Bupivacaine is used to decrease sensation in a specific area. It is injected around a nerve that supplies the area, or into the spinal canal’s epidural space.

The maximum volume of 0.5% bupivacaine that should be administered to a 10kg child is 5 ml

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 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.

Nitrous oxide increases cerebral blood flow by direct cerebral stimulation and tends to elevate intracranial pressure (ICP)

It increases the cerebral metabolic rate of oxygen consumption (CMRO2)

It is not an NMDA agonist as it antagonizes NMDA receptors.

Cerebral autoregulation is impaired with the use of nitrous oxide but when used with propofol, it is maintained.

Carbon dioxide reactivity is not affected by it.

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%.

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.

Cephalosporin belongs to a family of beta-lactam antibiotics. All ?-lactam antibiotics interfere with the synthesis of the bacterial cell walls. The ?-lactam antibiotics inhibit the transpeptidases so that cross-linking (which maintains the close-knit structure of the cell wall) does not take place i.e. they inhibit bacterial cell wall formation.

Caudal analgesia using bupivacaine is a widely employed technique for achieving both intraoperative and early postoperative pain relief. 0.5 ml/kg of 0.25% plain bupivacaine is favoured by many practitioners who employ this fixed scheme for procedures involving sacral dermatomes (circumcision, hypospadias repair) as well as lower thoracic dermatomes (orchidopexy). However, there are other dosing regimens for caudal blocks with variable analgesic success rates: These include 0.75 ml/kg, 1.0 ml/kg and 1.25 ml/kg.

A study indicated that plain bupivacaine 0.25% at a dose of 0.75 ml/kg compared to a dose of 0.5 ml/kg when administered for herniotomies provided improved quality of caudal analgesia with a low side effects profile. There were consistently more patients with favourable objective pain scale (OPS) scores at all timelines, increased the time to the analgesic request with similar postoperative consumption of paracetamol in the group of patients who received 0.75 ml/kg of 0.25% bupivacaine.

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

The maximum safe amount of bupivacaine is 2mg/kg. Addition of adrenaline slows down absorption of the local anaesthetic and allows a maximum dose of 2.5mg/kg to be used.

The maximum safe dose of bupivacaine for this patient is 125 mg.

A 0.125% solution will contain 0.125g/100mL or 125mg/100 mL.

The maximum volume of local anaesthetic is approximately 80-100 mL.

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 action of class 1 anti-arrhythmic is sodium channel blockade. Subclasses of this action reflect effects on the action potential duration (APD) and the kinetics of sodium channel blockade.

Drugs with class 1A prolong the APD and refractory period, and dissociate from the channel with intermediate kinetics.

Drugs with class 1B action shorten the APD in some tissues of the heart, shorten the refractory period, and dissociate from the channel with rapid kinetics.

Drugs with class 1C action have minimal effects on the APD and the refractory period, and dissociate from the channel with slow kinetics.

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).

When the loading dose of Digoxin is given, the primary thing to consider is the volume of distribution. The volume of distribution is the proportionality factor that relates the total amount of drug in the body to the concentration. LD is computed as:

LD = Volume of distribution X (desired plasma concentration/bioavailability)

Digoxin is an anti-arrhythmic drug with a large volume of distribution and high bioavailability, and only a small percentage of Digoxin is bound to plasma proteins (,20%).

In the case, since the arrhythmia is not life-threatening, there is no need for the medication to work rapidly.

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic ? and?1 (but not ?2 ) agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of Dopamine 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?1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (?1 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 ? and ? receptors; does not penetrate the blood-brain barrier—no CNS effects.

Dopamine is less arrhythmogenic than adrenaline

Regarding dopamine part of the dose is converted to Noradrenaline in sympathetic nerve terminals.

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.

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

Oxytocin is secreted by the posterior pituitary along with ADH. It increases uterine contractions – 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.

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.

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

The National Institute for Health and Care Excellence (NICE) has published guidelines on infective endocarditis prophylaxis (IE). The goal was to create clear guidelines for antibiotic prophylaxis in patients undergoing dental procedures as well as certain non-dental interventional procedures. A number of studies have found an inconsistent link between recent interventional procedures and the development of infective endocarditis in both dental and non-dental procedures.

Antibiotic prophylaxis against infective endocarditis is not advised or required in the following situations:

Dental patients undergoing procedures
Patients undergoing procedures involving the upper and lower gastrointestinal tracts, the genitourinary tract (including urological, gynaecological, and obstetric procedures, as well as childbirth), and the upper and lower respiratory tract (including ear, nose and throat procedures and bronchoscopy).

Antibiotic resistance can be exacerbated by the indiscriminate use of prophylactic antibiotics, but this is not the primary reason for avoiding their use in these situations.

To reduce the risk of endocarditis, any patient who is at risk of developing IE should be investigated and treated as soon as possible. Patients with the following conditions are at risk of developing IE:
acquired valvular heart disease with regurgitation or stenosis
previous valve replacement
structural congenital heart disease
past history of IE, or
hypertrophic cardiomyopathy (HOCM)

It would also be appropriate for high-risk dental procedures and those with severe gingival disease.

Although this patient may not have structural heart disease, ABs should be administered on a case-by-case basis.

Sucralfate is an octasulfate of glucose to which Al(OH)3 has been added. It undergoes extensive cross-linking in an acidic environment and forms a polymer which adheres to the ulcer base for up to 6 hours and protects it from further erosion. Since it is not systemically absorbed it is virtually devoid of side effects. However, it may cause constipation in about 2% of cases due to the Aluminium component in it.

Sucralfate does not have antibacterial action against Helicobacter pylori. However, Bismuth has antibacterial action due to its oligodynamic effect.

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.

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

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

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

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

Benzodiazepines are GABAA receptor agonists that affect chloride influx.

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

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

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.

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

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

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

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

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

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.

In first order kinetics the rate of elimination is proportional to plasma concentration.

Rate of elimination is described by the following equation:

C = C0. e^-kt

Where:
C=drug concentration,
C0= drug concentration at time zero (extrapolated),
k = rate constant and
t = time.

The initial concentration of this drug is 12 mcg/ml therefore:

The plasma concentration will have halved to 6 mcg/ml at 2 hours.
The plasma concentration will have halved to 3 mcg/ml at 4 hours and
The plasma concentration will have halved to 1.5 mcg/ml t 6 hours.

Mast cell tryptase is a reliable marker of mast cell degranulation. Tryptase is a protease enzyme that acts via widespread protease-activated receptors (PARs).

Erythromycin binds to the 50s subunit of bacterial rRNA complex and inhibits protein synthesis.

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.