Τόμος 17 (1999) – Τεύχος 3 – Άρθρο 3 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 17 (1999) – Issue 3 – Article 3 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Από | | Άρθρο - Article, Αχιλλέας Μπενάκης - Achilles Benakis, Πλήρες Κείμενο στα Ελληνικά - Full Text in Greek, Σταύρος Τ. Πλέσσας - Stavros T. Plessas, Χαράλαμπος Τ. Πλέσσας - Charalambos T. Plessas

 

Τίτλος – Title

Μυοχαλαρωτικά Φάρμακα στην Αναισθησιολογία

Pharmacology of Skeletal Muscle Relaxants
Συγγραφέας – Author

Σταύρος Τ. Πλέσσας1, Χαράλαμπος Τ. Πλέσσας2, Αχιλλέας Μπενάκης3

1 Τμήμα Νοσηλευτικής, Πανεπιστήμιο Αθηνών, Αθήνα, Ελλάς 2 Τμήμα Επιστημονικής Πληροφόρησης του ΦΑΡΜΑΚΟΝ-Τύπος, Αθήνα, Ελλάς 3 Εργαστήριο Φαρμακολογίας, Ιατρική Σχολή Πανεπιστημίου Θεσσαλίας, Λάρισσα, Ελλάς

Stavros T. Plessas1, Charalampos T. Plessas2, Achilles Benakis3

1 Department of Nursing, University of Athens, Athens, Greece 2 Pharmakon-Press Information Services, Ath­ens, Greece 3 Department of Pharmacology, Medical School, University of Thessalia, Larissa, Greece
Παραπομπή – Citation

Πλέσσας,Σ.Τ., Πλέσσας,Χ.Τ.,  Μπενάκης,Α. : Μυοχαλαρωτικά Φάρμακα στην Αναισθησιολογία, Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 17 : 177-197 (1999)

Plessas,S.T., Plessas,C.T., Benakis,A. : Pharmacology of Skeletal Muscle Relaxants, Epitheorese Klin. Farmakol. Farmakokinet. 17: 177-197 (1999)
Ημερομηνία Δημοσιευσης – Publication Date
– 2000 –
Γλώσσα Πλήρους Κειμένου –
Full Text Language

Ελληνικά – Greek
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Λέξεις κλειδιά – Keywords

Μυοχαλαρωτικά φάρμακα, μη εκπολωτικά, εκπολωτικά, χημεία, προέλευση, φυσικοχημικές ιδιότητες, φαρμακοδυναμική, σχέσεις δομής και δράσης, κλινική φαρμακοκινητική, αλληλεπιδράσεις φαρμάκων, παθολογικές καταστάσεις, ανεπιθύμητες δράσεις, αλκουρόνιο, ατρακούριο, cis-ατρακούριο, βεκουρόνιο, γαλλαμίνη, δοξακούριο, μιβακούριο, ORG 9487, πανκουρόνιο, πιπεκουρόνιο, ροκουρόνιο, σουκινυλοχολίνη, d-τουμποκουραρίνη

Neuromuscular blocking agents, nondepolarising, depolarising, chemistry, sources, physicochemical properties, Pharmacodynamics, structure-activity relation­ships, clinical Pharmacokinetics, drug interac­tions, pathological conditions, alcuronium, atracu­rium, cis-atracurium, doxacurium, gallamine, mivacurium, ORG 9487, pan­curonium, pipecuronium, rocuronium, succinyl­choline, d-tubocurarine, vecuronium
Λοιποί Όροι – Other Terms

Άρθρο

Article
Περίληψη – Summary

–

During the 16th century, European explorers found that the Indians along the Ama­zon and Orinoco Rivers were using an arrow poison, named curare, that produced death by skeletal paralysis. Curare is one of several differ­ent resinous substances obtained from extracts of South American trees including species of chon­drodendron. The pharmacological active ingredi­ent of curare used medically is the alkaloid d-tubocurarine.

Muscle relaxation or paralysis re­sults from an interruption in the pathways for nervous impulses between the nervous system and muscle. Most drugs may also exert a variable degree of prejunctional effect. Several drugs have as their major action the interruption of transmis­sion of the nerve impulse at the skeletal neuromuscular junc­tion (NMJ).

The neuromuscular blocking drugs (NMB) are quaternary ammonium com­pounds. Positive charges at these sites in the molecules mimic the quaternary nitro­gen atom of the transmitter ACh and are the principal reason for the attraction of these drugs to cholinergic receptors. All muscle relaxants contain two posi­tive charges or at least two po­tential positive charges (except gallamine which has 3); these are separated by a bridging struc­ture that is lipophilic, different for various series of muscle relaxants and is a major deter­minant of potency.

The NMBs are classified either as nondepo­larising (competitive blocking) agents, or as de­po­larising agents. Non­depolaris­ing drugs are for the most part relatively bulky, rigid molecules (e.g., d-tubocurarine, the toxiferi­nes, the benzyli­soquino­lines, the ammonium ster­oids such as pan­curonium) and occupy one or both of the recep­tor sites and thus prevent depo­larisation by de­nying ACh ac­cess to the recep­tors. These drugs can be an­tagonised by anti­cholinesterase agents such as neostigmine, which prevent breakdown of ACh so that more of it is present to compete with the relaxant drug. Depo­larising NMBs (e.g., de­camethonium, succinyl­choline) generally have a more flexible structure that enables free bond rotation. Succinylcholine is the only one depolar­is­ing drug currently used; it acts by causing a prolonged depolarisa­tion of the muscle end plate, making it unrespon­sive to ACh. Such a block is not antagonised by neostig-mine. Anti­cholinesterase drugs, in fact, prolong a suc­cinyl­choline block.

All muscle relaxants are ion­ised and positively charged irrespective of the pH and thus poorly lipid soluble. Because of this they do not readily cross the bloodbrain barrier, cell membranes or placenta and are generally not actively metabo­lised by the liver, although some of the steroidal derivatives are an exception. The Pharmacokinet­ics of NMBs is described by 2- or 3-compart­ment models. The volume of distri­bution of these drugs is relatively small due to their poor lipid solubility. The pharmacokinetic behaviour of this class of agents is little influ­enced by age or an­aesthetic agents; however, hepatic or renal dis­ease may profoundly alter their excre­tion pattern, resulting in prolonged duration of neuromuscular blockade. For most of these agents, biotransfor­mation plays an impor­tant role in their total elimi­nation.

Adverse side effects that may accompany the administration of succinyl­choline include cardiac dysrhythmias, hy­perkalemia, myalgia, myoglobin­uria, increased in­tragastric pressure, increased intraocular pres­sure, increased intracranial pres­sure, and sus­tained skeletal muscle contractions.

Drugs admin­istered in the perioperative period, such as (a) volatile anaesthetics, (b) aminogly­coside antibiot­ics, (c) local anaesthetics, (d) car­diac antidys­rhythmic drugs, (e) diuretics, and (f) magnesium, lithium and gaglionic-blocking drugs, may enhance the effects of nondepolarising NMBs at the NMJ. Changes unrelated to concur­rent drug therapy, such as (a) hypotension, (b) acid-base alterations, (c) changes in serum po­tassium concentrations, (d) adrenocortical dys­function, (e) thermal (burn) injury and allergic reactions, may also influence the characteristics of neuromuscu­lar blockade produced by nonde­polarising NMBs. Combinations of nondepolaris­ing NMBs may pro­duce a degree of neuromus­cular  blockade that is differ­ent from the degree that would be produced by either drug alone. In addition, gender may influ­ence the duration of neuromuscular blockade produced by nondepo­larising NMBs.

Ageing may influence the duration of action of NMBs. In paediatric patients there are alterations in neuromuscular function across the age ranges: the neonatal NMJ is more sensitive than that of the adult, but pharmacokinetic factors often counterbalance this sensitivity and conse­quently, in many cases, the nondepolarising-blocking agents requirement in the neonate is similar to that of the adult. The onset of action is more rapid in infants than in children and that, in gen­eral, children require more NMB by weight than do infants or adult to obtain similar levels of pa­ralysis. Children recover more rapidly than other age groups, although infants may recover more rapidly from drugs which are metabolised in the plasma. In elderly patients, the duration of action of nondepolarising NMBs is often pro­longed, probably owing to decreased clearance of drugs by the liver and kidneys; as a result, the dose of NMBs should probably be reduced.

Several diseases can diminish or augment the neuromuscular blockade produced by nondepo­lar­ising NMBs. The duration of effect and time to recovery are increased in patients with renal and hepatic failure, possibly due to reduced plasma cholinesterase concentrations. Myasthenia gravis markedly augments the neuromuscular blockade from these drugs.

Pancuronium is the most commonly used long-acting nondepolarising neuromuscular blocking drug. Doxacurium and pipecuronium resemble puncuronium, but, unlike pancuronium, these drugs are devoid of cardiovascular side effects. d-tubocurarine, metocurine and gallamine are largely replaced in clinical practice with drugs possessing more efficient and predictable clear­ance mechanisms. The intermediate-acting non­depolarising neuromuscular drugs, atracurium, vecuronium, rocuronium and cisatracurium pos­sess efficient clearance mechanisms that mini­mise the likelihood of significant cumulative ef­fects with repeated injections or continuous infu­sions; these drugs are useful especially when tracheal intubation or skeletal muscle relaxation are needed for short operations, such as outpa­tient procedures. Mivacurium is the only clinically use­ful short-acting nondepolarising neuromus­cular-blocking drug; ORG 9487 is more rapid in onset than mivacurium, but has a similar duration of action.

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