Lecture 12 - Anestethics Flashcards
How do local anesthetics work
- block vg Na+ channels in nerves and other tissues
- acts at a site within the channel: access to this site is intracellular so LAs must first cross the cell membrane
Physiochemical properties of LAs
- LAs are weak bases -> poorly water soluble and unstable
- when combined with strong acid they form water soluble and stable salts
- non ionised form of LA crosses the membrane
- ionised form binds to the sodium channel
Hydrophilic pathway of LA
- non ionised form crosses the membrane
- ionised form binds to channel
- channel needs to be open for binding to occur -> ude dependent
Hydrophobic pathway
Only 10 % of LA work with that
- not use ependent
Method of anesthesia: Surface (spray)
- nose, mouth, cornea
- eg: Lignocaine
MEthod of anesthesia: infiltration
- minor surgery
- eg: most drugs
Method of anesthesia: IV regional
- limb surgery
- eg: Lignocaine, prilocaine
Method of anesthesia: Nerve block
- use: surgery, dentistry
- eg: most drugs
Method of anesthesia: spinal, inject into subarachnoid space
- use: Major surgery when GA cannot be used
- eg: lignocaine
MEthod of anesthesia: epidural
- use: major surgery or childbirth
- eg: mainly lignocaine and bupivacaine
Speed of onset of LA is determined by
- degree of ionisation (pKa)
Duration of action is determined by
- protein binding to Na+ channel (increases duration)
- vascularity at the site of action (decreases duration)
Advantages of vasoconstrictors in relation to LA
- reduce blood flow -> increase duration of action
- minimise dosage
- decrease toxicity
Toxicity due to LA
- toxic effect related to action: CNS (initial stimulation followed by depression)
- cardiotoxicity: profound bradychardia
- allergic reactions
GA: Premedication
- relieve anxiety
- produce sedation and amnesia
- relieve pain
- reduce secretion
- reduce nausea and vomiting
- neuromuscular blockade
Fours stafes of anesthesia
- analgesia
- excitement
- surgical anesthesia
- medullary depression
Intravenous GA: THIOPENTAL
- ultra short, fast acting barbiturate
- loss of consciousness in 10-20 sec, regained in 2-3 min
- hangover for 24hr
- adverse effects: laryngeal spasm, cardiac and respiratory depression, hypersensitivity
Intravenous GA: Midazolam
- benzodiazepine, water soluble
- slow onset of recovery
- less risk of of respiratory, cardiovascular depression
Intravenous GA: propofol
- may be used alone for short procedures
- acts in 30 sec
- no hangover, and little to no nausea
- cardiac and respiratory depressant`
Inahalation GA
- Halothane: associated with hepatotoxicity, cardiovascular and respiratory depression (bradychardia + arrythmia)
- isoflurane: tends to cause hypotension but less cardiodepression
- Desflurane and sevoflurane: faster induction and recovery
- Nausea and vomiting concern for all
Sedative effects of GA
- occur early on at low doses
- act on prefrontal cortex
Loss of consciousness effect
- occurs at higher doses
- acts on thalamus
Effects on CNS
- enhance inhibition (via GABA receptor potentiation)
- inhibit excitation (block NMDA receptors)
- reduce excitation (open K+ channels)
