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.

Chloramphenicol binds to the 50s subunit and inhibits peptidyl transferase

Clindamycin binds to the 50s ribosomal subunit of bacteria and disrupts protein synthesis by interfering with the transpeptidation reaction, which thereby inhibits early chain elongation.

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.

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).

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

Elimination of phenytoin from the body follows first-order kinetics. This means that the rate of elimination is proportional to plasma concentration.

The rate of elimination can be described by the equation:

C = C0·e-kt

Where:

C = drug concentration
C0 = drug concentration at time zero (extrapolated)
k = Rate constant
t = Time

Enzyme systems become saturated when phenytoin concentrations exceed the normal range and elimination of the drug becomes zero-order. At this point, the drug is metabolised at a fixed rate and metabolism is independent of plasma concentration.

Aspirin and ethyl alcohol are other drugs that behave this way.

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.

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.

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.

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.

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.