Pharma 8.2 Anasthetics

Question 1

What is dissociative anasthesia?

Answer 1

inhibits transmission of nerve impulses between higher and lower centres of the brain

Question 2

Name 4 inhalational anaesthetic agents

Answer 2

N2O, isoflurane, desflurane, sevoflurane

Question 3

Name 2 IV anaesthetic agents

Answer 3

Propofol, ketamine

Question 4

Which anasthetics act on GABA LGIC?

Answer 4

Propofol

Question 5

How do anasthetics that work on GABA LGICs work?

Answer 5

bind to GABA(A) and increase sensitivity to GABA and increase chloride currents, hyperpolarising neurone and decreasing its excitability.

Question 6

Glycine activated chloride channels anasthetics - How does this exert an effect?

Answer 6

Increases sensitivity to glycine to increase chloride currents. Hyperpolarises neurones and decreases its excitability.

Question 7

How do anasthetics that block nAChRs work? What effects does this have on the patient?

Answer 7

reduces excitatory Na currents caused by ACh binding. Contributes to analgesia and amensia rather than sedation

Question 8

Which anasthetics work on NMDA receptors? How do they work?

Answer 8

e.g. nitrous oxide and ketamine

Binding at NMDA reduces calcium currents

Question 9

What compounds is the principle anasthetic agent mixed with?

Answer 9

oxygen, air, and often nitrous oxide.

Question 10

Define minimal alveolar concentration

Answer 10

MAC - percentage of inhaled anasthetic that abolishes response to surgical incision in 50% of patients.

Lower MAC value = more potent anasthetic

Question 11

At how many MACs is surgical depth usually achieved?

Answer 11

1.2 - 1.5

Question 12

Why is nitrous oxide given alongside the inhaled anasthetic?

Answer 12

Reduces the MAC for individual agents.

Question 13

What is the blood:gas coefficient?

Answer 13

Describes the volume of gas in litres that can dissolve in one litre of blood.

Higher blood:gas cofficient = more readily it will enter blood

Question 14

What 2 factors affect the distribution of anasthetic around the body?

Answer 14

Relative blood supply to each organ and the specific tissue uptake capacity for the anasthetic

Question 15

What is the relative blood supply to the organs at rest?

Answer 15

brain, liver and kidneys = 75%

Muscle = 20%

fat = 5%

Question 16

How are modern fluranes metabolised?

Answer 16

does not undergo metabolism

Question 17

Why does full recovery from anasthetics take hours to days? What factors affect recovery?

Answer 17

As the drug moves out of its compartments to be excreted from the lungs it is free to redistribute around the body during circulation and gain entry back into the CNS, affecting consciousness.

Duration of recovery related to legnth of procedure and amount of anasthetic in muscles and fat.

Question 18

How long does inhalational agents and IV agents take to get sufficient anasthetic depth?

Answer 18

Inhalational - minutes

IV - <20 seconds

Question 19

How is propofol metabolism?

Answer 19

Undergoes hepatic and extrahepatic conjugation, half life of 2 hrs.

Question 20

Explain the pharmacodynamics of anasthetics that affect GABA and glycine

Answer 20

Increase the potency of GABA and glycine receptors. This means a lower level of GABA or glycine is needed to produce the same effect.

Also increase relative efficacy of GABA or glycine so that binding of any channel results in more chloride current allowed to flow - Positive allosteric modulation

Question 21

Explain the pharmacodynamics of anasthetics that affect the excitatory LGIC such as NAChR or NMDAR

Answer 21

Efficacy of excitatory ligand decreases as the anasthetic antagonist inactivates the receptor non-competitively. The bound receptors have reduced efficacy but the remaining unbound receptors have unchanged efficacy.

Overall effect is to reduce inward movement of excitatory currents.

Question 22

What adjuvant is given to induce anxiolysis and amnesia?

Answer 22

benzodiazepines e.g. midazolam

Question 23

What adjuvant is given for rapid induction of deep initial sedation

Answer 23

propofol

Question 24

What adjuvant is given for analgesia and reducing main inhalational agent MAC?

Answer 24

Nitrous oxide.

Question 25

What adjuvant is given only for analgesia?

Answer 25

Opioids e.g. morphine or fentanyl. Fentanyl much more potent.

Question 26

What adjuvant is given for neuromuscular blocking to abolish reflexes and induce muscular relaxation?

Answer 26

tubocurarine or pancuronium - competitive nAChR antagonist

Succinylcholine - depolarising agonist of nAChR

Question 27

Why does using more than 1 drug allow for finer control of anasthetic depth?

Answer 27

Can exert certain effects without risking more serious side effects by increased anasthetic depth e.g. neuromuscular blockade can be achieved without changing MAC.

Question 28

What ADRs can result from fluranes?

Answer 28

cardio and resp depression

arrhythmia

hypotension

increased ICP - cerebral blood flow increases due to decreased vascular resistance

Malignant hyperthermia

Question 29

What ADRs can result from nitrous oxide?

Answer 29

expansion of airway cavities

Diffusion hypoxia - In recovery, NO diffuses rapidly out of blood into alveoli, decreasing alveolar o2 conc.

Question 30

What ADRs result from propofol and opiates?

Answer 30

resp depression

Question 31

What would a pre-surgical review of the patient undergoing anasthesia involvE?

Answer 31

age, BMi, prior medical and surgical history, current meds, history of drug abuse, fasting time, airway assessment.

Question 32

What might peri-surgical monitoring during anasthesia involve?

Answer 32

ECG, BP, pulse oximetry, expired Co2 (assessing ventilation state), core temp (malignant hyperthermia)

Question 33

Name the 4 stages of anasthetic depth

Answer 33

1 - analgesia

2 - Excitement

3 - Surgical anasthesia

4 - resp paralysis