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.

Marsh (adult) model, when used with children caused over-estimation of plasma concentration. To address this issue Kataria et al developed a three-compartmental model for propofol in children. The pharmacokinetic models used by Target controlled infusion (TCI) systems are used to calculate the relative sizes of the central (vascular), vessel-rich peripheral, and vessel-poor peripheral compartments. The relative volumes of these compartments are different in young children when compared to adults.

Kataria, therefore, is the correct option as described above.

The Maitre model is a three-compartmental model for alfentanil TCI.

The Marsh model describes a propofol TCI model for adults

The Minto model applies to TCI remifentanil.

The Schnider model is also an adult model for propofol that incorporates age and lean body mass as covariates.

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%

Elimination of phenytoin from the body follows first-order kinetics. This means that the rate of elimination is proportional to plasma concentration.

The rate of elimination can be described by the equation:

C = C0·e-kt

Where:

C = drug concentration
C0 = drug concentration at time zero (extrapolated)
k = Rate constant
t = Time

Enzyme systems become saturated when phenytoin concentrations exceed the normal range and elimination of the drug becomes zero-order. At this point, the drug is metabolised at a fixed rate and metabolism is independent of plasma concentration.

Aspirin and ethyl alcohol are other drugs that behave this way.

The temperature above which a gas cannot be liquefied no matter how much pressure is applied is its critical temperature. The critical temperature of nitrous oxide is 36.5°C

The minimum pressure that causes liquefaction is the critical pressure of that gas.

The Poynting effect refers to the phenomenon where mixing of liquid nitrous oxide at low pressure with oxygen at high pressure (in Entonox) leads to formation of gas of nitrous oxide.

There is no relevance of molecular weight to this question. it does not change with phase of a substance.

Penicillinase is a narrow spectrum ?-lactamase that opens the ?-lactam ring and inactivates Penicillin G and some closely related congeners. The majority of Staphylococci and some strains of gonococci, B. subtilis, E. coli, and a few other bacteria produce penicillinase.

N. meningitidis is sensitive to penicillin and less than 20% resistance is found in pseudomonas.

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.

Entonox is a gas that consists of 50% oxygen and 50% Nitrous oxide. Nitrous oxide is sometimes used for anaesthetics but in this combination, it works as a short-acting painkiller.

Under normal working conditions, it exists only in gaseous form in a cylinder. The gauge pressure of a full Entonox cylinder is 137 bar.

Entonox cylinders should be stored horizontally at a temperature above 0 C. At temperatures below this the nitrous oxide component may separate.

Pseudocritical temperature and pseudocritical pressure can be defined as the molal average critical temperature and pressure of mixture components. In other words, the pseudo-critical temperature is the temperature at which the two gases separate. The pseudo-critical temperature of Entonox is approximately -5.50 C

Nitroglycerine is rapidly denitrated enzymatically in the smooth muscle cell to release the free radical nitric oxide (NO).

Released NO activated cytosolic guanylyl cyclase which increases cGMP (cyclin guanosine monophosphate) which causes dephosphorylation of myosin light chain kinase (MLCK) through a cGMP-dependent protein kinase.

Reduced availability of phosphorylated (active) MLCK interferes with activation of myosin and in turn, it fails to interact with actin to cause contraction. Consequently, relaxation occurs.

Mivacurium, when administered at doses greater than 0.2 mg/kg,increases the risk for hypotension, tachycardia, and erythema. This is due to the ability of mivacurium to release histamine with increasing dose. Contrary to this fact, anaphylaxis is rare for mivacurium because of the short duration of histamine release.

The effective dose 50 (ED50) of mivacurium is between 0.08-0.15 mg/kg. It is administered slowly to prevent and decrease the risk of developing adverse effects.

Mivacurium has a high potency thus a longer duration of action, however this is not the answer that we are looking for.

Although drug metabolism takes longer for mivacurium than succinylcholine, it has no effect on the dose required for intubation.

Always call for help early. This patient is at risk of gastro-oesophageal reflux, which is why a rapid sequence induction has been chosen. The patient is not pregnant, and the surgery is not urgent.

Plan A is to perform a rapid sequence induction under optimal conditions and secure the airway with a tracheal tube.

No more than three attempts with a direct laryngoscope (plus one attempt with a videolaryngoscope) should be made to intubate the trachea. Keep in mind that suxamethonium is wearing off. Ensuring adequate neuromuscular blockade at this stage is crucial; this might include administering a non-depolarizing relaxant if oxygenation can be maintained with bag-mask ventilation. Given the non-immediate nature of the surgery, there should be a low threshold to abandon intubation attempts and resort to Plan B.

An alternative strategy can then be planned.

The most important initial step is to declare a “failed intubation.” This will prevent further intubation attempts and alert your assistant that Plan A has failed. Maintaining oxygenation and anesthesia is also critical before implementing Plan B.

Do not administer another dose of suxamethonium. Insert a supraglottic airway if oxygenation fails and adequate ventilation cannot be maintained.

Plan D follows the declaration of a CICO (Cannot Intubate, Cannot Oxygenate) situation.

Because enflurane is much less soluble in blood and has a blood: gas partition coefficient of 1.8, both wash-in and wash-out should be faster.

Sevoflurane’s sweet-smelling, non-irritant nature, combined with a low blood: gas partition coefficient, would result in similar offset and onset characteristics.

Isoflurane and enflurane have a molecular weight of 184.

The oil: gas partition coefficient on a volatile agent is a measure of lipid solubility, potency, and thus MAC. Halothane has an oil: gas partition coefficient of 220 and a MAC of 0.74. One would expect the MAC to be higher with an oil gas partition coefficient of 180 (less lipid soluble).

The conversion of halothane (20%) to trifluoroacetic acid via oxidative metabolism has been linked to the development of hepatitis.

P450 2E1 converts sevoflurane to hexafluoroisopropanol, which results in the release of inorganic fluoride ions. It’s the only fluorinated volatile anaesthetic that doesn’t break down into trifluoracetic acid.

Desflurane is likely to cause airway irritation, which can lead to coughing, apnoea, and laryngospasm, despite its low blood:gas partition coefficient (0.42).

Lorazepam is an intermediate-acting benzodiazepine that binds to the GABA-A receptor subunit to increase the frequency of chloride channel opening and cause membrane hyperpolarization.

Lorazepam has emerged as the preferred benzodiazepine for acute management of status epilepticus. Lorazepam differs from diazepam in two important respects. It is less lipid-soluble than diazepam, with a distribution half-life of two to three hours versus 15 minutes for diazepam. Therefore, it should have a longer duration of clinical effect. Lorazepam also binds the GABAergic receptor more tightly than diazepam, resulting in a longer duration of action. The anticonvulsant effects of lorazepam last six to 12 hours, and the typical dose ranges from 4 to 8 mg. This agent also has a broad spectrum of efficacy, terminating seizures in 75-80% of cases. Its adverse effects are identical to those of diazepam. Thus, lorazepam also is an effective choice for acute seizure management, with the added possibility of a longer duration of action than diazepam.

Phenobarbitone is a long-acting barbiturate that binds to GABA-A receptor site and increase the duration of chloride channel opening. It also blocks glutamic acid neurotransmission, and, at high doses, can block sodium channels. It is considered as the drug of choice for seizures in infants.

Phenytoin is an anti-seizure drug that blocks voltage-gated sodium channels. It is preferred in prolonged therapy of status epilepticus because it is less sedating.

In cases wherein airway protection is required, thiopentone and propofol are the preferred drugs.

Gentamicin is a broad-spectrum antibiotic whose mechanism of action involves inhibition of protein synthesis by binding to 30s ribosomes. Its major adverse effect is nephrotoxicity and ototoxicity

Aminoglycoside bind to 30s subunit of ribosome causing misreading of mRNA

Tetracyclines inhibit protein synthesis through reversible binding to bacterial 30s ribosomal subunits, which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

Chloramphenicol binds to the 50s subunit and inhibits peptidyl transferase

Clindamycin binds to the 50s ribosomal subunit of bacteria and disrupts protein synthesis by interfering with the transpeptidation reaction, which thereby inhibits early chain elongation.

Choosing an appropriate dose of local anaesthetic to reduce the chance of toxicity is the most important safety aspect in performing a caudal block.

The caudal will have to be inserted following induction of anaesthesia as performing it in an awake child is not a viable option.

The patient is placed in the lateral position and the sacral hiatus is identified. Under strict asepsis, a needle ( usually a 21-23FG needle) is advanced at an angle of approximately 55-65° to the coronal plane at the apex of the sacrococcygeal membrane. When there is loss of resistance, thats the endpoint. The needle must first be aspirated before anaesthetic agent is injected because there is a risk (1 in 2000) of perforating the dura or vascular puncture.

Alternatively, a 22-gauge plastic cannula can be used. Following perforation of the sacrococcygeal membrane, the stilette is removed and only the blunter plastic cannula is advanced. This reduces the risk of intravascular perforation.

Eliciting an appropriate end motor response at an appropriate current strength when the caudal and epidural spaces are stimulated helps in improving the efficacy and safety of neural blockade. A 22G insulated needle is advanced in the caudal canal until a pop is felt. If the needle is placed correctly, an anal sphincter contractions (S2 to S4) is seen when an electrical stimulation of 1-10 mA is applied.

The application of ultrasound guidance in identification of the caudal epidural space has been shown to prevent inadvertent dural puncture and to increase the safety and efficacy of the block in children.

Thiopental has the longest elimination half-life of 6-15 hours.

Elimination half-life of other drugs are given as:
– Propofol: 5-12 h
– Methohexitone: 3-5 h
– Ketamine: 2 h
– Etomidate: 1-4 h

Ketamine is a phencyclidine (hallucinogenic) derivative that is administered in a dose of 2 mg/kg and acts by blocking NMDA (N-methyl-D-aspartate) receptors of glutamate.

It is a powerful bronchodilator agent and is, therefore, an intravenous anaesthetic of choice in bronchial asthma (halothane is an inhalational anaesthetic agent of choice for bronchial asthma). It is also used in the management of refractory status epilepticus.

It is an acid solution with an elimination half-life of three hours.

It has S (+) enantiomer and R (-) enantiomer. the S(+) enantiomer is two to four times more potent than the R(-) and is less likely to produce hallucinations.

Its use is contraindicated in patients with ischaemic heart disease because it increased sympathetic outflow leading to tachycardia and increased cardiac output which in turn increases the myocardial oxygen demand.

Prednisolone 5 mg is the same as 20 mg hydrocortisone.

Prednisolone 40 mg is the same as 8 x 20 mg or 160 mg of prednisolone.

Mineralocorticoid effects and variations in action duration are not taken into account in these comparisons.

5 mg of prednisolone is the same as Dexamethasone 750 mcg, Hydrocortisone 20 mg, Methylprednisolone 4 mg, and Cortisone acetate 25 mg.

The clinical picture best describes a probable drug interaction with pethidine.

Phenelzine, a monoamine oxidase (MAO) inhibitor, when given with pethidine, an opioid analgesic, may lead to episodes of hypertension, rigidity, excitation, hyperpyrexia, seizures, coma and death. Studies have shown that pethidine reacts more significantly with MAO inhibitors than morphine.

When pethidine is metabolised to normeperidine, it acts as a serotonin reuptake inhibitor and cause an increase in serotonin levels in the brain. MAO inhibitors can also lead to elevated levels of serotonin because of its mechanism of action by inhibiting the enzyme monoamine oxidase that degrades serotonin.

The excess serotonin levels may lead to serotonin syndrome, of which some of the common precipitating drugs are selective serotonin reuptake inhibitors, MAO inhibitors, tricyclic antidepressants, meperidine, and St. John’s Wort. Onset of symptoms is within hours, which includes fever, agitation, tremor, clonus, hyperreflexia and diaphoresis.

Drug interaction between phenelzine and paracetamol do not commonly precipitate serotonin syndrome.

Neuroleptic malignant syndrome is due to dopamine antagonism, precipitated commonly by antipsychotics. Its onset of symptoms occur in 1 to 3 days, and is characterized by fever, encephalopathy, unstable vitals signs, elevated CPK, and rigidity.

Altered mental status is the most common manifestation of sepsis-associated encephalopathy. Patient also exhibit confusional states and inappropriate behaviour. In some cases, this may lead to coma and death.

Adrenaline acts on ?1, ?2,?1, and ?2 receptors and also on dopamine receptors (D1, D2) and have sympathomimetic effects.

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

Adrenaline is a sympathomimetic amine with both alpha and beta-adrenergic stimulating properties.
Adrenaline is the drug of choice for anaphylactic shock
Adrenaline is also used in patients with cardiac arrest. The preferred route is i.v. followed by the intra-osseous and endotracheal route.

Adrenaline is released by the adrenal glands, acts on ? 1 and 2, ? 1 and 2 receptors, and is responsible for fight or flight response.

It acts on ? 2 receptors in skeletal muscle vessels-causing vasodilation.

It acts on ? adrenergic receptors to inhibit insulin secretion by the pancreas. It also stimulates glycogenolysis in the liver and muscle, stimulates glycolysis in muscle.

It acts on ? adrenergic receptors to stimulate glucagon secretion in the pancreas. It also stimulates Adrenocorticotrophic Hormone (ACTH) and stimulates lipolysis by adipose tissue

Structural isomers have a similar molecular formula, but they have a different structural formula as their atoms are arranged in a different manner. Such small changes lead to the differential pharmacological activity. Enflurane and isoflurane are two prime examples of structural isomers.

Stereoisomers are those substances that have a similar molecular and structural formula, but the arrangement spatially of atoms are different and have optical activity.

Enantiomers are a pair of stereoisomers, which are non-superimposable mirror images of each other. They also have chiral centres of molecular symmetry. Ketamine is considered as an example of racemic mixture (contain 50% R and 50% S enantiomers)

Geometric isomers contain a carbon-carbon double bond (i.e. C=C) or a rigid carbon-carbon single bond in a heterocyclic ring. Cis-atracurium is one example.

Dynamic isomers or Tautomers are a pait of unstable structural isomers, which are present in equilibrium. One isomer can easily change after the change in pH. Midazolam and thiopentone are their examples.

Propofol infusion syndrome (PRIS) is characterized by lactic acidosis, bradyarrhythmia, rhabdomyolysis, cardiac and renal failure, and often leads to death. So, lactate monitoring is advised in patients with propofol infusion syndrome.

Noradrenaline acts as a sympathomimetic effect via alpha as well as a beta receptor. However, they have weak ?2 action.

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

Dabigatran template is a prodrug and its active metabolite is a direct thrombin inhibitor. It is a synthetic, reversible, non-peptide thrombin inhibitor. This inhibition of thrombin results in a decrease of fibrin and reduces platelet aggregation.

Drugs like warfarin act by inhibiting the activation of vitamin K-dependent clotting factors. These factors are synthesized by the liver and activated by gamma-carboxylation of glutamate residues with the help of vitamin K. Hydroquinone form of vitamin K is converted to epoxide form in this reaction and regeneration of hydroquinone form by enzyme vitamin K epoxide reductase (VKOR) is required for this activity. Oral anticoagulants prevent this regeneration by inhibiting VKOR, thus vitamin K-dependent factors are not activated. These factors include clotting factors II, VII, IX, and X as well as anti-clotting proteins, protein C and protein S.

There are two types of drug dose-response relationships, namely, the graded dose-response and the quantal dose-response relationships.

Drug response curves are plotted as percentage response again LOG drug concentration. This graph is sigmoid in shape.

Agonists are drugs with high affinity and high intrinsic activity. Meanwhile, the antagonist is a drug with high affinity but no intrinsic activity. Intrinsic activity determines the maximal response. The maximal response can be achieved even by activation of a small proportion of receptor sites.

Barbituric acid is the barbiturates’ pharmacologically inactive precursor. A pyrimidine heterocyclic nucleus is formed by the condensation of urea and malonic acid. Its pharmacological activity can be influenced by minor structural changes (structure function relationship).

The duration of action and potency as a sedative are influenced by the length of the side chains at C5. Barbiturates with three carbon atoms in their chain last longer than those with two. Anticonvulsant properties are enhanced by branched chains.

The addition of a methyl group at N1 causes a faster onset/offset of action, but it also causes excitatory phenomena (twitching/lower convulsive threshold).

The addition of oxygen and sulphur to C2 increases the molecule’s lipid solubility and thus its potency. Thiopentone (thiobarbiturate) has sulphur groups at C2, making it 20-200 times more lipid soluble than oxybarbiturates.

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

The first line of defence against acid-base disorder is buffering. The blood mainly utilizes bicarbonate ion (HCO3-) for its buffering capacity (total of 53%, plasma and red blood cells combined).

Strong acids, when acted upon by a buffer, release H+, which then combines to HCO3- and forms carbonic acid (H2CO3). When acted upon by the enzyme carbonic anhydrase, H2CO3 dissociates into H2O and CO.

The rest are the percentage of utilization for the following buffers:
Haemoglobin (by RBCs) – 35%
Plasma proteins (by plasma) – 7%
Organic phosphates (by RBCs) – 3%
Inorganic phosphates (by plasma) – 2%

Tramadol is weak agonist at the mu receptor. It inhibits the neuronal reuptake of serotonin and norepinephrine, and inhibits pain neurotransmission. It is given for moderate pain, chronic pain syndromes, and neuropathic pain.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). It inhibits the neuronal reuptake of serotonin by inhibiting the serotonin transporter (SERT). It is the drug of choice for major depressive disorder, and is given for other psychiatric disorders such as anxiety, obsessive-compulsive, post-traumatic stress, and phobias.

When tramadol is given with SSRIs, serotonin syndrome may occur. Serotonin syndrome is characterized by fever, agitation, tremors, clonus, hyperreflexia and diaphoresis. The onset of symptoms may occur within a few hours, and the first-line treatment is sedation, paralysis, intubation and ventilation.

After ingestion of more than 150 mg/kg paracetamol within 24 hours, hepatotoxicity can occur but can also develop rarely after ingestion of doses as low as 75 mg/kg within 24 hours. Hepatocellular damage will not occur in this patient and therefore no need to engage management pathway for paracetamol overdose. If his weight was <33 kg or he already had a history of impaired liver function, then the management would bde different. Subsequent post-operative doses will be a standard dose of 1 g 6 hourly. This is a drug administration error and should be reported as an incident even though the patient will not be harmed.

Unionised molecules are more likely than ionised molecules to cross membranes (such as the blood-brain barrier).

Because alfentanil and fentanyl are weak bases, the Henderson-Hasselbalch equation says that the ratio of ionised to unionised molecules is determined by the parent compound’s pKa in relation to physiological pH.

Alfentanil has a pKa of 6.5, while fentanyl has a pKa of 8.4.
At a pH of 7.4, 89 percent of alfentanil is unionised, whereas 9% of fentanyl is.

As a result, alfentanil has a faster onset than fentanyl.

Fentanyl is 83% plasma protein bound
Alfentanil is 90% plasma protein bound.

Alfentanil’s pharmacokinetics are affected by its higher plasma protein binding. Because alfentanil has a low hepatic extraction ratio (0.4), clearance is determined by the degree of protein binding rather than the time it takes to take effect.

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

Propofol is cleared at the fastest rate at the rate of 60ml/kg/min.

Clearance rate of other drugs are as follows:
– Thiopental: 3.5 ml/kg/min
– Methohexitone: 11 ml/kg/min
– Ketamine: 17 ml/kg/min
– Etomidate: 10-20 ml/kg/min

The reasons for adding adrenaline to a local anaesthetic solution are:

1. To Increase the duration of block
2. To reduce absorption of the local anaesthetic into the circulation
3. To Increase the upper safe limit of local anaesthetic (2.5 mg/kg instead of 2 mg/kg, in this case).

The addition of adrenaline to bupivacaine does not affect its potency, lipid solubility, protein binding, or pKa(8.1 with or without adrenaline).

The pH of bupivacaine is between 5-7. Premixed with adrenaline, it is 3.3-5.5.
The onset of a local anaesthetic and its ability to penetrate membranes depends upon degree of ionisation. Compared with the ionised fraction, unionised local anaesthetic readily penetrates tissue membranes to site of action. The onset of action of solution B is slower. this is because the relationship between pKa(8.1) and pH(3.3-5.5) of the solution results in a greater proportion of ionised local anaesthetic molecules compared with solution A.

Calcium channel blocker (CCB) blocks L-type of voltage-gated calcium channels present in blood vessels and the heart. By inhibiting the calcium channels, these agents decrease the frequency of opening of calcium channels activity of the heart, decrease heart rate, AV conduction, and contractility.

Three groups of CCBs include
1) Phenylalkylamines: Verapamil, Norverapamil
2) Benzothiazepines : Diltiazem
3) Dihydropyridine : Nifedipine, Nicardipine, Nimodipine, Nislodipine, Nitrendipine, Isradipine, Lacidipine, Felodipine and Amlodipine.

Even though verapamil as good absorption from GIT, its oral bioavailability is low due to high first-pass metabolism.

Nimodipine is a Cerebro-selective CCB, used to reverse the compensatory vasoconstriction after sub-arachnoid haemorrhage and is more lipid soluble analogue of nifedipine

Calcium channel antagonist can potentiate the effect of non-depolarising muscle relaxants.

Using a lean body weight metric encompasses a more scientific approach to weight-based dosing. Lean body weight reflects the weight of all ‘non-fat’ body components, including muscle and vascular organs such as the liver and kidneys. As lean body weight contributes to approximately 99% of a drug’s clearance, it is useful for guiding dosing in obesity.

This metric has undergone a number of transformations. The most commonly cited formula derived by Cheymol is not optimal for dosing across body compositions and can even produce a negative result. A new formula has been developed that appears stable across different body sizes, in particular the obese to morbidly obese.

A practical downfall of the calculation of lean body weight (and other body size descriptors) is the numerical complexity, which may not be palatable to a busy clinician. Often limited time is available for prescribing and an immediate calculation is required. Lean body weight calculators are available online, for example in the Therapeutic Guidelines.

Using total body weight assumes that the pharmacokinetics of the drug are linearly scalable from normal-weight patients to those who are obese. This is inaccurate. For example, we cannot assume that a 150 kg patient eliminates a drug twice as fast as a 75 kg patient and therefore double the dose. Clinicians are alert to toxicities with higher doses, for example nephro- and neurotoxicity with some antibiotics and chemotherapeutics, and bleeding with anticoagulants. Arbitrary dose reductions or ‘caps’ are used to avoid these toxicities, but if too low can result in sub-therapeutic exposure and treatment failure.

Body surface area is traditionally used to dose chemotherapeutics. It is a function of weight and height and has been shown to correlate with cardiac output, blood volume and renal function. However, it is controversial in patients at extremes of size because it does not account for varying body compositions. As a consequence, some older drugs such as cyclophosphamide, paclitaxel and doxorubicin were ‘capped’ (commonly at 2 m^2) potentially resulting in sub-therapeutic treatment. Recent guidelines suggest that unless there is a justifiable reason to reduce the dose (e.g. renal disease), total body weight should be used in the calculation of body surface area, until further research is done. Little research into dosing based on body surface area has been conducted for other medicines.

Ideal body weight was developed for insurance purposes not for drug dosing. It is a function of height and gender only and, like body surface area, does not take into account body composition. Using ideal body weight, all patients of the same height and sex would receive the same dose, which is inadequate and generally results in under-dosing. For example a male who has a total body weight of 150 kg and a height of 170 cm will have the same ideal body weight as a male who is 80 kg and 170 cm tall. Both could potentially receive a mg/kg dose based on 65 kg (ideal body weight).

Propranolol is a nonselective beta-blocker with a half-life of 3 to 6 hours.

Since it is lipid-soluble it crosses the blood-brain barrier and causes Central Nervous System side effects like sedation, nightmares, and depression.

They are contraindicated in asthma, Congestive heart failure, and diabetes.

It has a large volume of distribution with no intrinsic sympathomimetic action.

Sevoflurane is highly fluorinated methyl isopropyl ether widely used as an inhalational anaesthetic. It is suggested that sevoflurane preconditioning occurs via the opening of mitochondrial Potassium ATP dependent channel similar to that of Ischemic Preconditioning protection.

Noradrenaline has a short half-life of about 2 minutes. It is rapidly cleared from plasma by a combination of cellular reuptake and metabolism.

It acts as sympathomimetics by acting on ?1 receptors and also on ? receptors.

It decreases renal and hepatic blood flow.

Norepinephrine is metabolized by the enzymes monoamine oxidase and catechol-O-methyltransferase to 3-methoxy-4-hydroxymandelic acid and 3-methoxy-4-hydroxyphenylglycol (MHPG).

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine