Agonists activate the receptor as a direct result of binding to it with a characteristic affinity. Moreover, intrinsic activity of an agonist to its receptor determines the ability to create a maximal response.

Responses to low doses of a drug usually increase in direct proportion to dose. As doses increase, however, the response increment diminishes; finally, doses may be reached at which no further increase in response can be achieved. The relationship formed between the dose and response when plotted graphically is hyperbolic. This also shows that even at low receptor occupancy, a maximal response may be produced.

Antagonists bind to receptors in the same affinity as agonists, but they have no intrinsic efficacy. They do not activate generation of signal. Instead, they interfere with the ability of the agonist to activate the receptor.

Partial agonists are similar to full agonists in that they have similar affinity to the target receptor, but they produce a lower response than full agonists.

Medical gas cylinders are made up of molybdenum steel but not cast iron. They are checked and assessed at a regular interval.

At least one cylinder in each hundred are tested for tensile, pressure, smash, twist and straightening.

Nitrous Oxide cylinders contain a mixture of liquid and vapour at a pressure of approx. 4500 kPa or 45 Bar. Carbon dioxide cylinder contain gas at the pressure of 5000kPa.

The filling ratio is the ratio of mass of liquified gas in the cylinder to the mass of water required to fill the cylinder at the temperature of 15ºC. In the united kingdom, filling ratio of liquid nitrous oxide is 0.75. The cylinders are usually attached to the anaesthetic machine. As nitrous oxide is an N-methyl-d-aspartate receptor antagonist that may reduce the incidence of chronic post-surgical pain.

Cardiac conduction

Phase 0 – Rapid depolarization. Opening of fast sodium channels with large influx of sodium

Phase 1 – Rapid partial depolarization. Opening of potassium channels and efflux of potassium ions. Sodium channels close and influx of sodium ions stop

Phase 2 – Plateau phase with large influx of calcium ions. Offsets action of potassium channels. The absolute refractory period

Phase 3 – Repolarization due to potassium efflux after calcium channels close. Relative refractory period

Phase 4 – Repolarization continues as sodium/potassium pump restores the ionic gradient by pumping out 3 sodium ions in exchange for 2 potassium ions coming into the cell. Relative refractory period

Hydrochloric acid is lost when you vomit for a long time (HCl). As a result, the following can be expected, in varying degrees of severity:

Hypokalaemia
Hypochloraemia
Increased bicarbonate to compensate for chloride loss and metabolic alkalosis

The alkalosis causes potassium to move from the intracellular to the extracellular compartment at first. Long-term vomiting and dehydration cause potassium to be excreted by the kidneys in order to conserve sodium. Dehydration can cause urea and creatinine levels to rise.

The actual base excess is always greater than the standard base excess.

The actual base excess (BE) is a measurement of a base’s contribution to a blood gas picture’s metabolic component. It’s the amount of base that needs to be added to a blood sample to bring the pH back to 7.4 after the respiratory component of a blood gas picture has been corrected (PaCO2 of 40 mmHg or 5.3 kPa). The BE has a normal range of +2 to 2. A large positive BE indicates a severe metabolic alkalosis, while a large negative BE indicates a severe metabolic acidosis. As a result, the actual BE in vitro is unaffected by CO2.

In vivo, however, standard BE is not independent of pCO2 because blood with haemoglobin acts as a better buffer than total ECF.

As a result, it is impossible to tell the difference between compensating for a respiratory disorder and compensating for the presence of a primary metabolic disorder.

The differences between in vitro and in vivo behaviour can be mostly eliminated if the BE is calculated for a haemoglobin concentration of 50 g/L (the ‘effective’ or virtual value of Hb if it was distributed throughout the extracellular space) rather than the actual haemoglobin. Because haemoglobin has a lower buffering capacity, the standard BE is higher than the actual BE. It reflects the BE better in the extracellular space rather than just the intravascular compartment.

Potassium maintains the resting potential of cardiac myocytes, with depolarization triggered by a rapid influx of sodium ions, and repolarization due to efflux of potassium. A slow influx of calcium is responsible for the longer duration of a cardiac action potential compared with skeletal muscle.

The cardiac action potential has several phases which have different mechanisms of action as seen below:

Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms.

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

The following is the alveolar gas equation:

PAO2 = PiO2 − PaCO2/R

Where:

PAO2 is the partial pressure of oxygen in the alveoli.
PiO2 is the partial pressure of oxygen inhaled.
PaCO2 stands for partial pressure of carbon dioxide in the arteries.
The amount of carbon dioxide produced (200 mL/minute) divided by the amount of oxygen consumed (250 mL/minute) equals R = respiratory quotient. With a normal diet, the value is 0.8.

By subtracting the partial pressure exerted by water vapour at body temperature, the PiO2 can be calculated:

PiO2 = 0.21 × (100 kPa − 6.3 kPa)
PiO2 = 19.8

Substituting:
PAO2 = 19.8 − 10/0.8
PAO2 = 19.8 − 12.5
PAO2 = 7.3k Pa

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic ? and ?1 (but not ?2 )agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of DA dilates these vessels (by raising intracellular cyclic adenosine monophosphate).

Moderately high doses produce a positive inotropic (direct ?1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (?1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular ? and ? receptors; does not penetrate the blood-brain barrier – no Central nervous system effects.

Dopamine is less arrhythmogenic than adrenaline

Regarding dopamine part of the dose is converted to Noradrenaline in sympathetic nerve terminals.

The SI unit of pressure is the pascal (Pa) and it is equal to one newton (N) per square meter (m2) or N/m2.

1 atmosphere (atm) is the equivalent of:

101325 Pa760 mmHg
1.01325 bar
1033.23 cmH2O.
14.69 pounds per square inch (psi)
1013.25 millibar (mbar) or hectopascals (hPa), and

14.69 psi is equal to one atmosphere. The other values are equal to two atmospheres of pressure.

Malignant hyperthermia (MH) is a autosomal dominant inherited medical condition which predisposes affected individuals to a clinical syndrome of hypermetabolism which involves abnormal ryanodine receptors in skeletal muscle causing a deregulation of calcium in muscle.

It is a life threatening condition requiring immediate medical intervention. It often lies dormant until triggered in susceptible individuals mostly by volatile inhaled anaesthetic agents and succinylcholine which is a muscle relaxant.

The signs and symptoms of MH are related to this hypermetabolism, which includes an increase in carbon dioxide production, metabolic and respiratory acidosis, accelerated oxygen consumption, heat production, activation of the sympathetic nervous system, hyperkalaemia, disseminated intravascular coagulation (DIC), and multiple organ dysfunction and failure.

Early signs of MH to look out for in patients includes an uptick in end-tidal carbon dioxide (even with increasing minute ventilation), tachycardia, muscle rigidity, tachypnoea, and hyperkalaemia. Later signs include fever, myoglobinuria, and multiple organ failure.

In vitro muscle contracture test (IVCT) is the standard for determining individual susceptibility to MH. It is conducted by measuring the force of muscle contraction after exposing the patient’s muscle sample to halothane and caffeine., the sample is normally taken from the vastus medialis or lateralis under regional anaesthesia.

The incidence of a disease is the number of new cases of the disease in a population over a defined time period.

The prevalence of a disease is the number of cases of the disease in a population over a defined time period describes. It is NOT the number of new cases.

The number of new cases of a disease only, has no denominator (time period or population) from which to derive an incidence.

The number of new cases of a disease seeking medical treatment is the incidence of patients seeking medical treatment NOT the incidence of the disease in a population.

The death rate from a disease is the number of patients dying from the disease in a population.