Ketamine is the substance in question. Its structure and pharmacodynamic effects make it a one-of-a-kind intravenous induction agent. The molecule is made up of two cyclohexanone rings (2-(O-chlorophenyl)-2-methylamino cyclohexanone and 2-(O-chlorophenyl)-2-methylamino cyclohexanone). Ketamine has local anaesthetic properties and acts primarily on the brain and spinal cord.

It affects Ca2+ channels as a non-competitive antagonist for the N-D-methyl-aspartate (NMDA) receptor. It also acts as a local anaesthetic by interfering with neuronal Na+ channels.

Ketamine causes profound dissociative anaesthesia (profound amnesia and analgesia) as well as sedation.

Phenoxybenzamine, an alpha-1 adrenoreceptor antagonist, is an example of an irreversible competitive antagonist. It forms a covalent bond with the calcium influx receptor.

Benzodiazepines are GABAA receptor agonists that affect chloride influx.

Flumazenil is an inverse agonist that affects GABAA receptor chloride influx.

Ketamine is a cyclohexanone derivative that acts as a non-competitive Ca2+ channel antagonist.

All of the muscles of the larynx are innervated by the recurrent laryngeal nerve, except the cricothyroid muscle.

Cricothyroid muscle is located deep in the anterior neck, between the cricoid and thyroid cartilage and is innervated by the external laryngeal nerve. Any injury to this muscle can cause paralysis and lead to hoarseness. When cricothyroid muscle contracts, it leads to tightening, stretching and thinning of the vocal folds. This produces higher-pitched sounds during vocalization.

A patient experiencing hoarseness due to possible injury to the external laryngeal nerve should be reassured that the hoarseness will resolve in time due to increased compensation from the other muscles.

Gas is composed of large numbers of molecules moving in random directions, separated by distances. They undergo perfectly elastic collisions with each other and the walls of a container and transfer kinetic energy in form of heat. These assumptions bring the characteristics of gases within the range and reasonable approximation to a real gas, particularly how any change in temperature and pressure affect the behaviour of gas. According to different theories and laws proposed, mathematical equations are derived to calculate the volume of gas, also different abbreviations are being used according to given conditions. The abbreviations used are ATP, BTPS, and STPD.
ATP stands for ambient temperature and barometric pressure, it is used to describe the conditions under which volume of gas is measured.
BTPS stands for body temperature and pressure saturated with water vapor. These are conditions under which volume of gas exist and all results of lung volume determination should be quoted at BTPS.
STPD stands for standard temperature and pressure, dry (0C and 760 mm Hg). These are the conditions that are used to describe quantities of individual gases exchanged in the lungs.

The common peroneal (fibular) nerve descends obliquely along the lateral side of the popliteal fossa to the fibular head, medial to biceps femoris.

The sural nerve exits at the fossa’s lower inferolateral aspect and is more at risk in short saphenous vein surgery.

The tibial nerve lies more medially and is even less likely to be injured in this location.

The boundaries of the popliteal fossa are:
Superolateral – the biceps femoris tendon
Superomedial – semimembranosus reinforced by semitendinosus
Inferomedial and inferolateral – medial and lateral heads of gastrocnemius

The contents of the Popliteal fossa are:

1. The popliteal artery
2. The popliteal vein
3. The Tibial nerve and common Fibular nerve
4. Posterior femoral cutaneous nerve: descends and pierces the roof
5. Small saphenous vein
6. popliteal lymph nodes
7. fat

Ketamine is primarily used for the induction and maintenance of anaesthesia. It induces dissociative anaesthesia. But it is contraindicated in cardiovascular diseases such as unstable angina or poorly controlled hypertension.

Tricyclic antidepressants (TCA) are primarily used as antidepressants which is important for the management of depression. These are second-line drugs next to SSRI. They work by competitively preventing re-uptake of amines (noradrenaline and serotonin) from the synaptic cleft so increasing their concentration. But TCA overdoses are toxic and have cardiovascular effects, central effects, and anticholinergics effects. Cardiovascular effects like prolonged QT and widened QRS at lower doses progressing to ventricular arrhythmias and refractory hypotension at higher doses can be life-threatening. When used in the perioperative period, it can lead to increased sensitivity to circulating catecholamines therefore care is needed perioperatively.

The level of statistical significance required influences the sample size used. This is because sample size is used in the calculation of SD/SE.

Sample size does not affect

The level of acceptance
The alternative hypothesis with a general level set at p<0.05
The test to be used.

Experience of the investigator and the type of patient recruited should have no bearing on the required sample size.

Creatinine clearance is a test used to approximate the glomerular filtration rate (GFR) as an assessment of kidney function.

Creatinine is formed during the breakdown of dietary sources of meat and skeletal muscle. It is secreted at a consistent concentration and pace into the body’s circulation, and is easily filtered across the glomerulus without being reabsorbed or metabolized by the kidney.

It is represented mathematically as:
Creatinine clearance (CL) = U x V/P
where,
U: Urinary creatinine concentration (mg/mL)
V: Volume of urine (mL/min)
P: Plasma creatinine concentration (mg/mL)

Therefore, in this case:
CL: 1.25 x 1 = 125mL/min
0.1

Loop diuretics act by causing inhibition of Na+ K+ 2Cl– symporter present at the luminal membrane of the ascending limb of the loop of Henle.

Furosemide, torsemide, bumetanide, ethacrynic acid, furosemide, piretanide, tripamide, and mersalyl are the important members of this group

The main use of loop diuretics is to remove the oedema fluid in renal, hepatic, or cardiac diseases. Thus they are useful in the treatment of acute heart failure. These can be administered i.v. for prompt relief of acute pulmonary oedema (due to vasodilatory action).

Hypokalaemia, hypomagnesemia, hyponatremia, alkalosis, hyperglycaemia, hyperuricemia, and dyslipidaemia are seen with both thiazides as well as loop diuretics

Cough is an important defensive reflex that helps clear secretions and particulates from the airways. A complex reflex arc generates each cough.

The cough reflex begins with irritation of the cough receptors present in the epithelium of the trachea, main carina, branching points of large airways, and more distal smaller airways. These receptors are responsive to both mechanical and chemical stimuli.

Afferent pathway:
Impulses from stimulated receptors are transmitted via sensory nerve fibres of the vagus nerve (mainly) and glossopharyngeal nerve and travel to the medulla diffusely. CN 5 is also thought to contribute to the afferent limb. However, the vagus is the main nerve.

Central pathway:
The cough centre is located in the upper brain stem and pons

Efferent pathway:
Impulses from the centre travel via the vagus, phrenic nerve, and spinal motor nerves to the diaphragm, abdominal wall, and muscles.

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

Only 1 percent of the calcium in the human body is found in the plasma where it performs the most critical functions.

Out of this 1 percent, approximately 15% is complexed calcium bound to organic and inorganic anions, 40% is bound to albumin, and the remaining 45% circulates as free ionized calcium.

The Chvostek sign is a clinical finding associated with hypocalcaemia, or low levels of calcium in the blood. This clinical sign refers to a twitch of the facial muscles that occurs when gently tapping an individual’s cheek, in front of the ear.

Prolonged QT interval are associated with hypocalcaemia as reported in multiple studies.

The metabolism of drugs in the liver occurs in 3 phases

Phase I: This involves functionalization reactions, which are of 3 types, namely hydrolysis, oxidation and reduction reactions catalysed by the cytochrome P450 (CYP) enzymes.

Phase II: This involves conjugation or acetylation reactions. The goal is to create water soluble metabolites that can be excreted from the body.

The liver is the second largest organ. It’s smallest functional unit is the acinus which is divided into 3 zones:

Zone I (periportal): This zone receives the largest amount of oxygen supply as it is the closest to the blood vessels. It is the site of plasma protein synthesis.

Zone II (mediolobular): This is located between the portal triad and central vein.

Zone III (centrilobular): This is closest to the central vein and receives the least amount of oxygen supply.

Kupffer cells are specialized macrophages found in the periportal zone of the liver, and function to remove foreign particles and breakdown red blood cells via phagocytosis.

Ito cells are fat-storing liver cells found in the space of Disse. Their function is to take-uo, store and secrete retinoids, as well as manufacture and release proteins that make up the extracellular matrix.

Case control studies in particular are prone to recall bias, people who are suffering from COPD might sometimes relate the ailment to marijuana usage in past and hence contrary to the control group, they are more able to describe to what extent they have been using the drug in the past.

As recommended, all the doctors should make sure that there practice is based on evidence and thus it is paramount that the doctors learn to appraise the paper in a critical manner i.e. ability to detect any potential source of bias.

Detection Bias: Outcomes are more looked for in one group than the other.

Observer Bias: Subjectivity of observers regarding the outcome.

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

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

Response Bias: The participants that filled out the response forms containing information that was going to be used for a trial, don’t represent the target population.

Paediatric life support differs from adult life support in that hypoxia is the primary cause of deterioration.

After checking for danger, the child should be given a gentle stimulus (such as holding the head and shaking the arm) and asked, Are you alright? according to current advanced paediatric life support (APLS) guidelines. Safety, Stimulate, Shout is a phrase that is frequently remembered. Any airway assessment should be preceded by these actions.

Although the algorithm includes five rescue breaths, they are performed after the airway assessment.

It is not recommended to ask parents to leave unless they are obstructing the resuscitation. A team member should be with them at all times to explain what is going on and answer any questions they may have.

CPR should not begin until the child has been properly assessed and rescue breaths have been administered.

The principal innervation of the small muscles of the hand is T1.

Cardiac output = stroke volume x heart rate

Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) x 100%

Stroke volume = end diastolic LV volume – end systolic LV volume

Pulse pressure = Systolic Pressure – Diastolic Pressure

Systemic vascular resistance = mean arterial pressure / cardiac output
Factors that increase pulse pressure include:
-a less compliant aorta (this tends to occur with advancing age)
-increased stroke volume

The inguinal triangle of Hesselbach’s is an important clinical landmark on the posterior wall of the inguinal canal. It has the following relations:
Inferiorly – medial third of the inguinal ligament
Medially – lower lateral border of the rectus abdominis
Laterally – inferior epigastric vessels

Direct inguinal hernia is when the bowel bulges directly through the abdominal wall. These hernias usually protrude through Hesselbach’s triangle

Tetracyclines inhibit protein synthesis through reversible binding to bacterial 30s ribosomal subunits (not 50s) which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

They penetrate macrophages and are thus a drug of choice for treating infections due to intracellular organisms.

Tetracycline does not inhibit transpeptidation. Meanwhile, it is chloramphenicol which is responsible for inhibiting transpeptidation.

Tetracycline can get deposited in growing bone and teeth due to its calcium-binding effect and thus causes dental discoloration and dental hypoplasia. Due to this reason, they should be avoided in pregnant or lactating mothers.

Simultaneous administration of aluminium hydroxide can impede the absorption of tetracyclines.

When there is a fall in ionised plasma calcium levels, the chief cells of the parathyroid glands are stimulated to secrete parathyroid hormone (PTH).

50% of extracellular calcium occurs as non-ionised, protein- (albumin-)bound calcium.

The degree of ionisation increases with low ph and decreases with high pH.

There is increased renal calcium excretion with secretion of calcitonin.

It is well known that atropine will cross the placenta and that maternal administration results in an increase in fetal heart rate.

Atropine is highly selective for muscarinic receptors. Its potency at nicotinic receptors is much lower, and actions at non-muscarinic receptors are generally undetectable clinically. Atropine does not distinguish among the M1, M2, and M3 subgroups of muscarinic receptors. In contrast, other antimuscarinic drugs are moderately selective for one or another of these subgroups. Most synthetic antimuscarinic drugs are considerably less selective than atropine in interactions with nonmuscarinic receptors.

A study on glycopyrrolate, a quaternary ammonium salt, was found to have a fetal: maternal serum concentration ratio of 0.4 indicating partial transfer.

Heparin, suxamethonium, and vecuronium do not cross the placenta.

Bilirubin is formed by metabolizing heme, mostly from haemoglobin in red blood cells.

Bilirubin is conjugated to glucuronic acid in the hepatocytes by the glucuronyl transferase enzyme in order to enable it to become soluble and allow for its secretion across the canalicular membrane and into bile.

The conjugation process is increased by rifampicin and decreased by valproate.

Gilbert’s syndrome is caused by a decrease in glucuronyl transferase in the hepatic system, decreasing the transport of bilirubin into the hepatocyte, causing unconjugated bilirubinaemia.

Crigler-Najjer syndrome is caused by mutations in the genes responsible for hepatic glucuronyl transferase, decreasing the activity of the enzyme, meaning bilirubin cannot be conjugated, causing unconjugated bilirubinaemia.

Dubin-Johnson syndrome does not cause an impairment in the conjugation of bilirubin, but it blocks the transport of bilirubin out of the hepatocyte resulting in conjugated bilirubinaemia.

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%

Adenosine is the first line for AV nodal re-entry tachycardia. An initial dose of 6 mg is given, and a consequent second dose or third dose of 12 mg is administered if the initial dose fails to terminate the arrhythmia.

Aside from Adenosine, a vagal manoeuvre (e.g. carotid massage) is done to help terminate the supraventricular arrhythmia.

Amiodarone is not a first-line drug for supraventricular tachycardias. Digoxin and Propranolol can be considered if the arrhythmia is of a narrow complex irregular type. Verapamil is an alternative to Adenosine if the latter is contraindicated.

The Nernst equation is used to calculate the membrane potential at which the ions are in equilibrium across the cell membrane.

The normal resting membrane potential is -70 mV (not + 70 mV).

The equation is:
E = RT/FZ ln {[X]o
/[X]i}

Where:
E is the equilibrium potential
R is the universal gas constant
T is the absolute temperature
F is the Faraday constant
Z is the valency of the ion
[X]o is the extracellular concentration of ion X
[X]i is the intracellular concentration of ion X.

ACTH production is stimulated through the secretion of corticotropin-releasing hormone (CRH) from the hypothalamic nuclei.

ACTH secretion has a circadian rhythm. A high level of cortisol in the body stops its production. ACTH is secreted maximally in the morning and concentrations are lowest at midnight.

ACTH can be expressed in the placenta, the pituitary and other tissues.

Conditions where ACTH concentrations rise include: stress, disease and pregnancy.

Glucocorticoids (not mineralocorticoids – aldosterone) switch off ACTH production through a negative feedback loop .

Magnesium is a unique calcium antagonist as it can act on most types of calcium channels in vascular smooth muscle and as such would be expected to decrease intracellular calcium. One major effect of decreased intracellular calcium would be inactivation of calmodulin-dependent myosin light chain kinase activity and decreased contraction, causing arterial relaxation that may subsequently lower peripheral and cerebral vascular resistance, relieve vasospasm, and decrease arterial blood pressure.

The vasodilatory effect of MgSO4 has been investigated in a wide variety of vessels. For example, both in vivo and in vitro animal studies have shown that it is a vasodilator of large conduit arteries such as the aorta, as well as smaller resistance vessels including mesenteric, skeletal muscle, uterine, and cerebral arteries.

The theory of cerebrovascular vasospasm as the aetiology of eclampsia seemed to be reinforced by transcranial Doppler (TCD) studies which suggested that MgSO4 treatment caused dilation in the cerebral circulation as well as in animal studies that used large cerebral arteries.

Phase IIa studies are usually pilot studies designed to demonstrate clinical efficacy or biological activity (‘proof of concept’ studies) whereas phase IIb studies determine the optimal dose at which the drug shows biological activity with minimal side-effects (definite dose-finding studies).

Phase III and Phase IV studies are performed on larger set of participants (usually hundreds to thousands) when safety and efficacy have been established.

CBF is defined as the blood volume that flows per unit mass per unit time in brain tissue and is typically expressed in units of ml blood/100 g tissue/minute. The normal average CBF in adults human is about 50 ml/100 g/min, with lower values in the white matter (,20 ml/100 g/min) and greater values in the gray matter (,80 ml/100 g/min).

Low CBF levels between 30-40 ml/100 g/min may begin to show poor prognostic EEG. EEG findings consistently associated with a poor outcome are isoelectric EEG, low voltage EEG, and burst suppression (specifically burst suppression with identical bursts), as well as the absence of EEG reactivity.

The arteries of the midgut (superior mesenteric artery) and hindgut (inferior mesenteric artery) give off terminal branches that form an anastomotic vessel called the marginal artery of Drummond. It runs in the inner margins of the colon and gives off short terminal branches to the bowel wall.

The marginal artery is formed by the main branches and arcades arising from the ileocolic, right colic, middle colic, and left colic arteries. It is most apparent in the ascending, transverse, and descending colons and poorly developed in the sigmoid colon.