13. LA’s Flashcards
How do local anaesthetics bring around analgesia?
Block sodium channels to stabilise membranes, causing increased threshold for AP, slower impulse conduction and decrease in rise and amplitude of AP.
How do sodium channels on neurones work?
- RMP maintained by Na/K pump. 3na exchanged for 2 K for one molecule of ATP.
- AP causes channel to open. Membrane potential rises to +30mv. Then channels close (depolarisation)
- Repolarisation. Voltage gated K channels open and it moves out, NA/K pump keeps working in background to restore RMP to -80mv
How do LA’s get to and inside neurones to work?
What happens once they are inside?
All heavily protein bound. Less protein bound = faster onset as free drug exerts effect. More protein bound = longer duration as gradually dissociates down concentration gradient
Weak bases, whose pKA means more are unionised at physiological pH than ionised. Unionised crosses lipid membrane to inside of cell.
Once inside it ionises to activate receptor. Bind to open channels to cause a conformational change. Means they have more affinity for active neurones than resting ones.
What are the amides and esters?
Which are more stable?
Esters: cocaine, amethocaine and procaine
Amides: bupivicaine, prilocaine, ropivicaine and lidocaine
Amides are more stable
What is the preparation for LA’s?
Water soluble so produces as clear liquids with hydrochloric salts. Also have preservatives and antifungals.
Intrathecal are preservative free and no additive except glucose in heavy.
What is a 1% solution?
10mg per ml
What does LA absorption depend on?
Local blood supply and vasoconstrictors effects of LA/ adrenaline.
Lidocaine dilates, whereas ropivicaine constricts. Adding adrenaline will have a better effect with lidocaine.
What is the metabolism and secretion of LA’s?
Esters undergo rapid ester hydrolysis by plasma esterases, mainly psueudocholinesterase.
Breakdown produces PABA which can cause anaphylaxis.
Amides are metabolised in the liver and renally excreted with 5% unchanged
What different preparations/ strengths does lidocaine come in?
1% or 2%
5% patches for post herpetic neuralgia
10% for airway topicalisation
What is the onset and duration of lidocaine?
2 minutes and lasts 20-40m
What is the main risk with bupivicaine and how is this related to Levo?
Increased risk of cardio toxicity due to prolonged cardiac Na blockade
Levo is the pure s entatiomer with less cardiac S/E. undergoes more hepatic secretion and no unchanged secretion
What is the preparation of ropivicaine and how does it compare to bupivicaine?
Pure S entatiomer which has lower toxicity than R.
Less potent than bupivicaine, shorter acting and less cardio toxic.
What are the uses of prilocaine and how does it compare to lidocaine?
What are the side effects?
Biers block and 2% prep for day surgery, with motor block lasting 60-75m.
Lidocaine:
More intermediate duration
Less vasodilation
Less bound so greater Vd causing less cardio toxicity
S/E: only amide to cause methaemaglobinaemia. Aromatic ring is metabolised to toluidine which converts Hb to metHb which binds more strongly to O2 for longer
How does cocaine work for illegal purposes?
Crosses the BBB and causes euphoria via blockade of catecholamine re-uptake
What are the two topical LAs and their features?
Euteric mixture of LA’s EMLA, contains 2.5% lidocaine and 2.5% prilocaine
Ametop gel has 4% tetracaine which causes vasodilation 40m post application. Area is red and numb for up to 4h
