15)Local anaesthetics

Question 1

Local anaesthetics

Answer 1

• Drugs that cause reversible loss of sensation in a localised area
• Achieved by blocking nerve conduction without loss of consciousness

Requirements:

• Cannot be toxic
• Should be topical or liquid for easy application/infiltration
• Not long lasting
• Stable
• Non-allergic

Question 2

Classification: Amides

Answer 2

• Hydrolysed in liver + rarely cause hypersensitivity reactions
• Eg: lidocaine, articaine, Bupivacaine
• Lidocaine often mixed/small amounts of adrenaline for vasoconstriction ⇢ Blocks Na⁺ volt-gated ion channels ⇢ prevents APs
• Side effects ⇢ sleepiness, muscle twitching, confusion + low blood pressure

Structure

• Aromatic portion, intermediate chain, amine portion
• they are significantly bound to plasma proteins

Question 3

Classification: PABA - Esters

Answer 3

• Have a shorter duration of action w/less intense anaesthesia
• Hydrolysed by plasma
• Eg: cocaine, Procaine, tetracaine
• NOT significantly bound to plasma proteins

Vasoconstrictors are added to ⇣ vessel perfusion:

• ⇣ absorption of LA into blood stream = ⇣ Toxicity
• ⇡ Duration of action
• ⇣ Bleeding

Question 4

Pharmacodynamics/Mechanism

Answer 4

All LAs ⇢ ⇣ Rate of membrane depolarisation + repolarisation

Majority act by inhibiting sodium influx in sodium ion channels of membrane:

• In order to block channel ⇢ LA must first get into the cell
• This is possible as it is a weak base in un-ionised form
• Once inside cell ⇢ LA will exist in ionised form ⇢ Prevents it from leaving cell
• It blocks Na⁺ ion channels
• This ⇡ Threshold required for electrical excitation
• Therefore ⇢ ⇣ Rate of APs

Question 5

Pharmacokinetics

Answer 5

Only the non-ionised form of LA diffuses across the membrane

• LAs are administered as hydrochloride salts ⇢ Release non-ionised base into EC fluid

Question 6

Clinical use + side effects

Answer 6

Clinical use:

• Topical application ⇢ in dental clinic at mucous membrane/site before injection ⇢ Reduces pain of injection
• Nerve Blocks ⇢ PSA,MSA,ASA/infraorbital (Maxillary) + ISA Mandibular
• Spinal anaesthesia
• Intravenous

Side effects:

• Allergic reactions
• CNA + Cardiovascular toxicity at high levels
• Can cross placenta

Contraindications:

Patients w/impaired liver/kidney function