McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 2 8 Neuromuscular junction blocking agents

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with xanthines (e.g. theophylline, aminophylline) could result in reversal of the neuromuscular blockage. Indi- viduals receiving this combination of drugs should be monitored very closely during the procedure for the potential of early arousal and return of muscle function. Do not mix the drug with any alkaline solutions such as barbiturates because a precipitate may form, making it inappropriate for use. Prototype summary: Pancuronium Indications: As an adjunct to general anaesthesia; to induce skeletal muscle relaxation; to reduce the intensity of muscle contractions in electroconvulsive therapy; to facilitate the care of people undergoing mechanical ventilation. Actions: Occupies the muscular cholinergic receptor site, preventing ACh from reacting with the receptor; does not cause activation of muscle cells; causes a flaccid paralysis. Pharmacokinetics: Route Onset Duration IV 4–6 mins 120–180 mins T 1/2 : 89 to 161 minutes; metabolised in the tissues, excreted unchanged in the urine. Adverse effects: Respiratory depression, apnoea, bronchospasm, cardiac arrhythmias. D epolarising neuromuscular junction (NMJ) blocker There is only one agent classified as a depolarising NMJ blocker: succinylcholine, also known as suxamethonium (generic). Therapeutic actions and indications Suxamethonium, a depolarising NMJ blocker, attaches to the ACh-receptor site on the muscle cell, causing a prolonged depolarisation of the muscle. This depolar- isation causes stimulation of the muscle and muscle contraction (seen as twitching) and then flaccid paral- ysis. Both effects cause muscles to stop responding to stimuli and paralysis occurs. Suxamethonium has a rapid onset and a short duration of action because it is broken down by cho- linesterase in the plasma. Unlike endogenous ACh, however, suxamethonium is not broken down instantly. The result is a prolonged contraction of the muscle, which cannot be re-stimulated. Eventually a gradual repolarisation occurs as continually stimulated channels

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Minutes 80 70 60 50 40 30 20 10 0

Onset Duration

atracurium

rocuronium

vecuronium

pancuronium

cisatracurium

suxamethonium

FIGURE 28.3  Onset and duration of non-depolarising NMJ blockers.

who do not adapt to the drugs effectively, use the drugs for prolonged periods, have certain underlying conditions or take certain drugs that are known to affect cardiovas- cular receptors. Prolonged drug use may also result in gastrointestinal (GI) dysfunction related to paralysis of the muscles in the GI tract; constipation, vomiting, regur- gitation and aspiration may occur. Pressure ulcers may develop because the person loses reflex muscle movement that protects the body. Hyperkalaemia may occur as a result of muscle membrane alterations. Clinically important drug–drug interactions Many drugs are known to react with the non- depolarising NMJ blockers. Some drug combinations result in an increased neuromuscular effect. Halogen- ated hydrocarbon anaesthetics such as halothane cause a membrane-stabilising effect, which greatly enhances the paralysis induced by the non-depolarising NMJ blockers. If these drugs are used together for a pro­ cedure, dose adjustments are necessary, and individuals should be monitored closely until they recover fully. A combination of non-depolarising NMJ blockers and aminoglycoside antibiotics (e.g. gentamicin) also leads to increased neuromuscular blockage. Individuals who receive this drug combination require a lower dose of the non-depolarising NMJ blocker and prolonged support and monitoring after the procedure. Calcium-channel blockers may also greatly increase the paralysis caused by non-depolarising NMJ blockers because of their effects on the calcium channels in the muscle. If this combination cannot be avoided, the dose of the non-depolarising NMJ agent should be lowered and the person should be monitored closely until complete recovery occurs. If non-depolarising NMJ blockers are combined with cholinesterase inhibitors, the effectiveness of the non-depolarising NMJ blockers is decreased because of a build-up of ACh in the synaptic cleft. Combination