Anaesthetic agents Flashcards
A patient requires ongoing muscle relaxation during a lengthy operation. His past medical includes renal and liver impairment form alcohol. Which of the non depolarising blocking drugs can be used?
A Pancuronium
B Rocuronium
C Atracurium
D Vecuronium
C
Explanation
Atracurium is cleared form circulation via Hofamnn elimination-nonenzymatic and enzymatic hydrolysis of ester bonds. It is not dependent of organ function. Fever and alkalosis does increase metabolism of atracurium (Hofmann elimination increases)
Mivacurium metabolized via plasma cholinesterase and would be useful to use as well
Pancuronium, rocuronium and vecuronium rely on liver and/or kidney metabolism to clear the drug
Extra:
Atracurium kinetics and dynamics are near-normal even in patients with fulminant hepatic failure and renal failure; laudanosine accumulation will occur, but this is not associated with measurable central neurological effects. Implantation of a functioning liver graft results in clearance of laudanosine, which seems to be independent of renal function. Atracurium is an appropriate choice for producing neuromuscular blockade for periods of several days in patients with fulminant hepatic failure and renal impairment.
Intensive Care Med 1993;19 Suppl 2:S94-8.Atracurium infusions in patients with fulminant hepatic failure awaiting liver transplantation. Bion JF et al
Which volatile anaesthetic is the least metabolized?
A Sevoflurane
B Desflurane
C Isoflurane
D Halothane
B
Explanation
The extent of hepatic metabolism, the order (most to least) of inhaled anaesthetic are methoxyflurane, halothane, enflurane, sevoflurane, isoflurane, desflurane, nitrous oxide. Nitrous oxide undergoes zero metabolism.
Which of the following is an amide local anaesthetic agent?
A Benzocaine
B Prilocaine
C Cocaine
D Tetracaine
B
Explanation
All the rest are Ester type local anaesthetics. Examples of Amide local anaesthetics are: lignociane, mepivacaine, bupivacaine, etidocaine and ropivacaine
Note- a nice way to remember it: local anaesthetics that are Esters :have just one ‘’ i ‘’ in their names eg procaine ,cocaine but Amides :have more than one ‘’ i ‘’ in their names lidocaine, bupivacaine.
In pseudo (plasma) cholinesterase deficiency which of these two drugs will have a prolonged effect?
A Remifentanil and Esmolol
B Succinylcholine and Esmolol
C Mivacurium and Esmolol
D Succinylcholine and Procaine
D
Explanation
Pseudocholinesterase deficiency will result in a prolonged effect of the following: succinylcholine, mivacurium, procaine, and cocaine.
Iatrogenic causes of lower plasma pseudocholinesterase activity include medications such as the following:
Anticholinesterase inhibitors
Bambuterol
Chlorpromazine
Contraceptives
Cyclophosphamide
Echothiophate eye drops
Esmolol (esmolol is metabolised by esterases in the cytosol of red cells, not plasma or red cell membrane acetylcholinesterases)
Glucocorticoids
Hexafluorenium
Metoclopramide
Monoamine oxidase inhibitors
Pancuronium
Phenelzine
Tetrahydroaminacrine
Prolonged duration of neuromuscular blockade is seen following a vecuronium infusion. Which of the following is NOT a possible cause?
A Acidosis
B Long term steroid use
C Severe burns
D Hypothermia
B
Explanation
In rare cases, long-term use of neuromuscular blocking drugs to fascilitate mechanical ventilation in ICU settings may be associated with prolonged paralysis and/or skeletal muscle weakness. Patients may have received other drugs such as broad spectrum antibiotics, narcotics and steroids and may have severe diseases which lead to electrolyte imbalances, hypoxic episodes of varying duration, acid-base imbalance, hyperthermia and extreme debilitation any of which may enhance the actions of a neuromuscular blocking agent.
Hypothermia increases the duration of action and increases the time to recovery. Reduced clearance and rate of effect site equilibration may explain vecuronium’s increased duration of action when core temperature is reduced.
Severe burns and those with upper motor neuron disease are resistant to nondepolarising muscle relaxants. This desensitization is probably caused by proliferation of extrajunctional receptors, which result in an increased dose requirement for the nondepolarising relaxant to block a sufficient number of receptors
Which of these drugs can be used to treat central anticholinergic syndrome?
A Physostigmine
B Atropine
C Pyridostigmine
D Benztropine
A
Explanation
Physositgmine is the only carbamate that is well absorbed form all sites (lungs, skin, eye, gut) and is distributed into the central nervous system.
EXTRA
Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS–but unpredictable from laboratory findings or other signs
Which of the following opioids have only INACTIVE metabolites?
A Oxycodone
B Codeine
C Methadone
D Morphine
C
Explanation
Morphine=hydromorphone.
Codeine= morphine
Oxycodone= oxymorphone.
Pethidine = norpethidine
Unlike codeine, morphine, hydromorphone, pethidine or oxycodone-methadone has no active metabolites and is therefore a good choice for patients at risk for toxicity from metabolite accumulation
Extra:
Morphine is primarily conjugated to morphine-3-glucuronide (M3G), a compound with neuroexcitatory properties. 10% of morphine is metabolised to morphine-6-glucuronide (M6G), an active metabolite with analgesic potency of four to six times that of its parent compound. These relative polar metabolites have limited ability to cross the BBB and probably do not contribute significantly to the usual CNS effects of a single dose of morphine. More importantly, accumulation of these metabolites may produce unexpected adverse effects in patients with renal failure or when exceptionally large doses of morphine are administered or high doses are administered over long periods. This can result in M3G-induced CNS excitation (seizures) or enhanced and prolonged opioid action produced by M6G.
With the MAOI tranylcypromine, which drug will be least problematic?
A Propofol
B Phenylephrine
C Ephedrine
D Pethidine
A
Explanation
Tranylcypromine is a MAOI, which will inhibit the catabolism of dietary amines-prevents breakdown of tyramine in the gut. When foods containing tyramine (cheese, tap beer, soy products and dried sausage) are ingested, the patient may develop a hypertensive crisis. The mechanism is poorly understood but is thought that tyramine displaces noradrenaline from the storage vesicles and enhance peripheral noradrenergic effects, including raising blood pressure dramatically. Similarly drugs with sympathommimetic properties may cause significant hypertension when combined with MAOIs. Over-the-counter preparations that contain pseudoephedrine and phenylpropanolamine are contraindicated in patients taking MAOIs. Pethidine is associated with serotonin syndrome when given with the MAOI drug group
Which drug does NOT have antiemetic properties?
A Ketamine
B Dexamethasone
C Midazolam
D Ondansetron
A
Explanation
Ketamine does not have antiemetic properties but is often used with propofol=Ketofol, as Propofol has antiemetic effects. The antiemetic effect of Propofol is stated in the current texts, but there is some controversy as to whether it really works as an antiemetic. See different articles reports below.
In a study reported in the clinical journal of anaesthetics it stated that many anaesthesiologists used propofol for its antiemetic effect. There is strong evidence for its antiemetic efficacy after anaesthesia maintained by a propofol infusion and also for its use in the post anaesthetic patient. However, there is little evidence to support its use purely at induction of anaesthesia or using it at the beginning or end of a case in an attempt to reduce postoperative nausea and vomiting. This is especially true in cases lasting longer than a few minutes
Other studies have reported: The group anaesthetised with propofol had significantly fewer emetic sequelae and the results suggest that propofol has a definite antiemetic action.
Online reports: Propofol is known to possess direct antiemetic effects. Propofol antiemetic use for induction and maintenance of anaesthesia has been shown to be associated with a lower incidence of postoperative nausea and vomiting (PONV) when compared to any other anaesthetic drug or technique.
Extra: The antiemetic effect of midazolam or/and ondansetron added to intravenous patient controlled analgesia in patients of pelviscopic surgery: 2012: Dae Seong Kimetal etal. Conclusion: Midazolam added to PCA using fentanyl proved more effective than ondansetron in preventing PONV without adverse effects.
Which of the following inhaled gases are metabolised greater than 10%?
A Isoflurane
B Nitrous oxide
C Halothane
D Sevoflurane
C
Explanation
Metabolism of inhaled anaesthetics:
Halothane >40%
Enflurane 8%
Sevoflurane 2-5%
Isoflurane <2%
Nitrous oxide 0%
Which of the following is most likely to cause raised intracranial pressure?
A Diazepam
B Ketamine
C Propofol
D Thiopentone
B
Explanation
Ketamine markedly increases cerebral blood flow, cerebral oxygen consumption and intracranial pressure. Inhaled anaesthetics decrease the metabolic rate of the brain but do increase cerebral blood flow. Thiopentone decreases cerebral metabolism, oxygen consumption and cerebral blood flow. Propofol reduces cerebral blood flow and cerebral metabolism. Benzodiazepines decrease cerebral blood flow and ICP but to a smaller extent
Note: I have seen nitrous oxide as an option. Nitrous does increase cerebral blood flow and ICP
Extra: the latest review of ketamine in the prescribed TB states that ketamine is considered to be a vasodilator that increases cerebral blood flow as well as CMR02. Traditionally ketamine has not been used in patient with an already raised ICP. New evidence suggests that this undesired effect on cerebral blood flow may be blunted by the maintenance of normocapnia
Life in the fast lane literature review, states that there is no evidence that ketamine causes harm in traumatic brain injury and that Ketamine haemodynamic stability may actually be of benefit in TBI requiring rapid sequence induction
The following cause an increase in intra-abdominal pressure?
A Metoclopramide
B Neostigmine
C Suxamethonium
D Morphine
C
Explanation
In some patients especially muscular ones, the fasiculations associated with suxamethonium will cause a rise in intra gastric pressure from 5-40cmH20. The result of which may cause vomiting and aspiration. This effect is not seen with the non depolarising muscle relaxants
Succinylcholine is a depolarizing neuromuscular blocker, meaning it causes a prolonged period of membrane depolarization in order to exert its therapeutic effects. It binds to the post-synaptic cholinergic receptors found on motor endplates, thereby inducing first transient fasciculations followed by skeletal muscle paralysis
Neostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor. The drug inhibits acetylcholinesterase which is responsible for the degredation of acetylcholine. So, with acetylcholinesterase inhibited, more acetylcholine is present. By interfering with the breakdown of acetylcholine, neostigmine indirectly stimulates both nicotinic and muscarinic receptors which are involved in muscle contraction.. It does not cross the blood-brain barrier. Neostigmine is a cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. By inhibiting acetylcholinesterase, more acetylcholine is available in the synapse, therefore, more of it can bind to the fewer receptors present in myasthenia gravis and can better trigger muscular contraction.
Metoclopramide causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain. Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D2 receptors, agonism of serotonin 5-HT4 receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. Metoclopramide antagonizes the dopamine D2 receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D2 receptor. Because of its antidopaminergic activity, metoclopramide can cause symptoms of tardive dyskinesia (TD), dystonia, and akathisia, and should therefore not be administered for longer than 12 weeks
Which of the following increase intra-ocular pressure?
A Hypoventilation
B Halothane
C Suxamethonium
D Ketamine
C
Explanation
Intraocular pressure increases following administration of suxamethonium. It occurs 1 min after injection, is maximal at 2-4 min and starts to subside after 5min. The mechanism may involve contractions of tonic myofibrils or transient dilation of chorodial blood vessels. Despite this increase, the use of suxamethonium is not contraindicated unless the anterior chamber is to be opened.
Note: in the current textbook, there is no mention of Ketamine’s effect on IOP. A web review states that ketamine does cause a small rise in IOP but not enough to be a concern. At dosages of 4 mg/kg or less, there are not clinically meaningful associations of ketamine with elevation of IOP.
Thiopentone is a “short-lasting” barbiturate because?
A It is administrated by IV injection
B It is metabolised rapidly by brain and liver
C It is rapidly distributed throughout the body
D It is bound to the “sleep centre” in the brain
C
Explanation
It is “short lasting” because of the rapid removal form brain tissue into the other highly vascularised tissues and is redistributed to muscle, fat and eventually all body tissues. It is only metabolised at a rate of 12-16% following a single dose. It facilitates the action of GABA and increase the opening of the Cl channels.
Which of the following may be administered via the tracheal mucosa?
A Calcium chloride
B Theophylline
C Lignocaine
D Suxamethonium
C
Explanation
Resuscitation drugs such as Naloxone, Atropine, Vasopressin, Epinephrine, Lignocaine.
(Mnemonic for resuscitation drugs that may be given down the ET tube is NAVEL) are absorbed via the trachea. Administration of resuscitation drugs into the trachea, however, results in lower blood concentrations than the same dose given intravascularly.
Which of the following local anaesthetics shortens the action potential duration?
A Lignocaine
B Bupivacaine
C Ropivacaine
D Prilocaine
A
Explanation
Class 1b antiarrhytmic drugs shorten the action potential. Lignocaine is a 1b antiarrhythmic drug. Other drugs include mexiletine. Class 1a lengthens the action potential and class 1c does not affect the action potential. Lignociane is the drug of choice for the termination of ventricular tachycardia and prevention of ventricular fibrillation after cardioversion in the ischaemic setting.
From the textbook:
Drugs with class 1B action shortens the APD (action potential duration) in some tissues of the heart and dissociate from the channel with rapid kinetics
