Review of Pharmacology - 9E (2015)

Review of Pharmacology
Succinylcholine can cause hyperkalemia
especially in patients
with nerve and muscle disorders.
Therefore it is contra-indicated
in patients with nerve diseases
(like paraplegia, hemiplegia and
Guillain barre syndrome) and
muscle diseases (muscular dystrophy,
myasthenia gravis, crush
injury, burns and rhabdomyolysis).
• SCh is the shortest and the fastest acting SMR. Due to its quick onset of action,
it is the preferred SMR for endotracheal intubation. It is metabolized by
pseudocholinesterase that may be non-functioning (atypical pseudocholinesterase)
in some individuals. This is a genetic condition and may result in prolonged
apnea on SCh administration (due to decreased metabolism, action of SCh is
prolonged). Activity of atypical enzyme can be assessed by dibucaine number.
• SCh can stimulate the autonomic ganglia whereas non-depolarizing blockers
inhibit the ganglia.
• It can cause hyperkalemia especially in patients with nerve and muscle disorders.
Therefore it is contra-indicated in patients with nerve diseases (like paraplegia,
hemiplegia and Guillain barre syndrome) and muscle diseases (muscular dystrophy,
myasthenia gravis, crush injury, burns and rhabdomyolysis).
• SCh increases all pressures i.e. intraocular pressure (C/I in glaucoma), intracranial
tension (C/I in head injury), blood pressure (due to stimulation of sympathetic
ganglia) and intragastric pressure (responsible for nausea and vomiting).
• It may trigger malignant hyperthermia specially when given in combination with
halothane.
(b) Non Depolarizing Blockers or Competitive Skeletal Muscle Relaxants
These drugs act by competitively inhibiting N M
receptors and thus cause muscle relaxation
without any fasciculations (no postoperative muscle soreness). Further, due to competitive
nature of inhibition, effect of these drugs can be reversed by anticholinesterases like
neostigmine. These are divided into two major groups (benzylisoquinolines and steroidal)
on the basis of chemical structure.
Anaesthesia
Rapacuronium has been withdrawn
due to reports of severe
bronchoconstriction
(i) Steroidal skeletal muscle relaxants
Pancuronium, vecuronium, pipecuronium, rocuronium and rapacuronium are the drugs in
this group. These drugs have very little histamine releasing action and no effect on autonomic
ganglia.
• Pancuronium can produce tachycardia due to its vagolytic action (M 2
blocker).
• Rocuronium is the fastest acting non depolarizing skeletal muscle relaxant and
can be used for rapid sequence endotracheal intubation as an alternative to SCh.
• Rapacuronium has been withdrawn due to reports of severe broncho cons triction. It
was the fastest acting non-depolarizing skeletal mus cle relaxant.
• Vecuronium is preferred in cardiac patients because of better cardiovascular
stability. It is contra-indicated in hepatic disease and biliary obstruction.
• Gantacurium is shortest (< 10 min.) and fastest acting non-depolarizing neuromuscular
blocker in phase 3 clinical trials. It is being investigated as an alternative to sch. It
causes less release of histamine. Its metabolism is carried out non-enzymatically by
cysteine.
Sugammadex is first selective
relaxant binding agent (SRBA).
Sugammadex is a modified gamma cyclodextrin that can be used to reverse neuromuscular
blockade by rocuronium. It is the first selective relaxant binding agent (SRBA). It encapsulates
rocuronium and inhibits its access to N M
receptors at neuromuscular junction. It can also be used to
reverse vecuromium and pancuronium induced muscle relaxation. It is ineffective against sch and
benzylisoquinolines (curiums) . Major advantage of sugammadex over neostigmine is that is produces
reliable and rapid reversal without producing autonomic instability. However, it has not been granted
approval by FDA due to risk of hypersensitivity reactions.
(ii) Benzylisoquinoline derivatives
This group includes d-Tubocurarine (d-TC), metocurine, doxacurium, atracurium, cisatracurium
and mivacurium.
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