RNFA MASTER EXAM TEST
1. DEPOLARIZING BLOCKERS: The extremely short duration of action of
succinylcholine (5-10 minutes) is due to its rapid hydrolysis by plasma (and hepatic)
butyrylcholinesterase.
Neuromuscular blockade by succinylcholine (and mivacurium) may be prolonged inpatients
with an abnormal variant of butyrylcholinesterase. Prolonged paralysis fromsuccinylcholine
caused by abnormal butyrylcholinesterase should be treated with continued mechanical
ventilation until muscle function returns to normal.
Because of the rarity of these variants, butyrylcholinesterase testing is not routineclinical
procedure.
2. NON-DEPOLARIZING BLOCKERS: • Some benzylisoquinolines may produce
hypotension due to histamine release and ganglionic blockade.
• Some ammonio steroids may produce tachycardia due to blockade of muscarinic
receptors, which may lead to arrhythmias. These drugs should be used cautiouslyin patients
with cardiovascular disease.
3. HISTAMINE RELEASE: Tubocurarine, and to a lesser extent, mivacurium and
atracurium can produce
hypotension as a result of histamine release. Tubocurarine is seldom used clinicallyat this time.
Clinical signs of histamine release are erythema at the face and upper chest, atransient
decrease in blood pressure, and an increase in heart rate.
More severe reactions of histamine release include bronchospasm and circulatorycollapse.
Antihistamines can counteract responses that follow histamine release, particularlyif given
before the neuromuscular blocker.
4. GANGLION BLOCKADE: Tubocurarine may cause some blockade of nicotinicreceptors
of the autonomic ganglia
and the adrenal medulla; this results in a fall in blood pressure and tachycardia.
5. BLOCKADE OF CARDIAC MUSCARINIC RECEPTORS: The ammoniosteroid
pancuronium causes moderate tachycardia due to blockade of cardiac muscarinic receptors.
The cardiovascular effects of pancuronium are usually not considered tobe a clinically
relevant problem (see table below).
6. DEPOLARIZING BLOCKERS: Succinylcholine stimulates all autonomiccholinoceptors:
,nicotinic receptors in both
sympathetic and parasympathetic ganglia and muscarinic receptors in the heart.
HISTAMINE RELEASE
Succinylcholine has a slight tendency to release histamine.
7. BRADYCARDIA: Bradycardia may occur due to activation of muscarinic recep- tors. It
can be prevented by thiopental, atropine, ganglionic blockers and non-depo- larizing muscle
relaxants.
8. MUSCLE PAIN: Important postoperative complaint. Due to damage produced by the
unsynchronized contractions of adjacent muscle fibers.
9. HYPERKALEMIA: Due to loss of tissue potassium during depolarization. Risk of
hyperkalemia is enhanced in patients with burns or muscle trauma. Hyperkalemiamay lead to
cardiac arrest or circulatory collapse.
10. INCREASED INTRAOCULAR PRESSURE: Due to extraocular muscle con- tractions.
Despite this effect, the use of succinylcholine for eye operations is not contraindicated unless
the anterior chamber is to be opened.
11. INCREASED INTRAGASTRIC PRESSURE: In some patients, the fascicula- tions
caused by succinylcholine cause an increase in intragastric pressure. This makes emesis more
likely, with the potential hazard of aspiration of gastric contents.
12. MALIGNANT HYPERTHERMIA: Malignant hyperthermia susceptibility, an au-tosomal
dominant disorder of skeletal muscle, is one of the main causes of death due to anesthesia.
The halogenated hydrocarbon anesthetics and succinylcholine alone have been reported to
precipitate the response; however, most of the incidents arise from thecombination of
succinylcholine and an halogenated anesthetic.
Treatment of malignant hyperthermia entails IV administration of dantrolene; dantro- lene
prevents Ca2+ and calmodulin from activating the RyR-1, thus blocking release of Ca2+ from
the SR.
13. CNS EFFECTS: All neuromuscular blockers are virtually devoid of central effectsfollowing
IV administration of ordinary clinical doses because of their inability to penetrate the blood-
brain barrier.
14. DRUG INTERACTIONS: ...
15. ANESTHETICS: Inhaled anesthetics (e.g. halothane, isoflurane and enflurane)increase
neuromuscular blockade evoked by nondepolarizing muscle relaxants.
16. ANTIBIOTICS: Aminoglycosides produce neuromuscular blockade by inhibiting
acetylcholine release from the preganglionic terminal (through competition with Ca2+) and to
a lesser extent by stabilizing the postjunctional membrane.
,Tetracyclines can also produce neuromuscular blockade, possibly by chelation ofCa2+.
17. EFFECTS OF DISEASE AND AGEING ON DRUG RESPONSE: Several dis- eases can
decrease or increase the neuromuscular blockade caused by nondepo-larizing muscle
relaxants.
• Myasthenia gravis increases neuromuscular blockade caused by these agents.
• Advanced age is often associated with a prolonged duration of action from non-depolarizing
relaxants, probably due to decreased clearance of drugs by liver or kidneys.
• Patients with severe burns and those with upper motor neuron disease are resis-tant to
nondepolarizing muscle relaxants. This is probably because of proliferationof extrajunctional
receptors, which requires additional nondepolarizing relaxant to block a sufficient number of
receptors to produce neuromuscular blockade.
18. DEPOLARIZING BLOCKERS: CONTRAINDICATIONS: • Succinylcholine is
contraindicated in persons with personal or familial history of malignant hyperther-mia,
skeletal muscle myopathies, and known hypersensitivity to the drug.
• Succinylcholine is contraindicated in patients with major burns, multiple trauma,
extensive denervation of skeletal muscle, or upper motor neuron injury, because
succinylcholine may lead to severe hyperkalemia which may result in cardiac arrest.
19. REVERSAL OF NONDEPOLARIZING NEUROMUSCULAR BLOCKADE: • The
acetylcholinesterase inhibitors neostigmine, pyridostigmine and edrophonium preserve
endogenous acetylcholine and also act directly on the neuromuscular junction, therefore they
can be used in the treatment of overdosage with competitiveblocking agents.
• Similarly, upon completion of a surgical procedure many anaesthesiologists employ
neostigmine or edrophonium to reverse and decrease the duration of competitive
neuromuscular blockade. A muscarinic antagonist (atropine or glycopyrrolate) is used
concomitantly to prevent stimulation of muscarinic receptors and thereby avoidbradycardia.
20. USES OF NEUROMUSCULAR BLOCKERS: SURGICAL RELAXATION The main
clinical use of the neuromuscular blockers is as adjuvants in surgical
anesthesia to obtain relaxation of skeletal muscle. Neuromuscular blockers of shortduration are
often used to facilitate intubation with an endotracheal tube.
CONTROL OF VENTILATION
In patients who have ventilatory failure from various causes, e.g. obstructive airwaydisease, it
is often desirable to control ventilation to provide adequate volumes andexpansion of lungs.
Paralysis is sometimes induced by administration of neuro- muscular blockers to eliminate
chest wall resistance and ineffective spontaneous ventilation.
TREATMENT OF CONVULSIONS
Neuromuscular blockers are sometimes used to attenuate or eliminate the periph- eral
, manifestations of convulsions from such causes as epilepsy or local anesthetictoxicity.
PREVENTION OF TRAUMA DURING ELECTROSHOCK THERAPY
ECT therapy of psychiatric disorders occasionally is complicated by trauma to the patient; the
seizures induced may cause dislocations or fractures. Neuromuscular blockers and thiopental
are used. Succinylcholine or mivacurium are the neuromus-cular blockers most often used
because of the brevity of the relaxation
21. Neuromuscular blockers: Tubocurarine Atracurium Cisatracurium Mivacurium
Rocuronium Pancuronium Vecuronium Succinylcholine
22. AchE inhibitors: Neostigmine Edrophonium
23. Muscarinic Antagonists: Glycopyrrolate
24. Spasmolytics: Dantrolene Diazepam Baclofen Tizanidine Gabapentin Pro- gabide
Glycine Idrocilamide Riluzole Dantrolene Botulinum toxin Cyclobenzaprine
25. Neuromuscular blockers.: Used during surgical procedures and in intensivecare units to
cause paralysis.
26. NONDEPOLARIZING BLOCKERS: • They are competitive antagonists. In small
clinical doses they act predominantly at the nicotinic receptor site by competing with
acetylcholine. Their action can be overcome by increasing the concentration of acetylcholine
in the synaptic cleft; this can be achieved, for example, by ad- ministration of
acetylcholinesterase inhibitors such as neostigmine or edrophonium.Anaesthesiologists use
this strategy to shorten the duration of the neuromuscular blockade.
• In larger doses, nondepolarizing blockers also enter the pore of the ion channel tocause a
more intense motor blockade. This further weakens neuromuscular trans- mission and
diminishes the ability of acetylcholinesterase inhibitors to antagonize the action of
nondepolarizing blockers.
• Nondepolarizing blockers may also block prejunctional sodium channels. As aresult, they
reduce the release of acetylcholine at the nerve ending.
• During anesthesia, the IV administration of a nondepolarizing blocker first causesmotor
weakness; ultimately, skeletal muscles become totally flaccid and inexcitableto stimulation.
Larger muscles (e.g. those of the trunk) are more resistant to block and recover more rapidly
than smaller ones (e.g. muscles of the hand).
27. DEPOLARIZING BLOCKERS: Succinylcholine is the only depolarizing neuro-
muscular blocker used clinically in the USA. succinylcholine remains popular be- cause it is
the only ultrarapid onset/ultrashort duration neuromuscular blocker avail-able.
1. DEPOLARIZING BLOCKERS: The extremely short duration of action of
succinylcholine (5-10 minutes) is due to its rapid hydrolysis by plasma (and hepatic)
butyrylcholinesterase.
Neuromuscular blockade by succinylcholine (and mivacurium) may be prolonged inpatients
with an abnormal variant of butyrylcholinesterase. Prolonged paralysis fromsuccinylcholine
caused by abnormal butyrylcholinesterase should be treated with continued mechanical
ventilation until muscle function returns to normal.
Because of the rarity of these variants, butyrylcholinesterase testing is not routineclinical
procedure.
2. NON-DEPOLARIZING BLOCKERS: • Some benzylisoquinolines may produce
hypotension due to histamine release and ganglionic blockade.
• Some ammonio steroids may produce tachycardia due to blockade of muscarinic
receptors, which may lead to arrhythmias. These drugs should be used cautiouslyin patients
with cardiovascular disease.
3. HISTAMINE RELEASE: Tubocurarine, and to a lesser extent, mivacurium and
atracurium can produce
hypotension as a result of histamine release. Tubocurarine is seldom used clinicallyat this time.
Clinical signs of histamine release are erythema at the face and upper chest, atransient
decrease in blood pressure, and an increase in heart rate.
More severe reactions of histamine release include bronchospasm and circulatorycollapse.
Antihistamines can counteract responses that follow histamine release, particularlyif given
before the neuromuscular blocker.
4. GANGLION BLOCKADE: Tubocurarine may cause some blockade of nicotinicreceptors
of the autonomic ganglia
and the adrenal medulla; this results in a fall in blood pressure and tachycardia.
5. BLOCKADE OF CARDIAC MUSCARINIC RECEPTORS: The ammoniosteroid
pancuronium causes moderate tachycardia due to blockade of cardiac muscarinic receptors.
The cardiovascular effects of pancuronium are usually not considered tobe a clinically
relevant problem (see table below).
6. DEPOLARIZING BLOCKERS: Succinylcholine stimulates all autonomiccholinoceptors:
,nicotinic receptors in both
sympathetic and parasympathetic ganglia and muscarinic receptors in the heart.
HISTAMINE RELEASE
Succinylcholine has a slight tendency to release histamine.
7. BRADYCARDIA: Bradycardia may occur due to activation of muscarinic recep- tors. It
can be prevented by thiopental, atropine, ganglionic blockers and non-depo- larizing muscle
relaxants.
8. MUSCLE PAIN: Important postoperative complaint. Due to damage produced by the
unsynchronized contractions of adjacent muscle fibers.
9. HYPERKALEMIA: Due to loss of tissue potassium during depolarization. Risk of
hyperkalemia is enhanced in patients with burns or muscle trauma. Hyperkalemiamay lead to
cardiac arrest or circulatory collapse.
10. INCREASED INTRAOCULAR PRESSURE: Due to extraocular muscle con- tractions.
Despite this effect, the use of succinylcholine for eye operations is not contraindicated unless
the anterior chamber is to be opened.
11. INCREASED INTRAGASTRIC PRESSURE: In some patients, the fascicula- tions
caused by succinylcholine cause an increase in intragastric pressure. This makes emesis more
likely, with the potential hazard of aspiration of gastric contents.
12. MALIGNANT HYPERTHERMIA: Malignant hyperthermia susceptibility, an au-tosomal
dominant disorder of skeletal muscle, is one of the main causes of death due to anesthesia.
The halogenated hydrocarbon anesthetics and succinylcholine alone have been reported to
precipitate the response; however, most of the incidents arise from thecombination of
succinylcholine and an halogenated anesthetic.
Treatment of malignant hyperthermia entails IV administration of dantrolene; dantro- lene
prevents Ca2+ and calmodulin from activating the RyR-1, thus blocking release of Ca2+ from
the SR.
13. CNS EFFECTS: All neuromuscular blockers are virtually devoid of central effectsfollowing
IV administration of ordinary clinical doses because of their inability to penetrate the blood-
brain barrier.
14. DRUG INTERACTIONS: ...
15. ANESTHETICS: Inhaled anesthetics (e.g. halothane, isoflurane and enflurane)increase
neuromuscular blockade evoked by nondepolarizing muscle relaxants.
16. ANTIBIOTICS: Aminoglycosides produce neuromuscular blockade by inhibiting
acetylcholine release from the preganglionic terminal (through competition with Ca2+) and to
a lesser extent by stabilizing the postjunctional membrane.
,Tetracyclines can also produce neuromuscular blockade, possibly by chelation ofCa2+.
17. EFFECTS OF DISEASE AND AGEING ON DRUG RESPONSE: Several dis- eases can
decrease or increase the neuromuscular blockade caused by nondepo-larizing muscle
relaxants.
• Myasthenia gravis increases neuromuscular blockade caused by these agents.
• Advanced age is often associated with a prolonged duration of action from non-depolarizing
relaxants, probably due to decreased clearance of drugs by liver or kidneys.
• Patients with severe burns and those with upper motor neuron disease are resis-tant to
nondepolarizing muscle relaxants. This is probably because of proliferationof extrajunctional
receptors, which requires additional nondepolarizing relaxant to block a sufficient number of
receptors to produce neuromuscular blockade.
18. DEPOLARIZING BLOCKERS: CONTRAINDICATIONS: • Succinylcholine is
contraindicated in persons with personal or familial history of malignant hyperther-mia,
skeletal muscle myopathies, and known hypersensitivity to the drug.
• Succinylcholine is contraindicated in patients with major burns, multiple trauma,
extensive denervation of skeletal muscle, or upper motor neuron injury, because
succinylcholine may lead to severe hyperkalemia which may result in cardiac arrest.
19. REVERSAL OF NONDEPOLARIZING NEUROMUSCULAR BLOCKADE: • The
acetylcholinesterase inhibitors neostigmine, pyridostigmine and edrophonium preserve
endogenous acetylcholine and also act directly on the neuromuscular junction, therefore they
can be used in the treatment of overdosage with competitiveblocking agents.
• Similarly, upon completion of a surgical procedure many anaesthesiologists employ
neostigmine or edrophonium to reverse and decrease the duration of competitive
neuromuscular blockade. A muscarinic antagonist (atropine or glycopyrrolate) is used
concomitantly to prevent stimulation of muscarinic receptors and thereby avoidbradycardia.
20. USES OF NEUROMUSCULAR BLOCKERS: SURGICAL RELAXATION The main
clinical use of the neuromuscular blockers is as adjuvants in surgical
anesthesia to obtain relaxation of skeletal muscle. Neuromuscular blockers of shortduration are
often used to facilitate intubation with an endotracheal tube.
CONTROL OF VENTILATION
In patients who have ventilatory failure from various causes, e.g. obstructive airwaydisease, it
is often desirable to control ventilation to provide adequate volumes andexpansion of lungs.
Paralysis is sometimes induced by administration of neuro- muscular blockers to eliminate
chest wall resistance and ineffective spontaneous ventilation.
TREATMENT OF CONVULSIONS
Neuromuscular blockers are sometimes used to attenuate or eliminate the periph- eral
, manifestations of convulsions from such causes as epilepsy or local anesthetictoxicity.
PREVENTION OF TRAUMA DURING ELECTROSHOCK THERAPY
ECT therapy of psychiatric disorders occasionally is complicated by trauma to the patient; the
seizures induced may cause dislocations or fractures. Neuromuscular blockers and thiopental
are used. Succinylcholine or mivacurium are the neuromus-cular blockers most often used
because of the brevity of the relaxation
21. Neuromuscular blockers: Tubocurarine Atracurium Cisatracurium Mivacurium
Rocuronium Pancuronium Vecuronium Succinylcholine
22. AchE inhibitors: Neostigmine Edrophonium
23. Muscarinic Antagonists: Glycopyrrolate
24. Spasmolytics: Dantrolene Diazepam Baclofen Tizanidine Gabapentin Pro- gabide
Glycine Idrocilamide Riluzole Dantrolene Botulinum toxin Cyclobenzaprine
25. Neuromuscular blockers.: Used during surgical procedures and in intensivecare units to
cause paralysis.
26. NONDEPOLARIZING BLOCKERS: • They are competitive antagonists. In small
clinical doses they act predominantly at the nicotinic receptor site by competing with
acetylcholine. Their action can be overcome by increasing the concentration of acetylcholine
in the synaptic cleft; this can be achieved, for example, by ad- ministration of
acetylcholinesterase inhibitors such as neostigmine or edrophonium.Anaesthesiologists use
this strategy to shorten the duration of the neuromuscular blockade.
• In larger doses, nondepolarizing blockers also enter the pore of the ion channel tocause a
more intense motor blockade. This further weakens neuromuscular trans- mission and
diminishes the ability of acetylcholinesterase inhibitors to antagonize the action of
nondepolarizing blockers.
• Nondepolarizing blockers may also block prejunctional sodium channels. As aresult, they
reduce the release of acetylcholine at the nerve ending.
• During anesthesia, the IV administration of a nondepolarizing blocker first causesmotor
weakness; ultimately, skeletal muscles become totally flaccid and inexcitableto stimulation.
Larger muscles (e.g. those of the trunk) are more resistant to block and recover more rapidly
than smaller ones (e.g. muscles of the hand).
27. DEPOLARIZING BLOCKERS: Succinylcholine is the only depolarizing neuro-
muscular blocker used clinically in the USA. succinylcholine remains popular be- cause it is
the only ultrarapid onset/ultrashort duration neuromuscular blocker avail-able.
