Anaesthetic drugs and Analgesia

Question 1

General Anaesthesia

Answer 1

A reversible loss of consciousness with absence of recall of noxious stimuli

Question 2

Pain

Answer 2

An unpleasant sensory and emotional experience resulting from a noicioceptive stimulus, or expressed in terms of damage

Question 3

Mechanisms of Anaesthesia

Answer 3

Affects various sites including the reticular activating system, cerebral cortex, hippocampus, limbic system and spinal cord
Synaptic transmission is decreased.
Efficacy correlates with oil/gas partition coefficient and protein binding affinity

Question 4

Intravenous anesthetics

Answer 4

Increase GABA and glycine transmission
Used for IV induction of anaesthesia
Eg Propofol

Question 5

Volatile anaesthetics

Answer 5

Inhalational agents used for maintenance
Potency correlates with lipid solubility as does onset/offset time
Isoflurane (sevoflurane can be used for gas induction)

Question 6

Triad of anaesthesia

Answer 6

Hypnosis – Sleep component
Analgesia – pain relief
Paralysis – allow intubation and surgical access – if neuromuscular blocker is used risk of apnoea

Question 7

Stages of anaesthesia (Guedel)

Answer 7

Stage 1 – Induction, from awake to analgesia with amnesia
Stage 2 – Excitement with delirious and irregular breathing and muscular activity with risk of aspiration
Stage 3 – Surgical, skeletal muscles relax and breathing is regular. eye movements slow and stop
Stage 4 – Overdose, severe brain stem or medullary depression with risk of death

Question 8

Risks of anaesthesia (4,1,7)

Answer 8

Common – pain, sore throat, nausea, vomiting
Uncommon – Dental damage
Rare – Allergic reaction, aspiration, resp complications, VTE, pressure effects, awareness, death
Specific – eg central lines risk pneumothorax

Question 9

Local Anaesthesia

Answer 9

Selective loss of sensation of a selective circumscribed region of skin/body by a controlled reversible procedure

Question 10

Regional Anaesthesia

Answer 10

Local anaesthesia by produced by ‘up-stream’ administration of drugs

Question 11

Mechanism of LA action

Answer 11

blockade of Na+ ion channels

Minimal blocking concentration (Cm) – influenced by temp, Ca2+, pH, nerve penetration and tissue binding

Question 12

Succession of nervous blockade

Answer 12

Sympathetic –> pain –> temp –> touch –> motor

Question 13

Structure of LA

Answer 13

Lipophillic aromatic head, intermediate ester or amide linkage and basic, hydrophilic head (amines)

Question 14

Short duration/low potency LAs

Answer 14

Procaine or Chloroprocaine
Amino-esters. hydrolysed by pseudocholinesterases
LAs are all weak bases, in equilibrium between charged quarternary and uncharged tertiary amines

Question 15

Intermediate duration and potency LAs

Answer 15

Lignocaine, prilocaine, cocaine

amino-amides

Question 16

Long duration and high potency LAs

Answer 16

Bupivacaine, Ropivacaine & Tetracaine

Question 17

Relationship of charge and function

Answer 17

The uncharged tertiary, lipophilic form can cross the epineurium and enter the nerve axon but the quarternary, charged form can exits the ion channels
Lipid solubility and protein binding determines potency and duration

Question 18

What determines the potency of LAs?

Answer 18

Lipid solubility

Question 19

What determines the duration of LAs?

Answer 19

Protein binding

Question 20

What determines the rate of onset of LAs?

Answer 20

pH of the solution and pKa of the drug – lower pKa means more is in lipid soluble form so faster absorption and more rapid onset
Higher pKa means more effective blockade once within nerve

Question 21

Factors changing the pharmacokinetics of LAs

Answer 21

Site of injection
Use of vasoconstrictors
Carbonation – decrease in pH
Alkalinisation – increases pH

Question 22

Metabolism of LAs

Answer 22

Amides – Liver – conjugated and excreted in urine (2-3hr)
Easters – plasma and liver esterases (half life short)
Some metabolites are a risk of hypersensitivity

Question 23

LA Toxicity

Answer 23

Common – accidental IV injection or CNS toxicity

Allergy – rare, metabolites

Question 24

LA Overdose

Answer 24

Lignocaine >10ug/ml, Bupivacaine >3-5ug/ml
CNS stimulation then depression – sedation –> seizures due to selective inhibition of inhibitory fibres
early signs are circumoral and tongue numbness

Question 25

LA CVS toxicity

Answer 25

at 2-3x CNS dose –> at first peripheral arteriolar vasodilatation –> dose related decrease in cardiac contracility and conduction
Particularly Bupivacaine

Question 26

Treatment of toxicity

Answer 26

Supportive –> CNS –> oxygen, anticonvulsants

CVS –> Bretylium, phenytoin, Mg2+, Propofol, give lipid TPN to increase volume of dilution

Question 27

CVS/CNS ratio

Answer 27

the ratio of drug needed to induce convulsions compared to cause CVS collapse –> Lignocaine is 7 while Bupivacaine is 2.7 (more cardiotoxic)

Question 28

Safe dose of LA

Answer 28

Depends on injection site but generally Lignocaine 3mg/kg or 7mg/kg with Adr (Bupivacaine 2mg/kg)

Question 29

1% lignocaine contains?

Answer 29

10mg per ml
So for a 70kg man max dose is 70x3=210mg=21ml of 1% or 10.5ml of 2%
With Adr this increases to 70x7=490ml=48ml of 1% or 24ml of 2%

Question 30

Benefits of central blocks (spinals or Epidurals)

Answer 30

Avoid the risks of GA (difficult intubation, malignant hyperthermia, etc), good post-op analgesia, avoids sedation/N&V, reduced blood loss and reduced stress response

Question 31

Epidurals

Answer 31

A needle with a catheter is inserted into the epidural space and the catheter left in place to provide anaesthetia to the epidural space - numbing just the area supplied and lasts longer (can be topped up) than spinals

Question 32

Malignant Hyperpyrexia

Answer 32

triggered by volatile agents or suxamethonium resulting in the loss of normal Ca metabolism in muscle. An autosomal dominant condition with a defect in the ryanodine receptor. This leads to hypoxia, hypercapnia, hyperthermia and acidosis. Cell death then leads to release of K+, myoglobin and CK.

Question 33

Spinals

Answer 33

25/27G blunt Needle introduced into the CSF and LA (may be mixed with dextrose to weight it down) is injected. this will anaesthise the whole body below the site of injection and some above as well.

Question 34

Side effects of central blocks (spinals or Epidurals)

Answer 34

hypotension if sympathetic block (this can lead to N&V), post-dural puncture headache (worse with bigger needles and in the young), high blocks can effect the limbs and breathing,

Question 35

Contraindications of central blocks

Answer 35

hypovolaemia, sepsis, LA allergy, advanced CVS disease, INR>1.5, care should be taken if there is previous major spinal surgery or CNS disease

Question 36

Treatment of Malignant hyperthermia (MH)

Answer 36

100% oxygen, removal of trigger, active cooling and 1mg/kg (up to 10mg/kg) IV dantrolene. mortality is reduced from 80% to 5%.

Question 37

Dantrolene

Answer 37

A skeletal muscle relaxant which prevents Ca release from the sacroplasmic reticulum.

Question 38

Investigations for MH

Answer 38

a muscle biopsy should be taken and exposed to caffeine and halothane (contracture test). patients identified from this test should wear a medic alert bracelet.

Question 39

Scoline apnoea (Suxamethonium apnoea)

Answer 39

4% of the population posess genetic variants in plasma cholinesterase enzymes meaning they process suxamethonium slower and this lead to immobilised awareness or hypoxiaemia if ventilation is not properly maintained. treatment is to maintain anaesthesia & ventilation until the paralysis has worn off. Mivacurium can produce a similar syndrome.

Question 40

Cutaneous Porphryia

Answer 40

Cause photosensitivity/photodermatitis, blisters, necrosis of the skin and gums, itching, swelling and hair growth on the forehead. After exposure to sunlight urine can be red, brown or purple. Diagnosis is by PBG (porphobilinogen) in the urine.

Question 41

Porphyria in anaesthesia

Answer 41

Can be triggered by anaesthetics like ketamin or etomidate. Many other drugs can also trigger attacks.

Question 42

Corticospinal tracts

Answer 42

Upper motor neurons which decussate (80% forming the lateral tract but 20% don’t remaining the anterior tract) at the medulla and travel from the cortex anterior to the central gyrus and synapse with LMNs in the anterior horn

Question 43

Epidurals are indicated in?

Answer 43

C-sections, Hernia Repair, Lower limb surgery, Total knee or hip replacement, Urological surgery, Vascular Surgery, Gynae or pelvic surgery, Pain relief for labour, Post-op after trunk/abdominal/orthopaedic surgery.

Question 44

Nerves effected by epidurals

Answer 44

C fibres first, then progresses based on size. Clinically cold sensation is lost first and then pain then motor function. LA will also block Autonomic function (dangerous if T1 or above).

Question 45

Spinal technique

Answer 45

As for epidural. Non-cutting dural-fibre splitting needle (24G sprotte or 26G Whitacre) - once in SAS check by presence of CSF then inject LA/opiod over 10-15seconds.