Anaesthetic agents (sedatives and opioids)

Question 1

Name some induction agents

Answer 1

Propofol
Benzodiazepines 
Barbiturates
Etomidate
Ketamine

Question 2

Name some opiods

Answer 2

Morphine
Fentanyl
Codeine
Tramadol
Remifentanil

Question 3

What are some of the characteristics of propofol?

Answer 3

-Quick onset for sleep
-Rapid onset/offset with distribution
-Gives a Euphoric feeling
-Use; Anaesthetic induction, maintenance
of anaesthesia, sedation, anti-emesis
-Decreases serotonin in area postrema (antiemetic)
-Enhances GABA-induced chloride currents +
inhibits NMDA glutamate receptors
-Increases dopamine in nucleus accumbens
(sense of well-being)

Question 4

What is propofol used for?

Answer 4

• Anaesthetic induction
• maintenance of anaesthesia
• sedation
• anti-emesis

Question 5

Outline the pharmacokinetics of Propofol

Answer 5

-Oxidized and conjugated in liver
-Excreted by kidneys
-Competitive inhibitor of CYP3A4, increases duration
of action of midazolam

Question 6

What is one of the pros of propofol for someone with MH(malignant hyperthermia)

Answer 6

-Doesn’t cause a fast rise in body temp and severe muscle contractions when someone with MH gets general anesthesia

Question 7

What are some of the characteristics of barbiturates?

Answer 7

-Bind to GABA-A receptor and enhance
GABA effects (low doses)
-Directly stimulates GABA receptors (high
doses) causing increased chloride current
and hyperpolarization.

Question 8

What are barbiturates used for ?

Answer 8

• Thiopental: Induction, cerebral protection (e.g. status epilepticus)
• Methohexital: Induction, especially for ECT
• Phenobarbital: Seizure suppression
• Anxiolysis

Question 9

Outline the pharmacokinetics of barbiturates

Answer 9

-All hepatically metabolized then excreted in
urine except phenobarbital (60-90% renal
unchanged)
-Rapid redistribution terminates action of
single dose
-Much longer context sensitive half-time
than propofol

Question 10

What are some of the characteristics of benzodiazepines?

Answer 10

-Bind to GABA-A receptor, enhance response
to GABA
-Leading to hypnotic, sedative, anxiolytic,
amnestic, anticonvulsant, muscle-relaxation
properties
-Increases seizure threshold
-Midazolam (short acting)
-Lorazepam and Temazepam (intermediate)
-Diazepam (long acting)

Question 11

Outline the pharmacokinetics of benzoazepines

Answer 11

 Midazolam
- Rapid onset <1min, peak 2-3 min
-Distribution half life 6-15 min
-Hepatically metabolized by CYP system including active metabolite 1-hydroxymidazolam
 Lorazepam
- Conjugated in liver (not by CYP) to inactive compounds. Liver failure
can prolong effect.
-Infusion can cause propylene glycol toxicity
 Remimazolam
-New, cleared by non-specific tissue esterases

Question 12

What are some of the characteristics of ketamine?

Answer 12

-Phencyclidine-binds to NMDA Receptor
(antagonist)
-Racemic mixture of S and R ketamine. (S
isomer is more potent)
-Produces “dissociative anesthesia” because
patients may not appear asleep (eyes open,
reflexes intact)

Question 13

What are the uses of ketamine?

Answer 13

• Dissociative anaesthesia / Anaesthetic induction
  -Sedation (maintains RR, common in paeds)
  -Analgesia (opioid sparing / acute procedures)
  -Bronchodilatation
  (Particularly in haemodynamically unstable patients)

Question 14

Outline the pharmacokinetics of ketamine.

Answer 14

• Metabolized in liver to norketamine and hydroxynorketamine
• Norketamine has some activity but less than ketamine
• Metabolites excreted in urine
• Bioavailability orally is 20-30%, intranasally is 40-50%

Question 15

What are some of the characteristics of flumazenil?

Answer 15

-Competitive antagonist
-Short half-life, may get rebound effect of agonist, can use infusion (30-
60mcg/min)
-Rapid onset, 1-3 min, lasts 3-30 min
-Can cause seizures in patients on chronic benzos

Question 16

What are some of the characteristics of Etomidate?

Answer 16

-GABA-A facilitation (lower dose of GABA
required to activate receptor)
-At higher doses can activate receptor
independently

Question 17

Outline the pharmacokinetics of Etomidate

Answer 17

-Rapid onset 15-45 seconds
-Initial offset due to redistribution
-Cleared by Liver by ester hydrolysis then
excreted by kidneys and in bile, metabolites
not active

Question 18

What are the endocrine effects of etomidate?

Answer 18

-Dose dependent inhibition of 11B-hydroxylase.
-Occurs at lower doses than hypnosis by more than 20x so suppression lasts much
longer, up to 72h
-Can be used to treat hypercortisolaemia

Question 19

What are some of the characteristics of Dexmedetomidine?

Answer 19

-Alpha-2 receptor agonist (brain /spine)
-Used for sedation, anxiolysis, withdrawal,
delirium, opioid sparing analgesia.
-Useful for awake craniectomy / fibreoptic
intubation (sedation without respiratory
depression)

Question 20

Outline the pharmacokinetics of dexmedetomidine.

Answer 20

-Almost complete biotransformation in liver
with P450 system involvement
-Clearance is impaired in liver failure but not
renal impairment due to inactive
metabolites

Question 21

What is the ascending pain pathway used for?

Answer 21

Transmitting stimulus.

-Made up of fast& slow afferents

Question 22

What is the descending pain pathway used for?

Answer 22

Inhibiting transmission

-Made up of Substantia Gelatinosa.

Question 23

List the 4 opiod receptors?

Answer 23

• MOP (mu)
• KOP (kappa)
• DOP (delta)
• NOP (nociceptin)

Question 24

List the different opiods.

Answer 24

• Morphine
• Codeine
• Fentanyl
• Tramadol
• Remifentanyl

Question 25

What are the benefits of TIVA?

Answer 25

- Avoids conventional anaesthetic gases - Improved cardiovascular profile - Less nausea and vomiting - Improved tube tolerance

Question 26

What are the cons of TIVA?

Answer 26

- Need dedicated IV line - Based on algorithms ( Compartment model assumptions) - Risk of awareness

Question 27

What are some of the characteristics of morphine?

Answer 27

Highly potent opioid ( MOP>DOP/KOP) - Used for - analgesia - palliation - peri-operative - Oral (poor bioavailability; 40-60%) - Subcutaneous/IV/intrathecal/transdermal - Metabolised in liver (glucorinated) - Active metabolite (morphine 6 – glucoronide) - potent + longer lived - Excreted via urine - Low lipid solubility - slow BBB penetration - slow onset

Question 28

What is the vomiting center of the brain?

Answer 28

-The fourth ventricle of the brain hosts the vomiting centre. The floor of the fourth ventricle contains an area called the chemoreceptor trigger zone (CTZ).aka area postrema. When the CTZ is stimulated, vomiting may occur.

Question 29

What are some of the characteristics of fentanyl ?

Answer 29

Synthetic opioid - 80-100 times more potent than morphine - Few cardiovascular effects - Less histamine release. - Targets mu + delta receptors

Question 30

What are some of the characteristics of codeine?

Answer 30

- 50% analgesic potency compared to morphine - Given orally - PRO-DRUG > Active metabolites (codeine – 6 glucuronidate morphine; 10%) - Metabolized by CYP2D6 - Caution in ultra-rapid metabolizers - Lack of efficacy in poor metabolizers - Susceptible to drug-drug interactions. - Risk to neonate ( breast feeding if mothers rapid metabolizers) - Half life – 3 hrs -Weakly targets mu + kappa receptors

Question 31

What are some of the characteristics of Tramadol?

Answer 31

``` Atypical opioid ( analogue of codeine) - Administered oral / iv - 1/10 potency of oral morphine - Dual action – mu agonist (weak) - serotinergic/noradrenergic reuptake inhbition ( enhances descending inhibition) - Safer cardio - respiratory profile - Risk of serotonin syndrome ( caution with other drugs) -targets mu receptors -NA /5HT reuptake ```

Question 32

What are some of the characteristics of Remifentanil?

Answer 32

-Potent mu receptor agonist -Ultra-short acting drug -Unique pharmacokinetics - Rapid onset (1.3 mins) - Rapid offset (context sensitive ½ time = 3.7 min) (metabolized by non specific blood/tissue esterases

Question 33

What are some of the uses of Remifentanil?

Answer 33

- Sedation in ICU - PCA in obstetrics - Pain relief during surgery - Total IntraVenous Anaesthesia ( TIVA)