Write brief notes on the pharmacology of tramadol.
A question like this is a gift because it requires little more than reproducing what is on one of your summary cards! This question requires no higher order application or integration of knowledge, but it is still important for core drugs like tramadol, to be able to recall pharmacological data in significant detail. This is what you should be doing when you draw up the drug!!
T / F tramadol is a racemic mixture of 2 enantiomers – the (-) isomer inhibits noradrenaline reuptake and the (+) isomer inhibits serotonin reuptake
T / F tramadol is metabolised by CYP2D6 to O-desmethyltramadol, which is responsible for most of the opioid effect
T / F patients who are ultra-rapid codeine metabolisers, are also ultra-rapid tramadol metabolisers
T / F tramadol is 90% renally excreted, with 30% being excreted as unchanged drug
T / F tramadol has low potential for dependence and abuse
T / F tramadol does not cause respiratory depression or constipation
T / F some anaesthetists describe tramadol as a weak analgesic that reliably causes nausea and vomiting
Describe the pharmacodynamic properties of propofol EXCLUDING its effect on the central nervous system. Describe how these influence clinical use.
Propofol is a drug which anaesthetists use every day. Candidates should not be surprised to find that the primary exam requires an in depth and intimate knowledge of this drug. Many candidates did not address the second part of this SAQ at all.
T / F propofol does not inhibit hypoxic pulmonary vasoconstriction, and is a slight bronchodilator so it is suitable to use in patients with COAD
T / F propofol reduces uterine tone, so it can increase the risk of PPH
T / F a dangerous fall in blood pressure can result from a propofol induction if the patient is hypovolaemic, because propofol is a direct vasodilator and inhibits the baroreceptor reflex
T / F propofol blunts upper airway reflexes – it was serendipitous that propofol came into clinical use at the same time as Dr Archie Brain delevloped the LMA
T / F propofol increases intraocular pressure, so it should not be used in cases of eye trauma
T / F a propofol infusion alone can reliably prevent movement during surgery in an unparalysed patient
Describe the determinants of left ventricular myocardial oxygen supply and demand.
A perioperative MI is associated with a significant increase in mortality. An in-depth understanding of the factors involved in supplying oxygen to the myocardium is therefore essential knowledge in order to prevent and/or manage these events in at risk patients.
T / F at rest, per 100 g of myocardium, oxygen consumption is 8 mL/min – this increases to 70 mL/min during strenuous exercise
T / F 70% of coronary flow to the left ventricle occurs during diastole
T / F ventricular wall tension is a major determinant of oxygen consumption – with a dilated ventricle, a higher wall tension is needed to generate a given intraventricular pressure
T / F arterial oxygen content is an important factor in myocardial oxygen supply – therefore, all patients having an acute coronary event should receive supplemental oxygen
T / F coronary blood flow is autoregulated by both myogenic and metabolic mechanisms
T / F an increase in right atrial pressure can reduce coronary flow to the left ventricle
T / F the main role of glyceryl trinitrate in treating myocardial ischaemia is to reduce diastolic BP, and therefore LV afterload
Describe the clinical effects of non-steroidal anti-inflammatory drugs including the mechanisms through which they exert these effects.
Anaesthetists prescribe NSAIDS frequently. These drugs are very effective analgesics, but have significant potential adverse effects. Obviously, an in depth pharmacological knowledge is required.
T / F NSAIDS produce analgesia by inhibiting the synthesis of prostaglandins in injured tissue. Prostaglandins act directly on free nerve endings to produce pain.
T / F inhibiting prostaglandin synthesis decreases renal blood flow because PGE2 maintains efferent arteriolar dilation
T / F an advantage of COX-2 selective agents is that there is less inhibition of PGE2 and therefore less reduction in renal blood flow
T / F NSAIDS produce gastric mucosal ulceration via a direct irritant effect – therefore, they should not be taken on an empty stomach
T / F NSAIDS provide an overall reduction in the risk of acute coronary events because they inhibit platelet thromboxane
T / F inhibition of either COX-1 or COX-2 promotes the production of leukotrienes from arachidonic acid, which can precipitate asthma in some patients
Describe the immunology, mediators and pathophysiology of anaphylaxis. Do not discuss management.
Anaphylaxis continues to be a major cause of anaesthetic morbidity and mortality. Understanding the pathophysiology is essential in order to comprehend the management of this complex, challenging emergency.
T / F histamine is released from MAST cells during anaphylaxis – it causes bronchospasm via H1 receptors
T / F anaphylaxis to muscle relaxants can occur due to prior sensitisation from exposure to some cosmetics, or pholcodeine cough mixture
T / F MAST cell degranulation occurs when an allergen binds to IgG on the MAST cell surface
T / F histamine, leukotrienes and platelet activaing factor all increase vascular permeability during anaphylaxis – many litres of IV fluid can be needed during resuscitation
T / F patients with anaphylaxis will reliably show a rash or urticaria
T / F if you suspect a penicillin allergy, 100 mg of cephazolin can be given IV to determine if it is safe to give that drug
Describe the physiological processes that influence the rate of gastric emptying.
Anaesthetists are always concerned about the fasting status of a patient, and whether the stomach might not be empty. The reason for this is that aspiration can cause serious complications including death (see NAP 4 Audit, page 9 “…Aspiration was the single commonest cause of death in anaesthesia events”)
T / F the emptying of fat and protein from the stomach occurs at a similar rate
T / F 50% of an average meal leaves the stomach in about 2 hours
T / F an increased volume of gastric contents promotes emptying via a vagal reflex
T / F gastric emptying is delayed in pregnancy due to the effect of progesterone
T / F both opioids and pain tend to delay gastric emptying
T / F cholecystokinin slows gastric emptying – it is secreted from cells in the duodenum, in response to fatty acids and amino acids in the duodenum
T / F chewing gum increases gastric acid production AND slows gastric emptying (see ANZCA PS07 page 7)
Draw and explain the characteristics of a quantal dose-response curve that describes the major clinical effects of rocuronium. Outline medications and medical conditions that shift the curve to the left or the right.
Neuromuscular blockers and opioids can be used as clinical examples to test candidates’ understanding of the various types of dose response curves. Why do we recommend 2 to 3 times the “ED95” as the intubating dose for muscle relaxants?
T / F a quantal dose-response curve is semi-logarithmic
T / F the y-axis shows % twitch height reduction, from 0 to 100%
T / F for the specific case of muscle relaxants, the ED50 refers to 50% of the population achieving a 95% reduction in twitch height, and is also referred to as the ED95, or ED50(95%)
T / F a right shift in the curve reflects reduced potency, and could be caused by a recent dose of neostigmine, or one week of bed rest
T / F hypothermia increases the potency of rocuronium
T / F patients with myasthenia gravis would have a left shifted curve
Discuss the factors affecting duration of action of a local anaesthetic block to a major peripheral nerve.
Candidates have difficulty with the LA duration of action and speed of onset questions, often confusing the two. Many candidates try to force the answer into Fick’s law of diffusion, with disappointing results.
T / F an increased local anaesthetic concentration, but not the total dose, will prolong duration of action
T / F plasma cholinesterase deficiency will prolong the duration of cocaine
T / F increased lipid solubility will prolong the duration of action, AND increase the speed of onset of a local anaesthetic
T / F the presence of an active metabolite will contribute to LA duration of action
T / F lignocaine is shorter acting than bupivacaine because its pKa is closer to physiological pH
T / F with a brachial plexus block, analgesia of the hand will last longer than analgesia of the shoulder
There have been some really good study / exam tips lately, so I thought I’d post something with a motivational flavour. (Also, I resisted doing a history post because it’s too close to the exam to risk taking you on a procrastination tangent).
“Corpus Curare Spiritumque” is the Latin motto which appears on the ANZCA coat of arms.
It translates as “To care for the body and its breath of life”. I think this encapsulates really well, so much of what anaesthetists do.
Whether we are in theatre, attending a trauma, in pre-admission clinic, or on a ward round, we are always focused on the whole patient. Especially in theatre, sometimes we are the only doctors who seem to have a handle on the big picture!
We are doctors who are good at keeping people alive. However, the full meaning of the “breath of life” can extend to include every aspect of homeostasis.
In order to live up to the lofty motto chosen by the Founding Fellows of the College, anaesthetists need a solid grounding in basic sciences. That’s because we are surrounded every day by pharmacology, altered physiology, and technology.
At the end of the day, I hope that you can see the value and impact of all your study for the primary exam, in terms of your ability as an anaesthetist to “care for the body and its breath of life”.
BT_GS 1.30 Describe and compare the pharmacokinetics of intravenous induction agents …
BT_GS 1.31 Describe and compare the pharmacodynamics of intravenous induction agents …
Thiopentone is a terrific drug. Unfortunately, the current generation of trainees lack familiarity and confidence with it.
T / F compared with propofol, a standard induction dose of thiopentone causes less vasodilation and less hypotension
T / F when diluted with 20 mL water, 500 mg thiopentone makes a 2.5% solution, with a pH of 11 (regarding the pH, can you explain why you think this is true or false? Why is this pH necessary / not necessary?)
T / F in plasma, thiopentone is 80% bound to albumin
T / F thiopentone is a weak base with pKa 7.6 – therefore, 12% of an injected dose will be available to cross the blood brain barrier
T / F the majority of thiopentone is metabolised to inactive metabolites
T / F thiopentone effectively blunts the upper airway reflexes
Now that you’ve become fascinated by thiopentone, it would be useful to use this knowledge to answer some SAQ’s.
- Write short notes on the pharmacology of thiopentone.
- Compare and contrast the pharmacology of propofol and thiopentone.
- Explain the advantages and disadvantages of propofol and thiopentone for induction of general anaesthesia.
These 3 SAQ’s are in ascending order of complexity, in terms of the level of understanding they are testing. Regurgitating your summary notes (Q1) is low level knowledge – a candidate may score highly without really understanding what they are writing. But Q3 requires not only the application of PK and PD data – this information must be further organised to address the advantages and disadvantages. Scoring well on this question would demonstrate a high level of understanding (appropriate given the “core” nature of the drugs in question).
Have a go at answering the 3 SAQ’s above. While the 3 answers will each contain some of the same information, the final answers will be quite different. Hopefully this will help you reflect on the importance of reading the question!!