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.

Soda-lime contains mostly calcium hydroxide (about 94%) and remaining sodium hydroxide.

CO2 + Ca(OH)2 → CaCO3 + H2O + heat
Here in this exothermic reaction, we can see that the production of calcium carbonate does not require heat.

When soda lime is allowed to dry with subsequent use of desflurane, isoflurane, and enflurane, it can lead to the generation of carbon monoxide.

Silica hardens the granules and can thus prevent disintegration.

The size of soda-lime granules is 4-8 mesh because it allows sufficient surface area for chemical reaction to occur without critically increasing the resistance to airflow.

Because of the low pH in the stomach, paracetamol absorption is minimal (pKa value is 9.5). Paracetamol is absorbed quickly and completely in the alkaline environment of the small intestine. Oral bioavailability is approaching 100%. As a result, measuring paracetamol levels in plasma after an oral paracetamol dose has been used as a surrogate marker of gastric emptying. This method has been used to investigate the effects of drugs on gastric emptying. At clinically used doses, paracetamol is ideal because it has very few side effects.

Scintigraphic imaging is the gold standard for determining gastric emptying.

Although aspirin (acetyl salicylic acid) is absorbed primarily in the small intestine, some may also be absorbed in the stomach. The oral bioavailability ranges from 70 to 100 percent, making it less reliable than paracetamol.

Propranolol is a lipophilic drug that is rapidly absorbed after administration. However, it is highly metabolised by the liver in the first pass, and only about 25% of propranolol reaches the systemic circulation. It’s not the best indicator of gastric emptying.

Oral bioavailability of gentamicin and vancomycin is low. Only antibiotic-induced pseudomembranous colitis is treated with oral vancomycin.

Erythromycin is a pro-kinetic agent that acts as a motilin receptor agonist.

The Wolff-Parkinson-White syndrome (WPWS) is linked to an additional electrical conduction pathway between the atria and ventricles. This accessory pathway (bundle of Kent), unlike the atrioventricular (AV) node, is incapable of slowing down a rapid rate of atrial depolarization. In other words, a short circuit bypasses the AV node. Patients with a rapid ventricular response or narrow complex AV re-entry tachycardia are more likely to develop atrial fibrillation or flutter.

Digoxin can promote impulse transmission through this accessory pathway if a patient with WPWS develops atrial fibrillation because it works by blocking the AV node. This can cause ventricular fibrillation and an extremely rapid ventricular rate. As a result, it’s not advised.

Adenosine, beta-blockers, and calcium channel blockers, among other drugs that interfere with AV nodal conduction, are also generally contraindicated.

The class III antiarrhythmic drugs amiodarone and ibutilide (K+ channel block) and procainamide (Na+ channel block) are the drugs of choice.

Giardiasis is known to have a longer incubation time and doesn’t cause bloody diarrhoea.

Cholera usually doesn’t cause bloody diarrhoea.

Generally, most of the E.coli strains do not cause bloody diarrhoea.

Diverticulitis can be a cause of bloody stool but the history here points out to an infectious cause.

Campylobacter infection is the most probable cause as it is characterized by a prodrome, abdominal pain and bloody diarrhoea

Increasing temperature increases the amount of water vapour contained in air; for example, at 20°C, air contains about 17 g/m3, and at 37°C, air contains about 44 g/m3. The wet and dry bulb hygrometer, like the hair hygrometer, measures relative humidity.

Under normal operating conditions, Heat and moisture exchangers (HMEs) allows relative humidity of up to 70% to be achieved. Mucus can impair their performance, and they should not be used for longer than 24 hours.

Hot water bath humidifiers might cause scalding, condensed water in the tubing can interfere with gas flow, and there is a danger of infection.

The ultrasonic humidifier operates at roughly 2 MHz and may attain relative humidity levels much above 100%.

The internal carotid artery passes through the carotid canal in the petrous part of the temporal bone into the cranial cavity. It does NOT groove the sphenoid bone.

The internal carotid artery gives off no branches in the neck and is a terminal branch of the common carotid artery.

These structures pass between the external and internal carotid arteries: the styloglossus and stylopharyngeus muscles, the glossopharyngeal nerve (CN IX), and the pharyngeal branch of the vagus.

Accompanied by its sympathetic plexus, the internal carotid artery, passes through the cavernous sinus and is crossed by the abducent nerve.

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.

The most likely diagnosis is a spinal epidural haematoma, a neurological emergency. A full examination must be carried out to determine the nature of the neurological problem before conducting any investigations or imaging.

The effects of spinal anaesthesia should have worn off by this time point, and the severe back pain is a red flag.

The patient will also require an urgent neurological team referral as a spinal epidural haematoma requires immediate evacuation for spinal decompression. Analgesics may be prescribed for pain management.

Heparin would have been fully metabolised and so a reversal is unnecessary.

A spinal epidural haematoma is a pooling of blood in the epidural space, which can cause compression of the spinal cord. Its presenting symptoms are:

Usually begins with severe backpain and percussion tenderness
Cauda equina syndrome
Paralysis of the lower extremities.
If infected, a fever occurs in 66% of cases
Lower limb weakness developing after stopping an epidural infusion or weakness of the lower limbs which does not resolve within four hours of cessation of infusion of epidural local anaesthetic
Meningism.

The apex of an equilateral triangle completed by the posterior superior iliac spines is where the sacral hiatus or sacrococcygeal membrane can normally located. The failure of posterior fusion of the laminae of the fourth and fifth sacral vertebrae allows the sacral canal to be accessible via the membrane.

In adults, the spine of L4 usually lies on a line drawn between the highest points of the iliac crests (Tuffier’s line). A line connecting each anterior iliac spine, approximates to the L3/4 interspace in the sitting position. Both of these options are incorrect.

A line connecting the greater trochanters is also incorrect.

A line connecting the posterior superior iliac spines is correct, but in adults the presence of a sacral fat pad can still make identification of this landmark less straightforward.

The processes of S5 are remnants only and form the sacral cornua, which are also used to help identify the sacral hiatus.

When the eye is compressed or the extra-ocular muscles are tractioned, the oculocardiac reflex causes a decrease in heart rate.

The ophthalmic division of the trigeminal nerve provides the afferent limb. This synapses with the vagus nerve’s visceral motor nucleus in the brainstem. The efferent signal is carried by the vagus nerve to the heart, where increased parasympathetic tone reduces sinoatrial node output and slows heart rate.

The most common symptom is sinus bradycardia, but junctional rhythm and asystole can also occur.

Since an arterial pressure transducer, and every other measuring apparatus, is prone to errors due to offset and gradient drifts, regular calibration is required to maintain accuracy of the instrument. The two-point calibration pressure values of 0 mmHg and 200 mmHg are within the physiologic range and can best compensate for the gradient drift.

The abdominal aorta begins at the level of the body of T12 near the midline, as a continuation of the thoracic aorta. It descends and bifurcates at the level of L4 into the common iliac arteries.

The branches of the abdominal aorta (with their vertebra level) are:
1. Inferior phrenic arteries: T12 (upper border)
2. Coeliac artery: T12
3. Superior mesenteric artery: L1
4. Middle suprarenal arteries: L1
5. Renal arteries: Between L1 and L2
6. Gonadal arteries: L2 (in males, it is the testicular artery, and in females, the ovarian artery)
7. Inferior mesenteric artery: L3
8. Median sacral artery: L4
9. Lumbar arteries: Between L1 and L4

The superior phrenic artery branches from the thoracic aorta.

To denote large measured units, the following SI mathematical prefixes are used:

1 deca = 10 bytes (101)
1 hecto (h) = 100 bytes
1 kilo (k)= 1,000 bytes
1 mega (M) = 1,000,000 bytes
1 giga (G) = 1,000,000,000 bytes
1 Tera (T) = 1,000,000,000,000 bytes
1 Peta (P) = 1,000,000,000,000,000 bytes

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.

The left gastric artery is the smallest branch that originates from the coeliac trunk—the coeliac trunk branches of the abdominal aorta at the vertebral level of T12.

The left gastric artery runs along the superior portion of the lesser curvature of the stomach. A peptic ulcer that is serious enough to erode through the stomach mucosa into a branch of the left gastric artery can cause massive blood loss in the stomach, leading to hematemesis. The patient also takes Naproxen, a non-steroidal anti-inflammatory drug that is a common cause for peptic ulcers in otherwise healthy patients.

The left gastric artery is responsible for 85% of upper GI bleeds. In cases refractory to initial treatment, angiography is sometimes needed to embolise the vessel at its origin and stop bleeding. During an angiogram, the radiologist will enter the aorta via the femoral artery, ascend to the level of the 12th vertebrae and then enter the left gastric artery via the coeliac trunk.

The important landmarks of vessels arising from the abdominal aorta at different levels of vertebrae are:

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

The abdominal arteries are divided into 3 branches;
– 3 main unpaired trunks (celiac trunk, superior mesenteric, inferior mesenteric arteries)
– 6 paired branches
– unpaired median sacral artery.

We can group the abdominal aorta as follows;
-Ventral which includes: Coeliac trunk, superior mesenteric and inferior mesenteric arteries
-Lateral: Inferior phrenic, middle suprarenal, renal and gonadal arteries
-Dorsal: Lumbar and median sacral arteries
-Terminal : Right and left common iliac arteries

The celiac trunk (L1) takes blood the foregut and its found posterior to the stomach. The unpaired superior mesenteric artery supplies blood to the mid-gut.

The paired renal arteries form the inferior suprarenal arteries. The renal arteries arise around L1/L2 and takes blood to either side of the kidneys.

The median sacral artery supplies blood to the lumbar vertebrae the L4 and L5.

The diaphragm has three opening through which different structures pass from the thoracic cavity to the abdominal cavity:

Inferior vena cava passes at the level of T8.

Oesophagus, oesophageal vessels and vagi at T10.

Aorta, thoracic duct and azygous vein through T12.

Sympathetic trunk and pulmonary branches of vagus nerve form a posterior pulmonary plexus at the root of the lung. Fibres continue posteriorly from superficial cardiac plexus to form Anterior pulmonary plexus. It contains vagi nerves and superficial cardiac plexus. These fibres then follow the blood vessel and bronchi into the lungs.

The lower border of the pleura is at the level of:

8th rib in the midclavicular line

10th rib in the lower level of midaxillary line

T12 at its termination.

Both lungs have oblique fissure while right lung has transverse fissure too.

The trachea expands from the lower edge of the cricoid cartilage (at the level of the 6th cervical vertebra) to the carina.

Drug interactions can be seen in the following examples:

Additive interaction (summation).

Additive effects are described for intravenous drug combinations such as ketamine and thiopentone or ketamine and midazolam. Different mechanisms of action are used by them. Thiopentone and midazolam are GABAA receptor agonists, whereas ketamine is an NMDA receptor antagonist. Nitrous oxide and halothane are two other examples.

Synergism is a supra-additive interaction.

Refers to the administration of two drugs with similar pharmacological properties and closely related sites of action, resulting in a combined effect that is greater than the sum of the contributions of each component. The construction of an isobologram can be used to interpret and understand these. The best example is the hypnotic effect of benzodiazepines and intravenous induction agents like propofol. As part of a co-induction technique, midazolam is frequently given before propofol.

Potentiation

In a dose-dependent manner, volatile agents enhance the effects of neuromuscular blocking agents. Electrolyte disturbance (hypomagnesaemia), Penicillin, and probenecid can all increase the effects of neuromuscular blocking agents (the latter has no similar pharmacological activity).

Infra-additive interaction (antagonism).

This can be subdivided into the following categories:

-Pharmacokinetic interference occurs when one drug affects the absorption of another through the gastrointestinal tract or when hepatic microsomal enzyme induction influences metabolism.
-Heparin and protamine, for example, or heavy metals and chelating agents, are examples of chemical antagonists.
-Competitive reversible antagonistic antagonism of receptors, such as opioids and naloxone, and irreversible antagonistic antagonism of receptors

It’s a minute volume divider – True
The Manley MP3 ventilator is classed as a minute volume divider. The entire fresh gas flow or minute volume is delivered to the patient, having been divided into readily set tidal volumes.

Can efficiently ventilate patients with poor pulmonary compliance – False
Ventilating patients with poor pulmonary compliance is not easily achieved, which makes it an unsuitable ventilator for a modern ICU.

Can generate tidal volume up to 1500ml – False
It can generate tidal volumes up to 1000 ml (not 1500 ml), and the inflation pressure can be adjusted by sliding a weight along a rail.

Functions like a Mapleson A system during spontaneous ventilation – False
The ventilator functions like a Mapleson D breathing system (not Mapleson A) during spontaneous ventilation.

Has three sets of bellows – False
The fresh gas flow drives the ventilator which allows rapid detection of gas supply failure. It has two sets of bellows (not three) and three unidirectional valves.

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.

Opioid receptors are a large family of seven transmembrane domain receptors. They are of four types:

1) Delta opioid receptor

2) Mu opioid receptor

3) Kappa opioid receptor

4) Orphan receptor-like 1

They contain about 372-400 amino acids and thus their molecular weight is different.

Opioid receptor activation reduces the intracellular cAMP formation and opens K+ channels (mainly through µ and δ receptors) or suppresses voltage-gated N-type Ca2+ channels (mainly κ receptor). These actions result in neuronal hyperpolarization and reduced availability of intracellular Ca2+ which results in decreased neurotransmitter release by cerebral, spinal, and myenteric neurons (e.g. glutamate from primary nociceptive afferents).

However, other mechanisms and second messengers may also be involved, particularly in the long-term

When a drug is given via intravenous infusion, the plasma concentration rises exponentially as a wash-in curve until it reaches steady-state concentration (the point at which the infusion rate is balanced by the elimination rate or clearance). To reach this steady state, the drug will take 4-5 half-lives.

Cpss (target plasma concentration at steady state) and clearance (CL) in ml/minute or litre/hour are the two factors that determine the infusion rate or dose (ID) in mg/hour of a drug.

ID = Cpss × CL

We know the infusion rate is 20 ml/hour in this case. The drug’s concentration is 5 mg/mL. The patient is receiving 100 mg of the drug per hour, with a 20 L/hour clearance rate.

ID = Cpss × 20

Therefore,

Cpss = 100 mg/20000 ml

Cpss = 0.005 mg/mL or 5 mcg/mL

Warfarin prevents reductive metabolism of the inactive vitamin K epoxide back to its active hydroquinone form. Thus, warfarin inhibits the synthesis of vitamin K dependent clotting factors: X, IX, VII, II (prothrombin), and of the anticoagulants protein C and protein S. The therapeutic range for oral anticoagulant therapy is defined in terms of an international normalized ratio (INR). The INR is the prothrombin time ratio (patient prothrombin time/mean of normal prothrombin time for lab)ISI, where the ISI exponent refers to the International Sensitivity Index and is dependent on the specific reagents and instruments used for the determination. A prolonged INR is widely used as an indication of integrity of the coagulation system in liver disease and other disorders, it has been validated only in patients in steady state on chronic warfarin therapy.

Prothrombin complex concentrate (PCC) is used to replace congenital or acquired vitamin-K deficiency warfarin-induced anticoagulant effect, particularly in the emergent setting.

Intravenous vitamin K has a slower onset of action compared to PCC, but is useful for long term therapy.

Fresh frozen plasma (FFP) prepared from freshly donated blood is the usual source of the vitamin K-dependent factors and is the only source of factor V. The factors needed, however, are found in small quantities compared to PCC.

Cryoprecipitate is indicated for hypofibrinogenemia/dysfibrinogenemia, von Willebrand disease, haemophilia A, factor XIII deficiency, and management of bleeding related to thrombolytic therapy.

The shaft of the humerus has two prominent features:
1. Deltoid tuberosity – attachment for the deltoid muscle
2. Radial or spiral groove – The radial nerve and profunda brachii artery lie in the groove

Mid-shaft fractures of the humerus usually occur after a direct blow to the upper arm, which can occur after a fall or RTAs. The most important clinical significance of a mid-shaft humeral fracture is an injury to the radial nerve. The radial nerve originates from the brachial plexus and has roots of C5-T1. It crosses the spiral groove on the posterior side of the shaft of the humerus.
On examination, the patient may have a wrist drop, loss or weakness of finger extension, and decreased or absent sensation to the posterior forearm, digits 1 to 3, and the radial half of the fourth digit.

The following parts of the humerus are in direct contact with the indicated
nerves:
Surgical neck: axillary nerve.
Radial groove: radial nerve.
Distal end of humerus: median nerve.
Medial epicondyle: ulnar nerve.

The derived unit of energy, work or amount of heat is joule (J). It is defined as the amount of energy expended if a force of one newton (N) is applied through a distance of one metre (N·m)

J = 1 kg·m/s2·m = 1 kg·m2/s2 or 1 kg·m2·s-2

Kinetic energy (KE) = ½ MV2

An object with a mass of 1500 kg moving at 30 m/s correlates to 675 kJ:

KE = ½ (1500) × (30)2 = 750 × 900 = 675 kJ

Total energy released when 1 kg fat is metabolised to CO2 and water is 37 MJ. 1 g fat produces 37 kJ/g, therefore 1 kg fat produces 37,000 × 1000 = 37 MJ.

Raising the temperature of 1 kg water from 0°C to 100°C correlates to 420 kJ. The amount of energy needed to change the temperature of 1 kg of the substance by 1°C is the specific heat capacity. We have 1 kg water therefore:

4,200 J × 100 = 420,000 J = 420 kJ

In order to calculate the energy involved in raising a 100 kg mass to a height of 1 km against gravity, we need to calculate the potential energy (PE) of the mass:

PE = mass × height attained × acceleration due to gravity
PE = 100 kg × 1000 m × 10 m/s2 = 1 MJ

The heat generated when a direct current of 10 amps flows through a heating element for 10 seconds when the potential difference across the element is 1000 volts can be calculated by applying Joule’s law of heating:

Work done (WD) = V (potential difference) × I (current) × t (time)
WD = 10 × 10 × 1000 = 100 kJ

The umbilical vein closes once the umbilical cord is clamped following birth. This causes a rise in systemic vascular resistance, closing the ductus venosus.

Upon birth, the pulmonary vascular resistance is decreased as the lungs are aerated.

At birth, there is a rise in oxygen tension which causes the corresponding constriction of the ductus arteriosus. This prevents a left to right shunt as it stops aortic blood and blood from the pulmonary artery from mixing. The ventricles do no have an opening connecting them.

The foramen ovale closes soon after birth. It is the septum opening between the left and right atrium.

An adult’s cardiac output is expected to be 5 L/min

Gabapentin is an amino acid-like molecules that was originally synthesized as an analogue of GABA but is now known not to act through GABA mechanisms. It is used in the treatment of focal seizures and various nonepilepsy indications, such as neuropathic pain, restless legs syndrome, and anxiety disorders.

Despite its close structural resemblance to GABA, gabapentin does not act through effects on GABA receptors or any other mechanism related to GABA-mediated neurotransmission. Rather gabapentin binds avidly to ?2?, a protein that serves as an auxiliary subunit of voltage-gated calcium channels. Moreover, it binds to NMDA receptor to modulate its transmission.

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.