Lecture 10: Inhalation Anaesthetic and Intravenous Anaesthetics

Question 1

What is the “triad of anaesthesia”?

Answer 1

What we mean by “anaesthesia” 1) Cause Hypnosis/Amnnesia -e.g. IV of volatile agents 2) Muscle relaxant - immobility 3) Opioids -Autonomic areflexia Enough ether can achieve all 3, but now the modern approach is “balanced anaesthesia”.

Question 2

Describe the equilirbium of uptake of inhaled anaesthetic agents

Answer 2

We do not metabolise the inhaled anaesthetic agents.

At the beginning of the anaesthetic, the equilibrium shifts to the right

At the end of the anaesthetic, the equilibrium shifts to the left.

Question 3

What is a hypotheses of how inhaled anaesthetics work?

Answer 3

1) Meyer-Overton hypothesis

They suggested that general anaesthetics may act by dissolving in the fatty fraction of brain cells and removing fatty constituents from them, thus changing activity of brain cells and inducing anaesthesia.

This hypothesis had problems, as not all lipophilic volatile agents produce anaethesia.

Question 4

What is MAC?

Answer 4

The means of describing potency and dose

MAC is the minimal alveolar concentration producing imobility on standard surgical stimulus in 50% of patients

More potent agents with a lower MAC

The use of another drug can move the MAC.

Question 5

Name some things that increases or decreases the MAC

Answer 5

Increases: (need higher dose to have the same effect)

1) Young age
2) Hyperthermia
3) Hyperthyroid
4) Heavy alcohol
5) Drugs e.g. amphetamine

Decreases: (need lower dose to the have the same effect)

1) Old age
2) Hypothermia
3) Hypothyroid
4) Drugs (e.g. opioids, depressants)
5) Pregnancy
6) Low O2, high CO2.

Question 6

MAC for desflurane is 6%. Does setting 6% on the vaporizer mean the patient has an alveolar concentration of 6%?

Answer 6

No. because what happens is the drug goes into the alveolar, but some also go into the blood.

Question 7

What does pharmacodnyamics mean?

Answer 7

The branch of pharmacology concerned with the effects of drugs and the mechanism of their action.

Question 8

Describe the phamacodynmaics effect anaesthetics has on the CNS

Pharmacokinetics is the study of what the body does to the drug. Pharmacodynamics is the study of what the drug does to the body.

Answer 8

• Cause: 1) Hyponosis, 2) Immobility, 3) Amnesia
• but also decrease CMRO2 (cerebral metabolic rate of oxygen)
• Dose dependent increase CBF (Cerebral blood flow) and ICP (Intracranial pressure) (You must take care with use in neurosurgery)
• Cerebral protection (but not demonstrated in humans)

Question 9

Describe the phamacodynamics of anaesthesia on the CVS

Answer 9

1) Peripheral vasodilation, lower BP
2) HR unchanged (except desflurane- which causes an increase in HR)
3) Modern agents don’t really affect Stroke Volume greatly
4) Holthane pro-arrythmogenic

Question 10

Describe the pharmacodynamics of INHALED anaesthesia on the Respiratory System

Answer 10

1) Respiratory Depressant (Sevoflurane is least)
2) Impair ventilatory response to hypoxia
3) Impair ventilatory response to CO2
4) Bronchodilation (but desflurane is an airway irritant- so is useful for COPD patients, but don’t give to acute patients)

Question 11

How is desflurane unique?

Answer 11

Changes HR (unlike other anaesthetics)

Question 12

Describe Nitrous Oxide- Anaesthesia

Answer 12

1) Odourless non-flammable gas
2) Low potency (MAC 101%- cannot just use this for anaesthesia)
3) Low blood-gas solubility, rapid onset
4) Analgesic
5) Many adverse effects (e.g. nausea and vommitting)

Question 13

Describe Halothane- Anaesthesia

Answer 13

1) Sweet non-pungent halogenated alkane
2) Highly potent (MAC- 0.86%)
3) Intermediate blood-gas solubility, slow onset
4) Metabolised 2% in vivo
5) Rarely causes fatal hepatitis

Question 14

Name 5 common inhaled anasthetics

Answer 14

1) Halothane
2) Isoflurane
3) Sevoflurane
4) Desflurane
5) Nitrous Oxide (not used as much)

Question 15

Describe Isoflurane- Inhaled anaesthetics

Answer 15

1) Pungent
2) Potent (MAC- 1.1%)
3) Intermediate solubility, medium onset
4) Cardiovascular stability

Question 16

Describe Sevoflurane- Inhaled Anaesthesia

Answer 16

1) Non-pungent and least respiratory depression (good for gaseous inductions)
2) Intermediate potency (MAC 1.7%)
3) Low sikyvukutym raoud onset
4) Little airway stimulation
5) Little airway stimulation
6) reacts with CO2 absorbent

(avoid in renal failure patients)

In adults- often administered intravenously.

Question 17

What INHALED anaesthetics shoudl you avoid in renal patients?

Answer 17

Sevoflurane

Question 18

What inhaled-anaesthetics are pungent and what are non-pungent?

Answer 18

Halothane- non-pungent (sweet)

Isoflurane - pungent

Sevoflurane -non-pungent

Desflurane -pungent

Question 19

Describe Desflurane

Answer 19

1) Pungent
2) Intermediate potency (MAC 6.0%)
3) Low blood-gas solubility, rapid onset and offset (therefore is ideal for long cases where fast wake up is desired)
4) Sympathetic stimulation (where most causes depression)

Question 20

Name 5 types of intravenous anaesthetic agents

Answer 20

1) Barbiturates (e.g. Thiopentone)
2) Phenols (e.g. Propofol)
3) Imidazols (e.g. Ethomidate)
4) Phencyclidine derivatives (e.g. Ketamine)
5) Benzodiazepines (e.g. Midazolam)

Question 21

What are the mechanisms of action of intravenous anaesthetic agents?

Answer 21

1 (Thiopentone, profol, etomidate, midazolam)

Enhance GABA which prolongs Cl- current. THis causes hyperpolarisation

2 (Ketamine)

Bind to NMDA and antagonises glumatae and supresses exciation

Also has analgesic effects, whilst the other 4 do not.

Question 22

Name an intravenous anaesthetic that has analgesic effects

Answer 22

Ketamine

Question 23

Describe the Pharmacokinetics of Intravenous Anaesthetic agents

Answer 23

1) Highly lipid soluble and cross BBB easily
2) Drug from IV bolus taken up by VRG (vessel rich group e.g. brain, kidney, lung, liver, heart) organs, then leaves these organs as lean (less perfused) tissues take up drug and concentration in blood falls
3) Offset after single IV dose is therefore due to redistribution - patient may wake even though the total drug in body has not changed much
4) Metabolism is much slower for most agents

Question 24

Describe the Intravenous anaesthetics: Thiopentone

Answer 24

1) Very rapid onset (10s)
2) Rapid offset by redistribution
3) Slow clearance (therefore will accumulate in multi-dosing or infusion)
4) Metabolized in liver, induces liver enzymes
5) Some decrease in Peripheral vascular resistance and BP (enahnced in shock)
6) Respiratory depression and loss of airway reflexes

Good for emergency cesarean sections. The mother falls asleep 10s after administration of the anaesthetics

Question 25

What anaesthetics is good for C-sections?

Answer 25

Thiopentone

Because of its rapid onset.

Question 26

Describe the Intravenous Anaesthetics: Propofol

Answer 26

1) Moderate rapid onset (30-40s)
2) Rapid offset by redistribution
3) Fast clearance (up to 10x thiopentone).
- Clearner offset (no ‘hangover’)
- does not accumualte in infusion
- can be used as infusion for maintenance
4) Metabolized in liver
5) Significant decrease in PVR and BP (enahnced and in shock)
6) respiratory depression and loss of airway reflexes

Question 27

Which intravenous anaesthetics can be used as infusion for maintenance?

Answer 27

Propofol

Question 28

Between propofol and thiopentone, which would you use? (3 reasons)

Answer 28

Both are intravenously used anesthetics

• Propofol has replaced thiopentone as the ‘standard’ IV anaesthetic in most developed countries
  1) because of its high turn over/day stay surgery (propofol wears off faster and does not have a hangover)
  2) Can be used in infusion for maintenance (therefore is good in neurosurgery)
  3) less enzyme induction

Question 29

In what cases would you not use either propofol or thiopentone?

Answer 29

Both agents cause CV instabilitiy.

Question 30

Describe the Intravenous Anaesthetic: Etomidate

Answer 30

1) Imidazole
2) Formulated as emulsion
3) Remarkable CV stability
4) Less respiratory depression
5) Rapid clearance and good recovery profile
but: causes…
a) adrenocrotical inhibition (supress stress hormone production)
b) myoclonus (spasmodic jerky contraction of groups of muscles.) and epileptogenic

Question 31

Which Intravenous Anaesthetic is good for CV stability?

Answer 31

Etomidate

(Ketamine is a stimulant)

Question 32

Describe the Intravenous Anaesthetic: Ketamine

Answer 32

1) Phenyclidine derivative
2) Analgesic
3) Cardiovascular stimulant (opposite to most)- therefore is good for a shocked patient
4) Preserves airway reflexes and respiratory drive
5) Increases CMRO2, CBF and ICP (not good for neurosurery)
6) Dissociative state, emergence slower and complicated by dysphroia.

Question 33

Which Instravenous Anaesthetic is good for neurosurgery?

Answer 33

Propofol- because it can used in infusion for maintenance.

Question 34

Name 5 Common Intravenously administered Anaesthetics

Answer 34

1) Thipentone
2) Propofol
3) Etomidate
4) Midazolam
5) Ketamine

Question 35

Describe the Intravenous Anaesthetic: Midazolam

Answer 35

1) Benzodiazepine
2) Reduce CMRO2 (Cerebral blood flow and cerebral metabolic rate) and CBF
3) Potent anti-epileptic action
4) Modest haemodynamic and respiratory depression
5) Very high margin of safety
6) Slow onset and offset limits use.

Question 36

What are some good and bad sides to total intravenous anaesthesia?

Answer 36

1) Avoids inhalation route
2) Avoids complications of vapours (e.g. intracranial hypertension, malignant hyperthermia, PONV)
1) Expensive
2) No agent monitoring.