Anaesthetic agents (sedatives and opioids)

Question 1

Which is the most common induction agent in surgery?

Answer 1

Propofol.

Question 2

What are the three effects of anaesthetics?

(and some examples of drugs)

Answer 2

Remember A.S.A.

ANAESTHESIA – To render unconscious;

• Propofol.
• Etomidate.

SEDATION – Reduce anxiety;

• Benzodiazepines.
• Barbiturates.

ANALGESIA – Relief of pain;

• Morphine.
• Fentanyl.
• Codeine.
• Tramadol.
• Remifentanil.

Question 3

What effects does Propofol have?

Answer 3

Anaesthetic induction,

Maintenance of anaesthesia,

Sedation,

Anti-emesis.

Question 4

What is the mechanism of action of Propofol?

Answer 4

Enhances GABA-induced chloride currents.

Inhibits NMDA glutamate receptors.

• Therefore supresses CNS.

Question 5

What are the pharmacokinetics of Propofol?

Answer 5

Rapid onset and offset:

• About 30 secs onset!!
• Onset (1 arm brain circulation).
  
  • However, does also have a fast offset.
• Offset (redistribution).
  
  • So should give something else to maintain anaesthetics.

Oxidized and conjugated in liver.

• Excreted by kidneys.

Question 6

What are Propofols neurological pharmacodynamics?

Answer 6

Loss of consciousness.

Seizure suppression.

• Because it’s inhibitory (to NMDA Rs)

Decrease ICP (intercranial pressure).

Decrease IOP / CPP.

Antiemesis.

Question 7

What are Propofols respiratory pharmacodynamics?

Answer 7

With infusion: Increases RR.

With a bolus: Apnoea (stop breathing).

• So should only be given when ventilation is possible.

Question 8

What are some pros of Propofol?

Answer 8

Does not trigger malignant hyperpyrexia (MH).

Gives pleasant dreams.

Anti-emetic even at low doses.

Question 9

What effects do Barbiturates have?

Answer 9

Anxiolytic (reduces anxiety),

Anaesthetic induction,

Seizure suppression,

Sleeping aids,

Question 10

What are some examples of barbiturates?

Answer 10

Phenobarbital.

Butabarbital (Butisol).

Question 11

What is the mechanism of action of Barbiturates?

Answer 11

Low dose;

• Positive allosteric modulator,
• (enhances GABA-A receptor effect).

High dose;

• Directly stimulates GABA- A receptors causing increased chloride current and hyperpolarization.

Question 12

What are the pharmacokinetics of Barbiturates?

Answer 12

Rapid onset and offset.

• Hepatically metabolized then excreted in urine.

Much longer context sensitive half- time than propofol

Question 13

What are Barbiturates neurological pharmacodynamics?

Answer 13

Loss of consciousness.

Seizure suppression.

Decreased CMRO₂ (cerebral oxygen demand).

Question 14

What are Barbiturates respiratory pharmacodynamics?

Answer 14

Increases RR.

Apnoea (temporary cessation of breathing).

Bronchoconstriction.

Question 15

What are Barbiturates cardiovascular pharmacodynamics?

Answer 15

Peripheral vasodilation.

Increased HR.

Question 16

What effects do Benzodiazepines have?

Answer 16

Sedative,

Anticonvulsant,

Co-induction agent,

• Doesnt induce unconsciousness on its own.

Sleeping aid.

Question 17

What are some examples of benzodiazepines?

Answer 17

Alprazolam (Xanax).

Midazolam (short acting).

Lorazepam (intermediate acting)

Diazepam (long acting)

Question 18

What is the mechanism of action of benzodiazepines?

Answer 18

Bind to GABA-A receptor,

Enhance response to GABA.

Question 19

What are the pharmacokinetics of benzodiazepines?

Answer 19

Rapid onset <1min, peak 2-3 min.

Hepatically metabolized.

Question 20

What are benzodiazepines neurological pharmacodynamics?

Answer 20

Anxiolysis.

Sedation.

Amnesia.

• both anterograde and retrograde.

Anticonvulsant.

Question 21

What effects does ketamine have?

Answer 21

Analgesia (acute),

Sedation (paeds),

Anaesthetic induction.

Question 22

What is the mechanism of action of ketamine?

Answer 22

Binds to NMDA Receptor (antagonist)

Question 23

What are the four opioid receptors?

Answer 23

MOP: (mu)

• Main receptor.

KOP: (kappa)

DOP: (delta)

NOP: (nociceptin)

Question 24

What is the opioid mechanism of action?

Answer 24

They inhibit neurotransmitter release in the pain pathway.

Therefore less pain transmission.

Question 25

What are the pharmacokinetics of Morphine?

Answer 25

A highly potent opioid.

Orally, has poor bioavailability, so given:

• Subcutaneous / IV / intrathecal / transdermal.

Low lipid solubility;

• Slow BBB penetration.
• Slow onset.

Question 26

What is a common side effect of morphine?

And why does it occur?

Answer 26

Morphine can cause nausea and vomiting.

Because it stimulates the chemoreceptor trigger zone (CTZ).

Question 27

What synthetic opioid is around 80-100x more potent than morphine?

Answer 27

Fentanyl.

Question 28

What are some benefits of fentanyl over morphine?

Answer 28

Few cardiovascular effects.

Less histamine release.

Because of high lipid solubility, it enters brain rapidly and produces peak analgesia in 5 min after IV injection.

Short duration of action:

• Starts wearing off after 30-40 min (redistribution).