Patients who present for surgery may be on prescription medication or natural/herbal therapies. These have relevance for anaesthesia since they can cause drug interactions.

Ephedra (Ma Huang) is a drug derived from the plant Ephedra sinica that is used as a CNS stimulant, weight reduction aid, and asthma therapy. It is a combination of alkaloids that includes ephedrine which stimulates noradrenaline release from pre-synaptic neurones by acting directly on alpha and beta adrenoreceptors. The use of sympathomimetic drugs together can cause cardiovascular instability.

Ginkgo Biloba contains anti-oxidant characteristics and is used to treat Alzheimer’s disease, vascular dementia, and peripheral vascular disease. It lowers platelet adhesiveness and raises the risk of bleeding by decreasing platelet activating factor (PAF), especially in individuals who are also taking anticoagulants and antiplatelet drugs.

The extract from St. John’s Wort is utilised as an antidepressant because it is a cytochrome P450 isoenzyme inhibitor as well as a serotonin uptake inhibitor. When drugs like fentanyl or tramadol are used during an anaesthetic, there is a risk of serotonin syndrome developing.

The root of a pepper is used to make kava (Piper methysticum). It is a weak GABAA agonist which has the potential to augment the effects of propofol and benzodiazepines, which are volatile anaesthetics.

Garlic is made from the allium sativum plant and is used to treat hypertension and hyperlipidaemia. It includes cysteine, which inhibits platelet aggregation irreversibly, amplifying the effects of aspirin and NSAIDs.

Echinacea is a common herbal medicine that stimulates the immune system by modulating cytokine signalling. In individuals who require organ transplantation, it should be avoided.

Nausea and vomiting occur commonly due to Chemoreceptor Trigger Zone (CTZ) stimulation by dopamine (Domperidone but not metoclopramide can be used for the treatment of this vomiting)

Dopamine itself cannot cross the blood-brain barrier (BBB) but its precursor levodopa can cross BBB.

Dopamine can modulate extrapyramidal symptoms like acute dyskinesia, tardive dyskinesia, Parkinsonism, and Neuroleptic malignant syndrome.

Dopamine inhibits the secretion of prolactin from the pituitary gland.

Staphylococcus aureus colonizes the nasopharynx in >20% of the general population.

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to flucloxacillin.

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.

All ?-lactam antibiotics like penicillin 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

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.

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.

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

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

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

Doxazosin is selective alpha 1 blocker (it causes less tachycardia than a non-selective alpha-blocker) and is the drug of choice for a patient with hypertension and benign hyperplasia of the prostate (BHP).

The major adverse effect of an alpha-blocker is first-dose hypotension.

Atenolol and Labetalol are beta blockers. It works by relaxing blood vessels and slowing heart rate to improve blood flow and decrease blood pressure.

Clonidine is an α2A-adrenergic agonist used to treat high blood pressure, ADHD, drug withdrawal (alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and certain pain conditions.

Methyldopa is a centrally-acting alpha-2 adrenergic agonist used to manage hypertension alone or in combination with hydrochlorothiazide, and to treat hypertensive crises.

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.

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

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

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

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

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

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).

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.

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.

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.

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

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.

Selective ?1 -Blockers like prazosin, terazosin, doxazosin, and alfuzosin cause a decrease in blood pressure with lesser tachycardia than nonselective blockers (due to lack of ?2 blocking action.

The major adverse effect of these drugs is postural hypotension. It is seen with the first few doses or on-dose escalation (First dose effect).

Its half-life is approximately three hours.

It is excreted primarily through bile and faeces (not through kidneys)

Epoprostenol has a half-life of only 42 seconds and has rapid offset. It is used for the treatment of pulmonary hypertension.

Aspirin inhibits the COX enzyme irreversibly. It inhibits thromboxane synthesis but does not inhibit the enzyme thromboxane synthetase.

Ticlopidine, clopidogrel and prasugrel act as irreversible antagonists of P2 Y12 receptor of Adenosine Diphosphate (ADP). These drugs interfere with the activation of platelets by ADP and fibrinogen. Both aspirin and clopidogrel act irreversibly so they are not correct.

Paclitaxel is a long-acting antiproliferative agent used for the prevention of restenosis (recurrent narrowing) of coronary and peripheral stents and is not the correct answer.

Tirofiban has the next shortest duration of action after epoprostenol. If epoprostenol is not given in the question, it would be the best answer.

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.

Drug elimination is the termination of drug action, and may involve metabolism into inactive state and excretion out of the body. Duration of drug action is determined by the dose administered and the rate of elimination following the last dose.

There are two types of elimination: first-order and zero-order elimination.

In first-order elimination, the rate of elimination is proportionate to the concentration; the concentration decreases exponentially over time. It observes the characteristic half-life elimination, where the concentration decreases by 50% for every half-life.

In zero-order elimination, the rate of elimination is constant regardless of concentration; the concentration decreases linearly over time. A constant amount of the drug being excreted over time, and it occurs when drugs have saturated their elimination mechanisms.

Since phenytoin is observed in elevated levels, the elimination mechanisms for it has been saturated and, thus, will have to undergo zero-order elimination.

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.

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.

Lesser the potency of the drug, the higher the dose required to produce maximal receptor occupation. So, the least potent drug will have a log dose-response curve furthest to the right on X-axis.

Based on the option given, tramadol is the least potent drug and thus higher dose is required to produce maximal opioid receptor occupation.

Thus, Tramadol is the least potent opioid with a log dose-response curve furthest to the right on X-axis.

Note, Fentanyl is the most potent opioid with a log dose-response curve furthest to the left on the X-axis.

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.

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

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.

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.

10 mcg/kg (0.1 ml/kg of 1 in 10 000 adrenaline) = 180 mcg is the appropriate dose of intravenous or intraosseous adrenaline.

The correct energy level to deliver is 4 J/kg, which equals 72 joules.

The pad size that is appropriate for this patient is 8-12 cm. For an infant, a 4.5 cm pad is appropriate.

To allow adequate separation in infants and small children, the pads should be placed anteriorly and posteriorly on the chest.

When using a bag and mask to ventilate, take two breaths for every 15 chest compressions. If chest compressions are being applied intubated and without interruption, a ventilation rate of 10-20 breaths per minute should be given.

Chest compressions should be done at a rate of 100-120 per minute, the same as an adult.

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.

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.

The pH at which the drug exists in 50 percent ionised and 50 percent unionised forms is known as the pKa.

To calculate the proportion of ionised to unionised form of an ACID, use the Henderson-Hasselbalch equation.

pH = pKa + log ([A-]/[HA])

or

pH = pKa + log [(salt)/(acid)]
pH = pKa + log ([ionised]/[unionised]).

Hence, if the pKa − pH = 0, then 50% of drug is ionised and 50% is unionised.

In this example:

7.4 = 4.3 + log ([ionised]/[unionised])
7.4 − 4.3 = log ([ionised]/[unionised])
log 3.1 = log ([ionised]/[unionised])

Simply put, the antilog is the inverse log calculation. In other words, if you know the logarithm of a number, you can use the antilog to find the value of the number. The antilogarithm’s definition is as follows:

y = antilog x = 10x

Antilog to the base 10 of 0 = 1, 1 = 10, 2 =100, 3 = 1000, and 4 = 10,000.

If you want to find the antilogarithm of 3.1, for a number between 3 and 4, the antilogarithm will return a value between 1000 and 10,000. The ratio is 1:1 if pKa = pH, that is, pH pKa = log 0. (50 percent ionised and unionised).

According to the above value, there is only one unionised molecule for every approximately 1000 (1259) ionised molecules of this drug in plasma, implying that this drug is largely ionised in plasma (99.99 percent ).

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.

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

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

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

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

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

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.

The statement Epinephrine is formulated as 1 in 1000 solution means 1 gm epinephrine is present in 1000 ml of solution.

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

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.

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.

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.

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.

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.

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%.

The Beers criteria, a US set of criteria for good prescribing in the older patient, preclude the use of metoclopramide in Parkinson’s disease. The Adverse Reactions Register of the UK Committee on Safety of Medicines (CSM) for the years 1967 to 1982 contained 479 reports of extrapyramidal reactions in which metoclopramide was the suspected drug; 455 were for dystonic-dyskinetic reactions, 20 for parkinsonism and four for tardive dyskinesia. Effects can occur within days of initiation of treatment and may take months to wear off.

Other antiemetics are available, such as cyclizine (Valoid), domperidone and ondansetron, which would be more appropriate to use in those with Parkinson’s disease.

Cyclizine is a piperazine derivative with histamine H1 receptor antagonist and anticholinergic activity. It is used for the treatment of nausea, vomiting, (particularly opioid-induced vomiting), vertigo, motion sickness, and labyrinthine disorders.

Prochlorperazine is an antipsychotic known to cause tardive dyskinesia, tremor and parkinsonian symptoms and is therefore likely to exacerbate Parkinson’s disease. Prochlorperazine is not favoured for older patients because of the increased risk of stroke and transient ischaemic attack (TIA).

Droperidol and phenothiazine are also potent antagonists on D2 receptors and must also be avoided.

An agonist is a molecule with intrinsic efficacy and affinity for a receptor. The ability of a drug-receptor interaction to produce a maximal response is referred to as intrinsic efficacy or activity. Efficacy also refers to a drug’s ability to have a therapeutic or beneficial effect. Although the potencies of morphine and fentanyl differ, they both have the same intrinsic efficacy.

The amount of drug required to produce a given effect is referred to as potency. If drug X is effective in a dose of 100 mcg, its potency is greater than if drug Y is effective in a dose of 10 mg.

The therapeutic index, also known as the margin of safety, is a ratio of the lethal or serious side effect dose of a drug divided by the therapeutic dose of the same drug.

The term bioavailability refers to the ability of a substance to be absorbed. The area under a curve (AUC) of a graphic plot of plasma concentration and time is used to calculate oral bioavailability. It’s used to figure out how much of a drug to take and when to take it.

Sugammadex is a modified cyclodextrin that works as an aminosteroid neuromuscular blocking (nmb) reversal agent. By encapsulating each molecule in the plasma, it rapidly reverses rocuronium and, to a lesser extent, vecuronium-induced neuromuscular blockade. Consequently, a  concentration gradient favours the movement of these nmb agents away from the neuromuscular junction.  Pancuronium-induced neuromuscular blockade at low levels has also been reversed.

By inhibiting voltage-dependent calcium channels at the neuromuscular junction, antibiotics in the aminoglycoside group potentiate neuromuscular blocking agents. This can be reversed by giving calcium but not neostigmine or sugammadex.

Sugammadex will not reverse the effects of mivacurium, which belongs to the benzylisoquinolinium class of drugs.

A phase II or desensitisation block occurs when the motor end-plate becomes less sensitive to acetylcholine as a result of an overdose or repeated administration of suxamethonium. The use of neostigmine has been shown to be effective in reversing this weakness.

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.

When responsiveness diminishes rapidly after administration of a drug, the response is said to be subject to tachyphylaxis. This may be due to frequent or continuous exposure to agonists, which often results in short-term diminution of the receptor response.

Many mechanisms may be responsible, such as blocking access of G protein to activated receptor, or receptor molecules internalized by endocytosis to prevent exposure to extracellular molecules.

Tolerance occurs when larger doses are required to produce the same effect. This may be due to changes in receptor number or function due to exposure to the drug.

Desensitization refers to the common situation where the biological response to a drug diminishes when it is given continuously or repeatedly. It is a chronic loss of response, occurring over a longer period than tachyphylaxis. It may be possible to restore the response by increasing the dose (or concentration) of the drug but, in some cases, the tissues may become completely refractory to its effect.

Drug dependence is defined as a psychic and physical state of the person characterized by behavioural and other responses resulting in compulsions to take a drug, on a continuous or periodic basis in order to experience its psychic effect and at times to avoid the discomfort of its absence.

A compound that contains an asymmetric centre (chiral atom or chiral centre) and thus can occur in two non-superimposable mirror-image forms (enantiomers) are called chiral compounds.

Desflurane, Halothane, and isoflurane are chiral compounds but Sevoflurane is not a chiral compound.

The ideal gas equation makes the following assumptions:

The gas particles have a small volume in comparison to the volume occupied by the gas.
Between the gas particles, there are no forces of interaction.
Individual gas particle collisions, as well as gas particle collisions with container walls, are elastic, meaning momentum is conserved.
PV = nRT
Where:

P = pressure
V = volume
n = moles of gas
T = temperature
R = universal gas constant

Helium is a monoatomic gas with a small helium atom. The attractive forces between helium atoms are small because the helium atom is spherical and has no dipole moment. Because helium atoms are spherical, collisions between them approach the ideal state of elasticity.

Most real gases behave qualitatively like ideal gases at standard temperatures and pressures. When intermolecular forces and molecular size become important, the ideal gas model tends to fail at lower temperatures or higher pressures. It also fails to work with the majority of heavy gases.

Helium, argon, neon, and xenon are noble or inert gases that behave the most like an ideal gas. Xenon is a noble gas with a much larger atomic size than helium.

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.

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

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

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

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

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

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

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

Prednisolone 5 mg is the same as 20 mg hydrocortisone.

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

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

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