IV Agents and neuromuscular blockers Flashcards
Plasma cholinesterase:
Acquired deficiencies of the enzyme in genotypically normal patients prolongs suxamethonium activity for several hours
False. The prolongation of action in genotypically normal patients, i.e. with acquired deficiencies of the enzyme, is usually no longer than 30 minutes.
Plasma cholinesterase:
The commonest genotype for cholinesterase activity is Eu:Eu
True. Eu:Eu is the commonest genotype and it is present in 96% of the population. These homozygotes have a completely normal recovery from suxemethonium.
Plasma cholinesterase:
Deficiency occurs in pregnancy
True. Pregancy is an acquired factor associated with reduced plasma cholinesterase deficiency. Other causes are Liver disease, Renal and Cardiac Failure, Thyrotoxicosis, Cancer and a number of drugs.
Plasma cholinesterase:
Homozygotes always experience a prolonged suxamethonium block
False. Eu:Eu is a homozygote.
Plasma cholinesterase:
Patients who are homozygotes for the fluoride resistant gene have a near normal dibucaine number
True. Their dibucaine number is around 70 (compared with 80 for Eu homozygotes).
Dibucaine is an amide local anaesthetic. The dibucaine number indicates the percentage that it inhibits the various forms of plasma cholinesterase. The normal Eu Eu genotype is most inhibited (80%), Ea Ea and Es Ea genotypes are least inhibited (20%).
The silent gene homozygotes Es Es have no plasma cholinesterase activity to inhibit and so do not have a dibucaine number.
Contraindications to suxemethonium include:
The presence of renal failure
False. Renal failure does not itself cause a hyperkalaemic response to suxemethonium, however hyperkalaemia secondary to acute renal failure would increase the risk of arrhythmias.
Contraindications to suxemethonium include:
48 hours following major burns
True. Burns patients (>10% of body surface) are at greatest risk of suxemethonium induced hyperkalaemia from 24 hours after the injury until around 18 months.
Contraindications to suxemethonium include:
Malignant hyperpyrexia
True. Along with all the volatile inhalational agents.
Contraindications to suxemethonium include:
Pregnancy
False. Though it’s action may be slightly prolonged.
Contraindications to suxemethonium include:
Day case anaesthesia
False
Malignant hyperthermia:
Exhibits autosomal recessive inheritance
False. MH is a rare autosomal-dominant condition. Incidence in UK 1 in 200,000.
Malignant hyperthermia:
Is associated with a defect on the ryanodine receptor encoded on chromosome 19
True
Malignant hyperthermia:
Diagnosis is based on response of biopsied skeletal muscle to 2% halothane and cafffeine (2mmol/L)
True
Malignant hyperthermia:
Without dantrolene the mortality can be as high as 70%
True
Malignant hyperthermia:
Each vial of dantrolene reconstituted with 60ml water produces a solution of pH 8.0
False. Dantrolene is available as capsules and in vials as an orange powder containing 20 mg dantrolene, 3 g mannitol and sodium hydroxide. Each vial when reconstituted with 60 ml water has a pH of 9.5.
The effects of non-depolarising musle relaxants are prolonged by:
Volatile anaesthetics
True
The effects of non-depolarising musle relaxants are prolonged by:
Hyperthermia
False. Action is prolonged by hypothermia.
The effects of non-depolarising musle relaxants are prolonged by:
Lithium
True
The effects of non-depolarising musle relaxants are prolonged by:
Calcium channel antagonists
True. There is a reduced calcium influx resulting in reduced ACh release.
The effects of non-depolarising musle relaxants are prolonged by:
Hypomagnesaemia
False. Effects are prolonged by hypermagnesaemia due to the decrease in ACh release caused by competition with calcium and by stabilization of the post juntional membrane.
Atracurium:
Has 4 chiral centres and 10 stereoisomers
True
Atracurium:
Undergoes Hofmann elimination accounting for 60% of its metabolism
False. Hofmann elimination only accounts for 40% of atracurium’s metabolism.
Atracurium:
Hofmann elimination is potentiated by acidosis and hypothermia
False. Acidosis and hypothermia will slow down the process of Hofmann elimination.
Atracurium:
A product of its metabolism is laudanosine, a glycine antagonist
True
Atracurium:
Laudanosine is a breakdown product of both ester hydrolysis and Hofmann degradation.
True
Cis-atracurium:
Is one of the 10 stereoisomers present in atracurium
True
Cis-atracurium:
Is 10 times more potent than atracurium
False. It is approximately 3 to 4 times more potent than atracurium.
Cis-atracurium:
Is predominantly eliminated by ester hydrolysis
False. It is predominantly eliminated by Hofmann elimination and its metabolites have no neuromuscular blocking properties.
Cis-atracurium:
Is safe for use in patients with renal failure
True. It can be used safely in both renal and hepatic failure.
Cis-atracurium:
Has metabolites with neuromuscular blocking properties
False. It is predominantly eliminated by Hofmann elimination and its metabolites have no neuromuscular blocking properties.
The following are benzylisoquinolinium compounds:
Atracurium
True.
The following are benzylisoquinolinium compounds:
Midazolam
False. Midazolam is a benzodiazepine.
The following are benzylisoquinolinium compounds:
Pancuronium
False. Pancuronium is an aminosteroidal compound.
The following are benzylisoquinolinium compounds:
Tubocurarine
True
The following are benzylisoquinolinium compounds:
Mivacurium
True
Other effects of suxemethonium:
Sinus or nodal bradycardia secondary to sympathetic ablation
False. Sinus or nodal bradycardia is caused via stimulation of muscarinic receptors in the sinus node.
Other effects of suxemethonium:
Myalgia, particularly in young women
True. Muscle pains are commonest in young females mobilizing rapidly in the post operative period.
Other effects of suxemethonium:
Patients with severe burns or neuromuscular disorders are susceptible to sudden, massive release of potassium
True. May be large enough to provoke cardiac arrest.
Other effects of suxemethonium:
Can cause a rise in intra-occular pressure by about 10mmHg for a matter of minutes following administration
True. Normal intraocular pressure is 10-15 mmHg making this a 100% rise in intra-ocular pressure which can be significant in the presence of globe perforation.
Other effects of suxemethonium:
Raises intragastric pressure by 10 cmH2O
True. Though suxemethonium simultaneously increases lower oesophageal sphincter tone so there is no increased risk of reflux.
Vecuronium:
Is relatively cardio-stable
True. The aminosteroids are not assocciated with the histamine release seen with the benzylisoquinolinium compounds.
Vecuronium:
Is presented as a powder containing mannitol and sodium hydroxide.
True. It is unstable in solution and therefore presented as a freeze-dried powder containing mannitol and sodium hydroxide.
Vecuronium:
May cause critical illness myopathy
True. As can all muscle relaxants if used long term.
Vecuronium:
Precipitates histamine release
False
Vecuronium:
Its chemical structure differs from pancuronium by a single methyl group
True
Propofol
Is highly protein bound
True. 97% protein bound.
Propofol
Produces vasodilatation by nitric oxide production
True. Propofol causes hypotension (reduction in sytsemic vascular resistance and cardiac output) without tachycardia. Bradycardia is common, especially with opiate co-administration.
Propofol
Is only partly unionized at physiological pH
False. The pka of propofol is 11, therefore at pH 7.4 it is almost entirely unionized.
Propofol
Has a hydroxyl group situated on its 4th carbon
False. The hydroxyl group is situated on the 1st carbon. Phase 1 metabolism into a quinol derivative involves hydroxylation of the 4th carbon.
Propofol
Undergoes both phase 1 and phase 2 metabolism
True. Glucuronidation is the predominant metabolic pathway, hydroxylation by cytochrome P450 to a quinol derivative prior to conjugation is also an important pathway. The relative importance of each pathway varies amongst patients.
Propofol
Is used at a dose of around 4 mg/kg for IV paediatric induction
True. Approx double the typical adult dose.
Propofol
Causes a reduction in cardiac output solely by reducing heart rate
False. Propofol also reduces myocardial contractility and sympathetic tone.
Propofol
Clearance is by hepatic metabolism alone
False. Extra-hepatic metabolism is significant, suggested by the fact that clearance is higher than hepatic bolod flow. Sites for extra-hepatic metabolism include the kidneys (responsible for about a third of extra-hepatic metabolism) and lungs (to 2, 6 - diisopropyl - 1, 4 - quinol).
Propofol
Acts as an anti-emetic by competitive antagonism of central serotonin receptors situated in the chemoreceptor trigger zone
False. The anti-emetic effect of propofol is probably mediated through dopamine receptor antagonism.
Propofol
Is a cause of hypertrigylcerideaemia
True. This may be a part of the metabolic syndrome seen in children after prologed infusion. Propofol infusions have been linked to organ fatty infiltration with severe bradycardias, metabolic acidosis and increased mortality.
With regards to IV induction agents:
Propofol has the same volume of distribution as ketamine
False. Propofol 4 L/kg. Ketamine 3 L/kg. Etomidate 3 L/kg. Thiopentone 2.5 L/kg.
With regards to IV induction agents:
Propofol has the highest clearance rate
True. 30-60 ml/kg/min.
With regards to IV induction agents:
The clearance rate of etomidate is 5 ml/kg/min
False. Etomidate 10-20 ml/kg/min, Ketamine 17 ml/kg/min, Thiopentone 3.5 ml/kg/min
With regards to IV induction agents:
Thiopentone has a higher percentage of protein binding that methohexitone
True. Thiopentone 80%. Methohexitone 60%.
With regards to IV induction agents:
Thiopentone has a pKa of 10.6
False. pKa of thiopentone is 7.6
Midazolam:
Is 68% protein bound
False. 98% protein bound.
Midazolam:
Is 40% unionized at physiological pH
False. Midazolam is a tautomeric molecule consisting of benzene and diazepine rings. In a pH > 4 the diazepine ring closes producing a lipid soluble unionized molecule. With a pKa of 6.5 around 89% of molecules are unionized at physiological pH.
Midazolam:
Has inactive metabolites
False. The phase 1 metabolite 1-alpha-hydroxy-midazolam is active. This may then be conjugated (glucuronidation) prior to excretion.
Midazolam:
Is metabolised by the same cytochrome P450 system as alfentanil
True. CP450 3A3/4. The action of midazolam may be prolonged by co-administration of alfentanil.
Midazolam:
Is given in oral doses of up to 1 mg/kg in paediatric premedication
True. 30 minues prior to induction. Monitoring is required if doses >0.5 mg/kg are used.
Ketamine:
Is a competitive antagonist of NMDA receptors
False. Non-competitive antagonist.
Ketamine:
Is prepared as a racemic mixture in which the R- isomer is more potent than the S+
False. S+ is 2-3 times more potent than the R- isomer. It may also produce less intense emergence phenomena.
Ketamine:
Is used as an oral premedication in doses of 2-5 mg/kg
True. 20% bioavailability. Doses of up to 10 mg/kg have be used in extreme cases.
Ketamine:
Emergence phenomena is less common in the young and elderly
True
Ketamine:
Undergoes cytochrome P450 de-methylation to the inactive metabolite norketamine
False. Norketamine is active, this then undergoes glucuronidation to an inactive metabolite which is excreted.
Ketamine:
Is stored as an aciditc solution
True. pH 3.5-5.5. Ampoules can contain 10, 50 or 100 mg/ml.
Ketamine:
Induces dissociative anaesthesia with predominant beta activity on EEG
False. Theta and delta activity is pre-dominant during ketamine induced dissociative anaesthesia.
Ketamine:
Reduces cerebral oxygen consumption
False. Cerebral oxygen consumption, blood flow and intracranial pressure are all increased by ketamine.
Ketamine:
Is 25-50% protein bound
True
Ketamine:
Is a direct myocardial depressant
True. Ketamine increases sympathetic tone and circulating levels of adrenaline and noradrenaline. This produces the cardiovascular effects seen clinically of tachycardia, increased cardiac output, increased / maintained blood pressure and elevated CVP. However, ketamine also produces a mild direct myocardial depressant effect that is masked, less so for the S+ isomer.
Etomidate:
Is prepared with 35% propylene glycol
True
Etomidate:
Produces pain on injection in 75% of cases
False. Produces pain in around only 25%.
Etomidate:
Causes nausea and vomiting
True
Etomidate:
Is given as an IV induction dose of 2-3 mg/kg
False. The IV induction dose is 0.2-0.3 mg/kg
Etomidate:
Produces excitatory movements with epileptiform activity on EEG
True. Etomidate is the most likely IV induction agent to cause myoclonic movements and epileptiform activity on EEG - in around 20% of cases.
Etomidate:
Has an ester bond
True. Etomidate is an imidazole derivative and an ester.
Etomidate:
May be used in patients with porphyria
False. Etomidate is known to cause a porphyric crisis.
Etomidate:
Is predominanlty protein bound
True. Around 75%.
Etomidate:
Inhibits adrenal medullary function
False. Etomidate has been shown to inhibit 11-beta and 17-alpha hydroxylase function and impair aldosterone and cortisol synthesis for up to 24 hours after administration. Steroidogenesis occur in the adrenal cortex.
Etomidate:
Has the same volume of distribution as ketamine
True. 3 l/kg
Thiopentone:
Is prepared as a hygroscopic yellow powder in 8% sodium carbonate
False. 6% sodium carbonate.
Thiopentone:
When reconstitued with water produces a 2.5% solution
True
Thiopentone:
At physiological pH 60% of the drug is unionized in blood
True
Thiopentone:
Is metabolised to pentobarbitone
True. Pentobarbitone is an active metabolite.
Thiopentone:
When in solution is found predominantly in its keto form
False. It is predominantly in its enol form when in solution. The enol form is soluble. Thiopentone is tautomeric and alkaline conditions promote the switch from keto to enol.
Thiopentone:
Has a sulphur group on its 2nd carbon
True. There is an oxygen group in this position in oxybarbiturates.
Thiopentone:
Is a bronchodilator
False. Thiopentone may produce laryngospasm and bronchospasm.
Thiopentone:
Stimulates anti-diuretic hormone release
True. This is one of the reasons why thiopentone causes a reduction in urine output.
Thiopentone:
Is an enzyme inhibitor
False. Thiopentone is an enzyme inducer.
Thiopentone:
Is more active in alkalotic conditions
False. Acidosis and hypoalbuminaemia increases the amount of free unionized drug. A lower dose is often needed in critically ill patients.
