L10-12 - Anaesthetics Flashcards Preview

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Flashcards in L10-12 - Anaesthetics Deck (56):
1

Anaesthetics work to achieve:

Hyponosis/amnesia
Immobility
Autonomic areflexia

2

Inhalation agents mechanisms of action

Not metabolised so must be inhaled down a concentration/pressure gradient.

More lipid soluble = smaller dose to get effect

Mechanism of action is not entirely known - most likely due to GABA modulation in brain and glycine modulation in spinal cord

3

Pharmacokinetics:
MAC:

MAC = minimal alveolar concentration to produce immobility on standard surgical stimulus in 50% of patients

More potent drugs = lower MAC

Increased MAC = youth, hyperthermia, hyperthyroid, drugs
Decreased MAC = elderly, hypothermia, hypothyroid, drugs

4

How is dosing measured?

By controlling the inspired fraction of vapour on a vaporiser

5

Pharmacodynamics: what are the effects of the inhaled drugs?
CNS:
Cardiovascular:
Respiratory:

CNS:
- hyponosis, immobility, amnesia (anaesthetics)
- decreases cerebral metabolic rate of oxygen consumption
- vasodilatory actions - increase cerebral blood flow (and thus pressure)

CV:
- peripheral vasodilation = lower BP
- no affect on heart rate other than desflurane (increases)
- halothane is pro-arrhythmogenic

Other:
- immune-mediated haptotoxocity
- reduced renal blood flow
- nephrotoxicity
- post-op nausea

6

Nitrous oxide

What is it?
Potency?
Onset?

Odourless non-flammable gas.

Low potency (101% MAC)/

Rapid onset analgesic.

Many adverse effects.

7

Halothane

What is it?
Potency?
Onset?

Sweet non-pungent alkane/

Highly potent (0.86% MAC).

Slow onset, intermediate solubility

8

Isoflurane

What is it?
Potency?
Onset?

Pungent gas.

Potent (MAC 1.1%)

Medium onset, intermediate solubility

9

Sevoflurane

What is it?
Potency?
Onset?

Non-pungent gas.

Intermediate pontency (MAC 1.7%)

Rapid onset, low solubility.

Causes the least amount of resp depression, little airway stimulation. Reacts with CO2 absorbant so to be AVOIDed in renal dys patients

10

Desflurane

What is it?
Potency?
Onset?

Pungent gas.

Intermediate potency (MAC 6%).

Rapid onset and offset with low solubility.

11

IV anaesthetics:
Method of action

(Thiopentone, propofol, etomidate, midazolam)

Enhance GABA receptor activity to prolong the Cl- current
= hyperpolarisation

12

IV anaesthetics:
Method of action

(ketamine)

Bind to PCP area of NMDA receptor and block the ion channel (antagonise glutamate).
Suppresses excitation

13

Pharmacokinetics of IV drugs

Highly lipid soluble and can cross BBB.
Drugs are taken up by vessel-rich organs and leave as less perfused tissues begin to take up the drug.

Offset is therefore primarily due to redistribution.

Most agents have slow metabolism = hangover effect

14

Thiopentone

Onset and offset?
Clearance?
Metabolism?
Side effects?

Rapid onset (10s)/
Rapid offset by redistribution.

Clearance is slow - will accumulate.

Metabolised in liver via enzymes.

Causes respiratory depression and loss of airways.

15

Propofol

Onset and offset?
Clearance?
Metabolism?
Side effects?

Moderately rapid onset (30-40s).
Rapid offset by redistribution.

Fast clearance (not much accumulation).

Metabolised in liver.

Used more often as it wears off faster, less hangover.

16

Etomidate

Onset and offset?
Clearance?
Metabolism?
Side effects?

given as emulsion.

Rapid clearnace.

Less respiratory depression, CV stability, does cause adrenocortical inhibition.

17

Ketamine

Actions:

Cardiovascular stimulant - good in shocked patients

Preserves airways

Not good for neurosurgery as it increases cerebral oxygen consumption, cerebral blood flow and intracranial pressure.

18

Midazolam

a benzodiazepine

potent anti-epileptic drug used as it reduces cerebral consumption of oxygen and blood flow

19

TIVA (total intravenous anaesthetic)

Avoids inhalation, complication of vapours and use of volatile agents that are often reactive.

But is expensive and harder to monitor.

20

Neuromuscular blocking agents
(NMBAs)

Used to paralyse patients during surgery by acting at the neuromuscular junction

21

NMBAs do not:

They do not sedate patients, or cause amnesia, or provide any pain relief

NEVER to be used in isolation - only paralyse the patient

22

Clinical use of NMBAs:

In the ventilation of critically ill patients - the intubation of the trachea.

Relaxes the airway to prevent damage to delicate structures, and does the work of ventilation for the patient to reduce the work of breathing

23

NMJ divisions:
1 = presynaptic

What happens here?

area where ACh is synthesised and stored in vesicles, and released.
Also where the reuptake of choline (from ACh hydrolysis) occurs, and where ion flow across the terminal occurs

24

NMJ divisions:
2 = synaptic cleft

What happens here?

50nm gap between the nerve terminal and muscle ending where ACh is released into.

Within the cleft there are enzymes such as acetylcholinesterase - degrades ACh.

25

NMJ divisions:
3 = postsynaptic

What happens here?

Has lots of clefts to give a large surface area.
Has AChRs (5 mil) positioned in folds, with a high density of v-gated Na+ channels for amplifying AChR-induced depolarisation

26

ACh release:

Quanta containing ACh are released within 200ns of an action potential.

50% of the ACh released is immediately hydrolysed. To overcome this, more ACh is released than is needed.

500,000 AChRs are activated and cause an influx of Na+ and Ca+ to depolarise the endplate

27

ACh receptors:

Ligand-gated ion channels with 5 subunits around a central pore.

a-subunits bind ACh, and both of the a-subunits must be bound simultaneously for the channel to open.

Causes a conformational change which allows ion flow

28

Acetylcholinesterases (AChE)

Enzyme found in the synaptic cleft. Hydrolyses ACh into acetate and choline

29

Depolarising muscle relaxants

Succinylcholine, suxamethonium. (SCh)

Binds to AChR to mimic the effect of ACh by opening the channel.

SCh is not hydrolysed in the cleft so has a longer duration of action compared to ACh. Its action is terminated by diffusion out of the cleft into the plasma where it is there hydrolysed by pseudocholinesterase.

Patients may have a pseudocholinesterase deficiency of absence = delayed recovery

30

Succinylcholine side effects

SCh cannot be reversed by other drugs - have to wait out.
Anaphylaxis occurs in 1 in 5,000-10,000 patients.
Fasciculations seen in 90% of patients due to initial agonist effect which can cause post-op muscle pain
Cardiac dysarrhythmias
Hyperkalaemia due to increased serum K+ due to depolarisation.
Increased ICP (intracranial pressure)

31

Non-depolarising neuromuscular blocking agents:

Block neuromuscular transmission by competitive antagonism of ACh at the AChR.

Bind to and block the AChR - with only one molecule required to block

32

Non-depolarising neuromuscular blocking classification:

Chemical structure
- aminosteroids e.g. pancuronium
- benzylisopquinolones e.g. atracurium

or

Duration of action
- short (10-15min) e.g. mivacurium
- medium (25-40min) e.g. atracurium
- long (40-90min) e.g. pancuronium

33

Atracurium:
elimination, side effect

Elimination:
- Hofmann elimiation (does not depend on temp, enzymes, pH)
- non-specific ester hydrolysis
- inactive breakdown products are eliminated via the kidneys

Causes dose-related histamine release which can cause a transient skin rash

34

Mivacurium:

3x more potent than atracurium.
Hydrolysed by psudocholinesterases.

Causes some histamine release but not as much as atracurium.

35

Rocuronium

Rapid onset, immediate action. Long duration of action.

Anaphylaxis higher in NZ

Elimination is 90% hepatic (rest renal)

36

Vecuronium

Intermediate duration with slow onset.

Active metabolites are excreted in urine so will accumulate in renal failure

37

Pancuronium

Long duration of action, high potency, slow onset of action.

Has vagolytic effects causing increased BP, heart rate, cardiac output.

Minimal histamine release.

Clearance is renal and hepatic.

38

Reversal of NMDAs

Only available for non-depolarising NMBAs.

Reversal by either:
- titrating the perfect dose of drug for the desired duration of action (difficult)
- accelerate reversal by increasing conc of competitor (ACh) or by decreasing plasma conc of the NMBA

39

Anticholinesterase drugs

These drugs act at ALL cholinergic synapses to have an effect.

Act to inhibit anticholinesterases to increase ACh in the synapse.

40

Sugammadex

Antidote for rocuronium and vecuronium. Selectively binds to the drug and makes it incapable of binding to the AChR.

Muscle function returns in 20s to 2min

41

Monitoring neuromuscular blockade

Due to considerable patient variability.

Use a nerve stimulator to see if nerve block has lifted and muscle responds.

42

Train of Four

Used to detect if neuromuscular blockade is lifted.

"train of four" - the number of twitches seen after 4 stimuli are applied. Should get all 4 at identical height when there is intact transmission.

43

Double Burst stimulation

Used to detect if neuromuscular blockade is lifted.

2-3 short bursts of high freq stimulation followed by a second series of short bursts. Compares the two twitches that are created. Full recovery = two equal twitches.

44

Local anaesthetics:
how do they act?

Prevent depolarisation.

Inhibit sodium influx through v-gated sodium channels.

45

Relationship between lipid solubility and potency

More lipid soluble = more potent

46

LAs: Acidic or basic?

All are weak bases.

Those with pKa closest to physiological pH have fastes onset of action.
More basic = faster

47

LAs and protein binding

Increased protein binding = increased duration of action

48

LA metabolism:

Esters via plasma cholinesterases

Amides via liver metabolism (dependent on liver blood flow)

49

Lignocaine

Solubility?
pKa?
Protein binding?
Use?

Amide
Low lipid solubility = low potency.
Low pKa = fast onset
Low protein binding = short duration of action

Ideal to cover short surgical procedures e.g. mole removal

50

Bupivacaine


Solubility?
pKa?
Protein binding?
Use?

Amide
High lipid solubility = high potency.
High pKa = slow onset.
High protein binding = long duration of action.

Ideal for nerve blocks for analgesia. More cardio-toxic than neuro-toxic

51

Cocaine

Ester, applied topically to nose, vasoconstrictor

52

LA toxicity

Dose-dependent injury is most commonly due to inadvertent IV placement.

Can have CNS effects (paraesthesia, seizures) or cardiac effects (heart block)

53

Administration routes:

Topical to skin (eutectic mixture as an oil preparation, for the insertion of IV in children)

Topical to mucus membranes (e.g. cocaine, lignocaine spray)

Soft tissue infiltration (for minor interventions where there is need for a short duration fast acting drug)

Nerve blocks

54

Peripheral nerve blocks (LAs)

LA injected around specific nerve.
Smaller sensory fibres are more affected than larger motor fibres.
Post-op pain, surgery without general

55

Spinal anaesthesia (LAs)

LA injected into intrathecal space beneath L2 (SC terminated).
Causes distal motor and sensory blockade.

Allows surgery in awake patients

56

Epidural anaesthesia (LAs)

Small catheter into epidural space with LA through catheter