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.

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

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.

With a history of drug abuse, the patient is likely dependent on and tolerant to opioids. He is also likely to experience significant pain from his injuries. Providing adequate pain relief with regular paracetamol and NSAIDs in combination with a pure opioid agonist while at the same time avoiding occurrence of acute withdrawal syndrome is the goal.

Administering a baseline dose of opioid corresponding to the patient’s usual opioid use plus an opioid dose required to address the level of pain the patient experience can help prevent opioid withdrawal. The best approach is by empowering the patient to use patient controlled analgesia (PCA). The infusion rate, bolus dose and lock-out time are adjusted accordingly. Using PCA helps in avoiding staff/patient confrontations about dose and dosing interval.

2.5 mg heroin is equivalent to 3.3 mg morphine. This patient is usually on 200 mg of heroin per 24 hours. The equivalent dose of morphine is 80 × 3.3 =254 mg per 24 hours (11 mg/hour).

Epidural or spinal opioids might be the best choice for providing a systemic dose of opioids when patients are in remission to avoid withdrawal. Lumbar vertebral fractures is a contraindication to this route of analgesia.

The long half life of Oral methadone make titration to response difficult. Also, absorption of methadone by the gastrointestinal tract is variable. It is therefore NOT the best choice for acute pain management.

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.

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.

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

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

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

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.

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

Because alpha glucosidase inhibitors slow starch digestion in the small intestine, glucose from a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity, glucose from a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity.

Biguanides decrease hepatic glucose output while increasing glucose uptake in peripheral cells.

The meglitinides are secretagogues that act on a different site of the KATP receptors.

Insulin secretion is stimulated by sulphonylureas, which stimulate insulin secretion from pancreatic beta cells. The KATP channels are inhibited by these substances.

Insulin-sensitive genes are influenced by thiazolidinediones, which increase the production of mRNAs for insulin-dependent enzymes. As a result, the cells make better use of glucose.

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.

The ideal volatile agent for a day case surgery inhalational induction should have the following characteristics:

It has a pleasant scent that is not overpowering.
Breathing difficulties, coughing, or laryngeal spasm are not caused by this substance.
The action has a quick onset and a quick reversal.

The blood:gas partition coefficient is a physicochemical property of a volatile agent that determines the onset and offset of anaesthesia. The greater an agent’s insolubility in plasma, the faster its alveolar concentration rises.

The blood gas partition coefficients of the most commonly used volatile anaesthetic agents are as follows:
Halothane 2.3
Desflurane 0.45
Sevoflurane 0.6
Nitrous oxide 0.47
Isoflurane 1.4

Although halothane has a pleasant odour, it has a slower offset than sevoflurane.

Sevoflurane also has a pleasant odour and is less likely than desflurane to cause airway irritation and breath-holding.

The choice of agent for inhalational induction is unaffected by potency/lipid solubility measures such as the oil: gas partition coefficient and MAC.

In this case, an agent’s saturated vapour pressure is irrelevant.

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.

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.

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 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?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 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

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.

Opioid should be avoided in the caesarean section as it crosses the placental membrane and causes respiratory depression.

Even though inhalational and intravenous anaesthetic agents readily cross the placenta, they do not have significant effects on APGAR score when used in clinical doses.

Vecuronium and suxamethonium are highly polar molecules and thus do not cross the placenta in significant amounts.

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.

Dystonia is characterised by repetitive twisting movements or abnormal postures. They are classified as either primary or secondary.

Primary dystonia is a genetic disorder that is inherited in an autosomal dominant pattern.
Secondary dystonia can be caused by focal brain lesions, Parkinson’s disease, or certain medications.

The following drugs cause the most common drug-induced dystonic reactions:
Antipsychotics, antiemetics (especially prochlorperazine and metoclopramide), and antidepressants.

Following the administration of the neuroleptic prochlorperazine, 16 percent of patients experience restlessness (akathisia) and 4% experience dystonia.

Several published reports have linked the anaesthetics thiopentone, fentanyl, and propofol to opisthotonos and other abnormal neurologic sequelae. Dystonias following a general anaesthetic are uncommon. Tramadol has been linked to serotonin syndrome, while remifentanil has been linked to muscle rigidity.

The following are some of the risk factors:

Positive family history
Male
Children
An episode of acute dystonia occurred previously.
Dopamine receptor (D2) antagonists at high doses and recent cocaine use

Dystonia is treated in a variety of ways, including:

Benztropine (as a first-line therapy):

1-2 mg intravenous injection for adults
Child: 0.02 mg/kg to 1 mg maximum

Benzodiazepines are a type of benzodiazepine (second line treatment).

Midazolam:

1-2 mg intravenously, or 5-10 mg IV/PO diazepam

Antihistamines with anticholinergic activity (H1receptor antagonists):

Promethazine 25-50 mg IV/IM, or diphenhydramine 50 mg IV/IM (1 mg/kg in children) are used when benztropine is not available.

Moderately high doses of dopamine produce a positive inotropic (direct?1 and D1 action + that due to Noradrenaline 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.

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.

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.

Therapeutic index is a measure which relates the dose of a drug required to produce a desired effect to that which produces an undesired effect.

In humans, it is usually defined as the ratio of the toxic dose for 50% of the population (TD50) to the minimum effective dose for 50% of the population (ED50) for some therapeutically relevant effect. In animal studies, the therapeutic index can be defined as the ratio of the median lethal dose (LD50) to the ED50.

Selegiline is a monoamine oxidase inhibitor. Inhibition of monoamine oxidase leads to increased levels of norepinephrine and serotonin in the central nervous system.

Pethidine, also known as meperidine, is a strong agonist at the mu and kappa receptors. It inhibits pain neurotransmission and blocks muscarinic-specific actions.

Administering opioid analgesic is relatively contraindicated to individuals taking monoamine oxidase inhibitors. This is because of the high incidence of serotonin syndrome, which is characterized by fever, agitation, tremor, clonus, hyperreflexia and diaphoresis. Onset of symptoms is within hours, and the treatment is mainly through sedation, paralysis, intubation and ventilation.

The clinical findings are more consistent with Serotonin syndrome rather than exacerbation of Parkinson’s. Parkinson’s Disease (PD) exacerbations are defined as patient-reported or caregiver-reported episodes of subacute worsening of PD motor function in 1 or more domains (bradykinesia, tremor, rigidity, or PD-related postural instability/gait disturbance) that caused a decline in functional status, developed over a period of < 2 months, did not fluctuate with medication timing, and are not caused by intentional adjustments of PD medications by the treating neurologist. Malignant hyperthermia usually occurs within minutes of administration of a volatile anaesthetic, such as halothane, or succinylcholine. There is massive release of calcium from the sarcoplasmic reticulum, leading to fever, acidosis, rhabdomyolysis, trismus, clonus, and hypertension. In sepsis, it more common for patients to present with hypotension rather than hypertension.

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.

Therapy with gabapentin requires dose adjustment with renal diseases. However, plasma monitoring of the drug is not necessary.

Gabapentin is not a liver enzyme inducer unlike other anticonvulsants like phenytoin and phenobarbitone

Gabapentin has not been shown to be associated with visual disturbances.

Gabapentin is used for add-on therapy in partial or generalized seizures and used in the management of chronic pain conditions but is of no use in petit mal.

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.

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.