38

Depolarizing Neuromuscular blocking drugs: Effects on skeletal muscle

Back 38

1) Brief muscular fasciculations precede paralysis.

2) Duration is brief ( i.e.5-10 MIN); can prolong effect by repeated injections.

Front 39

Depolarizing Neuromuscular blocking drugs:Other effects:

Back 39

1)Cardiac arrhythmias can occur;
- bradycardia prevented by atropine.

2)Hyperkalemia – can be life-threatening
• Cause:K-LOSS FROM mm
• Cautions in patients with burns, nerve damage, NM disease, children or digoxin

3)Slight histamine release

Front 40

Pharmacokinetics:
Depolarizing Neuromuscular blocking drugs:

Back 40

I.V.; short duration due to rapid inactivation by plasma cholinesterase

An unusually prolonged duration (apnea) will occur in patients with an abnormal variant of pseudocholinesterase. An Autosomal Recessive trait in ~ 1% of Caucasians but is rare in Asians and Blacks.-- IDIOSYNCRATIC

The “dibucaine number” – a test for ability to metabolize succinylcholine – can be used to screen such patients.
-- ENZYME RESISTANT TO DIBUCAINE INHIBITION (50% vs 80%)

Front 41

Clinical uses of Depolarizing Neuromuscular blocking drugs

Back 41

Adjunct to general anesthesia for brief procedures and to facilitate endotracheal intubation.

• Electroconvulsive therapy-- PREVENT CONVULSIONS

Front 42

Adverse reactions of Depolarizing Neuromuscular blocking drugs

Back 42

a. Apnea; hyperkalema, ↑intraocular P.
b. emesis, muscle pain; (up to 20%).
c. Malignant hyperthermia – life- threatening

• Results from a genetic defect of SR: SUDDEN & PROLONG RELEASE OF CA++ WITH MASSIVE MUSCLE CONTRACTION AND increased BODY TEMPERATURE
• The highest incidence occurs with succinylcholine + halothane.
• TX: COOLING, OXYGEN
DANTROLENE-- IV, DOC

Front 43

Contraindications, cautions of Neuromuscular blocking drugs

Back 43

•Genetic disorders of plasma cholinesterase

•History of malignant hyperthermia

• Acute angle-closure glaucoma-- ?

•Respiratory, liver, cardiovascular, renal disorders

•Electrolyte imbalance

Front 44

Drug interactions with Neuromuscular blocking drugs

Back 44

• Cholinesterase inhibitors

• Numerous drugs may enhance the NM blocking action:

- General anesthetics
- Antibiotics
- Quinidine

Front 45

Spasticity

Back 45

is ↑ skeletal muscle tone of CENTRAL ORIGIN – Increase in tonic stretch reflexes and flexor muscle spasms (together with muscle weakness).
The hyperactivity results from a loss of spinal and supraspinal descending inhibitory influences on motoneurons:
“upper motor neuron lesions.”

Front 46

Clinical uses of Nondepolarizing (Competitive) Blockers

Back 46

Adjuncts to general anesthetics during surgery.

Controlled mechanical ventilation--COPD

Prevent trauma during convulsions

Front 47

Nondepolarizing (Competitive) Blockers used during short surgical procedures

Back 47

atracurium, mivacurium

Front 48

Nondepolarizing (Competitive) Blockers used during Endotracheal intubation

Back 48

rocuronium

Front 49

Adverse reactions: Nondepolarizing (Competitive) Blockers

antagonized by

Back 49

Prolonged apnea

cholinesterase inhibitors (e.g. neostigmine(Prostigmin))

Front 50

Cautions, drug interactions:
Nondepolarizing (Competitive) Blockers

Back 50

Respiratory depression
Myasthenia gravis
Renal impairment
Liver or CV impairment

Front 51

drugs can enhance the effects of NM blocking agents

Back 51

Inhalation anesthetics e.g. halothane

Antibiotics, esp. aminoglycosides - ?
↓ ACH RELEASE

Calcium channel blockers-?
↓ CA INFLUX

Antiarrhythmic agents (e.g., quinidine)-
BLOCKS Na-CHANNELS

Local anesthetics-?

Front 52

Depolarizing Neuromuscular blocking drugs: MOA

Back 52

Depolarization block-- FLACCID PARALYSIS Can be divided into two phases.

1) Phase I block: Depolarization, fasciculations, unresponsiveness with continued depolarization.

Potentiated by cholinesterase inhibitors -- increase ACh

2)Phase II block-“desensitization”: With continued exposure to succinylcholine, repolarization occurs but the membrane is NOT easily depolarized again.

Closely resembles a nondepolarizing block.(= CURARE)REVERSED BY AChE INHIBITORS

Front 53

Depolarizing Neuromuscular blocking drugs: Effects on skeletal muscle

Back 53

1) Brief muscular fasciculations precede paralysis.

2) Duration is brief ( i.e.5-10 MIN); can prolong effect by repeated injections.

Front 54

Depolarizing Neuromuscular blocking drugs:Other effects:

Back 54

1)Cardiac arrhythmias can occur;
- bradycardia prevented by atropine.

2)Hyperkalemia – can be life-threatening
• Cause:K-LOSS FROM mm
• Cautions in patients with burns, nerve damage, NM disease, children or digoxin

3)Slight histamine release

Front 55

Pharmacokinetics:
Depolarizing Neuromuscular blocking drugs:

Back 55

I.V.; short duration due to rapid inactivation by plasma cholinesterase

An unusually prolonged duration (apnea) will occur in patients with an abnormal variant of pseudocholinesterase. An Autosomal Recessive trait in ~ 1% of Caucasians but is rare in Asians and Blacks.-- IDIOSYNCRATIC

The “dibucaine number” – a test for ability to metabolize succinylcholine – can be used to screen such patients.
-- ENZYME RESISTANT TO DIBUCAINE INHIBITION (50% vs 80%)

Front 56

Clinical uses of Depolarizing Neuromuscular blocking drugs

Back 56

Adjunct to general anesthesia for brief procedures and to facilitate endotracheal intubation.

• Electroconvulsive therapy-- PREVENT CONVULSIONS

Front 57

Adverse reactions of Depolarizing Neuromuscular blocking drugs

Back 57

a. Apnea; hyperkalema, ↑intraocular P.
• Apnea best treated by mechanical ventilation. Cholinesterase inhibitors will antagonize only Phase II.
b. emesis, muscle pain; (up to 20%).
c. Malignant hyperthermia – life- threatening

• Results from a genetic defect of SR: SUDDEN & PROLONG RELEASE OF CA++ WITH MASSIVE MUSCLE CONTRACTION AND increased BODY TEMPERATURE
• The highest incidence occurs with succinylcholine + halothane.
• TX: COOLING, OXYGEN
DANTROLENE-- IV, DOC

Front 58

Contraindications, cautions of Neuromuscular blocking drugs

Back 58

•Genetic disorders of plasma cholinesterase

•History of malignant hyperthermia

• Acute angle-closure glaucoma-- ?

•Respiratory, liver, cardiovascular, renal disorders

•Electrolyte imbalance

Front 59

Drug interactions with Neuromuscular blocking drugs

Back 59

• Cholinesterase inhibitors

• Numerous drugs may enhance the NM blocking action:

- General anesthetics
- Antibiotics
- Quinidine

Front 60

Spasticity

Back 60

is ↑ skeletal muscle tone of CENTRAL ORIGIN – Increase in tonic stretch reflexes and flexor muscle spasms (together with muscle weakness).
The hyperactivity results from a loss of spinal and supraspinal descending inhibitory influences on motoneurons:
“upper motor neuron lesions.”

Front 61

what is spasticity associated with

Back 61

The hyperactivity results from a loss of spinal and supraspinal descending inhibitory influences on motoneurons: “upper motor neuron lesions.”

Spasticity is associated with strokes, CNS injuries, cerebral palsy, and multiple sclerosis

Drugs may ameliorate some of the symptoms of spasticity by modifying the stretch reflex arc or by interfering directly with the process of excitation contraction coupling in the muscle.

Front 62

Spamolytic Drugs:

Back 62

A. Benzodiazepines: Diazepam(Valium)
B. Baclofen (generic, Lioresal)
C. Tazanidine (Zanaflex)

Front 63

Drugs Act Directly at Skeletal Muscle

Back 63

A Dantrolene (Dantrium)
B. Botulinium Toxin Type A (Botox)

Front 64

Benzodiazepines: Diazepam (Valium) -- MOA

Back 64

ENHANCED GABA-MEDIATED
PRESYN. INHIBITION

Front 65

Benzodiazepines: Diazepam (Valium)

Uses:

Back 65

Spastic states and spasm due to local muscle trauma; SEDATION -- at the doses required (2 – 10 mg 4X per day)-- LIMITING Greatest benefit seen in patients with multiple sclerosis and spinal cord injury.

Front 66

Benzodiazepines: Diazepam
Cautions

Back 66

Psychological and physical dependence can occur (Schedule IV):

Front 67

Baclofen (Lioresal)
MOA:

Back 67

GABA AGONIST--HYPERPOLARIZATION---PRESYN. INHIBITION
Results in inhibition of release of excitatory transmitters (e.g., glutamic acid; aspartic acid) involved in spinal reflex pathways.

Front 68

Baclofen (Lioresal)
Effects:

Back 68

Very effective in relieving involuntary flexor spasms and resistance to passive movements; LESS sedating than diazepam.

Front 69

Baclofen (Lioresal)Pharmacokinetics:

Back 69

a. Well absorbed orally; intrathecal via an implantable infusion pump.

b. Widely distributed, excreted primarily by the kidney unchanged. Plasma half-life is 3-4 hours.

Front 70

Baclofen (Lioresal)
Adverse reactions:

Back 70

a. Drowsiness, lassitude, dizziness.

b. Ataxia, confusion, hallucinations, seizures.

c. Intrathecal: coma, respiratory depession, seizures.

Front 71

Baclofen (Lioresal)
Cautions, drug interactions.

Back 71

•Hallucinations, psychosis, and seizures have been reported upon withdrawal; AVOID abrupt withdrawal.
•Impaired renal function
•Epilepsy
•CNS depressants

Front 72

Baclofen (Lioresal)
uses:

Back 72

•Spasticity in patients with multiple sclerosis and spinal cord injury; trigeminal neuralgia

•Begin with low oral dose and gradually ↑ to 40 – 80 mg/day in divided doses.

Front 73

Tizanidine (Zanaflex)
MOA

Back 73

Structurally related to clonidine.

Alpha-2 agonist--
↑ PRESYN. INHIBITION OF MOTOR NEURONS.
Also inhibits nociceptive transmission in the spinal cord.

Front 74

Tizanidine (Zanaflex)
Side effects:

Back 74

• Asthenia (41%); WEAKNESS
• Drowsiness, hypotension and dry mouth.

Front 75

DRUGS ACT DIRECTY ON SKELETAL MUSCLE

Back 75

Dantrolene (Dantrium)

Front 76

Dantrolene (Dantrium)
MOA:

Back 76

May bind to the ryanodine receptors on the calcium channel of the SR. DECREASE Ca++ RELEASE AND E-C COUPLING IN SK. M.

Front 77

Dantrolene (Dantrium)
Effects:

Back 77

Usually diminishes spasticity but, tends to cause generalized muscle weakness

Front 78

Dantrolene (Dantrium)Pharmacokinetics:

Back 78

Oral absorption is slow and incomplete; I.V. for malignant hyperthermia.

b.Slowly metabolized in the liver(hydroxylated). Half-life is about 8 hrs.

Front 79

Dantrolene (Dantrium)
Adverse reactions:

Back 79

a.Muscle Weakness, drowsiness

b.Severe liver toxicity, potentially fatal hepatitis.

Front 80

Dantrolene (Dantrium)
Contraindications, cautions:

Back 80

•Liver disease

•Ambulatory patients—caution

•Perform liver function tests periodically

•Patients over age of 35, esp females

Front 81

Dantrolene (Dantrium)
Clinical uses:

Back 81

•Spasticity of cerebral origin—oral.

•Malignant hyperthermia—I.V. DOC

Front 82

Botulinum toxin type A (Botox)
Where is it obtained

Back 82

clostridium botulinum

Front 83

Botulinum toxin type A (Botox)
How is it given

Back 83

IM.

Front 84

Botulinum toxin type A (Botox)
MOA:

Back 84

•↓ ACH RELEASE & NM CONDUCTION-- M. PARALYSIS; REDUCE WRINKLES
• Muscle function returns gradually over 3 – 6 months.

Front 85

Botulinum toxin type A (Botox)
Uses:

Back 85

•Strabismus, blepharospasm
•Cervical dystonia (spasmodic toricollis); writer’s cramp; spasms due to M.S. or cerebral palsy.
•Reduces wrinkles or frown lines

Front 86

Botulinum toxin type A (Botox)
Adverse reactions:

Back 86

• Dysphagia (20%), dyspnea, aspiration, pneumonia

• Muscle weakness, dyspepsia and pain at injection site.

• Severe headache; temporary ptosis, drooling and asymmetrical smile.

Front 87

DRUGS USED FOR ACUTE LOCAL MUSCLE SPASM:

“CENTRALLY ACTING SKELETAL MUSCLE RELAXANTS”

Back 87

cyclobenzaprine(generic,Flexeril)

carisoprodol (generic, Soma)

Front 88

uses and considerations of DRUGS USED FOR ACUTE LOCAL MUSCLE SPASM:

Back 88

Most muscle strains and minor injuries are self-limited and respond rapidly to rest and physical therapy—immobilization, cold compresses, whirlpool baths, etc.


These drugs may provide some symptomatic relief in localized muscle spasm; all are CNS depressants and act as sedatives.

Front 89

Cyclobenzaprine (Flexeril):
is sxlly related to _______

has some ___________ at doses of 30 mg

Has strong __________effects

Back 89

tricyclic antidepressants.

adjunctive muscle relaxant capabilities

antimuscarinic

Front 90

Cyclobenzaprine (Flexeril):
Adverse reactions:

Back 90

Sedation, dry mouth, dizziness.

Tachycardia, blurred vision, confusion,visual hallucination, urinary retention

Front 91

Cyclobenzaprine (Flexeril):
Cautions:

Back 91

urinary retention
glaucoma

Front 92

CASE STUDY
A patient underwent a surgical procedure lasting 2 hours. Anesthesia was provided by isoflurane, supplemented by intravenous midazolam and a nondepolarizing muscle relaxant.At the end of the procedure, glycopyrrolate, an antimuscurinic agent,was administered followed by pyridostigmine.
SEE NEXT

Back 92

--

Front 93

The main reason for administering glycopyrrolate is to:

a.Dry secretions induced by isoflurane

b.Reverse the effects of the muscle relaxant

c.Provide postoperative analgesia

d.Prevent activation of cardiac muscarinic receptors

e.Enhance the action of pyridostigmine

Back 93

--

Front 94

Glycopyrrolae would be LEAST likely to be needed during reversal of the effects of a nondepolarizing relaxant if the agent used was:

a. Atracurium

b. Mivacurium

c. Pancuronium

d. Tubocurarine

e. Vecuronium

Back 94

--

Front 95

Case 2:
A 22-year-old patient was given a bolus intravenous dose of a drug for muscle relaxation that should have lasted only 5-10 minutes. Instead, the patient required mechanical ventilation for over 8 hours. Which one of the following statements about this problem is LEAST accurate?

a. The agent administered was succinylcholine

b. Fewer than 1:2500 persons have the homozygous trait responsible for this type of problem.

c. Pseudocholinesterase in this patient is resistant to the inhibitory action of dibucaine.

d. About 1:500 persons may experience a slight prolongation of NM blockade when given this agent, i.e., have the heterozygous trait.

e. Neostigmine should be administered to establish the nature of the problem.

Back 95

--

Front 96

How is apnea best treated

Back 96

• Apnea best treated by mechanical ventilation. Cholinesterase inhibitors will antagonize only Phase II