L4 - Anaesthetics & Sedatives

Question 1

Structure of Anaesthetics – 3

Answer 1

1. pKa of the amine: rapid onset relies on sufficient molecules in non-protonated form (lipid soluble), activity at channel relies on quaternary protonated form
2. Ease of hydrolysis of esters means the amides are longer acting
3. Lidocaine (ester) & bupivacaine (amide) are widely used

Question 1

General Anaesthetics – 4

Answer 1

1. Sedative-hypnotics act by enhancing the inhibitory actions of GABA receptors
   Ideally, they should be/have:
2. Fast onset & recovery (titratable)
3. Few side effects/high therapeutic index
4. Aq solubility for easy formulation

Question 2

Propofol: “milk of amnesia” - 3

Answer 2

1. Very poor aqueous solubility (insoluble)
2. Formulated as an oil/water emulsion
3. Single use, any left is disposed

Question 3

Improving water solubility of Propfol – 3

Answer 3

1. Make esters with amine, to form a salt, increasing solubility, change branched alkyl chains to ethers
2. Water attacks, double bond to oxygen opens
3. Fospropofol metabolized by alkaline phosphates to propofol, formaldehyde & phosphate

Question 4

Ester’s effect on Metabolism- 3

Answer 4

1. Good sedative & anaesthetic, prolonged use can lead to increased mortality
2. Deactivated by esterases (so already is a soft-drug)
3. Intro of 2nd ester at end of chain is a less hindered ester - should be more rapidly metabolised

Question 5

Benzodiazepines - 2

Answer 5

1. Widely used as anxiolytics, amnestic & sedative-hypnotics, but less used as anaesthetic induction due to cardiovascular depression & prolonged recovery
2. Diazepam used but many active metabolites contribute to long duration of action

Question 6

Shorter acting benzodiapane – 3

Answer 6

1. Remifentanil undergoes organ & dose independent ester hydrolysis
2. Much shorter duration after infusion than midazolam
3. Can be used in patients with hepatic or renal impairment

Question 7

Non-benzodiazepine hypnotics, e.g. zolpidem & zopiclone - 4

Answer 7

Zolpidem:
1. Fast onset, short ½ life
2. Effective in initiating, but not maintaining sleep
3. Drowsiness the following day
Zopiclone:
4. Metabolite is the N-desmethyl which itself is a partial agonist