Hypnotica Chapter for the FRCA Primary

Contents

Propofol
Ketamine
Thiopentone
Etomidate
Midazolam
Clonidine
Dexmedetomidine

Hypnotic Drugs, cornerstone of anaesthesia. Herein lies a unifying page gathering up all the GasGasGas episodes on hypnotic drugs for the FRCA exam, these are commonly used in the UK. Including ketamine, propofol, thiopentone, and etomidate as well as soporific adjunctive agents, midazolam, dexmedetomidine and clonidine!

You shall know of induction agent onset times, side effect profiles and other uses. Make sure to also listen to the episode on Propofol TCI models, which will prime your brains for those slightly baffling conversations with TIVA boffins in your respective hospitals.

It’s funny that you should all feel so tired, so early in the afternoon….

Unsurprisingly hypnotic induction and sedation agents are key to the career, practice and knowledge base required of an anaesthetist, indulge yourself in seven hypnotising episodes on common agents for anaesthesia. There is no exam, and the demon headmaster will not be in attendance.

Propofol

Are you a Milkman or MilkWoman, on an electric powered milk float bobbing along at 4am placing milk at peoples doors? Probably not, but you still use the white stuff that dominates UK anaesthesia. This key stone episode covers everything from basic pharmacology to an introduction to how they used to do TIVA propofol. Learn why propofol’s exceptional pKa and protein binding state provides excellent onset characteristics, understand propofol infusion syndrome on the ITU and generally talk the soy stuff in the exam!

UK’s most common induction agent
GABA potentiator mechanism (technically not fully elucidated)
Highest pKa (11) = 98% unionised at pH 7.4
98% protein bound, volume of distribution 4 L/kg
Dose: 1-2 mg/kg induction, plasma conc of 4-8 mcg/ml maintains anaesthesia
Cardiovascular: ↓SVR,
Respiratory: initial apnoea, laryngeal reflex suppression,
Propofol infusion syndrome: high-dose infusions cause metabolic acidosis, rhabdomyolysis and other awfulness
Manual TCI: “10-8-6 formula” (mg/kg/hr for 10min increments, then maintenance at 6mg/kg/hr thereafter)
Synergistic with opioids, benzodiazepines, alpha 2 agonists, alcohol
Hesitant, careful use in shocked patients or those with a PE – even small doses cause cardiovascular collapse in particularly poorly people.

Listen to the propofol episode here!

Ketamine

Break the glass on the dogma that ketamine is your cardiovascular stability safety blanket—this episode reveals why it can still tank blood pressure in your sickest patients. It provides the NMDA receptor knowledge to understand its mechanism of effect, guide your management of emergence delirium and navigating its multi receptor proclivities (not just NMDA!), gain the confidence to use this dissociative agent appropriately for when you’ve a particularly poorly patient who needs a particularly planned anaesthetic.

NMDA receptor antagonist at PCP binding site
NOT cardiovascular “rescue” drug – causes direct myocardial depression, and relies on SNS stimulation to raise BP, those who are entirely clapped out and decompensating won’t release as much adrenaline.
S-ketamine 4x more potent than R-ketamine
Multiple mechanisms: NMDA, opioid, muscarinic, sodium channels
Anaesthetic dose: IV 0.5-2 mg/kg, IM 4-10 mg/kg
Analgesic dose: IV 0.1-0.5 mg/kg
Produces dissociative anaesthesia (thalamocortical disconnect)
Bronchodilator but causes hypersalivation
Emergence delirium manageable with midazolam
Suitable for head injury (hypotension prevention > minimal ICP rise)

Listen to the Ketamine episode here!

Thiopentone

This syringe that should definitely not be mistaken for CEFUROXIME is the fastest gun in anaesthesia—the original one arm-brain circulation rally car for rapid sequence induction before being dethroned by propofol and supraglottic airway devices for most anaesthesia. From Pearl Harbor’s tragic dosing lessons to modern applications in status epilepticus, learn why this bacteriostatic barbiturate still deserves respect and when it might save the day despite its old-school reputation.

Fastest onset: one arm-brain circulation time
Barbiturate with tautomerism (pH-dependent solubility)
Prepared at pH 10.5 (hence bacteriostatic and stable)
80% protein bound – ++ potent in hypoalbuminaemia / acidosis states
Zero-order kinetics with repeated dosing/infusions
Precipitates with most muscle relaxants except mivacurium
Dose: 2-7 mg/kg IV; Rectal: 1g/22kg body weight
Uses: RSI, refractory status epilepticus, raised ICP
Absolute contraindication: porphyria
Historical Pearl Harbor lesson: reduce dose in shocked patients

Listen to the Thiopentone episode here!

Etomidate

Explore anaesthesia’s most controversial pal: a drug with unmatched cardiovascular stability that’s been abandoned worldwide due to its initially unknown danger of adrenal suppression. Through a sherlockian discovery and subsequent fascinating molecular mechanisms, discover why etomidate’s impressive safety margin becomes meaningless and why some countries have completely withdrawn this once-promising agent.

Excellent cardiovascular stability but causes adrenal suppression
Inhibits 11β-hydroxylase and 17α-hydroxylase
Single dose suppresses cortisol for 24-48 hours
Historical ITU mortality when infused for sedation: 69% (etomidate) vs 25% (benzodiazepines)
50% incidence of myoclonus/involuntary movements
Therapeutic window is very wide.
Withdrawn from use in USA, Ireland, Canada, Australia
Absolute contraindication: porphyria
R-enantiomer 10x more potent than S-enantiomer

Listen to the Etomidate episode here

Midazolam

Uncover midazolams molecular magic of pH-dependent morphology change, from water-soluble in the ampoule to lipid/butter-loving in your patient and why getting the concentration wrong is a UK Never Event. This essential episode covers everything from navigating reversal with flumazenil to building confidence with anaesthesia’s most utilised benzodiazepine.

Exhibits tautomerism: water-soluble at pH <4, lipophilic at physiological pH
Wrong concentration use = UK Never Event
GABA-A receptor potentiation mechanism
IV sedation: 0.07-0.1 mg/kg; Paediatric PO: 0.5-1 mg/kg (max 20mg)
Minimal cardiovascular depression – suitable for unstable patients
Shifts CO2 response curve rightward – caution in sleep apnoea/COPD
96% protein bound – increased effect in hypoalbuminaemia
CYP3A4 metabolism – multiple drug interactions
Flumazenil reversal available but avoid in polydrug overdose

Listen to the Midazolam Episode Here

Clonidine

Learn why this “vintage” alpha-2 agonist remains indispensable in modern anaesthesia despite newer alternatives, from smoothing ICU ventilator weaning to helping your multi-modal analgesia plan out. Master the art of clonidine’s complex pharmacology including the crucial “five tropies” framework for understanding cardiovascular effects that will bolster your viva performance.

Partial alpha-2 agonist with 220:1 selectivity ratio
Ceiling effect at 50% MAC reduction, due to partial agonist nature
Near 100% oral bioavailability allows easy IV-to-PO conversion
ITU sedation: 0-2 mcg/kg/hr infusion
Requires gradual withdrawal over 36+ hours to prevent rebound hypertension
Effective for opioid and alcohol withdrawal and paediatric emergence delirium
Biphasic BP response: transient hypertension then sustained hypotension
“Five tropies” framework for understanding cardiovascular effects

Listen to the Clonidine Episode Here

Dexmedetomidine

Discover why dexmedetomidine is revolutionising ICU sedation and procedural anaesthesia with its unique ability to keep patients calm yet arousable, unlike any other sedative in your drug cupboard of wonders. This episode unpacks the fascinating neuroscience behind its selective alpha-2 agonism, practical dosing strategies from paediatric premedication to awake fibre-optic intubation, and critical safety pearls that could save you from dangerous pitfalls in hypovolaemic patients.

Highly selective alpha-2 agonist with 1620:1 selectivity ratio (8x more selective than clonidine)
Produces unique cooperative sedation preserving respiratory drive and arousability
Creates sleep-like state mimicking stage 2-3 non-REM sleep via locus coeruleus action
Biphasic cardiovascular response: initial hypertension followed by bradycardia/hypotension
Dosing: Loading 1 mcg/kg over 10 min, maintenance 0.2-0.7 mcg/kg/hr
Paediatric premedication: 3 mcg/kg intranasal (30-45 min onset)
Key uses: Augmenting your anaesthetic, and Asleep Awake Asleep neurosurgery, Awake fibre-optic intubation, neurophysiological monitoring, regional block augmentation.
Contraindicated in hypovolaemia; glycopyrrolate can cause paradoxical hypertension

Listen to the Dexmedetomidine Episode Here