ACEM Primary
General anaesthetic pharmacology
Induction agents
| Propofol | Hypnotic Anti-convulsant, anti-emetic Not an analgesic Reduced cerebral blood flow, reduced ICP reduced BP secondary to arterial and venous vasodilation Apnoea, reduced airway reflexes MOA = increase Cl- current via GABA-A R Metabolised in liver/ lungs 30% Inactive components excreted by kidney Awakening post induction dose in 8-10 min Dose = 1-2.5mg/kg IV induction 25-75mcg/ kg/ min infusion |
| Thiopental | Dose dependent CNS depression Not an analgesic Reduced cerebral blood flow, reduced ICP, reduced BP less pronounced than propofol Apnoea marked, requires second agent to depress airway reflexes MOA = inhibit excitatory neurotransmission Metabolised in liver Do not give in AIP, increases productions of porphyrins Dose = 3-5mg/kg IV Intra-arterial injection may cause gangrene |
| Midazolam | Anxiolytic, amnestic, anti-convulsant Only midazolam appropriate BDZ for IV infusion as shortest context sensitive t ½ Reduced cerebral blood flow, reduced ICP Minimal depression of ventilation Dose 1-2mg IV as premedication MOA = enhance GABA effect |
| Etomidate | Hypnotic Minimal haemodynamic effects Adverse effects – Adrenocortical suppression |
| Ketamine | Analgesia, amnesia, anti-convulsant MOA = inhibit NMDA R Metabolised in liver, low protein binding, may increase cerebral blood flow and ICP. Increased BP, HR and CO via SNS stimulation (unless maximal sympathetic drive) Airway reflexes more active Dose = 1-2mg/kg IV induction AE – unpleasant emergence reactions, nystagmic gaze |
| Dexmedetomidine | Hypnotic MOA = selective a2 R agonist in CNS-> reduced SNS activity, causing sedation 8 x more selective than clonidine Binds all 3 subtypes of alpha 2 R Reduced cerebral blood flow, ICP, reduced shivering and reduced circulating catecholamines |
Muscle relaxants
| Non depolarising | Depolarising |
| MOA = Block Nm R at NMJ-> Ach unable to bind-> nil end plate potential or depolarisation Immediate acting: DOA 20-35 min Rocuronium/ Vecuronium Low doses-> Ach inhibitor at Nm R High doses-> enters ion channel for more intense block Highly ionised, small volume of distribution 0.1L/kg Onset ~ 1 min, max effect 3-5 min Liver metabolism + biliary elimination Atracurium Hofman elimination, clearance not dependent on organ function Used in liver/ renal failure Laudanosine breakdown product (t ½ 150 min, crosses BBB +/- seizures) Cisatracurium Reduced laudanosine production Long acting Pancuronium AE: Vec/ Roc/ Cis = minimal CVS effects Atra = hypotension due to histamine release Patients with burns or UMND are resistant. Reversed by cholinesterase inhibitors Sugammadex: Binds tightly to rocuronium in 1:1 ratio > vecuronium Decreases free plasma concentration Dosing = 2mg/kg for reversal of shallow neuromuscular blockade, 4mg/kg for reversal of deeper blockade, 16mg/kg for immediate reversal following single dose | MOA = Block and occupy Nm R at NMJ + Nn R in ganglia-> Two phases: Phase I, 4-8 min = initial depolarisation of membrane due to activation of R (fasciculations)-> unresponsive to further stimuli (flaccid paralysis) AUGMENTED by cholinesterase inhibitors. Phase II, >20 min – slow repolarisation of membrane, however cannot depolarise as desensitized due to prolonged exposure. Succinylcholine/ Suxamethonium Extremely short duration of action <8 mins due to hydrolysis by cholinesterases in plasma/ liver can have prolonged action in patients with genetic defects in cholinesterases (suxamethonium apnoea) Dose 1-1.5mg/kg IV AE: Arrythymias (acts at muscarinic R in heart) Bradycardia, tachycardia Hyperkalaemia (in burns/ trauma/ head injury) IOP ~ 5 min gastric pressure, aspiration ICP Myalgia Malignant hyperthermia Salivation |
| Neuromuscular blockade is enhanced: myasthenia gravis on aminoglycosides Neuromuscular blockade is reduced: corticosteroids phenytoin Reduced clearance hepatic failureadvancing age |
Nitrous oxide
- MAC >100%
- Minimal alveolar concentration = anaesthetic concentration to produce no response in 50% patients exposed to noxious stimulus
- MOA = potentiate GABA-A R
- Absorption through gas exchange at alveoli, not metabolised
- Low solubility, reaches high arterial tension rapidly
- Low blood/ gas partition coefficient 0.47
- Blood gas partition coefficient = affinity of anaesthetic for blood vs gas
- Rapid equilibrium in brain and fast onset of action
- Rapid offset and recovery
- Organ system effects:
- Analgesia
- Increase cerebral blood flow and ICP
- Myocardial depression
Preserved CO due to simultaneous SNS activation
Volatile anaesthetics
| Volatiles | Gaseous |
| High boiling points, liquids at room temperature Halothane Enflurane Isoflurane Desflurane Sevoflurane Hepatic metabolism: Halothane (40%) > Enflurane (8%) > Sevoflurane (2-5%), Isoflurane (<2 %), Desflurane, N2O (0%) | Low boiling points, gases at room temperature Nitrous oxide Xenon |
Last Updated on August 12, 2021 by Andrew Crofton
Andrew Crofton
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