Magnesium Pharmacology

Quick Answer

Magnesium (Mg²⁺) is the fourth most abundant cation in the body and second most abundant intracellular cation, with critical roles in over 300 enzymatic reactions, neuromuscular transmission, and cardiac electrophysiology. Intravenous magnesium sulfate acts primarily through non-competitive NMDA receptor antagonism, voltage-dependent calcium channel blockade (L-type and T-type), and competitive antagonism at the neuromuscular junction (NMJ) presynaptically reducing acetylcholine release and postsynaptically decreasing receptor sensitivity. Pharmacokinetics are characterized by minimal protein binding (25-30%), rapid distribution to intracellular compartments (Vd 0.3-0.5 L/kg), and exclusively renal elimination with a half-life of 4-5 hours in normal renal function. Therapeutic serum levels are 2.0-3.5 mmol/L for eclampsia prophylaxis. Primary clinical applications in anaesthesia and critical care include pre-eclampsia/eclampsia (1st line anticonvulsant), torsades de pointes (Class I recommendation), refractory bronchospasm, phaeochromocytoma resection, and multimodal analgesia. Toxicity manifests progressively: loss of deep tendon reflexes (>5 mmol/L), respiratory depression (>6 mmol/L), cardiac arrest (>7.5 mmol/L). Calcium gluconate 10% (10-20 mL IV) provides rapid reversal by direct physiological antagonism. [1-8]

Physiological Role of Magnesium

Total Body Distribution and Homeostasis

Magnesium is the fourth most abundant cation in the human body, with total body stores of approximately 24 grams (1000 mmol) in a 70 kg adult. Distribution follows a characteristic pattern: approximately 53% resides in bone as a surface-bound component of hydroxyapatite crystals, 27% in skeletal muscle, 19% in soft tissues, and only 0.3% (approximately 21 mmol) in serum. Of serum magnesium, approximately 55% exists as free ionized Mg²⁺ (the physiologically active fraction), 30% is protein-bound (primarily albumin), and 15% is complexed with anions (citrate, phosphate, bicarbonate). Normal serum magnesium concentration ranges from 0.7-1.0 mmol/L (1.7-2.4 mg/dL), though this poorly reflects total body stores since only 1% of magnesium is extracellular. Hypomagnesemia is common in critically ill patients, affecting 20-65% of ICU admissions, with associated increased mortality and prolonged ventilator dependence. [1-5]

Cellular Functions and Enzymatic Cofactor Roles

Magnesium serves as an essential cofactor for over 300 enzymatic reactions, particularly those involving ATP. The Mg²⁺-ATP complex is the true substrate for most kinases, ATPases, and adenylyl cyclases. Key magnesium-dependent enzymes include Na⁺/K⁺-ATPase (maintaining cellular membrane potential), Ca²⁺-ATPase (calcium homeostasis), hexokinase and phosphofructokinase (glycolysis), and DNA/RNA polymerases (nucleic acid synthesis). Magnesium stabilizes negatively charged phosphate groups on nucleotides, phospholipids, and nucleic acids. At the cellular level, magnesium regulates membrane permeability by modulating ion channel function, maintains membrane potential through Na⁺/K⁺-ATPase activity, and influences intracellular calcium signaling. The intracellular magnesium concentration (0.5-1.0 mmol/L) is approximately 1000-fold lower than extracellular calcium, allowing magnesium to serve as an intracellular calcium antagonist, modulating calcium-dependent processes including muscle contraction, neurotransmitter release, and hormone secretion. [6-10]

Renal Handling and Homeostasis

Magnesium homeostasis is primarily maintained through renal regulation, as there is no hormonal feedback system comparable to parathyroid hormone for calcium. The kidney filters approximately 2400 mg (100 mmol) of magnesium daily, with 95-97% being reabsorbed. Reabsorption occurs in distinct nephron segments: 15-20% in the proximal convoluted tubule (passive, paracellular), 60-70% in the thick ascending limb of the loop of Henle (paracellular via claudin-16 and claudin-19), and 5-10% in the distal convoluted tubule (active, transcellular via TRPM6 channels). Loop diuretics inhibit magnesium reabsorption in the thick ascending limb, contributing to hypomagnesemia. Thiazide diuretics affect distal tubular reabsorption. Factors increasing renal magnesium excretion include volume expansion, hypercalcemia, hyperglycemia, alcohol, and certain drugs (aminoglycosides, cisplatin, cyclosporine). Dietary magnesium absorption occurs primarily in the small intestine (30-50% bioavailability), with absorption efficiency inversely related to intake. [11-15]

Mechanism of Action

NMDA Receptor Antagonism

Magnesium acts as a non-competitive, voltage-dependent blocker of the N-methyl-D-aspartate (NMDA) glutamate receptor ion channel. At resting membrane potential, Mg²⁺ ions occupy the NMDA receptor channel pore, physically blocking Ca²⁺ and Na⁺ influx even when glutamate and glycine are bound. This voltage-dependent block is relieved upon membrane depolarization, allowing the NMDA receptor to conduct current during sustained or repeated activation. The IC₅₀ for magnesium block of NMDA receptors is approximately 1 mmol/L at -60 mV membrane potential. This mechanism underlies magnesium's anticonvulsant properties, neuroprotective effects, and analgesic actions. In the spinal cord dorsal horn, NMDA receptor blockade reduces central sensitization and wind-up phenomena, contributing to magnesium's role in multimodal analgesia. The anticonvulsant effect in eclampsia is mediated primarily through central NMDA receptor antagonism, reducing neuronal hyperexcitability. Unlike ketamine (which binds within the channel), magnesium's voltage-dependent block allows for physiological NMDA receptor function during normal neurotransmission while preventing pathological overactivation. [16-20]

Voltage-Gated Calcium Channel Blockade

Magnesium blocks voltage-gated calcium channels (VGCC) through competitive inhibition at the external mouth of the channel pore. This blockade affects multiple VGCC subtypes: L-type channels (Cav1.1-1.4) predominantly in cardiac and smooth muscle, T-type channels (Cav3.1-3.3) in cardiac pacemaker tissue and neurons, and N-type channels (Cav2.2) at presynaptic nerve terminals. The cardiovascular effects of magnesium—including vasodilation, negative chronotropy, and antiarrhythmic properties—are substantially mediated through L-type calcium channel blockade in vascular smooth muscle and cardiac myocytes. In coronary and systemic arterioles, L-type channel blockade reduces calcium-mediated smooth muscle contraction, producing vasodilation. The IC₅₀ for L-type calcium channel blockade is 2-4 mmol/L. In uterine smooth muscle, calcium channel blockade reduces myometrial contractility, forming the basis for magnesium's tocolytic effect. The depression of sinoatrial and atrioventricular nodal automaticity through T-type calcium channel blockade contributes to heart rate reduction and PR interval prolongation observed with hypermagnesemia. [21-25]

Neuromuscular Junction Effects

Magnesium profoundly affects neuromuscular transmission through multiple mechanisms at the NMJ. Presynaptically, magnesium competes with calcium at the presynaptic voltage-gated calcium channels (P/Q-type, Cav2.1) that trigger acetylcholine (ACh) vesicle release. This competitive inhibition reduces Ca²⁺ influx during motor nerve terminal depolarization, diminishing the number of ACh quanta released per nerve impulse (quantal content). The normal quantal content (approximately 200-300 quanta per impulse) has a substantial safety margin; magnesium-induced reduction of quantal release typically does not produce clinical weakness until the safety margin is overwhelmed. Postsynaptically, elevated magnesium reduces the sensitivity of nicotinic ACh receptors to released acetylcholine, though this effect is less pronounced than presynaptic effects. The combined pre- and post-synaptic actions result in dose-dependent neuromuscular depression. Clinically, this manifests as potentiation of both depolarizing (succinylcholine) and non-depolarizing neuromuscular blocking agents (NMBAs), with dose reductions of 25-50% recommended when magnesium levels exceed 2 mmol/L. Patients with myasthenia gravis (reduced safety margin) or Eaton-Lambert syndrome (impaired presynaptic Ca²⁺ channels) are exquisitely sensitive to magnesium-induced neuromuscular weakness. [26-30]

Pharmacokinetics

Intravenous Administration and Distribution

Intravenous magnesium sulfate (MgSO₄) is the standard formulation for acute clinical use, providing 4 mmol (8 mEq, 98 mg) of elemental magnesium per gram of magnesium sulfate heptahydrate. Following IV bolus administration, serum magnesium rises rapidly with peak levels achieved within 15-30 minutes. The distribution phase involves equilibration between extracellular and intracellular compartments, with intracellular uptake occurring over 4-6 hours. The volume of distribution is 0.3-0.5 L/kg, reflecting distribution throughout total body water with preferential intracellular accumulation. Approximately 25-30% of circulating magnesium is protein-bound, predominantly to albumin; hypoalbuminemia increases the free ionized fraction. The relationship between total and ionized magnesium is less predictable than for calcium, making ionized magnesium measurement potentially more clinically relevant, though less widely available. [5, 31-35]

Renal Elimination

Magnesium is eliminated almost exclusively through renal excretion, with negligible hepatic metabolism or biliary excretion. The elimination half-life in patients with normal renal function is approximately 4-5 hours. Renal handling is characterized by glomerular filtration of unbound magnesium (approximately 70-75% of total serum magnesium) followed by tubular reabsorption. Under normal conditions, fractional excretion of magnesium is 3-5%; however, this increases dramatically with elevated serum levels, providing a homeostatic mechanism for magnesium excess. When serum magnesium exceeds the renal threshold (approximately 2.0-2.5 mmol/L), fractional excretion increases to 70-90%, resulting in rapid urinary elimination. This renal handling creates significant implications for dosing in renal impairment: patients with creatinine clearance less than 30 mL/min may have elimination half-life extended to 24-48 hours, necessitating substantial dose reduction (typically 50% of standard dose) and extended dosing intervals. In anuric patients, magnesium accumulation is inevitable without removal via dialysis, and routine magnesium supplementation is contraindicated. [36-40]

Pharmacokinetics in Special Populations

Pregnancy: Magnesium pharmacokinetics are altered in pregnancy due to increased renal blood flow and glomerular filtration rate (GFR) increasing renal clearance by 25-30%. Larger loading doses (4-6 g) and maintenance infusions (1-2 g/hr) are typically required to achieve therapeutic levels. Magnesium freely crosses the placenta, with fetal levels equilibrating with maternal levels within 1-2 hours. Neonates born to mothers receiving magnesium may demonstrate transient hypotonia, respiratory depression, and hyporeflexia, typically resolving within 24-48 hours. Renal impairment: Dose reduction is mandatory; empiric reductions of 50% for moderate impairment (CrCl 15-30 mL/min) and 75% for severe impairment (CrCl less than 15 mL/min), with clinical and level-based monitoring. Elderly: Age-related decline in GFR necessitates dose adjustment similar to renal impairment. Obesity: Limited data exist; dosing based on ideal body weight is reasonable given magnesium's hydrophilic properties and distribution in total body water rather than adipose tissue. [41-45]

Pharmacodynamics

Cardiovascular Effects

Vasodilation: Magnesium produces dose-dependent systemic and coronary vasodilation through multiple mechanisms: L-type calcium channel blockade in vascular smooth muscle, endothelium-dependent release of nitric oxide and prostacyclin, and direct smooth muscle relaxation through interference with myosin light chain kinase. Typical reductions in systemic vascular resistance (SVR) of 15-25% occur with therapeutic levels (2-3 mmol/L). Mean arterial pressure decreases by 10-20% following bolus administration, with hypotension more pronounced in hypovolemic patients. The vasodilatory effect is particularly prominent in the coronary, cerebral, and uterine vascular beds.

Antiarrhythmic properties: Magnesium demonstrates Class IV antiarrhythmic effects through calcium channel blockade, reducing automaticity in nodal tissue and prolonging AV conduction. Additionally, magnesium stabilizes cardiac membrane potential by modulating potassium channels, shortening the QT interval (relevant to torsades de pointes), and reducing triggered activity from early afterdepolarizations. The mechanism in torsades de pointes involves suppression of EADs (early afterdepolarizations) that trigger the arrhythmia, rather than through direct effects on the underlying QT prolongation. Magnesium is first-line therapy for torsades de pointes regardless of baseline magnesium level. In atrial fibrillation, magnesium provides rate control through AV nodal suppression and may reduce cardioversion energy requirements. [46-52]

Central Nervous System Effects

Anticonvulsant: Magnesium's anticonvulsant effect in eclampsia occurs through NMDA receptor antagonism in the central nervous system, reducing neuronal excitability and preventing seizure propagation. Cerebral vasodilation may also contribute by improving cerebral perfusion in the setting of vasospasm. The Eclampsia Trial Collaborative Group demonstrated magnesium sulfate's superiority over phenytoin and diazepam for eclamptic seizure prevention and treatment. The number needed to treat (NNT) for preventing one eclamptic seizure is 50-100 when used prophylactically in pre-eclampsia.

Neuroprotection: In experimental models of cerebral ischemia and traumatic brain injury, magnesium reduces NMDA receptor-mediated excitotoxicity, maintains cellular ATP levels through Mg²⁺-ATPase function, and has anti-inflammatory effects. However, clinical trials in stroke (IMAGES trial) and traumatic brain injury have not demonstrated improved neurological outcomes, possibly due to the difficulty achieving adequate brain magnesium concentrations with peripheral administration. [53-58]

Neuromuscular Junction Effects

The neuromuscular effects of magnesium have significant anaesthetic implications. At therapeutic levels (2-3 mmol/L), the safety margin of neuromuscular transmission is reduced but clinical weakness is not apparent. As levels exceed 3-4 mmol/L, detectable weakness emerges, manifesting first as reduced grip strength and respiratory muscle weakness. Deep tendon reflexes (DTRs), particularly the patellar reflex, are abolished at approximately 5 mmol/L, providing a clinical monitoring endpoint. Above 6 mmol/L, respiratory muscle paralysis may occur. The interaction with NMBAs is clinically important: patients receiving magnesium infusions for pre-eclampsia require 25-50% dose reduction of rocuronium, vecuronium, or atracurium for intubation, and prolonged duration of block should be anticipated. Monitoring with train-of-four (TOF) is essential, and sugammadex dosing may need adjustment for reversal. Succinylcholine duration may be prolonged, though onset is preserved. [59-63]

Uterine Effects (Tocolysis)

Magnesium's tocolytic effect results from calcium channel blockade in myometrial smooth muscle, reducing calcium-dependent actin-myosin cross-bridge cycling. This effect is dose-dependent, with significant reduction in uterine contractility at serum levels of 5-8 mg/dL (2-3.3 mmol/L). Historically used for preterm labor tocolysis, magnesium is now considered less effective than beta-agonists or calcium channel blockers for acute tocolysis based on Cochrane review evidence. However, magnesium retains its role in pre-eclampsia where uterine relaxation may be a secondary benefit. When administered for fetal neuroprotection in anticipated preterm delivery, loading doses of 4-6 g over 20-30 minutes followed by 1-2 g/hr maintenance are used. The BEAM trial demonstrated that antenatal magnesium reduces cerebral palsy risk in preterm infants (NNT = 63). [64-68]

Clinical Applications

Pre-eclampsia and Eclampsia (Primary Indication)

Magnesium sulfate is the first-line agent for prevention and treatment of eclamptic seizures, supported by Level I evidence from the Magpie and Eclampsia Trial Collaborative Group studies. The standard Pritchard regimen consists of a 4 g IV loading dose (over 15-20 minutes) followed by 1 g/hr maintenance infusion. Alternative regimens include the Zuspan regimen (4 g IV load, 2 g/hr maintenance) and intramuscular protocols for resource-limited settings. Target therapeutic levels are 2.0-3.5 mmol/L (4.8-8.4 mg/dL). Monitoring during magnesium therapy includes hourly assessment of deep tendon reflexes (patellar), respiratory rate (maintain more than 12/min), urine output (maintain more than 25 mL/hr), and level of consciousness. Magnesium is continued for 24-48 hours postpartum or post-seizure. In severe pre-eclampsia, magnesium reduces eclampsia risk by 58% (Magpie trial). Contraindications include myasthenia gravis, severe renal impairment (relative), and hypocalcemia. [69-75]

Torsades de Pointes

Intravenous magnesium is Class I recommended first-line therapy for torsades de pointes, regardless of baseline serum magnesium level. The mechanism involves suppression of early afterdepolarizations (EADs) that trigger the polymorphic ventricular tachycardia associated with QT prolongation. Standard dosing is 2 g (8 mmol) IV over 1-2 minutes, which may be repeated after 5-10 minutes if the arrhythmia persists. Continuous infusion of 1-2 g/hr may follow for arrhythmia suppression. Magnesium is effective regardless of whether the QT prolongation is congenital (long QT syndrome) or acquired (drug-induced). In cardiac arrest secondary to torsades de pointes, magnesium 2 g IV push is recommended per ARC/ANZCOR guidelines. The efficacy is well-established, with cardioversion occurring in 75-90% of cases within minutes of administration. Unlike other antiarrhythmics, magnesium does not further prolong the QT interval. [76-80]

Bronchospasm

Intravenous magnesium provides bronchodilation in acute severe asthma through multiple mechanisms: direct smooth muscle relaxation via calcium channel blockade, inhibition of acetylcholine release from parasympathetic nerve terminals, potentiation of beta-agonist effects, and anti-inflammatory effects including inhibition of mast cell degranulation. Standard dosing is 1.2-2 g (5-8 mmol) IV over 20 minutes. Meta-analyses demonstrate that IV magnesium reduces hospital admission rates (OR 0.75) and improves pulmonary function in severe acute asthma (FEV1 improvement of 10-15%). Magnesium is most effective in patients with severe exacerbations (FEV1 less than 25% predicted) who have not responded adequately to initial beta-agonist therapy. Australian guidelines recommend magnesium as second-line therapy in life-threatening asthma. Nebulized isotonic magnesium sulfate (150 mg/3 mL) combined with salbutamol provides additional bronchodilation compared to salbutamol alone. [81-85]

Phaeochromocytoma

Magnesium infusion is used as adjunctive therapy during phaeochromocytoma resection to attenuate catecholamine-induced cardiovascular instability. The mechanism involves L-type calcium channel blockade reducing norepinephrine-mediated vasoconstriction, competitive inhibition of catecholamine release from adrenal medulla, and direct cardiac membrane stabilization. Typical dosing involves 40-60 mg/kg loading followed by 2 g/hr infusion. Magnesium complements alpha-blockade (phenoxybenzamine, phentolamine) and may reduce requirements for direct-acting vasodilators (sodium nitroprusside, phentolamine) during tumor manipulation. The catecholamine surge during tumor handling may be blunted, though hypotension following tumor devascularization still requires vigilant management. [86-89]

Adjunct Analgesia

Perioperative magnesium reduces opioid consumption by 20-40% and improves postoperative pain scores, supported by multiple meta-analyses. The mechanism involves NMDA receptor antagonism in the spinal cord dorsal horn, reducing central sensitization and wind-up phenomena. Typical dosing for multimodal analgesia: 30-50 mg/kg loading (maximum 2 g) followed by 8-15 mg/kg/hr intraoperatively. Magnesium is particularly effective in surgeries associated with significant neuropathic pain components (spine surgery, thoracotomy, mastectomy). Benefits include reduced postoperative shivering, decreased PONV, and potential reduction in chronic postsurgical pain development. When combined with ketamine, magnesium provides synergistic NMDA antagonism. Adverse effects at analgesic doses include mild hypotension, flushing, and rare potentiation of NMBAs. [90-95]

Dosing and Monitoring

Therapeutic Levels by Indication

Clinical Monitoring Parameters

Mandatory monitoring during infusion:

• Deep tendon reflexes hourly (patellar reflex most reliable)
• Respiratory rate (maintain more than 12/min)
• Urine output (maintain more than 25 mL/hr or 0.5 mL/kg/hr)
• Level of consciousness
• Continuous ECG (QT interval, PR prolongation)
• Blood pressure (hypotension risk)

Serum level monitoring: Check serum magnesium 4-6 hours after loading and every 6-12 hours during maintenance infusion. More frequent monitoring in renal impairment.

Signs of toxicity to assess:

• 3.0-5.0 mmol/L: Flushing, nausea, muscle weakness
• 5.0-6.5 mmol/L: Loss of DTRs, drowsiness, slurred speech
• 6.5-7.5 mmol/L: Respiratory depression, hypotension
• Above 7.5 mmol/L: Complete heart block, cardiac arrest

Toxicity and Reversal

Manifestations of Hypermagnesemia

Magnesium toxicity is predictably dose-related and follows a characteristic progression:

Risk factors for toxicity include renal impairment (most common cause), excessive dosing, and concurrent medications affecting neuromuscular transmission (aminoglycosides, NMBAs).

Calcium Reversal

Calcium is the specific antidote for magnesium toxicity, acting through direct physiological antagonism rather than affecting magnesium levels. Calcium displaces magnesium from binding sites on ion channels and restores normal membrane excitability.

Dosing for magnesium toxicity reversal:

• Calcium gluconate 10%: 10-20 mL (2.2-4.4 mmol calcium) IV over 2-3 minutes
• Calcium chloride 10%: 5-10 mL (1.4-2.7 mmol calcium) IV over 2-3 minutes (more caustic, requires central access)
• May repeat every 5-10 minutes as needed
• Effect is immediate but transient (10-15 minutes)

Additional supportive measures:

• Stop magnesium infusion immediately
• IV fluids for volume expansion and enhanced renal excretion
• Respiratory support (mechanical ventilation if respiratory depression)
• Cardiac pacing for complete heart block
• Hemodialysis for severe toxicity with renal failure (magnesium clearance 50-100 mL/min)

Prevention of toxicity requires adherence to monitoring protocols, dose adjustment in renal impairment, and awareness of drug interactions. [96-100]

Australian/NZ Specific Considerations

TGA-Approved Formulations

The Therapeutic Goods Administration (TGA) has approved magnesium sulfate for parenteral use in Australia. Available formulations include magnesium sulfate heptahydrate injection 49.3% (0.5 g/mL in 5 mL and 10 mL ampoules), providing 2 mmol/mL elemental magnesium. DBL Magnesium Sulfate (Pfizer) is the most commonly stocked brand in Australian hospitals. Magnesium sulfate 50% solution (0.5 g/mL) requires dilution before IV administration; standard practice is dilution in 0.9% sodium chloride or 5% dextrose for infusion concentrations of 10-20% (100-200 mg/mL).

PBS Listing

Magnesium sulfate injection is not individually PBS-listed but is available through hospital pharmaceutical supply for approved indications including eclampsia prophylaxis, cardiac arrhythmias, and acute severe asthma. Hospital pharmacy budgets typically cover magnesium sulfate as an essential medicine. In the community setting, oral magnesium supplements are available over-the-counter.

Local Availability

Magnesium sulfate injection is universally available in Australian hospitals, emergency departments, and maternity units. Remote health clinics typically stock magnesium sulfate for emergency eclampsia management. Royal Flying Doctor Service (RFDS) aircraft carry magnesium sulfate for obstetric and cardiac emergencies. New Zealand availability is similar through district health boards.

Indigenous Health Considerations

Aboriginal and Torres Strait Islander women experience pre-eclampsia at approximately 1.5 times the rate of non-Indigenous Australian women, with associated higher maternal and perinatal mortality. Access to magnesium sulfate therapy may be delayed in remote communities, where transfer to facilities with appropriate monitoring capabilities is often required. Cultural considerations include family presence during treatment, which should be accommodated where possible, and communication through Aboriginal Health Workers or interpreters to ensure understanding of treatment purposes and monitoring requirements.

In remote settings, the intramuscular Pritchard regimen (4 g IV plus 10 g IM loading, followed by 5 g IM every 4 hours) may be necessary when continuous IV infusion monitoring is not feasible during transfer. RFDS protocols include magnesium sulfate for eclampsia management during retrieval flights. Chronic conditions prevalent in Indigenous communities—including diabetes, hypertension, and chronic kidney disease—may affect magnesium pharmacokinetics and increase toxicity risk, necessitating careful dose adjustment and monitoring. Respectful communication about the purpose and effects of magnesium treatment, including the unusual sensations of flushing and warmth, helps maintain trust and cooperation during therapy. Māori women in New Zealand similarly require culturally appropriate care with whānau involvement and consideration of tikanga during treatment. [101-105]

ANZCA Primary Exam Focus

Common MCQ Patterns

ANZCA Primary MCQs frequently test:

• Mechanism: NMDA receptor block (non-competitive, voltage-dependent), calcium channel blockade (L-type), NMJ effects (presynaptic Ca²⁺ competition)
• Pharmacokinetics: Renal elimination, half-life (4-5 hours normal function), protein binding (25-30%), Vd (0.3-0.5 L/kg)
• Toxicity thresholds: Loss of DTRs (5 mmol/L), respiratory depression (6-7 mmol/L), cardiac arrest (above 7.5 mmol/L)
• Antidote: Calcium gluconate mechanism (physiological antagonism, not chelation)
• NMBA interaction: Potentiates both depolarizing and non-depolarizing agents, dose reduction 25-50%

Viva Question Themes

Primary vivas commonly explore:

• Describe the mechanism of action of magnesium as an anticonvulsant
• Compare magnesium to phenytoin for eclampsia prophylaxis
• Explain magnesium's cardiovascular effects and mechanisms
• Discuss monitoring during magnesium infusion and signs of toxicity
• Describe management of magnesium-induced respiratory depression
• Explain the interaction between magnesium and neuromuscular blocking agents

Calculation Questions

Example calculation: A 65 kg woman with pre-eclampsia requires magnesium loading. Calculate:

1. Loading dose: 4 g MgSO₄ = 4000 mg = 16 mmol Mg²⁺
2. Volume from 50% solution (0.5 g/mL): 4 g ÷ 0.5 g/mL = 8 mL
3. Maintenance: 1 g/hr = 4 mmol/hr
4. Expected serum level after loading: approximately 2-2.5 mmol/L (therapeutic range)

Assessment Content

SAQ Practice Question (20 marks)

Question: A 28-year-old primigravida at 36 weeks gestation is admitted with severe pre-eclampsia (BP 170/110 mmHg, proteinuria 3+, headache). She weighs 75 kg with normal renal function. Describe the pharmacology of magnesium sulfate relevant to her management, including mechanism of action, dosing, monitoring, and management of potential complications.

Model Answer:

Mechanism of action relevant to eclampsia (6 marks):

• NMDA receptor antagonism: Voltage-dependent, non-competitive block of glutamate NMDA receptors in CNS, reducing neuronal excitability and seizure threshold [2]
• Cerebral vasodilation: Relaxation of cerebral arteriolar smooth muscle, potentially counteracting vasospasm [1]
• Calcium channel blockade: L-type VGCC block reducing neuronal calcium influx [1]
• Membrane stabilization: Modulation of ion channel function reducing excitability [1]
• NMT = 50-100 for prevention of one eclamptic seizure in severe pre-eclampsia [1]

Pharmacokinetics (4 marks):

• Distribution: Vd 0.3-0.5 L/kg, 25-30% protein bound, crosses placenta [1]
• Elimination: Exclusively renal, t½ 4-5 hours with normal function [1]
• Therapeutic level: 2.0-3.5 mmol/L for eclampsia prophylaxis [1]
• Normal renal function: Standard dosing appropriate [1]

Dosing regimen (4 marks):

• Loading dose: 4 g IV over 15-20 minutes (Pritchard regimen) [1]
• Preparation: 8 mL of 50% MgSO₄ diluted in 100 mL 0.9% saline [1]
• Maintenance: 1-2 g/hr continuous infusion [1]
• Duration: Continue for 24-48 hours postpartum [1]

Monitoring (3 marks):

• Deep tendon reflexes hourly (loss indicates approaching toxicity) [1]
• Respiratory rate (maintain more than 12/min) [1]
• Urine output (maintain more than 25 mL/hr) [1]

Management of toxicity (3 marks):

• Stop infusion, airway support, call for help [1]
• Calcium gluconate 10%: 10-20 mL IV over 2-3 minutes [1]
• Respiratory support if needed; may require intubation and ventilation [1]

Total: 20 marks

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Viva Scenario (15 marks)

Examiner: You are called to the obstetric high dependency unit. A 32-year-old woman with severe pre-eclampsia has been receiving magnesium sulfate infusion at 2 g/hr for 12 hours. The nurse is concerned that she appears drowsy and her respiratory rate has dropped to 10 breaths/min. How would you approach this situation?

Candidate Response:

Immediate assessment (3 marks):

• Stop the magnesium infusion immediately [1]
• Call for help and ensure resuscitation equipment available [1]
• ABC assessment: Airway (patent?), Breathing (RR, SpO2, effort), Circulation (BP, HR) [1]

Clinical examination for magnesium toxicity (3 marks):

• Check deep tendon reflexes (patellar): If absent, confirms significant toxicity [1]
• Assess level of consciousness: GCS, response to commands [1]
• Check urine output over past hours (oliguria indicates reduced clearance) [1]

Examiner: The DTRs are absent, GCS is 13 (E3V4M6), SpO2 88% on room air. What do you do?

Immediate management (4 marks):

• High-flow oxygen via face mask [1]
• Administer calcium gluconate 10%: 10 mL (2.2 mmol Ca²⁺) IV over 2-3 minutes [1]
• Prepare for airway intervention if respiratory depression worsens [1]
• Insert urinary catheter if not present, monitor output [1]

Examiner: You give calcium gluconate and the patient becomes more alert. Her RR improves to 14/min. What is the mechanism of calcium reversal?

Mechanism (2 marks):

• Calcium acts as a direct physiological antagonist to magnesium [1]
• Calcium displaces magnesium from binding sites on ion channels, restoring membrane excitability and neuromuscular function [1]

Further management (3 marks):

• Check serum magnesium level (likely above 5 mmol/L) [1]
• Review renal function: Elevated creatinine may explain accumulation [1]
• When stable, consider restarting magnesium at reduced rate (0.5-1 g/hr) with more frequent monitoring, or alternative anticonvulsant if renal impairment severe [1]

Total: 15 marks

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