Anaesthetics

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  • Created by: LBCW0502
  • Created on: 22-10-18 20:11
Outline the history of local anaesthetics
Coca leaves (Peruvian Indians, 1500s), cocaine (first used surgically in 1884), procaine (synthesis in 1905), lignocaine (synthesis in 1946)
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What are local anaesthetics used for?
Clinically in dentistry and minor surgery for temporary relief of pain. Given topically or parenterally (e.g. baby teething ring)
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Describe the functions of local anaesthetics
Reversibly block nerve conductance. Do not cause loss of consciousness. Do not interact with pain receptors. Do not inhibit release of pain mediators
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State the groups present in the chemical structure of cocaine
Benzoyl group, carbomethoxy group, tropine moiety, basic group (tertiary amine)
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Describe previous uses of cocaine
Cocaine toothache drops, cocaine in coca-cola drinks (10 mg per glass)
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Why is cocaine less effective as a local anaesthetic?
Cocaine contains two ester bonds which are hydrolysed easily in the body (lots of esterase enzymes). Effect is lost and the following products are formed - ecgonine, benzoic acid and methanol
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Describe the modifications made to cocaine to form procaine
Aromatic ring has an NH2 attached. The ester bond remains. The second ester bond is removed and the tertiary amine remains (easier to manufacture - effect lasts longer in the body/takes longer to hydrolyse)
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Describe the modifications made to tetracaine to form lidocaine
Aromatic ring in place, ester group changed to an amide (takes longer to hydrolyse in the body, longer lasting effects), tertiary amine in place
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Outline the process for sensation of pain
Stimulus - pain receptors - sensory nerve stimulation - sensation of pain (resting potential -70 mV with sodium efflux to action potential +40 mV with sodium influx). Pain - sodium influx - depolarisation of sensory neuron
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What is the general structure for a local anaesthetic?
Aromatic system (steric blockade), linker (ester/amide) and tertiary amine - pharmacophore (want effect to wear off/be hydrolysed and don't want effects to spread to the rest of the body)
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Describe features of local anaesthetics at the lipid membrane (1)
Constriction in Na channel, build up of Na (don't pass through), presence of anaesthetic (change in conformation of Na channel - influx). Balance of ionised/unionised anaesthetic depends on pKa/pH (inside cell)
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Describe features of local anaesthetics at the lipid membrane (2)
Unionised can enter cell but Na channel won't let ionised form pass through (charged). Anaesthetic needs to be unionised to pass into channel inside cell. Anaesthetic needs to be ionised inside cell to be active
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What is used to investigate functions of nerves?
Animals with large thick axons which can be manipulated (e.g. squid)
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Describe the first experiment which investigates the effect of local anaesthetics on nerves
Administer tertiary amine outside cell (blocks action potential. Administer to axoplasm (pH 7) more effective block of action potential (maximum effect) - electrodes used to get impulse generated
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Describe the second experiment which investigates the effect of local anaesthetics on nerves
Administer quaternary amine outside cell (no block of action potential/cannot pass lipid membrane due to charge). Administer to axoplasm (pH 7) blocks action potential
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Describe the third experiment which investigates the effect of local anaesthetics on nerves
Administer tertiary amine to axoplasm (pH adjusted to 8) - reduced block of action potential (application of Henderson-Hasselbalch equation, pH = pKa - log[BH+] / log[B])
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Describe features of the zwitterionic form of tetracaine
Movement of electrons on NH, aromatic ring and COO groups leads to NH+ and COO- charges (electron donating and electron withdrawing groups). Better anaesthetic - multiple charged groups interact with Na channel
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Describe features of benzocaine
Contains aromatic ring, ester but no tertiary amine. Still effective as a local anaesthetic (mechanism unclear - may bind outside cell rather than inside, pKa far away from 7)
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What are general anaesthetic used for?
To give pain relief, cause loss of consciousness, bring about muscle relaxation
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What are the requirements of a good inhalation general anaesthetic?
Highly volatile, good lipid solubility, non-toxic, chemically stable, doesn't cause respiratory irritancy
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What are the requirements of a good intravenous general anaesthetic?
Non-volatile, water soluble, non-toxic, chemically stable, good lipid solubility, rapid onset of action
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What are the two possible theories for the mechanism of action of general anaesthetics?
Lipid theory and protein theory (anaesthetic effect should increase which lipophilicity but not all general anaesthetics are lipophilic, might expect different enantiomers of optically active general anaesthetics to show different activities)
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Describe the lipid theory
Non-specific action, perturbation of neuronal cell membranes - increasing membrane fluidity and/or causing membrane bilayer expansion and indirectly affecting membrane proteins
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Describe the protein theory
Binding to specific neuronal cell membrane proteins and directly affecting their structure and/or conformational flexibility
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Give examples of intravenous general anaesthetics
Propofol, etomidate (enhance inhibitory action of GABA-A receptor), ketamine (inhibitory activity against NMDA receptor, S 2-3 x more potent, R isomer causes side effects/hallucinations)
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Give examples of inhalational general anaesthetics
Chloroform (toxic at high dose), diethylether (highly flammable), nitrous oxide (laughing gas, weak GA), halothane (enantiomers equally potent as GA)
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What are the complications during anaesthesia?
Respiratory depression, salivation/respiratory secretions, cardiac arrhythmias, fall in BP, aspiration, laryngospasm and asphyxia, awareness, delirium/convulsion, fire/explosion
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What are the complications after anaesthesia?
Nausea, vomiting, persisting sedation, pneumonia, organ damage (liver/kidney), nerve palsies, emergence delirium, cognitive defects
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Other cards in this set

Card 2

Front

What are local anaesthetics used for?

Back

Clinically in dentistry and minor surgery for temporary relief of pain. Given topically or parenterally (e.g. baby teething ring)

Card 3

Front

Describe the functions of local anaesthetics

Back

Preview of the front of card 3

Card 4

Front

State the groups present in the chemical structure of cocaine

Back

Preview of the front of card 4

Card 5

Front

Describe previous uses of cocaine

Back

Preview of the front of card 5
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