An agonist is a molecule with intrinsic efficacy and affinity for a receptor. The ability of a drug-receptor interaction to produce a maximal response is referred to as intrinsic efficacy or activity. Efficacy also refers to a drug’s ability to have a therapeutic or beneficial effect. Although the potencies of morphine and fentanyl differ, they both have the same intrinsic efficacy.

The amount of drug required to produce a given effect is referred to as potency. If drug X is effective in a dose of 100 mcg, its potency is greater than if drug Y is effective in a dose of 10 mg.

The therapeutic index, also known as the margin of safety, is a ratio of the lethal or serious side effect dose of a drug divided by the therapeutic dose of the same drug.

The term bioavailability refers to the ability of a substance to be absorbed. The area under a curve (AUC) of a graphic plot of plasma concentration and time is used to calculate oral bioavailability. It’s used to figure out how much of a drug to take and when to take it.

The vertebral (spinal) column is the skeletal central axis made up of approximately 33 bones called the vertebrae.

Cervical disc herniations occur when some or all of the nucleus pulposus extends through the annulus fibrosus. The most commonly affected discs are the C5-C6 and C6-C7 discs. Each vertebrae has a corresponding nerve root which arises at a level above it. This means that a hernation of the C5-C6 disc will cause a compression of the C6 nerve root.

The foramen transversarium is a part of the transverse process of each cervical vertebrae, however, the vertebral artery only runs through the C1-C6 foramen transversarium.

The costal facets are the point of joint formation between a rib and a vertebrae. As such, they are only present on the transverse processes of T1-T10.

The lumbar vertebrae do not form a joint with the ribs, nor do they possess a foramina in their transverse process.

Intervertebral discs are thickest in the cervical and lumbar regions of the spinal column. However, there are no discs between C1 and C2.

Sodium-chloride symporter inhibitor.

The thiazide sensitive sodium chloride symporter is inhibited by thiazides at the proximal portion of the distal convoluted tubule leading to increased sodium and water excretion. Increased delivery of sodium to the distal portion of the distal convoluted tubule promotes potassium loss. This is why thiazides are associated with hyponatraemia and hypokalaemia.

Carbonic anhydrase inhibitors are used mainly in the treatment of glaucoma. They act on the proximal convoluted tubule to promote bicarbonate, sodium and potassium loss.

Sodium potassium chloride symporter is inhibited by Loop diuretics.
Epithelial sodium channels are inhibited by Amiloride.
Drugs which lead to nephrogenic diabetes insipidus such as lithium and demeclocycline, are Inhibitors of vasopressin.

With respect to oxygen transport in cells, almost all oxygen is transported within erythrocytes. There is limited solubility and only 1% is carried as solution. Thus, the amount of oxygen transported depends upon haemoglobin concentration and its degree of saturation.

Haemoglobin is a globular protein composed of 4 subunits. Haem is made up of a protoporphyrin ring surrounding an iron atom in its ferrous state. The iron can form two additional bonds – one is with oxygen and the other with a polypeptide chain.
There are two alpha and two beta subunits to this polypeptide chain in an adult and together these form globin. Globin cannot bind oxygen but can bind to CO2 and hydrogen ions.
The beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule facilitates the binding of subsequent molecules.

The oxygen dissociation curve (ODC) describes the relationship between the percentage of saturated haemoglobin and partial pressure of oxygen in the blood.
Of note, it is not affected by haemoglobin concentration.

Chronic anaemia causes 2, 3 DPG levels to increase, hence shifting the curve to the right

Haldane effect – Causes the ODC to shift to the left. For a given oxygen tension there is increased saturation of Hb with oxygen i.e. Decreased oxygen delivery to tissues.
This can be caused by:
-HbF, methaemoglobin, carboxyhaemoglobin
-low [H+] (alkali)
-low pCO2
-ow 2,3-DPG
-ow temperature

Bohr effect – causes the ODC to shifts to the right = for given oxygen tension there is reduced saturation of Hb with oxygen i.e. Enhanced oxygen delivery to tissues. This can be caused by:
– raised [H+] (acidic)
– raised pCO2
-raised 2,3-DPG
-raised temperature

Spirometry measures the total volume of air that can be forced out in one maximum breath, that is the total lung capacity (TLC), to maximal expiration, that is the residual volume (RV).

It is conducted using a spirometer which is capable of measuring lung volumes using techniques of dilution.

During spirometry, the following measurements can be determined:
Forced vital capacity (FVC)/vital capacity (VC): The maximum volume of air exhaled in one single forced breathe.
Forced expiratory volume in one second (FEV1)
FEV1/FVC ratio
Peak expiratory flow (PEF): the maximum amount of air flow exhaled in one blow.
Forced expiratory flow (mid expiratory flow): the flow at 25%, 50% and 75% of FVC
Inspiratory vital capacity (IVC): The maximum volume of air inhaled after a full total expiration.

Anatomical dead space is measured using a single breath nitrogen washout called the Fowler’s method.

Residual volume and total lung capacity are both measured using the body plethysmograph or helium dilution

The functional residual capacity is usually measured using a nitrogen washout or the helium dilution technique.

Ferromagnetism is the property of a substance that is magnetically attracted and can be magnetised indefinitely. A material is said to be paramagnetic if it is attracted to a magnetic field. A substance is said to be diamagnetic if it is repelled by a magnetic field.

Cobalt, iron, gadolinium, neodymium, and nickel are ferromagnetic.

Gadolinium is a ferromagnetic rare earth metal that is ferromagnetic below 20 degrees Celsius (its Curie temperature). MRI scans are enhanced with gadolinium-based contrast media.

When ferromagnetic materials are exposed to a magnetic field, they can cause a variety of issues like magnetic field interactions, heating, and image artefacts.

Titanium, lead, chromium, copper, aluminium, silver, gold, and tin are non ferromagnetic.

Oxygen delivery depends on 2 variables.
1) Content of oxygen in blood
2) Cardiac output

Oxygen content (arterial) = (Hb (g/dL) x 1.39 x SaO2 (%) ) + (0.023 x PaO2 (kPa))

Oxygen content (mixed venous) = (Hb (g/dL) x 1.39 x mixed venous saturation) + (0.023 x mixed venous partial pressure of oxygen in kPA)

Huffner’s constant = 1.39 = 1g of Hb binds to 1.39 ml of O2

Oxygen delivery DO2 (ml/min) = 10 x Cardiac output (L/min) x Oxygen content
Normally 1000ml/min

Oxygen consumption VO2 (ml/min) = 10 x Cardiac output (L/min) x Difference in arterial and mixed venous oxygen content
Normally 250 ml/min

Oxygen extraction ratio (OER) = VO2/DO2
Normally approximately 25%

The following table shows the compartments and their relative oxygen reserve:
Compartment Factors Room air (mL) 100% O2 (mL)
Lung FAO2, FRC 630 2850
Plasma PaO2, DF, PV 7 45
Red blood cells Hb, TGV, SaO2 788 805
Myoglobin 200 200
Interstitial space 25 160

Oxygen reserves in the body, with room air and after oxygenation.

FAO2-alveolar fraction of oxygen rises to 95% after administration of 100% oxygen (CO2 = 5%)
FRC- Functional residual capacity – (the most important store of oxygen in the body) – 2,500-3,000 mL in medium sized adults
PaO2-partial pressure of oxygen dissolved in arterial blood (80 mmHg breathing room air and 500 mmHg breathing 100% oxygen)
DF -dissolved form (0.3%)
PV-plasma volume (3L)
TG-total globular volume (5L)
Hb-haemoglobin concentration
SaO2-arterial oxygen concentration (98% breathing air and 100% when preoxygenated)

Approximately 20% of halothane and 0.02% desflurane undergo hepatic biotransformation. Desflurane, halothane, and isoflurane are metabolised in the liver by cytochrome p450 to trifluoroacetate. Through an immunological mechanism involving trifluoroacetyl hapten formation, trifluoroacetate is thought to be responsible for hepatotoxicity.

Potency of inhaled anaesthetic agents is measured using the minimal alveolar concentration (MAC). The MAC of halothane is 0.74% while that of desflurane is 6.3%. The potency can also be compared using the oil: gas partition coefficient (224 and 18.7 for halothane and desflurane respectively).

Onset of action of volatile agents depends on the blood:gas partition coefficient. A lower blood:gas partition coefficient and insolubility in blood means faster onset and offset of action. The blood gas coefficient for halothane is 2.4 while that of desflurane is 0.42. Desflurane is less soluble than halothane in blood. Halothane has a pungent smell that can irritate the airway which limits its use for a gaseous induction especially in paediatric anaesthesia. desflurane is not pungent.

Desfluranes boiling point is only slightly above normal room temperature (22.8°C) making it extremely volatile while the boiling point of halothane is approximately 50.2°C.

Codeine is easily absorbed from the gastrointestinal tract and converted to morphine and norcodeine in the liver via O- and N-demethylation. Morphine and norcodeine are excreted almost entirely by the kidney, primarily as conjugates with glucuronic acid.

By glucuronidation, phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 converts morphine to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) (UGT2B7).

Approximately 60% of morphine is converted to M3G, with the remaining 6-10% converted to M6G. M3G is inactive, but M6G is said to be 4 to 650 times more potent on the MOP receptor than morphine.

When codeine is consumed, cytochrome P450 2D6 in the liver converts it to morphine (CYP2D6).

Some people have DNA variations that increase the activity of this enzyme, causing codeine to be converted to morphine more quickly and completely than in others. After taking codeine, these ultra-rapid metabolisers are more likely to have higher than normal levels of morphine in their blood.

Respiratory depression/obstruction can be caused by high levels of morphine and M6G, especially in people who have a history of obstructive sleep apnoea. The estimated number of ultra-rapid metabolisers ranges from 1 to 7 per 100 people, but some ethnic groups may have as many as 28 per 100 people.

Propofol is considered a safe drug to use in porphyria because even if causes mild elevation of porphyrins inpatient, it does not cause any symptoms.

Since barbiturates are inducers of ALA synthetase, they are contraindicated in porphyria patients. So, thiopentone most not be used.

Etomidate is a potent inhibitor of adrenal 11 beta-hydroxylase and 17 alpha-hydroxylase reducing cortisol and aldosterone synthesis in the adrenal cortex and has been associated with exacerbations of porphyria in animal studies and it is advisable not to use it in this condition.

Ketamine should be reserved for the hemodynamically unstable patient, however, it is a safe drug.

Diazepam is safe in porphyria but is not usually used for a rapid sequence induction.

Maintenance therapy aims to replace water and electrolytes lost under ordinary conditions. In the perioperative period, maintenance fluid administration may not sufficiently account for the increased fluid requirements caused by third-space losses into the interstitium and gut. Specific recommendations vary with the patient, the procedure, and the type and amount of fluid administered during the operation. The fluid for maintenance therapy replaces deficits arising primarily from insensible losses and urinary or gastrointestinal (GI) losses.

The maintenance fluid volume can be computed using the Holliday-Segar method.

Body weight Fluid volume
first 10 kg 4 ml/kg/hr
next 10-20 kg 2 ml/kg/hr
>20 kg 1 ml/kg/hr

In the past few years, there has been growing recognition of the increased risk of hyponatremia in hospitalized children in intensive care and postoperative settings who receive hypotonic maintenance fluids. Several studies, including a randomized controlled trial and a Cochrane analysis, found that the use of isotonic fluids is associated with fewer electrolyte derangements and concluded that isotonic maintenance fluids are preferable to hypotonic solutions in hospitalized children.

A European consensus statement suggests that an intraoperative fluid should have an osmolarity close to the physiologic range in children in order to avoid hyponatremia, an addition of 1-2.5% in order to avoid hypoglycaemia, lipolysis or hyperglycaemia and should also include metabolic anions as bicarbonate precursors to prevent hyperchloremic acidosis.

A rate of 40 ml/hr is suboptimal.

If 0.9% NaCl with 0% glucose is given at a rate of 65 ml/hr, despite of the correct infusion rate, large volumes can lead to hyperchloremic acidosis.

If 0.18% NaCl with 4% glucose is given at a rate of 65 ml/hr, infusion of this fluid regimen can lead to hyponatremia because of its hypotonicity.

This data is in a 2 × 2 contingency table so a chi square test can be used. There is a special chi squared formula that gives a value that can be looked up in a table giving the p value.

Since we are comparing proportions not means, the Student’s t test CANNOT be used.

There is no linear regression to plot so Pearson’s co-efficient cannot be calculated.

Nothing is so obvious that no statistical analysis is needed.

The ?-2 adrenoceptor has three subtypes (2a, 2b and 2c). The receptors are generally presynaptic, meaning they prevent noradrenaline from being released at nerve endings. Both the central and peripheral nerve systems are affected by the ?-2 agonists. ?-2 agonists cause drowsiness, analgesia, and euphoria centrally in the locus coeruleus (in the brainstem), lower the MAC of volatile anaesthetic drugs, and are used to treat acute withdrawal symptoms in chronic opioid addicts.

The most common impact of ?-2 agonists on heart rate is bradycardia. The adrenoreceptors ?-1 and ?-2 are blocked by phenoxybenzamine.

Clonidine is a selective agonist for the ? -2 receptor, having a 200:1 affinity ratio for the ?-2: ?-1 receptors, respectively.

Tizanidine is similar to clonidine but has a few key variances. It has the same sedative, anxiolytic, and analgesic characteristics as clonidine, although for a shorter period of time and with less effect on heart rate and blood pressure.

Dexmedetomidine, like clonidine, is a highly selective ?-2 adrenoreceptor agonist having a higher affinity for the ?-2 receptor. In the case of ?-2: ?-1 receptors, the affinity ratio is 1620:1. It has a biphasic blood pressure impact and induces a brief rise in blood pressure and reflex bradycardia (activation of ?-2b subtypes of receptors in vascular smooth muscles), followed by a reduction in sympathetic outflow from the brainstem and hypotension/bradycardia.

A prodrug is methyldopa. It blocks the enzyme dopa-decarboxylase, which converts L-dopa to dopamine (a precursor of noradrenaline and adrenaline). It is also converted to alpha-methyl noradrenaline, a centrally active agonist of the ?-2 adrenoreceptor. These two processes contribute to its blood pressure-lowering effect. Without a rise in heart rate, cardiac output is generally maintained. The heart rate of certain patients is slowed.

Phentolamine is a short-acting antagonist of peripheral ?-1 and ?-2 receptors that causes peripheral vascular resistance to reduce and vasodilation to increase. It’s used to treat hypertensive situations that aren’t life threatening (e.g. hypertension from phaeochromocytoma).

A baroreceptor reflex commonly causes reflex tachycardia when systemic vascular resistance drops.

In the Child-Pugh classification system, the following 5 components are determined or calculated in order:

Ascites

Grade of encephalopathy

Serum bilirubin (?mol/L)

Serum Albumin (g/L)

Prothrombin time or INR

Raised liver enzymes are not the component of the classification system.

Number needed to harm are a measure of the impact of a treatment or intervention that is often used to communicate results to patients, clinicians, the public and policymakers. It states how many patients need to be treated for one additional patient to experience an adverse outcome (e.g. a death). It is calculated as the inverse of the absolute risk reduction. It can equally well be applied to harmful outcomes as well as beneficial ones, where it becomes numbers needed to treat (NNT) instead.

In this way, they are both calculated the same but NNT usually refers to a therapeutic treatment whereas NNH refers to a risk-factor for disease.

The elimination of phenytoin follows first order kinetics. Plasma concentrations determine the rate of elimination. The relationship between drug X plasma concentration and time is described by an exponential process in the following equation used to describe the rate of elimination:

C = C0. e-kt

C=drug concentration, C0= drug concentration at time zero (extrapolated), k = rate constant and t=time

As enzyme systems become saturated when phenytoin concentrations are above the usual range, clearance of the medication becomes zero-order. The medication is metabolised at a constant pace, regardless of its plasma levels. Aspirin and ethyl alcohol are two more significant examples of medications that operate in this way.

A plot of drug concentration with time is a washout exponential curve.

A graph of concentration with time is a straight line i.e. Zero-order kinetics

The amount eliminated per unit time is constant defines the point at which zero order kinetics commences.

Elimination involves a rate-limiting reaction operating at its maximal velocity is incorrect.

The half life of the drug is proportional to the drug concentration in the plasma corresponds to a definition of first-order kinetics.

The ions found in higher concentrations intracellularly than outside the cells are:

ATP
AMP
Potassium
Phosphate, and
Magnesium Adenosine diphosphate (ADP)

Sodium is a primarily extracellular ion.

With respect to oxygen transport in cells, almost all oxygen is transported within erythrocytes. There is limited solubility and only 1% is carried as solution. Thus, the amount of oxygen transported depends upon haemoglobin concentration and its degree of saturation.

Haemoglobin is a globular protein composed of 4 subunits. Haem is made up of a protoporphyrin ring surrounding an iron atom in its ferrous state. The iron can form two additional bonds – one is with oxygen and the other with a polypeptide chain.
There are two alpha and two beta subunits to this polypeptide chain in an adult and together these form globin. Globin cannot bind oxygen but can bind to CO2 and hydrogen ions.
The beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule facilitates the binding of subsequent molecules.

The oxygen dissociation curve (ODC) describes the relationship between the percentage of saturated haemoglobin and partial pressure of oxygen in the blood.
Of note, it is not affected by haemoglobin concentration.

Chronic anaemia causes 2, 3 DPG levels to increase, hence shifting the curve to the right

Haldane effect – Causes the ODC to shift to the left. For a given oxygen tension there is increased saturation of Hb with oxygen i.e. Decreased oxygen delivery to tissues.
This can be caused by:
-HbF, methaemoglobin, carboxyhaemoglobin
-low [H+] (alkali)
-low pCO2
-ow 2,3-DPG
-ow temperature

Bohr effect – causes the ODC to shifts to the right = for given oxygen tension there is reduced saturation of Hb with oxygen i.e. Enhanced oxygen delivery to tissues. This can be caused by:
– raised [H+] (acidic)
– raised pCO2
-raised 2,3-DPG
-raised temperature

Erythromycin binds to the 50s subunit of bacterial rRNA complex and inhibits protein synthesis.

Vancomycin binds to the acyl-D-ala-D-ala portion of the growing cell wall in a susceptible gram-positive bacterium. After binding, it prevents the cell wall from forming the cross-linking.

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. Tetrahydrofolic acid is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.

During analytical stage a technique called stratification is used for controlling confounding variables. This technique involves sorting out the data into discernible groups.

Trigeminal neuralgia is characterized by excruciating paroxysms of pain in the lips, gums, cheek, or chin and, very rarely, in the distribution of the fifth nerve. The pain seldom lasts more than a few seconds or a minute or two but may be so intense that the patient winces, hence the term tic. The paroxysms, experienced as single jabs or clusters, tend to recur frequently, both day and night, for several weeks at a time. They may occur spontaneously or with movements of affected areas evoked by speaking, chewing, or smiling. Another characteristic feature is the presence of trigger zones, typically on the face, lips, or tongue, that provoke attacks; patients may report that tactile stimuli – e.g., washing the face, brushing the teeth, or exposure to a draft of air – generate excruciating pain. An essential feature of trigeminal neuralgia is that objective signs of sensory loss cannot be demonstrated on examination.

Trigeminal neuralgia is relatively common, with an estimated annual incidence of 4–8 per 100,000 individuals. Middle-aged and elderly persons are affected primarily, and ,60% of cases occur in women. Onset is typically sudden, and bouts tend to persist for weeks or months before remitting spontaneously. Remissions may be long-lasting, but in most patients, the disorder ultimately recurs.

An ESR or CRP is indicated if temporal arteritis is suspected. In typical cases of trigeminal neuralgia, neuroimaging studies are usually unnecessary but may be valuable if MS is a consideration or in assessing overlying vascular lesions in order to plan for decompression surgery.

After a paediatric case, you’ll frequently have to calculate and prescribe maintenance fluids. The ‘4-2-1 rule’ should be used as a guideline:

1st 10 kg – 4 ml/kg/hr
2nd 10 kg – 2 ml/kg/hr
Subsequent kg – 1 ml/kg/hr

Hence

1st 10 kg = 4 × 10 = 40 ml
2nd 10 kg = 2 × 10 = 20 ml
Subsequent kg = 1 × 1 = 1 ml
Total = 61 ml/hr

61 × 12 = 732 ml over 12 hrs.

The perfect glomerular filtration marker is:

The human body is not harmed by it.
Chemical or physical methods are used to accurately measure
Extracellular fluid (ECF) compartment is freely and evenly diffusible.
Inability to access the intracellular fluid (ICF) compartment
Filtration in the kidney is the only way to remove it from the blood.

The ideal marker should not be reabsorbed into the bloodstream by the renal tubules or other urinary system components.

Creatinine is an endogenous substance that is filtered freely by the glomerulus and secreted by the proximal tubule. As a result, creatinine clearance consistently underestimates GFR. In healthy people, this overestimation ranges from 10% to 40%, but it is higher and more unpredictable in patients with chronic kidney disease.

The gold standard method of inulin clearance necessitates an intravenous infusion and several hours of timed urine collection, making it costly and time-consuming. Inulin is hard to come by and is difficult to mix and keep as a solution.

Exogenous filtration markers include the following:

Although plasma clearance of 51chromium EDTA is a widely used method in Europe, tubular reabsorption can occur.
Because 125I-iothalamate can be excreted by renal tubules in the urine, it cannot be used in patients who have an iodine assay.

Radioactive substances must be stored, administered, and disposed of according to these methods.

The glomerulus filters para-aminohippuric acid (PAH) freely, and any that remains in the peritubular capillaries is secreted into the proximal convoluted tubules. This marker is used to determine the amount of blood flowing through the kidneys.

Metronidazole is a nitroimidazole antiprotozoal drug that is selectively absorbed by anaerobic bacteria and sensitive protozoa. Once taken up be anaerobes, it is nonenzymatically reduced by reacting with reduced ferredoxin. This reduction results in products that accumulate in and are toxic to anaerobic cells. The metabolites of metronidazole are taken up into bacterial DNA, forming unstable molecules. This action occurs only when metronidazole is partially reduced, and, because this reduction usually happens only in anaerobic cells, it has relatively little effect on human cells or aerobic bacteria.

The normal peak inspiratory flow in healthy individuals is 20-30 L/min during each normal tidal ventilation. This is expected to increase with greater respiratory rate and deeper inspiration.

Face masks are used to facilitate the delivery of oxygen from a breathing system to a patient. Face masks can be divided into two types: fixed performance or variable performance devices.

In fixed performance devices (also known as high air flow oxygen enrichment or HAFOE), fixed inspired oxygen concentration is delivered to the patent, independent and greater than that of the patient’s peak inspiratory flow rate (PIFR). No random entrainment is expected to occur at the time of PIFR, hence, the oxygen concentration in HAFOE devices is not dependent on the patient’s respiratory pattern.

Moreover, in HAFOE masks, the concentration of oxygen at a given oxygen flow rate is determined by the size of the constriction; a device with a greater entrainment aperture delivers a lower oxygen concentration. Therefore, a 40% Venturi device will have lesser entrainment aperture when compared to a 31% Venturi. Venturi masks allow relatively fixed concentrations of supplemental oxygen to be inspired e.g. 24%, 28%, 31%, 35%, 40% and 60% oxygen. These are colour coded and marked with the recommended oxygen flow rate.

Variable performance devices deliver variable inspired oxygen concentration to the patient, and is dependent on the PIFR. The PIFR can often exceed the flow rate at which oxygen or an oxygen/air mixture is supplied by the device, depending on a patient’s inspiratory effort. In addition, these masks allow expired air to be released through the holes in the sides of the mask. Thus, with increased respiratory rate, rebreathing of alveolar gas from inside the mask may occur.

Lidocaine 1% is formulated as 1000 mg/100 mL.

% solution is based on (grams of medicine) / 100 ml

% solution ~ (1000 mg) / 100 ml

% solution ~ 10 mg/ml

Examples:

• • Lidocaine 4% = 40 mg/ml of Lidocaine
  • Lidocaine 2% = 20 mg/ml of Lidocaine
  • Lidocaine 1% = 10 mg/ml of Lidocaine

Primary FRCA is concerned with two issues. The first is a working knowledge of the Henderson-Hasselbalch equation, and the second is a working knowledge of logarithms and antilogarithms.

The pH at which the drug exists in 50 percent ionised and 50 percent unionised forms is known as the pKa.

To calculate the proportion of ionised to unionised form of a drug, use the Henderson-Hasselbalch equation.

pH = pKa + log ([A-]/[HA])

or

pH = pKa + log [(salt)/(acid)]
pH = pKa + log ([ionised]/[unionised])

Hence, if the pKa − pH = 0, then 50% of drug is ionised and 50% is unionised.

In this example:
7.4 = 8.4 + log ([ionised]/[unionised])
7.4 − 8.4 = log ([ionised]/[unionised])
log −1 = log ([ionised]/[unionised])

Simply put, the antilog is the inverse log calculation. In other words, if you know the logarithm of a number, you can use the antilog to find the value of the number. The antilogarithm’s definition is as follows:

y = antilog x = 10x

Antilog to the base 10 of 0 = 1, −1 = 0.1, −2 = 0.01, −3 = 0.001 and, −4 = 0.0001.

[A-]/[HA] = 0.1

Assuming that we can apply the approximation [A-] << [HA} then this means the acid is 0.1 x 100% = 10% ionised so the percentage of (non-ionized) acid will be 100% – 10% = 90%

Level 1 – High-quality randomised controlled trial with statistically significant difference or no statistically significant difference but narrow confidence intervals (prospective controlled)

Level 2 – Prospective comparative study (prospective uncontrolled)

Level 3 – Case-control study, retrospective comparative study (retrospective controlled)

Level 4 – Case series (retrospective uncontrolled)

Level 5 – Expert opinion.

Warming, humidifying, and filtering inspired anaesthetic gases is done by heat and moisture exchangers (HME) and breathing system filters. They are made of glass fibres materials and are supported by a sturdy frame. Pleating increases the surface area to reduce resistance to air flow and boost efficiency.

Filters’ effectiveness is determined by the amount and size of particles they keep out of the patient’s airway. The efficiency of filters might be classified as 95, 99.95, or 99.97 percent. Pores with a diameter of 0.2 µm are common. The following are examples of typical particle sizes:
Red blood cell – 5 µm
Lymphocyte – 5-8 µm
Viruses – 0.02-0.3 µm
Bacteria – 0.5-1 µm
Depending on particle size, gas flow speed, and charge, particles are collected via a number of processes. Mechanical sieve, interception, diffusion, electrostatic filtration, and inertial impaction are some of the options:

Sieve:
The diameter of the particle the filter is supposed to collect is smaller than the apertures of the filter’s fibres.

Interception:
When a particle following a gas streamline approaches a fibre within one radius of itself, it becomes attached and captured.
Diffusion:

A particle’s random (Brownian) zig-zag path or motion causes it to collide with a fibre.
By attracting and capturing a particle from within the gas flow, it generates a lower-concentration patch within the gas flow into which another particle diffuses, only to be captured. At low gas velocities and with smaller particles (0.1µm diameter), this is more common.

Electrostatic:

These filters use large diameter fibre media and rely on electrostatic charges to improve fine particle removal effectiveness.

Impaction due to inertia:

When a particle is too large to respond fast to abrupt changes in streamline direction near a filter fibre, this happens. Because of its inertia, the particle will continue on its original course and collide with the filter fibre. When high gas velocities and dense fibre packing of the filter media are present, this sort of filtration mechanism is most prevalent.

Half life (T½) is the time required to change the amount of drug in the body by one-half (or 50%) during elimination. The time course of a drug in the body will depend on both the volume of distribution and the clearance.

Extrapolating the values from the plasma concentration vs time:

Plasma concentration at 0 hours = 800 mcg/mL
Plasma concentration at 2 hours = 400 mcg/mL
Plasma concentration at 4 hours = 200 mcg/mL
Plasma concentration at 6 hours = 100 mcg/mL
Plasma concentration at 8 hours = 50 mcg/mL
Plasma concentration at 10 hours = 25 mcg/mL
Plasma concentration at 12 hours = 12.5 mcg/mL
Plasma concentration at 14 hours = 6.25 mcg/mL

Cell membrane pore formation, Bacterial DNA damage, Peptidoglycan cross-linking inhibition, and peptidoglycan synthesis inhibitor are always lethal and such mechanisms are possible only in bactericidal drugs. But Protein synthesis inhibition would only prevent cell replication or cell growth and is responsible for bacteriostatic effects of the drug.

Interleukin-4 is a cytokine which acts to regulate the responses of B and T cells.

Erythropoietin is responsible for the signal that initiated red blood cell production.

Granulocyte-colony stimulating factor stimulates the bone marrow to produce granulocytes.

Interleukin-5 is a cytokine that stimulates the proliferation and activation of eosinophils.

Thrombopoietin is the primary signal responsible for megakaryocyte and thus platelet production.
Platelets are also called thrombocytes. They, like red blood cells, are also derived from myeloid stem cells. The process involves a megakaryocyte developing from a common myeloid progenitor cell. A megakaryocyte is a large cell with a multilobulated nucleus, this grows to become massive where it will then break up to form platelets.

Immune cells are generated from haematopoietic stem cells in bone marrow. They generate two main types of progenitors, myeloid and lymphoid progenitor cells, from which all immune cells are derived.

Arrhythmias and/or hypotension are the most common causes of death from tricyclic antidepressant (TCA) overdose.

The quinidine-like actions of tricyclic antidepressants on cardiac tissues are primarily responsible for their toxicity. Conduction through the His-Purkinje system and the myocardium slows as phase 0 depolarisation of the action potential slows. QRS prolongation and atrioventricular block are caused by slowed impulse conduction, which also contributes to ventricular arrhythmias and hypotension.

Arrhythmias can also be caused by abnormal repolarization, impaired automaticity, cholinergic blockade, and inhibition of neuronal catecholamine uptake, among other things.

Acidaemia, hypotension, and hyperthermia can all exacerbate toxicity.

The anticholinergic effects of tricyclic antidepressants, as well as the blockade of neuronal catecholamine reuptake, cause sinus tachycardia. Sinus tachycardia is usually well tolerated and does not require treatment. It can be difficult to tell the difference between sinus tachycardia and ventricular tachycardia with QRS prolongation.

A QRS duration of more than 100 milliseconds indicates a higher risk of arrhythmia and should be treated with systemic sodium bicarbonate.

The tricyclic is dissociated from myocardial sodium channels by serum alkalinization, and the extracellular sodium load improves sodium channel function.

Work up bias involves comparing the novel diagnostic test with the current standard test. A portion of the patients undergo the standard test while others undergo the new test as the standard test is costly. The result can be alteration in specify and sensitivity.

Recall bias is specifically appropriate to the case control studies that is when ever the memories retrieved by the participants differ in accuracy.

Not publishing the results of a valid study just because they are negative or uninteresting can be termed as publication bias.

When information gathering is ill suited with respect to time i.e. collecting the data regarding a fatal disease many years after the death of its patients, it is termed as Late – look bias.

The case in point is an instance of lead time bias when upon comparing two tests, one is able to detect the condition earlier than the other but the overall outcome doesn’t change. There is a possibility that this will make the survival rates for the newer test look more promising.

The patient is rebreathing carbon dioxide that has been exhaled.

Exhaustion of the soda lime and failure of the expiratory valve are the two most likely causes. A leak in the inspiratory limb is a less likely cause. Increased inhaled and exhaled carbon dioxide levels may appear with a normal-looking capnogram if the expiratory valve is ineffective.

The patient will exhale into both the inspiratory and expiratory limbs if the inspiratory valve is inoperable. A slanted downstroke inspiratory phase (as the patient inhales carbon dioxide-containing gas from the inspiratory limb) and increased end-tidal carbon dioxide can be seen on the capnogram.

Even if the soda lime were exhausted, a high fresh gas flow would be enough to prevent rebreathing. The difference in oxygen concentrations in inspired and expired breaths would be less pronounced.

Hypercapnia is caused by respiratory obstruction and malignant hyperthermia, but not by rebreathing.

Adenosine receptors are expressed on the surface of most cells.
Four subtypes are known to exist which are A1, A2A, A2B and A3.

Of these, the A1 and A2 receptors are present peripherally and centrally. There are agonists at the A1 receptors which are antinociceptive, which reduce the sensitivity to a painful stimuli for the individual. There are also agonists at the A2 receptors which are algogenic and activation of these results in pain.

The role of adenosine and other A1 receptor agonists is currently under investigation for use in acute and chronic pain states.

Major surgery induces the systemic inflammatory response and this causes endothelial leakage and a low albumin level.

Albumin is a single polypeptide which is made but not stored in the liver. Therefore, levels are a reflection of synthetic activity. It is negatively charged and very soluble.

Only 40% of albumin is intravascular, and the rest in the in interstitial compartment.

If there was normal liver function during starvation, albumin will be maintained and proteolysis will occur elsewhere.
It is not catabolised during starvation.
Starvation and malnutrition may, however, present as part of other disease processes that are associated with hypalbuminaemia.

Causes of low albumin are

1. Decreased production (hepatic dysfunction)
2. Increased loss (renal dysfunction)
3. Redistribution (endothelial leak/damage)
4. Increased catabolism (very rare)

The process used in the study is Delphi method. This method kicks off with an open ended questionnaire and uses its responses as a survey instrument for the next round in which each of the participants is asked to rate the items that the investigators have summarized on the basis of the data collected in the first round.

Any disagreement is further discussed in phases to come on the basis of information obtained from previous phases.

The potency of local anaesthetics is directly proportional to lipid solubility because they need to penetrate the lipid-soluble membrane to enter the cell.

Protein binding has a direct relationship with the duration of action because the higher the ability of the drug to bind with membrane protein, the higher is the duration of action.

Higher the pKa of a drug, slower the onset of action. Because a drug with higher pKa will be more ionized than the one with lower pKa at a given pH. Local anaesthetics are weak bases, and unionized form diffuses more rapidly across the nerve membrane than the protonated form. As a result drugs with higher pKa will be more ionized will diffuse less across the nerve membrane.

Lorazepam is an intermediate-acting benzodiazepine that binds to the GABA-A receptor subunit to increase the frequency of chloride channel opening and facilitate membrane hyperpolarization. It is the preferred treatment for status epilepticus, although Diazepam can also be used as an alternative.

Lorazepam has a longer duration of action than Diazepam, and binds with greater affinity to the GABA-A receptor subunit.

Phenobarbital is a barbiturate that acts on the GABA-A receptor site to increase the duration of chloride channel opening. Barbiturates, particularly phenobarbital, is considered the drug of choice for seizures in infants.

Phenytoin is a sodium-channel blocker that is given for generalized tonic-clonic seizures, partial seizures, and status epilepticus. Phenytoin is preferred in prolonged therapy for status epilepticus because it is less sedating.

Propofol or thiopentone is preferred when airway protection is required.

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.

For this patient, his forced expiratory volume in 1 second (FEV1) will decrease at the same rate as a non-smoker.

There is a notable, but slow, decline in FEV1 when an individual reaches the age of 26. An average reduction of 30 mls every year in non-smokers, while a more significant reduction of 50-70 mls is observed in approximately 20% of smokers.

Considering the age of the patient, individuals who begin smoking cessation by the age of 60 are far less likely to achieve normal FEV1 levels, even in the next five years. It is expected that their FEV1 will be approximately 14% less than their peers of the same age.

When using dry soda lime for VOCs, very high amounts of carbon monoxide may be produced, regardless of the inhalational anaesthetic agent used. The carbon monoxide produced is sufficient enough to cause cytotoxic and anaemic hypoxia. To prevent this, soda lime canisters are shaken well to even out the packing of granules. This can help to evenly distribute gas flow for proper CO2 absorption and ventilation.

Compound A is formed when dry soda lime, or soda lime in high temperature, reacts with the inhalational anaesthetic Sevoflurane. Animal studies have shown renal toxicity in rats, but renal adverse effects in humans are yet to be observed.

When monitors are not employed with VOCs, deleterious effects are not for certain. However, monitors not employed with vaporiser inside the circuit (VIC) can lead to significant adverse events.

Such a high rise of end-tidal CO2 (EtCO2) in a patient who is spontaneously breathing is often encountered.

Close observation should occur for further rises in EtCO2 and other signs of malignant hyperthermia. If this were to rise even more, it might be wise to ensure that ventilatory support is available.

A lot would depend on whether surgery was almost completed. At this stage of anaesthesia, it would be inappropriate to administer opioid antagonists or respiratory stimulants.

Atrial natriuretic peptide (ANP) is secreted mainly from myocytes of right atrium and ventricle in response to increased blood volume.
It is secreted by both the right and left atria (right >> left).

It is a 28 amino acid peptide hormone, which acts via cGMP
degraded by endopeptidases.

It serves to promote the excretion of sodium, lowers blood pressure, and antagonise the actions of angiotensin II and aldosterone.

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

Alfentanil is less lipid-soluble than fentanyl and thus is less permeable to the membrane making it less potent.

Alfentanil is a phenylpiperidine opioid analgesic with rapid onset and shorter duration of action.

Alfentanil has less volume of distribution due to its high plasma protein binding (92%)

It can cause respiratory depression and can cause sedation