Adenosine is the first line for AV nodal re-entry tachycardia. An initial dose of 6 mg is given, and a consequent second dose or third dose of 12 mg is administered if the initial dose fails to terminate the arrhythmia.

Aside from Adenosine, a vagal manoeuvre (e.g. carotid massage) is done to help terminate the supraventricular arrhythmia.

Amiodarone is not a first-line drug for supraventricular tachycardias. Digoxin and Propranolol can be considered if the arrhythmia is of a narrow complex irregular type. Verapamil is an alternative to Adenosine if the latter is contraindicated.

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

An INSIGNIFICANT amount of metabolism occurs in the intestinal mucosa.

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

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

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

The clinical potency of the anaesthetic agent is measured using minimal alveolar concentration(MAC).

MAC and oil: gas partition coefficient is inversely related. Anaesthetic agent Oil/gas partition coefficient and Minimal alveolar concentration (MAC) is given respectively as

Desflurane 18 6
Isoflurane 90 1.2
Nitrous oxide 1.4 104
Sevoflurane 53.4 2
Xenon 1.9 71

With these data, we can conclude Isoflurane is the most potent with the highest oil/gas partition coefficient of 90 and the lowest MAC of 1.2

Insulin is secreted from the ? 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)

The ?-2 adrenoceptor has three subtypes (2a, 2b and 2c). The receptors are generally presynaptic, meaning they prevent noradrenaline from being released at nerve endings. Both the central and peripheral nerve systems are affected by the ?-2 agonists. ?-2 agonists cause drowsiness, analgesia, and euphoria centrally in the locus coeruleus (in the brainstem), lower the MAC of volatile anaesthetic drugs, and are used to treat acute withdrawal symptoms in chronic opioid addicts.

The most common impact of ?-2 agonists on heart rate is bradycardia. The adrenoreceptors ?-1 and ?-2 are blocked by phenoxybenzamine.

Clonidine is a selective agonist for the ? -2 receptor, having a 200:1 affinity ratio for the ?-2: ?-1 receptors, respectively.

Tizanidine is similar to clonidine but has a few key variances. It has the same sedative, anxiolytic, and analgesic characteristics as clonidine, although for a shorter period of time and with less effect on heart rate and blood pressure.

Dexmedetomidine, like clonidine, is a highly selective ?-2 adrenoreceptor agonist having a higher affinity for the ?-2 receptor. In the case of ?-2: ?-1 receptors, the affinity ratio is 1620:1. It has a biphasic blood pressure impact and induces a brief rise in blood pressure and reflex bradycardia (activation of ?-2b subtypes of receptors in vascular smooth muscles), followed by a reduction in sympathetic outflow from the brainstem and hypotension/bradycardia.

A prodrug is methyldopa. It blocks the enzyme dopa-decarboxylase, which converts L-dopa to dopamine (a precursor of noradrenaline and adrenaline). It is also converted to alpha-methyl noradrenaline, a centrally active agonist of the ?-2 adrenoreceptor. These two processes contribute to its blood pressure-lowering effect. Without a rise in heart rate, cardiac output is generally maintained. The heart rate of certain patients is slowed.

Phentolamine is a short-acting antagonist of peripheral ?-1 and ?-2 receptors that causes peripheral vascular resistance to reduce and vasodilation to increase. It’s used to treat hypertensive situations that aren’t life threatening (e.g. hypertension from phaeochromocytoma).

A baroreceptor reflex commonly causes reflex tachycardia when systemic vascular resistance drops.

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

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).

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.

According to the 2015 National Institute for Health and Care Excellence (NICE) Guidelines, antibiotic prophylaxis against infective endocarditis (IE) is not recommended routinely for people with any cardiac defect (corrected or uncorrected) due to lack of sufficient evidence regarding its benefits. Instead, antibiotic prophylaxis is recommended for those who are at risk of developing IE, such as those with acquired valvular heart disease with stenosis or regurgitation; hypertrophic cardiomyopathy; valve replacement; and previous IE.

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.

Drug A is a pure agonist for the receptor, with high intrinsic efficacy and affinity, according to the log-dose response curve.

Drug B, on the other hand, works as a competitive antagonist. It binds to the receptor but has no inherent efficacy. Drug A’s efficacy will not change, but its potency will be reduced.

A partial agonist is a drug with partial intrinsic efficacy and affinity for the receptor. Giving a partial agonist after a pure agonist will not increase receptor occupancy or decrease receptor activity, and thus will not affect drug A’s efficacy. The inverse agonist flumazenil can reverse all benzodiazepines.

An inverse agonist is a drug that binds to the receptor but has the opposite pharmacological effect.

A non-competitive antagonist is a drug that has affinity for a receptor but has different pharmacological effects and reduces the efficacy of an agonist for that receptor.

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.

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.

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.

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.

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.

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.

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.

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.

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 cyclic adenosine monophosphate).

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 Central nervous system effects.

Dopamine is less arrhythmogenic than adrenaline

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

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.

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.

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

Soda-lime contains mostly calcium hydroxide (about 94%) and remaining sodium hydroxide.

CO2 + Ca(OH)2 → CaCO3 + H2O + heat
Here in this exothermic reaction, we can see that the production of calcium carbonate does not require heat.

When soda lime is allowed to dry with subsequent use of desflurane, isoflurane, and enflurane, it can lead to the generation of carbon monoxide.

Silica hardens the granules and can thus prevent disintegration.

The size of soda-lime granules is 4-8 mesh because it allows sufficient surface area for chemical reaction to occur without critically increasing the resistance to airflow.

Ketamine is primarily used for the induction and maintenance of anaesthesia. It induces dissociative anaesthesia. But it is contraindicated in cardiovascular diseases such as unstable angina or poorly controlled hypertension.

Tricyclic antidepressants (TCA) are primarily used as antidepressants which is important for the management of depression. These are second-line drugs next to SSRI. They work by competitively preventing re-uptake of amines (noradrenaline and serotonin) from the synaptic cleft so increasing their concentration. But TCA overdoses are toxic and have cardiovascular effects, central effects, and anticholinergics effects. Cardiovascular effects like prolonged QT and widened QRS at lower doses progressing to ventricular arrhythmias and refractory hypotension at higher doses can be life-threatening. When used in the perioperative period, it can lead to increased sensitivity to circulating catecholamines therefore care is needed perioperatively.

The neuroleptic malignant syndrome is a rare complication in response to neuroleptic or antipsychotic medication.

The main features are:
– Elevated creatinine kinase
– Hyperthermia and tachycardia
– Altered mental state
– Increased white cell count
– Insidious onset over 1-3 days
– Extrapyramidal dysfunction (muscle rigidity, tremor, dystonia)
– Autonomic dysfunction (Labile blood pressure, sweating, salivation, urinary incontinence)

Management is supportive ICU care, anticholinergic drugs, increasing dopaminergic activity with Amantadine, L-dopa, and dantrolene, and non- depolarising neuromuscular blockade drugs

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.

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

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).

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).