Principles of Pharamacology

Question 1

Define general anaesthesia

Answer 1

Produces insensibility in the whole body, usually causing unconsciousness.

Centrally acting drugs – hypnotics / analgesics

Question 2

Define regional anaesthetics

Answer 2

**Produces insensibility to an area/region of the body **

Essence is that the anaesthetic agent is applied to the nerve anywhere from the spinal cord to the periphery and anaesthesia produced in a distal site served by that nerve, therefore effect is remote from the injection.

Nerve and plexus blocks including central neuraxial block (spinal and epidural).

Question 3

Define local anaesthesia

Answer 3

Produces insensibility in only the relevant part of the body. (applied directly to the tissues)

Question 4

What is the difference between general anasethtics (GA) and sedation?

Answer 4

• General Anaesthesia (GA) : patient completely unaware of what is occurring
• Sedation: some awareness (although not necessarily recall!).

Question 5

What is the difference between region anasthesia and analgesia?

Answer 5

• Regional anaesthesia: patient should have little or no sensation of any sort from the blocked area, so warmth, proprioception, light touch and vibration sense will all be largely gone as well as pain sensation
• Regional analgesia: only pain sensation need be removed or reduced. Other sensation may be retained to varying extents

The border between these two is very blurred

Question 6

What are the functions performed by the modern anaestehtic machine?

Answer 6

• Regulation of fresh gases and mixing to deliver precise concentrations of gaseous agents
• Addition of precise concentrations of inhaled anaesthetic gases
• CO2 removal to allow recirculation of inhaled gases
• Mechanical ventilation, now microprocessor controlled contained within machine
• Most monitoring now normally integrated into anaesthetic machine

Question 7

What is the anaesthesia triad?

Answer 7

Components of Anaesthesia Triad:
* Hyponosis
* Analgesia
* Relaxation

Question 8

Define hyponsis in terms of analgesic triad

Answer 8

Unconsciousness

Necessary component of any general anaesthetic.

Question 9

Define analgesia in terms of analgesic triad

Answer 9

Pain relief

If patient is unconscious and therefore unaware of pain, analgesia is usually still required to suppress reflex autonomic responses to painful stimulus.

Question 10

Define relaxation in terms of analgesic triad

Answer 10

Skeletal muscle relaxation necessary to provide immobility for certain procedures, allow access to body cavities and to permit artificial ventilation amongst other things

Question 11

What properties of the analgesic triad does:
Local anaesthetics have?

Answer 11

• Analgesia
• Relaxation

Question 12

What properties of the analgesic triad do opiates have?

Answer 12

• Analgesia
• Hyponsis

Question 13

What properties of the analgesic triad do general anaesthetic agents have?

Answer 13

• Relaxation
• Hyponosis
• Analgesia

Question 14

What properties of the analgesic triad do muscle relaxants have?

Answer 14

• Relaxation only

Question 15

What is balanced anaesthesia?

Answer 15

• Using different drugs to tackle diffrenet property of teh analgesic triad
• Titrate doses seperately and more aculartely to requirements
• Avoid over-dosage
• Provides flexibility for patient variability

Question 16

Define polypharmacy

Answer 16

Increased chance of drug reactions/interactions/allergies due to the number of drugs taken by a patient

Question 17

What are some issues with using anaesthesia?

Answer 17

• Polyopharmacy: incraesed chance of drug reactions/allergies
• Muscle relaxation: requires artificial ventilation (needs airway control)
• Separation of relaxation and hyponosis ( awareness: due to the separation of hypnosis from muscle relaxation making the latter possible without the former)

Question 18

General anaesthesia:
What are the main groups of general anaesthesia?

Answer 18

• Inhalational
• IV

Question 19

List some general anaestehtic agents

Answer 19

• IV:Propofol, thiopentone
  *

Question 20

Describe the ways in which the different types of general anaesthetics work?

General anaesthetics

Answer 20

Global suppression of neuronal activity(dose dependant)

Interfere with neuroneal ion channels -> Hyperpolasize neurones making them less likely to fire

• Inhalational agents: dissolve in membarnes (direct phsyical effect on transmembrane proteins)
• IV agents: allosteric binding (GABA receptors, open chloride channels-> influx of Cl- -> hyperpolarisation of neuronal cells, less able or likely to reach their threshold potential and fire, sending signals (as propogated action potentials) to other neurons)

Question 21

What functions are lost first and last when under general anaesthetic agents?

What are the benefits of this?

General anaestehtics

Answer 21

• Complex functions affected first(rely on greatest and most complex neuronal activity (concioussness)). They’re more succeptible to inhibition, function is lost from “top down”
• Reflexes and other automatic functions go last (e.g. spinal reflex)

Beneficial as unconcioussness can be achieved, while some automatic/autonomic functions are preserves (e.g. respiration and BP hoemostasis) although these are imapired in dose dependant fashion

Question 22

Explain the properties of IV general anaesthetics

General anaestehtic: Intravenous agents

Answer 22

• **Rapid onset **(causes unconcioussness as soon as reached the brain)
• Highly fat soluble: cross the blood brain barrier rapidly and get into neural tissues very quickly
• If given as once off “bolus”, leaves circulation very quickly causing only temporary unconsciousness (disappear very rapidly from the circulation and consequently the brain). Rapid fall in blood concentration is due mainly to the drug leaving the circulation and moving to other parts of the body (compartments) such as muscle or splanchnic organs.
• **Little contribution from metabolism of the drug **(i.e. the process of the drug being destroyed and removed from the body) to the immediate termination of action of an intravenous anaesthetic agent given as a bolus.

Question 23

Explain what is happening to the concentration of IV bolus of general anaesthetic in the chart

Answer 23

Concentration of anaesthetic agent changes with time following a bolus dose

• Blood + vessel rich organs: Initially the blood level is very high but falls quickly as the drug moves into highly perfused tissues
• Muscle: picks up drug more slowly (because of the relative high mass of skeletal muscle in the body)
• Fat: picks up drug slowly, with long enough exposure, can store large amounts of drug due to high fat solubility of the drugs.

Question 24

Following a long surgical procedure, what are the levels of IV general anaesthetic agent in tissue?

Answer 24

Fat: high (due to high lipid solubility of IV anaesthetics)

Drug will leach out slowly over time

Question 25

What devices can be used to allow for very accurate infusion of anaesthetic agents?

Answer 25

Target Controlled Infusion (TCI) pump system
* Can calculate in real time the concentration of each anaesthetic drug in the system (using pharmacokinetic algorythms)

Uses lots of calculations and assumptions about patients physiology based on age, sex and size

Question 26

What are the downsides of Total IV anaesthesia (TIVA)?

Answer 26

Cannot measure drug concentration in real time

Question 27

What type of chemicals are inhalational anaesthetics?

Inhalational anaesthetics

Answer 27

Halogenated hydrocrabons

Question 28

What is the mechanism for absorbtion and excertion of inhalational general anaesthetics?

Inhalational anaesthetics

Answer 28

Absorbtion and excertion via lungs

Halogenated Hydrocarbons

Question 29

What is teh mechanism of inhalational general anaestehtics?

Inhalational anaesthetics

Answer 29

At induction the patient is given a relatively high concentration of the agent to breath. The gas then moves down the pressure gradient into the patients’ blood and finally brain to achieve a high enough partial pressure there to produce unconsciousness.

Question 30

What is MAC?

What des it mean when a MAC value is High and when its Low?

Answer 30

MAC: Minimum alveolar concentration
Concept of the concentration of the drug required in the alveoli which is required to produce anaesthesia with any particular agent

Low MAC: agent is potent (e.g. Halothane (MAC=0.8%)
High MAC: agent is lower potency (e.g. Desflurane MAC=6%)

Low MAC value -> lower ocncnetration of agent to produce the same effect

Question 31

How are inhalational anaesthetics used for:
a) Induction
b) Maintenance of anaesthesia
c) Awakening

Answer 31

a) Slow effect (can be advantageous if desirable)

b) Prolonged duration of anaesthetic effect (felxible): patient will remain unconcious for the duration of administartion of the agent

c)Inhalational administartion stopped, patient breathes a gas mix with no agent (This reversal of the concentration gradient we used at induction produces a fall in the alveolar concentration followed by the blood and then the brain and consciousness returns)

Question 32

What is the difefrence in metabolism of inhalational agents vs IV general anaetshetic agents?

Answer 32

• Inhalational: undergo little metabolism (almost completely breathed out unchanged)
• IV: Slower metabolism (due to storage in fat tissue as agents are lypophilic)

Question 33

What are advantages of using inhalational general anaesthetic?

Answer 33

• Flexible (patient remains anaesthetised for duration of admin of drug)
• Little metabolism of agent
• Once drug admin ceased, patient regains councioussness quickly
• Can measure alveolar gas concentrations to monitor real-time concnetration levels of the drug in the system

Question 34

What is the general sequance of conduction of general anaesthesia?

Answer 34

• Most common: IV induction -> Inhalational maintenance
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More modern agents with more sophisticated infusion techniques (computer controlled infusions) allow use of intravenous maintenance which has claimed advantages of better recovery.

Question 35

What are the effects of general anaesthetics on physiology?

Answer 35

Central (depress CVS centre)
* reduce sympatehtic outflow
* Negative inotropic/chronotropic effect on heart