Local anaesthetic agents Flashcards
What is general anaesthesia
Loss of sensation of the entire nervous system
What is local anaesthesia
Restricts loss of sensation to an area supplied by a limited number of nerves
Name and describe 4 routes of administration for local anesthetics
- Topical - cream, gel or spray for skin/mucous membranes
- Infiltration - for field blocks where superficial nerves are blocked locally using IV preparations
- Intravenously - Intravenous Regional Anaesthesia = Bier’s block for fractured wrist.
- Epidural or subarachnoid - regional anaesthesia - blocking spinal nerves
Which is more potent bupivacaine or lidocaine and why?
Bupivacaine is 4 x as potent as lidocaine because it is more lipid soluble
Why is bupivacaine 4 x as potent as lidocaine if it is 9 x the lipid solubility
Other factors also affect potency
Which form of the local anaesthetic drug is able to cross the cell membrane?
The unionized form. The more unionized, the more rapid the passage of the drug across the membrane and the faster the onset of the block.
Which form of the local anaesthetic drug is effective at blocking the voltage-gated sodium channels?
The ionized form
What is the pKa of a drug
this is the pH at which the ionized form of the drug equals the unionized form of the drug
What determines the proportion of any drug in the ionized form compared with the unionized form?
- Whether a drug is a weak acid or a weak base
- The pKa
- The pH of the environment
What % of lidocaine and bupivacaine are unionized at physiological pH of 7.4.
How does this relate to the respective onsets of action
Weak bases ionize at pH below their pKa
Lidocaine pKA = 7.9 —> 25% unionized at pH of 7.4
Bupivacaine p Ka = 8.1 —> 15% unionized at pH of 7.4
It correlates with the onset of action
Lidocaine –> Onset: 2 - 4 minutes
Bupivacaine –> Onset: 4 - 8 minutes
What can be added to increase the proportion of unionized drug
Sodium bicarbonate
What situation will cause for the regional pH to lower hence slowing the effect of the LA or rendering the LA ineffective?
Infected tissue/abscesses
What factors determine the duration of the local block?
Protein binding
Rate of removal from the site and subsequent metabolism
What can be added to lidocaine to increase its duration of action and what is the mechanism of this
Epinephrine 1: 200 000
Vasoconstriction reduces local blood flow to the site where the anaesthetic is infiltrated –> less lidocaine is cleared away.
Is the addition of adrenalin to bupivacaine clinically useful?
No. the duration of action of bupivacaine is determined mainly by tissue binding.
How does the addition of adrenalin to lidocaine alter the maximum dose of lidocaine that can be used safely?
Without adrenalin: 3mg/kg
With adrenalin: 7mg/kg
Does addition of adrenalin to bupivacaine allow for higher doses of bupivacaine to be administered safely.
No. Toxicity associated with bupivacaine is related to protein binding
How can local anaesthetic agents be classified in terms of chemical groups? How does this structural difference influence the pharmacokinetics of these agents?
There are two chemical groups
Amide local anaesthetics
- Amide linkage: N - C - C (middle C has double bonded O)
Ester local anaesthetics
- Ester linkage: C - C - O (middle C has a double bonded O)
Esterases are present in a variety of tissues and in the blood stream - Ester linkages are easily broken down and therefore have a shorter duration of action than amide LAs and are used less commonly for local blocks
Amidases are found in the liver
Which are more protein bound ester local anaesthetics or amide local anaesthetics and how does this effect the duration of action?
Amides are more protein bound which increases their relative duration of action
What is an amine?
An amine is a compound in which one or more of the hydrogen atoms in ammonia have been replaced by an organic functional group.
What is basic chemical structure of all local anaesthetics?
Lipid soluble ring joined to an amine-containing group by either an amide or and ester linkage
Name the amide local anaesthetic agents
- Lidocaine
- Bupivacaine
- Prilocaine
- Ropivacaine
What are the other names for lidocaine
Lignocaine, Xylocaine
What is lidocaine pKa
7.9
What is the partition co-efficient for lidocaine (relative lipid solubility)
3
What is the % protein binding of lidocaine?
65%
Describe the various presentations for lidocaine
- In solution 1% or 2% with/without adrenalin 1:200 000.
- Gel: 2% gel for catherization
- Metered spray: 10mg/dose
- Topical 4% solution
How long does lidocaine take to work?
2 - 4 minutes
What is lidocaines duration of action?
1 - 2 hours (medium duration)
What are other uses for lidocaine?
Antiarrythmic - Rx persistent ventricular ectopics
Adverse effects of lidocaine?
Circumoral tingling, seizures, coma, dysrythmia
In what two forms is bupivacaine available
Racemic mixture (bupivacaine) or a single isomer (levobupivacaine)
What is the partition co-efficient of bupivacaine versus lidocaine
Lidocaine 3 Bupivacaine 28 (9 x lipid solubility)
What is the pKa of bupivacaine?
8.1
Protein binding of bupivacaine?
95%
What is the common trade name for bupivacaine?
Marcain
What are the different presentations of Marcain
Marcain Spinal 0.5% Heavy Solution for Injection
- bupivacaine 0.5% (5mg/ml)
- Glucose 8% (80mg/ml)
Marcain Spinal 0.5% Solution for Injection
- bupivacaine 0.5% (5mg/ml
List the uses for bupivacaine
- Local nerve blocks
2. Regional anaesthesia and analgaesia (espcially obstetric analgaesia)
What is the onset of action of bupivacaine
ROUTE AND DOSE DEPENDENT
Epidural: Up to 17 minutes to spread to T6 dermatome (Scott 1980)
Infiltration: Fast (Barash 2009); Dental injection: 2 to 10 minutes
Spinal: Within 1 minute; maximum dermatome level achieved within 15 minutes in most cases
What is the duration of action of bupivacaine
ROUTE AND DOSE DEPENDENT
Epidural: 2 to 7.7 hours (Barash 2009)
Infiltration: 2 to 8 hours (Barash 2009); Dental injection: Up to 7 hours
Spinal: 1.5 to 2.5 hours (Tsai 2007)
What is the maximum dose of bupivacaine?
2mg/kg
What are adverse effects
CVS: Myocardial depression
CNS: Convulsions –> coma
levobupivacaine less toxic
Contraindications:
Established allergy/hypersensitivity
SHOULD NOT BE USED FOR BIER’s BLOCK
Name the ester local anaesthetics
Tetracaine
Cocaine
Procaine
How do ester LAs differ from amide LAs
Shorter duration
Higher incidence of hypersensitivity reactions
What can be used in children nervous of IV cannulation
- Eutectic Mixture of Local Anaesthesia (EMLA)
2. Ametop gel
What is the meaning of the word Eutectic?
Eutectic refers to a gel state that occurs in a mixture of different agents that WOULD NOT OCCUR with each component alone at a given temperature (room temp for EMLA)
How long before cannulation should EMLA/Ametop be applied?
30 - 60 minutes
What does EMLA contain?
Lidocaine 2.5%
Prilocaine 2.5%
Individual tubes contain 5g and come with occlusive dressings
Can EMLA be applied to mucous membranes?
Not useful –> Mucous membranes will be anaesthetized but absorption limits the duration of action –> systemic effects are not seen after a single application
How long does EMLA last?
Up to 5 hours
What is the problem with using EMLA
Causes vasoconstriction –> may make cannulation more difficult
Can EMLA be used over a large area in methaemoglobinaemia?
No. A metabolite can worsen the condition
What is the active ingredient in Ametop gel?
Tetracaine (amethocaine) 4% as a gel
1.5 g in indicidual tubes
Thick layer plus occlusive dressing applied
How long does ametop take to work
30 mins but shorter duration the EMLA
Does ametop cause VC like EMLA
No
What side effect occurs more frequently with ametop versus EMLA
hypersensitivity (contains ester linked tetracaine) - urticaria/erythema
