Pharmacology - drug characteristics

Question 1

Lidocaine

Answer 1

• Amide LA
• Prep - formulated as the hydrochloride. Presented as a colourless solution (0.5-2%) with or without adrenaline, a 2% gel, 5% ointment, a spray giving 10mg/dose and 4% soln for topicalising mucous membranes.
• Kinetics - 70% protein bound to alpha-acid glycoprotein.
• pKa 7.9 - 25% unionised at pH 7.4.
• Elimination half life 100 mins.
• Rapid onset of action - 2 minutes
• Lasts 20-40 minutes
• Class 2b antiarrhythmic - membrane stabilising properties

Question 2

Bupivacaine

Answer 2

Amide LA
Prep - 0.25% and 0.5% (+/- adrenaline). 0.5% prep with 80mg/ml glucose available for subarachnoid block.
Maximum dose - 2mgkg-1.
Kinetics - intermediate to slow onset of action. Most highly bound amide LA (95%).
Duration of action - long .
pKa - 8.1
% unionised at pH 7.4 - 15%
Metabolism - liver
Elimination half life - 160 mins
Due to the duration of time bupivacaine blocks sodium channels, there is an increased risk of cardio toxicity which is hard to treat

Question 3

Levobupivacaine

Answer 3

S-enantiomer of bupivacaine
Potential for reduced toxicity compared to bupivacaine - higher dose needed to block cardiac K+ channels and cause toxicity and CNS excitability effects occur at lower doses with bupivacaine.
Undergoes hepatic metabolisms with no unchanged drug excreted.

Question 4

Ropivacine

Answer 4

Amide LA
Pure S-enantiomer.
Long lasting local anaesthetic
Reduced side effect profile vs bupivacaine.
Slightly less potent than bupivacaine, slightly shorter duration and less cardiotoxic.

Question 5

Prilocaine

Answer 5

Amide LA
Similar to lidocaine but more intermediate duration of action
Less local vasodilation
Less protein bound
Increased Vd
Causes methaemoglobinaemia - treated with IV methylene blue
Used in Biers blocks (IV regional anaesthesia) - short duration of action and reduced risk of cardio toxicity. 2% hyperbaric solution can be used for day surgery - motor function returns in 60-75 mins.

Question 6

Cocaine

Answer 6

Ester of benzoic acid
Used to anaesthetise ENT surgery or fiberoptic intubation due to vasocontructive effects via local inhibition of noradrenaline reuptake
Readily crosses BBB when absorbed systemically
Abuse - euphoric side effect due to inhibition of catecholamine reuptake.
Cardiac dysrhythmias and death from vasoconstriction of coronary circulation

Question 7

Topical EMLA

Answer 7

Eutectic picture of local anaesthetics
Solid formed by combo of equal amounts of different agents. e.g.
EMLA 5% = 2.5% lidocaine with 2.5% prilocaine
Ametop = 4% tetracaine. Preferable as avoids prilocaine in paeds and causes local vasodilation. Onset approx 40 minutes, anaesthetised up to 4 hours