Rifampicin is a potent inducer of liver cytochrome enzymes. Other enzyme inducers are:
Carbamazepine
Sodium valproate
Phenytoin
Phenobarbitone

The minimal alveolar concentration (MAC) is the concentration of an inhalation anaesthetic agent in the lung alveoli required to stop a response to the surgical stimulus in 50% of the patient.

Following factors don’t affect the MAC of the inhaled anaesthetic agents:

Gender, acidosis, alkalosis, hypothyroidism, hyperthyroidism, body weight, serum potassium level, and the duration of the anaesthesia.

MAC increase in children, elevated temperature, high metabolic rate, sympathetic increase and chronic alcoholism.

MAC decrease in low temperature, low oxygen level, old age, hypotension ( 120mmHg is being used in anesthetic-Hinkman as an additive effect to decrease MAC, however, increase concentration of CO2 activates the sympathetic system resulting the MAC increases.

Risk ratio (relative risk) compares the probability of an event in an exposed (experimental) group to that of an event in the unexposed (control) group.

A relative risk of 1 suggests that there is no discernible difference in the outcome whether or not it has been exposed.

A relative risk of less than 1 indicates that probability of occurrence of an event is less if there is exposure.

A relative risk of greater than 1 highlights that an event is most likely to occur if it was provided exposure. Since you believe that exposure (the new drug) would have side effects, the value should be greater than 1.

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

The data is ideal for chi square test evaluation as it will help determine if observed outcomes are in line with expected outcomes, and also if results are significant or due to chance.

The student’s t test is not ideal as it requires comparison of means from different populations, rather than proportions.

Pearson’s coefficient of linear regression is not ideal as it requires the plotting of a linear regression.

The numbers should be analysed before determining if there are any statistical conclusions that can be drawn from the population.

Statistical analysis is always required to determine the performance of any treatment during a clinical drug trial. Conclusions cannot be drawn simply by looking at the data.

The right atrium receives blood supply from the SVC, IVC, and coronary sinus. It forms the right border of the heart.

The interior of the right atrium has 5 distinct features:
1. Sinus venarum – smooth, thin-walled posterior part of the right atrium where the SVC, IVC, and coronary sinus open
2. Musculi pectinati – an anterior rough, wall of pectinate muscles
3. Tricuspid valve orifice – the opening through which the right atrium empties blood into the right ventricle
4. Crista terminalis – separates the rough (musculi pectinati) from the smooth (sinus venarum) internally
5. Fossa ovalis – a thumbprint size depression in the interatrial septum which is a remnant of the oval foramen and its valve in the foetus

The trabeculae carneae are irregular muscular elevations that form the interior of the right ventricle.

Mixed venous oxygen content (CvO2) is the oxygen concentration in 100mL of mixed venous blood taken from the pulmonary artery. It is usually 12-17 mL/dL (70-75%). It is represented mathematically as:

CvO2 = (1.34 x Hgb x SvO2 x 0.01) + (0.003 x PvO2)

Where,

1.34 = Huffner’s constant
Hgb = Haemoglobin level (g/dL)
SvO2 = % oxyhaemoglobin saturation of mixed venous blood
PvO2 = 0.0225 = mL of O2 dissolved per 100mL plasma per kPa, or 0.003 mL per mmHg

Therefore,

CvO2 = (1.34 x 10 x 70 x 0.01) + (0.003 x 50)

CvO2 = 9.38 + 0.15 = 9.53 mL/100mL.

Compliance of the respiratory system describes the expandability of the lungs and chest wall. There are two types of compliance: dynamic and static.

Dynamic compliance describes the compliance measured during breathing, which involves a combination of lung compliance and airway resistance. Defined as the change in lung volume per unit change in pressure in the presence of flow.

Static compliance describes pulmonary compliance when there is no airflow, like an inspiratory pause. Defined as the change in lung volume per unit change in pressure in the absence of flow.

For example, if a person was to fill the lung with pressure and then not move it, the pressure would eventually decrease; this is the static compliance measurement. Dynamic compliance is measured by dividing the tidal volume, the average volume of air in one breath cycle, by the difference between the pressure of the lungs at full inspiration and full expiration. Static compliance is always a higher value than dynamic

Static compliance can be computed using the formula:

Cstat = Tidal volume/Plateau pressure – PEEP

Substituting the values given,

Cstat = 800/50-10
Cstat = 20 ml/cmH2O

The toxicity of organophosphorus (OP) nerve agents is manifested through irreversible inhibition of acetylcholinesterase (AChE) at the cholinergic synapses, which stops nerve signal transmission, resulting in a cholinergic crisis and eventually death of the poisoned person. Oxime compounds used in nerve agent antidote regimen reactivate nerve agent-inhibited AChE and halt the development of this cholinergic crisis.

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 starling forces operate to maintain a homeostatic flow across the pulmonary capillary bed.

The outward driving force comprises of the capillary hydrostatic pressure (13 mmHg), negative interstitial fluid pressure (zero to slightly negative), and interstitial colloid osmotic pressure (17 mmHg). The inward driving force is controlled by the plasma colloid osmotic pressure (25 mmHg).

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.

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 anterior cerebral artery supplies the midline portion of the frontal lobe and the superior medial parietal lobe of the brain. It also supplies the front four-fifths of the corpus callosum and provides blood to deep structures such as the anterior limb of the internal capsule, part of the caudate nucleus, and the anterior part of the globus pallidus.

The cerebral hemispheres are supplied by arteries that make up the Circle of Willis. The Circle of Willis is formed by the anastomosis of the two internal carotid arteries and two vertebral arteries.

Clinically, the internal carotid arteries and their branches are often referred to as the anterior circulation of the brain. The anterior cerebral arteries are connected by the anterior communicating artery. Near their termination, the internal carotid arteries are joined to the posterior cerebral arteries by the posterior communicating arteries, completing the cerebral arterial circle around the interpeduncular fossa, the deep depression on the inferior surface of the midbrain between the cerebral peduncles.

The middle cerebral artery supplies part of the frontal, temporal and parietal lobes.

The posterior cerebral artery supplies the occipital lobe.

The needle should be inserted just below the skin at the mid inguinal point which is the surface indicator for the femoral artery.

The Delphi technique was developed in the 1950s and is a widely used and accepted method for achieving convergence of opinion concerning real-world knowledge solicited from experts within certain topic areas. Choosing the appropriate subjects is the most important step in the entire process because it directly relates to the quality of the results generated, despite this, there is no exact criterion currently listed in the literature concerning the selection of Delphi participants.

Therefore, due to the potential scarcity of qualified participants and the relatively small number of subjects used in a Delphi study, the ability to achieve and maintain an ideal response rate can either ensure or jeopardize the validity of a Delphi study.

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 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 sacral hiatus is shaped by incomplete midline fusion of the posterior elements of the distal portion of S4 and S5. This inverted U shaped space is covered by the posterior aspect of the sacrococcygeal membrane and is an important landmark in caudal anaesthetic block. Distal most portion of the dural sac and the sacral hiatus usually terminate between levels S1 and S3. The dural sac ends at the level of S2 in adults and S3 in children.

An equilateral triangle is formed between the apex of the sacral hiatus and the posterior superior iliac spines. This triangle is used to determine the location of the sacral hiatus during caudal anaesthetic block.

Decreased platelet concentrations with eclampsia were described as early as 1922 by Stancke. The platelet count is routinely measured in women with any form of gestational hypertension. The frequency and intensity of thrombocytopenia vary and are dependent on the severity and duration of the preeclampsia syndrome and the frequency with which platelet counts are performed.

Overt thrombocytopenia defined by a platelet count < 100,000/microliter - indicates severe disease. In general, the lower the platelet count, the higher the rates of maternal and fetal morbidity and mortality. In most cases, delivery is advisable because thrombocytopenia usually continues to worsen. After delivery, the platelet count may continue to decline for the first day or so. It then usually increases progressively to reach a normal level within 3-5 days. In some instances with HELLP syndrome, the platelet count continues to fall after delivery. If these do not reach a nadir until 48 to 72 hours, then preeclampsia syndrome may be incorrectly attributed to one of the thrombotic microangiopathies. The following are other severe features associated with preeclampsia: Proteinuria: >/= 300 mg/24 hours; or urine protein: creatinine ratio >/= 0.3; or dipstick 1+

Renal insufficiency: serum creatinine > 1.1 mg/dL or doubling of creatinine in the absence of other renal disease

Impaired liver function: two times elevated AST/ALT or unexplained right upper quadrant pain or epigastric pain unresponsive to medications

Pulmonary oedema

Cerebral or visual symptoms: headache, visual disturbances.

The ideal agent for this case should have low blood: gas coefficient, pleasant smell, and high oil: gas coefficient (potent with a low Minimum alveolar coefficient (MAC)). Among the given options, Sevoflurane is perfect with 0.692 blood: gas partition coefficient and is low pungency, and is sweet.

Other drugs with their blood: gas partition coefficient and their smell are given as:
Blood/gas partition coefficient MAC Smell
Enflurane 1.8 1.68 Pungent, ethereal
Desflurane 0.42 7 Pungent, ethereal
Halothane 2.54 0.71 Sweet
Isoflurane 1.4 1.15 Pungent, ethereal

Lesser the potency of the drug, the higher the dose required to produce maximal receptor occupation. So, the least potent drug will have a log dose-response curve furthest to the right on X-axis.

Based on the option given, tramadol is the least potent drug and thus higher dose is required to produce maximal opioid receptor occupation.

Thus, Tramadol is the least potent opioid with a log dose-response curve furthest to the right on X-axis.

Note, Fentanyl is the most potent opioid with a log dose-response curve furthest to the left on the X-axis.

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.

Prerenal failure has a serum urea: creatinine ratio of >100, while acute kidney injury has a ratio of 40.
In prerenal failure, ADH levels are typically high, resulting in water, urea, and sodium resorption. The fractional sodium excretion is less than 1%, but it is greater than 2% in acute tubular necrosis.
Prerenal azotaemia has higher serum urea nitrogen/serum creatinine ratios (>20), whereas acute tubular necrosis has lower ratios (10-15). The normal range is between 12 and 20.
Urinary sodium is less than 20 in prerenal failure and greater than 40 in acute tubular necrosis.
Prerenal failure has a urine osmolality of >500, while acute tubular necrosis has an osmolality of 350.
Prerenal failure has a urine/serum creatinine ratio of >40, while acute tubular necrosis has a urine/serum creatinine ratio of 20.

The concentrations of serum urea or creatinine change in inverse proportion to glomerular filtration. Changes in serum creatinine concentrations are more reliable than changes in serum urea concentrations in predicting GFR. Creatinine is produced at a constant rate from creatine, and blood concentrations are almost entirely determined by GFR.

A number of factors influence urea formation, including liver function, protein intake, and protein catabolism rate. Urea excretion is also influenced by hydration status, the amount of water reabsorption, and GFR.

A high serum creatinine level, as well as a urine output of less than 10 mL/hour and the production of concentrated looking urine, do not necessarily indicate a specific cause of oliguria.

Glyceryl trinitrate (GTN) has a significant first pass metabolism. About 90% of a dose of GTN is metabolised in the liver by the enzyme glutathione organic nitrate reductase.

An INSIGNIFICANT amount of metabolism occurs in the intestinal mucosa.

There is approximately 1% bioavailability after oral administration and 38% after sublingual administration.

GTN does NOT cause gastric irritation and it is well absorbed in the gastrointestinal tract.

The volume of distribution of GTN is 2.1 to 4.5 L/kg. This is HIGH.

Ciprofloxacin belongs to the quinolone group of antibiotics, and doxycycline and minocycline are tetracyclines. So, they are not affected by beta-lactamase.
However, amoxicillin is a beta-lactam antibiotic and beta-lactamase cleaves the beta-lactam ring present in amoxicillin. This results in the breakdown of the antibiotic and thus the area of erythema dramatically increased.
Co-amoxiclav contains amoxicillin and clavulanic acid which protects amoxicillin from beta-lactamase.

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.

Noradrenaline also called norepinephrine belongs to the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter.

They have sympathomimetic effects acting via adrenoceptors (α1, α2, β1, β2, β3) or dopamine receptors (D1, D2).

May cause reflex bradycardia, reduce cardiac output and increase myocardial oxygen consumption

Phase 0 trials assist the scientists in studying the behaviour of drugs in humans by micro dosing patients. They are used to speed up the developmental process. They have no measurable therapeutic effect and efficiency.

Phase 1 is associated with assessing whether a drug is safe to use or not. The process is extensive and can take up to several months. It also involves healthy participants (less than 100) that are paid to take part in the study. The side effects upon increasing dosage are also addressed by the study. The effects the drug has on humans including how its absorbed, metabolized and excreted are studied. Approximately 70% of the drugs pass this phase.

Phase 2 trials involve patients that are suffering from the disease under study and are associated with determining the efficiency and the optimum dosage of the drug.

Phase 3 also assesses the efficacy but at a higher scale with larger population sample.

Phase 4 trials are involved with the long term effects and side effects of the drug.

Normally, the oesophagus is lined by non-keratinized stratified squamous epithelium. This epithelium can undergo metaplasia and convert to the columnar epithelium (stomach’s lining) in long-standing GERD that leads to Barret’s oesophagus.