Neuromuscular Blocking Drugs

Neuromuscular Blocking Drugs

“Don’t fight forces, use them.”

R. BUCKMINSTER FULLER

Overview

Neuromuscular blocking drugs (NMBDs), referred to as peripheral muscle relaxants, in contrast to centrally acting muscle relaxants such as guaifenesin or diazepam, interfere with or block neuromuscular transmission at the motor end plate. They are useful adjuncts to general anesthesia because they provide short-term or reversible skeletal muscle relaxation. NMBDs do not provide analgesia, sedation, amnesia, or hypnosis, and they predispose the animal to hypothermia. Animals are unable to breathe, necessitating controlled ventilation and constant monitoring.

General Considerations

I The primary pharmacologic effect of peripheral NMBDs is to produce skeletal muscle (SM) relaxation

II NMBDs are potentiated by many other drugs

A Volatile anesthetic agents

1. Order of potentiation: desflurane > sevoflurane > isoflurane > halothane > nitrous oxide

B Aminoglycoside antibiotics

C Local anesthetics

D Cardiac antiarrhythmic drugs

III Other factors that may influence the effects of NMBDs

B Acid-base alterations

C Changes in serum potassium concentration

D Adrenocortical dysfunction

E Thermal (burn) injury

IV Potential mechanisms of SM relaxation

A NMBDs interfere with cholinergic (nicotinic) neuromuscular transmission in the peripheral somatic nervous system

B Some NMBDs enhance the activity of endogenous inhibitory mechanisms in the central nervous system, which normally modulate SM tone

V NMBDs are used adjunctively during anesthesia to produce controlled muscle relaxation

VI NMBDs produce muscle relaxation but do not produce analgesia or unconsciousness

VII NMBDs produce respiratory paralysis, which necessitates manual or mechanical ventilation support

VIII Hypothermia is an important secondary effect of prolonged SM relaxation

IX NMBDs are positively charged (ionized) and therefore do not pass the blood-brain barrier or cross the placenta in significant amounts

X Various electrical stimulators and stimulation protocols can be used to determine the degree of neuromuscular blockade (Figs. 10-1 and 10-2)

FIG. 10-1 Peripheral nerve stimulators are used to test for the adequacy of neuromuscular blockade.

A Nondepolarizing neuromuscular blockade (see below) is monitored by nerve stimulation and more specifically by introducing a train of four (TOF) stimuli (see Chapter 14)

1. Method used to objectively monitor degree of chemical paralysis

2. Used to determine correct dosage or infusion rate

3. The number of responses to the TOF stimuli indicates the degree of neuromuscular blockade

Normal Neuromuscular Function

I Acetylcholine (ACh) is released in small amounts, even in resting muscles

A Random ACh release causes mini-endplate potentials at the postsynaptic muscle membrane, which help to maintain muscle tone but are insufficient to evoke muscle contraction

II Action–potential-dependent ACh release

A Nerve impulses (action potentials) cause large depolarization in nerve terminals of α-motor neurons

B Depolarization in the presence of extracellular Ca⁺⁺ causes simultaneous fusion of many ACh-containing vesicles with the terminal nerve membrane (Fig. 10-3)

FIG. 10-3 Synthesis, release reuptake, degradation and binding of acetylcholine at the neuromuscular junction. Physostigmine, neostigmine and edrophonium are acetylcholine esterase inhibitors that block acetylcholine metabolism and reverse nondepolarizing neuromuscular blocking drug (pancuronium, rocuronium) effects.

C Release of ACh packets (quanta) evokes a large endplate potential, leading to muscle contraction

III Combination of ACh with postjunctional nicotinic receptors (Nm receptors)

A Receptors on the muscle endplates are nicotinic, type IV cholinergic (Nm) receptors

B Strength of muscle contraction is proportional to the number of receptors activated by ACh

IV The duration of ACh activity at any cholinergic synapse is limited by the action of acetylcholinesterase (ACh esterase); ACh is metabolized to acetic acid plus choline at the synaptic cleft

A Choline produced by hydrolysis of ACh is taken up by the nerve terminals and resynthesized into ACh at the nerve terminal membrane

B ACh is packaged into vesicles or stored freely in the cytoplasm of the nerve terminals

Mechanisms of Skeletal Muscle Relaxation Evoked by Interference with Normal Peripheral Neuromuscular Function

I At presynaptic sites

A Inhibition of ACh synthesis (e.g., hemicholinium blocks choline uptake)

B Inhibition of ACh release

1. Ca⁺⁺ deficiency, Mg⁺⁺ increases

3. Tetracyclines and aminoglycoside antibiotics

4. Some β-blockers

5. Botulinum toxin

II At postsynaptic sites

A Persistent depolarization with an agonist that has a longer duration of action than ACh (e.g., succinylcholine chloride)

B Competitive block of ACh receptors causing nondepolarizing blockade (e.g., curare, edrophonium, atracurium)

Types of Neuromuscular Blocks

I Phase I block: depolarizing block (succinylcholine)

II Phase II block: nondepolarizing block (atracurium)

III Mixed block: any combination of I and II

IV Dual block: excessive amounts of depolarizing agents producing phase II block

V Nonacetylcholine block (procaine, botulinum, decreased Ca⁺⁺, increased Mg⁺⁺, increased K⁺, decreased K⁺)

Muscle Relaxation Sequence

I First to last: Oculomotor muscle (m.) → palpebral m., facial m. → tongue and pharynx → jaw and tail → limbs → pelvic m.→ caudal abdominal m. → cranial abdominal m. → intercostal m. → larynx → diaphragm

A The sequence of motor blockade is highly variable

1. Intercostal and diaphragmatic muscles are thought to be affected last but the clinical return of functional motor function is highly variable

B Motor activity to the limbs may appear to return (twitching, jerking) before the diaphragm is fully functional

II Recovery is generally in the reverse order of paralysis

III It is possible but difficult to titrate the dose of a specific NMBD to paralyze the muscles of the eye while maintaining diaphragmatic function

Specific Neuromuscular Blocking Drugs (Tables 10-1 and 10-2)

TABLE 10-1

Dose Of Neuromuscular Blocking Drugs with Side Effects and Contraindications

Agent	Species	Dose Intravenously (mg/kg)	Duration of Action (min)	Side Effects	Contraindications
Succinylcholine chloride	Dog	0.3-0.4	1-38	Little cardiovascular effect; muscarinic effect is bradycardia; nicotinic effects are hypertension, increased intraocular pressure; hyperpyrexia	Organophosphate anthelmintics, chronic liver disease, malnutrition, high-K⁺, glaucoma, penetrating eye injury
	Cat	3-5 (total)	2-6
	Pig	0.75-2	1-3
	Horse	0.1-0.33	1-10
Pancuronium bromide	Dog	0.02-0.06	15-108	Negligible	Liver or kidney disease
	Cat	0.02-0.06	14-15
	Pig	0.07-0.12	7-30
	Horse	0.08-0.14	16-35
	Cattle	0.1	30-40
	Calf	0.04	26
	Sheep	0.005	21
Vecuronium	Dog	0.01-0.2	10-42	Negligible
	Cat	0.02-0.04	5-9
	Pig	0.1-0.2	5-20
	Horse	0.1	20-40
	Sheep	0.004	14
Atracurium	Dog	0.1-0.4	10-30
	Cat	0.1-0.25	10-15	Negligible
	Pig	0.5-2.5	10-60
	Horse	0.07-0.09	8-24	Negligible
	Sheep	6 µg/kg/hr
	Llama	0.15	6
Cisatracurium	Dog	0.02-0.1	10-30	Negligible
Rocuronium	Dog	0.3-0.6 mg/kg	20-30 min	Negligible
Pipecuronium	Dog	70-90 µg/kg	16-81	Occasional hypotension
Pipecuronium	Cat	40-60 µg/kg	17-24

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Tags: Handbook of Veterinary Anesthesia

Sep 6, 2016 | Posted by admin in SUGERY, ORTHOPEDICS & ANESTHESIA | Comments Off

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