Muscle Relaxant Drugs (Wong)

Front 1

Sequence of muscle paralysis for muscle relaxants
(and recovery)

Back 1

- Small rapidly moving muscles affected earliest (fingers, toes, jaws, eyes)
- Next, Larger muscels of limb & trunk
- Last: Intercostal & diaphragm (death)
Recovery in Reverse order: diaphragm, then limbs/trunk, then fingers, toes

Front 2

Antagonism of nondepolarizing drugs

Back 2

Anticholinesterase drugs (neostigmine, edrophonium) can antagonize the effects of tubucurarine & other nondepolarizing NM drugs (Block is "Surmountable" - ↑ACH)

Front 3

Muscle relaxants with strong tendency to cause Histamine release

Back 3

Mivacurium, tubcurarine

Front 4

Muscle relaxant that blocks cardiac Muscarinic receptors

Back 4

Pancurarium

Front 5

Nondepolarizing short acting drugs muscle relaxants
Time frame?

Back 5

Mivacurium (rapidly hydrolyzed by plasma esterases; NO ganglionic blockade)
Last 10-20min

Front 6

Nondepolarizing Intermediate acting muscle relaxants
Time frame

Back 6

- Astracurium
- Cisatracurium (isomer of atracurium; 2-3x more potent
○ Preferred during renal failure (c/o spontaneous breakdown)
- Rocuronium (fastest onset of all (1-2min); useful for tracheal intubation
Last 25-45 minutes

Front 7

Nondepolarizing long acting muscle relaxants
Time frame

Back 7

More potent w/ slower onset (4-6min)
- Tubocurarine
- Pancuronium (NO histamine release; vagolytic (blocks Musc-R -> ↑HR)
Last 60-120min

Front 8

Muscle relaxant preferred in patients with renal failure

Back 8

Cistacurium (also Astracurium)
C/o spontaneous breakdown

Front 9

MOA of Nondepolarizing Muscle relaxants

Back 9

Block nicotinic-R competitively -> inhibit Na+ channel & EPP (end plate potential)
Reversible by increasing amt of ACH at Nm junction (surmountable)
Can be done by an acetylcholinesterase inhibitor

Front 10

Effects of Nondepolarizing muscle relaxants
Adverse

Back 10

Paralysis (Sequence: 1) small/rapid -> 2) limbs/neck/trunk -> 3) intecostal/Diaphragm (death)
CV: Reflex tachycardia from hypotension from Histamine release/Ganglion blockade
Adverse Rxn: Apnea (reversed by neostigmine), CV collapse

Front 11

Nondepolarizing muscle relaxant interactions

Back 11

Respiratory depression
Myasthenia Gravis
Renal impairment
Liver or CV impairment
Drugs enhancing (Antibiotics: Aminoglycosides; Ca++ blockers; Cholinesterase inhib (overcome block), Inhaled anesthetics increase block)

Front 12

Tubocurarine
Length of action
SE

Back 12

Nondepolarizing MR (block Nicotinic-R)
LONG acting (60-120 min)
SE: Histamine release & ganglion blockade -> Hypotension -> reflex TACHYcardia

Front 13

Atracurium (Tacrium)
Length of action
Use:
SE
Metabolism

Back 13

Nondepolarizng (block Nicotinic-R)
Intermediate (20-45min)
Use: short surgical procedures (preferred in renal failure)
SE: Spontaneous degrad & Plasma esterases

Front 14

Clinical Uses of Nondepolarizing Drugs

Back 14

Adjunct gen anesthetic for muscle relaxation during surgery
Endotracheal intubation/endoscopic procedures (mivacurium & rocuronium)

Front 15

Cistatracurium (Nimbex)
Length of action
Use:
SE
Metabolism

Back 15

Nondepolarizing muscle relaxant (Isomer of atracurium: 2-3x more potent)
Intermediate acting (20-45 min)
Use: Preferred in renal failure c/o degradation
SE:
Metabolism: Spontaneous degradation

Front 16

Mivacurium (Mivacron)
Length of action
Use:
SE
Metabolism

Back 16

Nondepolarizing muscle relaxant
Short acting (10-20min)
SE: No ganglionic blockade
Metab: Plasma esterases

Front 17

Rocuronium
Length of action
Use:
SE
Metabolism

Back 17

Nondepolarizing muscle relaxant
Intermediate acting (20-45min); RAPID onset (1-2min)
Use: Tracheal intubation (especially)

Front 18

Pancuronium
Length of action
Use:
SE
Metabolism

Back 18

Nondeoplarizing muscle relaxant
Long acting (60-120min)
SE: Vagolytic = Can increase HR by blocking Muscarinic-R
No histamine release

Front 19

Tubocurarine
Length of action
Use:
SE
Metabolism

Back 19

Prototypical nondepolarizing muscle relaxant
SE: HISTAMINE release & CV effects (reflex TACHYcardia from HYPOtension)

Front 20

Succinylcholine
Length of action
MOA
Metabolism
Use

Back 20

Depolarizing blocker
VERY short acting -> FLACCID paralysis:
MOA: Phase 1: "Depolarization block"; fasciculations precede flaccid paralysis (Interaction: Potentiated by Cholinesterase inhibitors)
Phase 2: "Desensitization"; repolarization but resistant to ACh depol (resembles nondepolarizing block); REVERSED by acetylcholinesterase inhibitors)
Metab/Kinetics: IV, SHORT acting (EXCEPTION: atypical pseudocholinesterase)
Use: anesthesia adjunct; endotracheal intub; ECT

Front 21

Succinylcholine Side effects
How to prevent?
Adverse?

Back 21

SE:
1) arrhythmias (Bradycardia) - prevent w/ Atropine
2) HYPERkalemia (life threatening; muscles lose K to plasma); caution in pt w burns, nerve dmg, NM disease, CHF
3) Histamine release (slight)
Adverse:
Apnea (mechanical ventilation); Hyperkalemia; Emesis, ↑IOP, muscle pain
MALIGNANT HYPERTHERMIA: genetic defect of SR -> sudden prolong release Ca++ w/ muscle contraction & ↑ temp

Front 22

Test for abnormal acetylcholinesterase
Prevalence/inheritance
Why do this?

Back 22

Dibucaine number: abnormal enzyme will RESIST dibucaine binding (20-50% in abnormal; 80% in normal)
Auto Recessive; 1% pop (Asian/Black less)
Do to prevent prolonged apnea in pt taking Succinylcholine

Front 23

Malignant hyperthermia treatment
Cause of?

Back 23

Tx: DANTRONE (IV, DOC); cooling, oxygen
Succinylcholine + genetic defect of SR -> sudden prolong release Ca++ w/ muscle contraction & ↑ temp

Front 24

Spasticity etiology
Associated with
MOA of drug

Back 24

Spasticity: ↑ muscle tone from CENTRAL origin; increase in tonic stretch reflexes & flexor muscle spasms; results from loss of Upper Motor Neurons
Assoc: w/ strokes, CNS injury, cerebral palsy & MS
Drugs ameliorate by:
- Modifying reflex arc
- Interfering w/ excitation-contraction coupling in muscle

Front 25

Diazepam
MOA
Use
SE

Back 25

1) MOA: ↑↑ GABA-mediated presynaptic inhibition on GABA(a)-Receptor at 1a axon terminal in spinal cord
2) Use: spastic states, spasm c/o muscle trauma
3) SE: Sedation at required doses - limits use
a. Greatest benefit in pt w/ MS & Spinal cord injury
b. Psych & physical dependence can occur

Front 26

Baclofen
MOA
Use
SE

Back 26

1) MOA: GABA (b) agonist at terminal of 1a afferent neuron -> HYPERpolarization by ↑K+ conductance -> PREsynaptic inhibition & ↓release of excitatory amino acid NT (e.g. glutamate)
2) Effects: a. Relief of involuntary flexor spams, b. Less sedating
3) Kinetics:
A: Orally; intrathecal via infusion pump
E: excrete via Kidney UNCHANGED
4) Adverse:
a. Sedation, lassitude, dizziness, headache, sz
b. Hallucination & seizure upon abrupt withrdrawal
5) Interactions:a.Avoid abrupt withdrawal, b. Impaired renal function, c. Epilepsy, d. CNS depressants
6) Clinical use:
a. Spasticity in pt w/ MS or spinal cord injury
b. Trigem Neuralgia

Front 27

Tizanidine (Zanaflex)
MOA
Use
SE

Back 27

1) MOA: Alpha-2 agonist -> ↑Presynaptic & postsynaptic inhibition in spinal cord -> ↓release of excitatory amino acid neurotx
2) SE: Asthenia (41%) (fatigue); sedation, also dry mouth, dizziness, hypotension
3) Use: SPASTICITY assoc. w/ MS & spinal cord injury

Front 28

Gabapentin
MOA
Use
SE

Back 28

"MANIC, Fat & tired, can't walk, Says GAGA c/o CNS distress, drinks Part Gin/tonic for neuropathic pain but does not affect his liver"
1) MOA: Unknown; may ↑ nonvesicular release of GABA
2) Kinetics: a. oral absorb = dose dependent b. NO liver metabolism -> excreted unchanged in kidney (T1/2: 5-8 hrs)
3) USE:
a. Spasticity w/ MS
b. Neuropathic pain (Diabetic neuropathy, postherpetic neuropathy)
c. Partial sz, General Tonic-Clonic sz (adjunctive)
4) Adverse: a. Sedation, dizziness, ataxia, fatigue

Front 29

Dantrolene
MOA
Kinetics
Clinical use
Adverse rxn
Contraindications

Back 29

1) MOA: bind to RYANODINE receptors on Ca++ channel of SR (Sarcoplasmic reticulum) -> ↓Ca++ release & E-coupling of Skel muscle
2) Kinetics:
a. IV (c/o oral slow/incomplete)
b. Slow metab in liver (T1/2: 8hrs)
3) Clinical use:
a. Spasticity of cerebral origin (oral)
b. MALIGNANT HYPERTHERMIA: IV (DOC)
4) Adverse rxn:
a. Muscle weakness, drowsiness
b. Severe liver toxicity, Hepatitis (potentially fatal)
5) Contraindications
a. Liver disease: LIVER FUNCTION TEST (More common in FEMALE over age of 35)
b. Ambulatory pt

Front 30

Botulinium Toxin Type A (Botox)

Back 30

1) MOA: Cleaves protein req. for ACH release & ↓NM conduction -> paralysis; ↓wrinkles (muscle function will return over 3-6 months)
2) USE:
a. Cervical dystonia (spasmodioc torticollis); writer's cramp;
b. Spasms c/o MS or Cerebral Palsy
c. Strabismus, blepharospasm
d. ↓Wrinkles or frown lines (for 3-6 months)
3) Adverse:
a. Dysphagia (20%)
b. Muscle weakness, dyspepsia, pain at inj site
c. Severe headache, temporary ptosis, drooling & asymmetrical smile

Front 31

Spasmolytic drugs

Back 31

Diazepam, Baclofen, Tizanidine, Gabapentin

Front 32

Drugs acting directly at Skeletal muscle

Back 32

Dantrolene, Botulinium Toxin Type A

Front 33

Drugs used for Acute Local Muscle Spasm

Back 33

Cyclobenzapine (symptomatic relief; most muscle strains/minor injuries respond to rest, immobilization, cold compress, whirlpool)

Front 34

Cyclobenzapine

Back 34

1) MOA: Related to TCA - may act on 5-HT to ↓Muscarinic tone (ANTIMUSCARINIC)
2) Adverse:
a. Sedation, dry mouth, blurred vision, tachycardia (anti-SLUD)
b. Caution: Glaucoma, urinary retention