Rifampicin is a derivative of a rifamycin (other derivatives are rifabutin and rifapentine). It is bactericidal against both dividing and non-dividing mycobacterium and acts by inhibiting DNA-dependent RNA polymerase. Thus this drug inhibits RNA synthesis.

Ketamine is usually used as a racemic mixture, i.e. (R/S)-ketamine. For over 20 years, use of the more potent (S)-enantiomer by anaesthesiologists has become a preferred option due to the assumption of increased anaesthetic and analgesic properties, a more suitable control of anaesthesia, and of an improved recovery from anaesthesia.

The use of ketamine in anaesthesia and psychiatry may be accompanied by the manifestation of somatic and especially psychomimetic symptoms such as perceptual disturbances, experiences of dissociation, euphoria, and anxiety.

Agitation or restlessness, Rapid heart rate, high Blood Pressure, loss of muscle coordination, or twitching muscles is common symptoms of Serotonin Syndrome.

Tramadol should not be given to patients taking selective serotonin receptor inhibitor (SSRI) therapy because of the risk of serotonin syndrome

Tramadol is a centrally acting analgesic that is an atypical opioid that relieves pain by opioids as well as additional mechanisms. Its affinity for µ opioid receptor is low, while that for κ and δ is very low. Unlike other opioids, it inhibits the reuptake of Noradrenaline (NA) and 5- Hydroxytryptamine (5-HT), increases 5-HT release, and thus activates monoaminergic spinal inhibition of pain.

Its analgesic action is only partially reversed by the opioid antagonist naloxone.

Insulin is secreted from the β cells of the pancreas. It consists of 51 amino acids arranged in two chains. It interacts with cell surface receptors (not the nuclear receptors and thus mechanism of action is not similar to steroids).
Since insulin can pass from plasma to interstitium and lymphatics, it can be measured in lymph but the concentrations here can be up to 30% less than that of plasma.

It decreases blood glucose by stimulating the entry of glucose in muscle and fat (by increasing the synthesis of Glucose transporters)

Daptomycin alters the curvature of the membrane, which creates holes that leak ions. This causes rapid depolarization, resulting in loss of membrane potential. Thus it interferes with the outer membrane of gram-positive bacteria resulting in cell death.

Oxytocin is structurally similar to Antidiuretic Hormone (ADH) and thus oxytocin cause water intoxication (due to ADH like action)

Oxytocin is secreted by the posterior pituitary along with ADH. It increases the uterine contractions with complete relaxation in between. It increases the contraction of the upper segment (fundus and body) of the uterus whereas the lower segment is relaxed facilitating the expulsion of the foetus

Antidiuretic hormone (ADH) also called vasopressin is released from the posterior pituitary in response to hypertonicity and increases fluid reabsorption from the kidney.

Vecuronium is used as a part of general anaesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is a monoquaternary aminosteroid (not quaternary) non- depolarising neuromuscular blocking drug.

It has a structure similar to both rocuronium and pancuronium. The only difference is the substitution of specific groups on the steroid structure.

Vecuronium is not associated with the release of norepinephrine from sympathetic nerve endings. However, Pancuronium has norepinephrine releasing the property.

Carbon dioxide absorbs the most infrared (IR) light between the wavelengths of 4.2-4.4m (4.26m is ideal).

Nitrous oxide absorbs infrared light at wavelengths of 4.4-4.6m (very similar to CO2) and less so at 3.9m.

At a frequency of 4.7m, carbon monoxide absorbs the most IR light.

At 3.3 m and throughout the ranges 8-12 m, the volatile agents have strong absorption bands.

Although oxygen does not absorb infrared light, it collides with CO2 molecules, interfering with absorption. The absorption band is widened as a result of this (so called collision or pressure broadening). A drop of 0.5 percent in measured CO2 can be caused by 95% oxygen.

Nitrous oxide causes a greater inaccuracy of 0.1 percent per ten percent of nitrous oxide.

Water vapour absorbs infrared light as well, resulting in absorption band overlap, collision broadening, and partial pressure dilution. Water traps and water permeable tubing are used to reduce inaccuracies.

Collision broadening is compensated for in modern gas multi-gas analysers.

Anticholinergic agents are a group of drugs that blocks the action of the neurotransmitter called acetylcholine at synapses in the central and peripheral nervous system.

Hyoscine, atropine, and glycopyrrolate are anticholinergic which acts at muscarinic receptors with little activity at the nicotinic receptors.

Hyoscine and atropine are naturally occurring esters. Since Glycopyrrolate is a synthetic quaternary amine, it does not cross the blood brain barrier. Noteworthy, hyoscine, butylbromide also does not cross the blood brain barrier significantly.

Phase I and phase II metabolism are used by the liver to break down paracetamol.

1st Phase:

Prostaglandin synthetase and cytochrome P450 (CYP1A2, CYP2E2, CYP3A4 and CYP2D6) to N-acetyl-p-benzoquinoneimine (NAPQI) and N-acetylbenzo-semiquinoneimine. NAPQI is a toxic metabolite that binds to the sulfhydryl groups of cellular proteins in hepatocytes, making it toxic. This can result in centrilobular necrosis.

Glutathione and glutathione transferases prevent NAPQI from binding to hepatocytes at low paracetamol doses by preferentially binding to these toxic metabolites. The cysteine and mercapturic acid conjugates are then excreted in the urine. Depletion of glutathione occurs at higher doses of paracetamol, resulting in high levels of NAPQI and the risk of hepatocellular damage. Hepatotoxicity would not be an issue if the body’s glutathione stores were sufficient.

N-acetylcysteine is a precursor for glutathione synthesis and is the drug of choice for the treatment of paracetamol overdose.

Phase II:

Conjugation with glucuronic acid to paracetamol glucuronide is the most common method of metabolism and excretion, accounting for 60% of renally excreted metabolites. Paracetamol sulphate (35%), unchanged paracetamol (5%), and mercapturic acid are among the other renally excreted metabolites (3 percent ). The capacity of conjugation pathways is limited. The capacity of the sulphate conjugation pathway is lower than that of the glucuronidation pathway.

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 extremely high, approaching 100%.

As a result, measuring paracetamol levels in plasma after an injury is important. Peak plasma concentrations are reached after 30-60 minutes, with a volume of distribution of 0.95 L/kg. It binds to plasma proteins at a rate of 10% to 25%.

Prilocaine is the drug of choice for intravenous regional anaesthesia. 0.5% prilocaine (40 ml) is indicated for this condition.
Lidocaine is another alternative for this condition but volume and dose are likely to be inadequate for the procedure.

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 α2δ, a protein that serves as an auxiliary subunit of voltage-gated calcium channels. Moreover, it binds to NMDA receptor to modulate its transmission.

Firstly, always call for an early help. This understanding is at hazard of gastro-oesophageal reflux, the reason a fast arrangement acceptance has been picked for within the first place. The patient isn’t pregnant and the critical surgery isn’t immediate.

The scheme A is to perform a fast arrangement acceptance under ideal conditions and effectively secure the respiratory tract with a tracheal tube.

Whilst no more than three attempts with coordinate laryngoscope (+ 1 endeavour with video laryngoscope) ought to be made to intubate the trachea, the reality is that the suxamethonium is wearing off ought to be borne in mind. One step is to make certain satisfactory neuromuscular blockade at this level, if oxygenation can be kept up by bag-mask ventilation, this might involve the administration of a non-depolarising relaxant. As the surgery isn’t prompt there should be a baseline to stop scheme A at intubation and resort to scheme B.

An elective procedure can be planned at that time.

The first most vital step is to report a failed intubation as this will halt you from continuing to intubate and notify your collaborator that scheme A has failed. Keeping up oxygenation and anaesthesia is additionally critical earlier to the initiation of scheme B.

Do not administer another dose of suxamethonium. If there’s collapse of oxygenation and failure to preserve satisfactory ventilation, then insert a supraglottic airway. Plan D takes after the affirmation of a CICO.

Drugs cross the placenta by Simple, Ion channel and Facilitated diffusion; Exocytosis and Endocytosis, Osmosis, and Active transport (primary and secondary)

The following factors influence rate of diffusion across the placenta:

Protein binding
Degree of ionisation
Placental blood flow
Maternal and foetal blood pH
Materno-foetal concentration gradient.
Thickness of placental membrane
Molecular weight of drug <600 Daltons cross by diffusion
Lipid solubility (lipid soluble molecules readily diffuse across the placenta)

Rocuronium has a F/M ratios of 0.16, a 30% plasma protein binding, low lipid solubility, a low volume of distribution (0.25L/kg), and a high molecular weight (530Da).

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic α and β1 (but not β2 ) agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of DA dilates these vessels (by raising intracellular cAMP). This increases g.f.r. In addition, DA exerts a natriuretic effect by D1 receptors on proximal tubular cells.

Moderately high doses produce a positive inotropic (direct β1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (α1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular α and β receptors; does not penetrate the blood-brain barrier€”no CNS effects.

Dopamine is used in patients with cardiogenic or septic shock and severe CHF wherein it increases BP and urine outflow.

It is administered by i.v. infusion (0.2€“1 mg/min) which is regulated by monitoring BP and rate of urine formation

To begin, one must determine the child’s approximate weight. There are a variety of formulas to choose from. It is acceptable to use the advanced paediatric life support formula:

(age + 4) 2 = weight

A 5-year-old child will weigh around 18 kilogrammes.

The following are the appropriate doses of the drugs listed above:

Gentamicin (once daily) – 5-7 mg/kg = 90-126 mg and subsequent dose modified according to plasma levels
Ondansetron – 0.1 mg/kg, but a maximum of 4 mg as a single dose = 1.8 mg
Codeine should be administered orally at a dose of 1 mg/kg rather than intravenously, as the latter can cause ‘dangerous’ hypotension due to histamine release.
15 mg/kg paracetamol = 270 mg orally or intravenously (a loading dose of 20 mg/kg, or 360 mg, is sometimes recommended, which is not far short of the doses listed above).
Cefuroxime – the initial intravenous dose is 20 mg/kg (360 mg) depending on the indication (again, similar to the dose given in the answer options above).

Oxytocin is secreted by the posterior pituitary along with Antidiuretic Hormone (ADH). It increases the contraction of the upper segment (fundus and body) of the uterus whereas the lower segment is relaxed facilitating the expulsion of the foetus.

Oxytocin acts through G protein-coupled receptor and phosphoinositide-calcium second messenger system to contract uterine smooth muscle.

It has 0.5 to 1 % ADH activity introducing possibilities of water intoxication when used in high doses.

The sensitivity of the uterus to oxytocin increases as the pregnancy progresses.

It is used for induction of labour in post maturity and uterine inertia.

A stock dose of Intravenous paracetamol available in the market is 10mg/ml. There is a recommended dose of IV paracetamol according to the profile of the patient (age, co-morbidities, weight).

Weight Recommended Dose Maximum per day
‰¤10 kg 7.5 mg/kg 30 mg/kg
>10 kg to ‰¤33 kg 15 mg/kg 60 mg/kg (not exceeding 2 g)
>33 kg to ‰¤50 kg 15 mg/kg 60 mg/kg (not exceeding 3 g)
>50 kg with additional risk factors for hepatotoxicity 1g 3 g
>50 kg with no additional risk factors for hepatotoxicity 1g 4 g

Special precaution must be observed for patients with hepatocellular insufficiency. The maximum dose per day should not exceed 3g.

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.

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.

30mL 0.5% bupivacaine, 1mL 1 in 1,000 adrenaline and 89mL 0.9% N. Saline is the correct answer.
Initial concentration of bupivacaine is 0.5% with a volume of 30mL

The volume is doubled (60mL) by the addition of 0.9% N. saline (30mls) and the concentration of bupivacaine is halved to (0.25%).

If the volume is doubled again (120mL) by the addition of further 0.9% N. saline (59mls) the final concentration of bupivacaine is halved again to 0.125%. Total N. saline = 89mls

The 1 mL of 1 in 1000 adrenaline has also been diluted into the final volume of 120 mL making it a 1 in 120000 concentration.

Barbiturates are derived from barbituric acid, which itself is nondepressant, but appropriate side-chain substitutions result in CNS depressant activity that varies in potency and duration with carbon chain length, branching, and saturation.

Oxybarbiturates retain an oxygen atom on number 2-carbon atom of the barbituric acid ring.

Thiobarbiturates replace this oxygen atom with a sulphur atom, which confers greater lipid solubility. Generally speaking, a substitution such as sulphuration that increases lipid solubility is associated with greater hypnotic potency and more rapid onset, but shorter duration of action.

Addition of a methyl group to the nitrogen atom of the barbituric acid ring, as with oxybarbiturate methohexital, also results in a compound with a short duration of action.

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.

Tramadol is a centrally acting analgesic with a multimode of action. It acts on serotonergic and noradrenergic nociception, while its metabolite O-desmethyltramadol acts on the mu opioid receptor. Its analgesic potency is claimed to be about one tenth that of morphine. Tramadol is used to treat both acute and chronic pain of moderate to (moderately) severe intensity.

Tramadol exists as the racemic (1:1) mixture of the (+) and (-)-enantiomer. It has a multimodal mechanism of action as on the one hand the (+) and (-)-enantiomer act on the serotonin and noradrenaline reuptake, and on the other hand the O-desmethyl metabolite of tramadol (called M1 or ODT) acts on the µ-opioid receptor. This implies that the analgesic mechanism of action of tramadol includes both non-opioid components, i.e., noradrenergic and serotonergic components, and opioid components. The (+)-enantiomer of tramadol contributes to analgesia by inhibiting the reuptake of serotonin, the (-)-enantiomer by inhibiting the reuptake of
noradrenaline, and the O-desmethyl metabolite by binding with relative high affinity (compared to tramadol) to the µ-opioid receptor.

(+/-)-Tramadol binds with low affinity to the human µ-opioid receptor with an affinity constant (Ki) of 2.4 µM.42 This affinity is approximately 4000-fold less than that of morphine (Ki = 0.34 nM). The affinity of tramadol for the δ- and κ-opioid receptors is even less. The (+/-)-O-desmethyl metabolite (M1) of tramadol, on the other hand, shows about 400-fold higher affinity for the µ-opioid receptor (Ki = 5.4 nM) than the parent compound, but still with much lower affinity than morphine. The affinity of M1 for the µ-opioid receptor is due to the (R) (+)-enantiomer (Ki = 3.4 nM) and not the (S) (-)-enantiomer (Ki = 240 nM). The affinity of the (R) (+)-enantiomer of M1 is one-tenth that of morphine for the µ-opioid receptor, and about 700 times that of (+/-)-tramadol. The metabolite (+/-)-M5 also has a higher affinity than (+/-)-tramadol for the µopioid receptor (Ki = 100 nM). However, animal studies indicate that M5 does not cross
the blood-brain barrier and does not contribute to the anti-nociceptive effect of tramadol. The metabolites M2, M3, and M4 of tramadol have negligible affinity for the human µ-opioid receptor.

Phase I metabolites of tramadol:

Mono-O-desmethyl-tramadol (M1)
Mono-N-desmethyl-tramadol (M2)
Di-N-desmethyl-tramadol (M3)
Tri-N,O-desmethyl-tramadol (M4)
Di-N,O-desmethyl-tramadol (M5)

Sugammadex is used for immediate reversal of rocuronium-induced neuromuscular blockade.
It is used at a dose of 16 mg/kg.

Since the patient in the question is 70 kg, the required dose of sugammadex can be calculated as:
16×70 = 1120 mg.

Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it can reverse any depth of neuromuscular block.

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.

Midazolam is the benzodiazepine in question. It’s the only benzodiazepine that undergoes tautomeric transformation (dynamic isomerism). The molecule is ionised and water soluble at pH 3.5, but when injected into the body at pH 7.4, it becomes unionised and lipid soluble, allowing it to easily pass through the blood brain barrier.

The half-life of midazolam is only 2-4 hours.

It is a GABAA receptor agonist because it is a benzodiazepine. GABAA receptors are found in abundance throughout the central nervous system, particularly in the cerebral cortex, hippocampus, thalamus, basal ganglia, and limbic system. GABAA receptors are ligand-gated ion channels, with the inhibitory neurotransmitter gamma-aminobutyric acid as the endogenous agonist. It is a pentameric protein (2, 2 and one subunit) that spans the cell membrane, and when the agonist interacts with the alpha subunit, a conformational change occurs, allowing chloride ions to enter the cell, resulting in neuronal hyperpolarization.

For status epilepticus, midazolam is not the drug of choice. Lorazepam is the benzodiazepine of choice for status epilepticus.

Amiodarone is the longest-acting anti-arrhythmic drug. It possesses the action of all classes of antiarrhythmic drugs (Sodium channel blockade, Beta blockade, Potassium channel blockade, and Calcium channel blockade). Due to this property, it has the widest anti-arrhythmic spectrum and thus can be used in both broad and narrow complex tachyarrhythmia.

Adenosine is shortest acting anti-arrhythmic drug.

Accumulation of morphine-6-glucuronide is a risk factor for opioid toxicity during morphine treatment. Morphine is metabolized in the liver to morphine-6-glucuronide and morphine-3-glucuronide, both of which are excreted by the kidneys. In the setting of renal failure, these metabolites can accumulate, resulting in a lowering of the seizure threshold. However, it does not occur in all patients with renal insufficiency, which is the most common reason for accumulation of morphine-6-glucuronide; this suggests that other risk factors can contribute to morphine-6-glucuronide toxicity.

The active metabolites of codeine are morphine and the morphine metabolite morphine-6-glucuronide. The enzyme systems responsible for this metabolism are: CYP2D for codeine and UGT2B7 for morphine, codeine-6-gluronide, and morphine-6-glucuronide. Both of these systems are subject to genetic variation. Some patients are ultrarapid metabolizers of codeine and produce higher levels of morphine and active metabolites in a very short period of time after administration. These increased levels will produce increased side effects, especially drowsiness and central nervous system depression.

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

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

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