Lecture 12: Local anaesthetics Flashcards
Describe the physiology of nerve conduction
Dendrites- nucleus - axon (myelinated), node of ranvier (with voltage sensitive ion channels) - axon terminals- new neuron
Describe the physiology of nerve conduction (conceptual operation of voltage gated sodium channels)
1) Resting -Activation gate (AG) = closed -Deactivation gate (DG) = open
2) Threshold depolarisation -AG = open -DG = open
3) Automatic deactivation -AG = open -DG = closed (after miliseconds)
4) Recovering -AG = closes -DG = opens
What is the effect of anaesthetic on Action Potentials?
1) depolarsiation is prevented
2) threshold and resting potential is unchanged
Describe the structure-activity relationship of local anaesthetics
Ester or amide bonds determine 1) site of metabolism and 2) potential to produce allergic reactions.
Esters are more rapidly metabolised (& shorter acting) and more allergenic (Don’t really use esters anymore)
Lengthening the akyl chain increases lipid solubility.
In general, more lipid soluble = more potent
Name 1 important ester and 4 important amides
Ester: Cocaine
Amide:
1) Prilocaine
2) Lignocaine
3) Bupivacaine
4) Ropivacaine
Lengthening the akyl chain _________________. In general, more lipid soluble = ______ potent
Lengthening the akyl chain increases lipid solubility. In general, more lipid soluble = more potent
What is the most important factor determining speed of onset for a local anaesthetic drug injected into health subcutaenous tissue?
The drug’s pKa
LAH+ -> <- LA + H+ (if pKa is high, LAH is high, if the pKa is low, LA is high)
(LA = free base. Only the free base can cross the membrane and enter cells so you want a drug with a low pKa)
All local anaesthetics are _________
Weak bases
LAs with pKa closest to physiological pH have __________
This explains ________________
Fastest onset of action
This explains poor quality of block when LA injected into acidic infected tissue.
_____________ affinity for protein = increased duration of action
Increased
What is the mechanism of action of local anaesthetics?
Prevention of voltage dependent increase in Na+ ion conductance (stop Na+ getting into the cell).
LAH and LA exists, but only the LA (non-ionised) form can cross the membrane into the intraceullar fluid. Once it crosses the memrbane, the LA ionises and blocks the ion channel from the inside.
How are Esters and Amides metabolised?
Esters: plasma cholinesterases
Amides: (and some cocaine)
1) Liver metabolism
2) Most dependent on liver blood flow because of high extraction ratio.
Describe the features of Lignocaine/Lidocaine
1) Amide (standard agent aginst which others are compared)
2) ‘low’ lipid solubility and low potency
3) ‘low’ pKa, highly non-ionized, fast onset
4) lowprotein binding = short duration of action
5) Ideal to cover short surgical procedures e.g. dental or mole removal
What local anaesthetics is ideal to cover short surgical procedures?
Lignocaine/Lidocaine
Describe Bupivacaine
1) Amide
2) High lipid solubility = more potent than lignocaine
3) High pKa = slower onset than lignocaine
4) High protein binding = Longer duration of action than lignocaine
5) May cause cardio before neurotoxicity (unlike most LA toxicity patterns)
6) Ideal for nerve blocks for analgesia
Compare Lignocaine with Bupivacaine
Bupivacaine is more potent than lignocaine
Bupivacaine is slower onset than lignocaine
Bupivacaine is Longer duration of action than lignocaine
Bupivacaine is Ideal for nerve blocks for analgesia
Lignocaine is ideal for short surgical procedures
Describe Cocaines
1) Ester
2) Topical to nose
3) Vasoconst.
Describe Prilocaines
1) Amide
2) Safest agent, used in IV regional anaesthesia (e.g. Bier’s block)
What are Bier’s block?
Intravenous regional anesthesia (IVRA) or Bier block anesthesia is an anesthetic technique for surgical procedures on the body’s extremities where a local anesthetic is injected intravenously.
(Often use Prilocaine)
Describe Ropivavaine
1) Amide
2) Slow onset
3) Long acting
4) Less cardaic toxicity compared with bupivacaine.
Describe Local Anaesthetic Toxicity
1) Allergic reactions- rare with amides
2) Dose dependent CNS toxicity (seizures, periordal paraesthesiae, tinnitus)
3) Dose dependent Cardiac toxicity (ventricular fibrillation and heart block)
- If you give a large LA into a vein- likely to get a siezure first before the cardiac arrest
- Lignocaine CC: CNS ratio is 7
- Bupivacaine CC: CNS ratio is 3 (therefore both are more likely and more dangerous with bupivacaine).
4) Dose dependent toxicity is usually because of inadvertent IV administration. (= accidently administer into the vein and not the muscle)
What are the maximum safe doses of lignocaine and bupivacaine?
5mg/Kg (LEAN body weight) - Lignocaine
2mg/Kg (LEAN body weight) - Bupivacaine
What does it mean by “Topical Administration”?
Most often topical administration means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments. Many topical medications are epicutaneous, meaning that they are applied directly to the skin.
Describe Topical Administration and uses
Topical to skin
- EMLA- eutectic mexture of LAs
- Mexure of lignocaine and prilocaine as an oil preparation that allows most to be free base and therefore able to cross skin
- For insertion of IV cannulae in children
Topical to mucous membranes
- Cocaine (added advantage of vasocontriction)
- Lignocaine spray and viscous preparations
- For instrumentaion of the nose/mouth/pharynx
