Local anaesthetics are applied to block nerve transmission when locally applied (not through IV). Local anaesthetics differentially block nerves with it primarily effecting the peripheral and central small afferent sensory fibres
Posology
Posology is the choice of dose, and depends on the following factors:
- Nature of treatment
- Extent of area to be anaesthetised
- Route of anaethesia
- Anatomical region
- Pathological state in patient - tissue infection, cardiac status and BP etc.
- Age and condition of patient.
LA routes of administration
- Epidural This is injection of LA into the epidural space.
- Intrathecal This is injection of LA into the CSF
- Nerve block This is injection into the space around a nerve to block transmission. It should be done upstream to the site of surgery
- Infiltration This is subcutaneous or intradermal.
- Topical Gel.
Local infiltrative vs nerve block
Local infiltrative is prefered for small quick and easy applications. Not good for larger areas.
Nerve block is more skillful and precise, but larger amounts needed. It is preferred in confined spaces.
Clinical considerations in LA administration
LAs are generally used in surgery where consciousness is preferred, and minor procedures.
Contraindications
- Extensive surgical procedures
- Risk of high dose LA toxicity
- Allergies or hypersensitivities
- Local inflammation, infections, and ischaemia.
Caution should be taked with paediatric elderly or pregnant patients
Amides vs esters
There are 2 types of local anaesthetics (LAs) , esters and amides. They are called this because the structure of LAs are that of an aromatic ring connected with an amide/ester to an amine group.
The distinction is important as amide and esters have different qualities. Those who have a hypersensitivity to esters are very unlikely to also have that allergy extend to amides.
Additionally the metabolism is different, with esters being metabolised quickly by pseudocholinesterase and the by products are excreted through urine. Naming convention is -caine with no i in the prefix (cocaine, procaine)
Amides are metabolised through hepatic CYP-450 to inactive agents. true allergic reactions to amides are rare. These can be identified by i-caine naming convention (lignocaine,bupivacaine, articaine).
Pharmcokinetics
Due to the pH-Partition Hypothesis we see drug pKa closer to physiological pH have faster onset and longer half life. Drugs with amide linkers have lower pKa compared to esters.
This means there is difficult when injecting into a site where there is infection, as infection often lowers pH, which means less LA gets into cells
Because of this injecting a LA with a bicarb buffer retains the unionised state in the site of injection, promoting permability into the cells, where the (relatively) acidic environment leads to ionised forms and the LA not being able to leave the cell.
Mechanism
ADRs of LAs
The ADRs of LAs mainly depend on systemic toxicity, with enough LA getting into the vascular system bad things will happen.
They include
- CNS effects These are headache, respiratory depression, and confusion
- Cardiac effects This comes from LA blocking Na+ channel in nodal tissue, leading to reduced cardiac depolarisation. This causes reduced excitability, pacemaker activity and increased refractory period of myocardial tissue.
- Vascular effects Blocking voltage gated Na+ channels on the vasculature will lead to vasodilation, endothelial Nitric oxide release and inhibition of vasodilators preventing NA release.
LAST
LA induced vasodilation leads to increased dispersion and washout of local anaesthetic leading to cardio- and neuro-toxic effects.
Local anaesthetic systemic toxicity (LAST) is a clinical presentation of arrhythmia and :
- at 5 - 10mg/L dizziness anxiety, confusion and muscular twitching
- at 10-15 mg/L disorientation, tremor, respiratory depression and seizure.
Prevention of LAST
Prevention of LAST includes inject with vasoconstrictors to prevent vascular diffusion and treat directly with lipid emulsion to mop up LA
Lignocaine
Lignocaine is the main LA talked about, It has a pKa close to blood pH and so allows for rapid induction of anaesthesia (1-2 mins) and medium duration (1-3 hrs).
I think the other information provided is broadly applicable and the main difference in LAs are amide vs ester and pKa.