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Therapeutic index, ED50, TD50 and LD50
Friday, May 26 (2023); Pharmacodynamics
Quantal dose-response graphs can be characterised by the median effective dose (ED50). The median effective dose is the dose at which 50% of individuals exhibit the specified quantal effect; the median toxic dose is the dose required to produce a defined toxic effect in 50% of subjects, and the median lethal dose is the dose required to kill 50% of subjects. The therapeutic index is the ratio of the TD50 to the ED 50, a parameter which reflects the selectivity of a drug to elicit the desired effect rather than toxicity. The therapeutic window is the range between the minimum toxic dose and the minimum therapeutic dose, or the range of doses over which the drug is effective for most of the population and the toxicity is acceptable.
Cardiac reflexes
Saturday, May 20 (2023); Cardiovascular system
Cardiac reflexes are reflex loops between the heart and central nervous system which regulate heart rate and peripheral vascular resistance. Some of these have homeostasis-maintaining roles, for example the baroreceptor reflex which maintains stable cardiac output and blood pressure. Others, such as the oculocardiac reflex and the vasovagal reflex, are not homeostatic in their function, but still have various protective roles. The efferent arms of these reflexes are inevitably the vagus nerve and the sympathetic nervous system.
Resistance of the respiratory system
Saturday, May 20 (2023); Respiratory system
Respiratory system resistance is mainly a combination of resistance to gas flow in the airways and resistance to deformation of tissues of both the lung and chest wall. It is usually expressed as a change in pressure per unit flow, usually in cmH2O per litre per second. Specifically, airway resistance is determined by the proportion of laminar and turbulent flow, which is in turn determined by Reynolds' number. Under normal conditions, most of the flow in the lower airways is thought to be laminar.
Invasive and non-invasive measurement of blood pressure
Monday, May 15 (2023); Cardiovascular system
Invasive (direct) blood pressure measurement collects data by connecting the bloodstream to a pressure transducer, usually by a column of incompressible fluid (eg. saline). Non-invasive (indirect) methods rely on the use of counterpressure (eg. an inflated cuff) to detect changes in peripheral pulse or to change the characteristics of downstream blood flow, which can be detected and related to the pressures in the circulation.
Effect site equilibration
Saturday, May 13 (2023); Pharmacokinetics
Effect site concentration is the concentration of drug at the site of its biological activity, eg. bound to the receptors. Effect site concentration is proportional to pharmacological effect, whereas plasma concentration may not be. The rate of effect onset is determined by the rate of distribution of the drug from other compartments (i.e. central compartment) into the effect site. Equilibration between the central and the effect-site compartment follows first-order kinetics, described by the constant ke0. t½ke0 is a value which describes the time taken to achieve 50% effect-site concentration when the plasma levels are maintained at steady state.
Response to 100ml of concentrated (20%) human albumin
Sunday, May 7 (2023);
These are the physiological effects of infusing 100ml of concentrated (20%) human albumin into a patient. 20% albumin is a sticky protein concentrate with a variable amount (48-100mmol/L) of sodium in it. Following the early pioneers, in 1976 post-op patients were infused with 50g of albumin in varying concentrations. The volume expansion for all these patients was about 500ml, working out to be 11ml of volume expansion per 1g of "retained" albumin (i.e. accounting for some "escaped" albumin). A similar study had later confirmed these findings in a group of bypass patients, arriving at a figure of 7.7ml volume expansion per 1g of albumin.
Ketamine
Sunday, May 7 (2023); Nervous system
Ketamine is a unique dissociative anaesthetic with a distinctive mechanism of action. It is an NMDA receptor antagonist, which produces sedation and analgesia without inhibiting cardiovascular stability or airway reflexes. From a pharmacodynamic perspective it has it has no equal in routine medical use. Its complex modulatory effects have multiple uses, including the management of acute and chronic pain, depression, and severe asthma.
Lung volumes and capacities
Sunday, May 7 (2023); Respiratory system
There are four volumes and four capacities recognised in respiratory physiology, where lung volumes are measurable gas-filled spaces in the lung, whereas capacities are combinations of two or more volumes (where the definition of capacity is the measure of the lungs' ability to hold a gas).
Dobutamine
Sunday, May 7 (2023); Cardiovascular system
Dobutamine is a synthetic catecholamine. As well as a well-defined catechol group, it possesses a humongous amine substituent group, which confer upon it a high level of beta-1 selectivity. This is the result of "intelligent drug design". The first paper to describe its properties (1975) is an amazing piece of work. The authors systematically produced a whole bucketfull of catecholamines with different side chains, amine substituents, hydroxyl group arrangements, etc etc - and then tested them for cardiovascular effect. Indeed, much of what we know about the structure and function relationship of catecholamines comes from such experiments.
Twitch, summation and tetanus
Saturday, May 6 (2023); Musculoskeletal system
A muscle contraction produced by a single action potential is a twitch, and sustained contraction is produced by the summation of the tension of multiple frequent action potentials. Tetany is produced with a high-frequency stimulus (50-100 Hz), where no relaxation occurs between stimuli.
Muscle spindles and Golgi tendon organs
Sunday, April 30 (2023); Musculoskeletal system
Muscle spindles and Golgi tendon organs are proprioceptive sensors which provide feedback about the length and tension of skeletal muscle. Muscle spindles are composed of intrafusal cells (modified muscle fibres that are still capable of contraction) and coordinate the monosynaptic stretch reflex. Golgi tendon organs are fusiform bundles of innervated collagen that insert into muscle at the musculotendnous junction.
Reflex arcs
Saturday, April 29 (2023); Nervous system
A reflex is a stereotypical predictable response to a stimulus that generally bypasses the higher levels of the central nervous system and occurs without any conscious voluntary control by the conscious mind. There are usually predictable components, eg. a sensor organ, a processor organ, and an effector of some sort. The most classical spinal reflexes are the monosynaptic deep tendon reflexes (eg. knee jerk), so called because they consist of a single pair of neurons connected by one synapse.
Extracorporeal cardiopulmonary resuscitation
Friday, April 28 (2023); Cardiac Arrest and Resuscitation
CPR yields a meagre 50% of normal cardiac output at best, so it makes sense that one would instead try to restore full circulatory support using ECMO during CPR. E-CPR is now done widely across the world with increased success and promising outcomes.
Important spinal cord injury syndromes
Tuesday, April 25 (2023); Neurology and Neurosurgery
This topic keeps coming up in the SAQs. One notable appearance was in Question 5 from the first paper of 2010, where the candidates needed to not only identify the features, but also the causes of the partial spinal cord injury syndrome. The canonical resource for this would have to be Ch.78 from Oh's Manual, Spinal injuries by Sumesh Arora and Oliver J Flower. Specifically, on page 798, cord syndromes are discussed with enough detail to pass Question 5. If one happens to not own the Manual, one may find a similar amount of detail in the "International standards for neurological and functional classification of spinal cord injury" from 1997, and in a similar article on classifying partial cord syndromes from 2000. And if one were for some reason in need of a massive amount of detail, one might instead wish to purchase a copy of Diseases of the Spine and Spinal Cord By Thomas N. Byrne, which remains a definitive text on this subject.