Intravenous anaesthetics Flashcards

1
Q

IV induction of anaesthesia?

A
  1. Dependent on cardiac output
  2. LOC in one arm brain circulation about 30-45 secs
  3. Action on ligand-gated ion channels - GABA-A and also potassium channels (Neural activity)
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2
Q

GABA-A receptors?

A
  1. Ligand-gated ion channels consisting of 5 subunits
  2. Three isoforms which determine its; Agonist affinity, ion channel opening and conductance
  3. In humans - 2-alpha, 2-Beta and 1-gamma
  4. Forms a chloride anion channel.
  5. Targeted by Benzodiazepines, barbiturates, propofol, etomidate and volatile agents
  6. Activation leads to post-synaptic hyperpolarisation of cell membrane, inhibition of post-synaptic currents and ultimately inhibition of neural activity.
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3
Q

Two-pore domain potassium channels?

A
  1. Contains 15 potassium ion channels
  2. They are voltage independent
  3. They are not inactivated by action potential
  4. They are responsible for leak currents determining the resting membrane potential
  5. Present in CNS & modeulated by GA
  6. They are present pre & post-synaptically
  7. Competitive inhibition of post-synaptic ion channel receptor sites.
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4
Q

Standard ATP-dependent potassium channels?

A

They are activated and inactivated by every action potential

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5
Q

Other mechanisms of action ?

A
  1. Potassium channels
  2. Extrasynaptic receptors

3.

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6
Q

Extrasynaptic receptors?

A
  1. Includes alpha-5 and delta-subunit containing GABA-A receptors expressed in the hippocampus
  2. Their activation inhibits long-term potentiation and memory
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7
Q

Presentation of anaesthetic agents?

A
  1. Presentation
  2. Uses
  3. Effects (Dynamics)
  4. Kinetics
  5. Toxicity / contraindications
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8
Q

Thiopentone?

A
  1. It is based on a barbiturate ring
  2. Hygroscopic pale yellow powder
  3. Contains 500mg of thio and 6% sodium carbonate in an inert atmosphere of nitrogen
  4. Its a 2.5% solution when mixed with water
  5. It has a pH of 10.8
  6. It is alkaline, bacteriostatic and safe to keep for 48 hours.
  7. Dose is 4-5mg/kg
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9
Q

Uses of Thiopentone?

A
  1. Induction of GA

2. Status epilepticus

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10
Q

Dynamics (effects) of Thiopentone?

A
  1. Dose is 4-5mg/kg
  2. Depresses cardiac contractility, reducing CO & BP
  3. Decrease of venous tone and pooling of blood in the peripheral veins
  4. Respiratory depression
  5. Airway reflexes are preserved (LMA not appropriate)
  6. Histamine release may occur
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11
Q

Dynamics (effects) of Thiopentone on CNS?

A
  1. Reduces CBF, CMR and oxygen demand
  2. Anticonvulsant properties
  3. Reduces intracranial pressure
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12
Q

Kinetics of Thiopentone?

A
  1. The pKa = 7.6
  2. About 60% unionized at pH=7.4
  3. Its about 65-85% protein bound. Only 12% immediately available.
  4. It is highly lipid soluble
  5. Rapid emergence due to redistribution and not metabolism
  6. Metabolism occurs in the liver and excretion in the kidney
  7. Metabolism follows zero order kinetics - Constant amount of drug is being eliminated per unit time irrespective of plasma concentration
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13
Q

Porphyrias?

A
  1. Characterised by the over over-production and excretion of porphyrins (intermediate compounds produced during haemoprotein synthesis).
  2. Attacks may be caused by drugs, stress, infection, alcohol, pregnancy and starvation.
  3. Caused by thiopentone due to hepatic enzyme induction
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14
Q

Etomidate?

A
  1. Its an imidazole ester
  2. Liquid emulsion or clear solution
  3. Contains propylene glycol at a conc. of 2mg/ml
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15
Q

Uses of Etomidate?

A
  1. Induction - 0.3mg/kg
  2. Induction may mimic seizure activity
  3. It can be used in CV compromised & elderly patients.
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16
Q

Effects of Etomidate?

A
  1. Recovery accompanied by N/V
  2. There is pain on injection
  3. Risk of thrombophlebitis
17
Q

CVS effect of Etomidate?

A
  1. The least CVS depression

2. Small reduction in CO and BP

18
Q

Respiratory effects of Etomidate?

A
  1. Transient apnoea
  2. Coughs or hiccups
  3. Laryngeal reflexes are preserved - LMA not suitable
  4. PONV is common after use.
19
Q

Kinetics of Etomidate?

A
  1. It is 75% albumin bound
  2. Rapidly distributed
  3. Rapidly metabolised by plasma and hepatic esterases to inactive metabolites
  4. Excreted in urine
  5. Half-life is 1-5 hours
20
Q

Toxicity of Etomidate?

A
  1. Inhibits 11-beta-hydroxylase (Important in adrenal steroid production)
  2. Single dose inhibits normal stress induced cortisol production for 4-8 hours and 24 hours in the elderly
  3. As infusion increases mortality significantly
21
Q

Ketamine?

A
  1. Derivative of phencyclidine
  2. Exists as R & S ketamine
  3. Exhibit stereo-isomerism
  4. Presented in racemic mixture of 2 stereo-isomers
  5. S-ketamine is 2-3 times more potent
  6. pH of 3.5-5.5
  7. contains preservatives which precludes it from spinal or epidural use
22
Q

Uses of Ketamine?

A
  1. Used via all routes

2. Induction 1-2mg/kg IV or 4-10mg/kg IM or 0.2-0.5mg/kg for analgesia

23
Q

Effects of Ketamine?

A
  1. Duration of action is for 5-10 mins
  2. Onset in 1-2 mins IV
  3. Metabolised in the liver and conjugated metabolites excreted in urine
  4. Elimination half-life is 2.5 hours
24
Q

CVS effect of Ketamine?

A
  1. Increased HR, BP & CO

2. Usful in shocked and unwell patients

25
Q

Respiratory effects of Ketamine?

A
  1. Minimal effect on RR
  2. Preserved airway reflexes
  3. Increased saliva production
  4. Bronchial smooth muscle relaxant - Mx of severe asthma
26
Q

CNS effect of Ketamine?

A
  1. Increases CBF & ICP - Avoided in head injury
  2. Action on NMDA receptors
  3. Safe to use in porphyria
27
Q

Kinetics of Ketamine?

A
  1. Bi-exponential decline by; Distribution & hepatic metabolism
  2. Least protein bound (25%)
  3. Demethylated to norketamine by P450 and this is 30% as potent
28
Q

Propofol?

A
  1. Called 2,6-Diisopropylphenol
  2. Presented in aqueous emulsion
  3. Isotonic to plasma
  4. pH is 7-8.5
  5. It can cause pain on injection
29
Q

Constituents of propofol ?

A
  1. Egg phosphatide
  2. Soya oil
  3. Glycerol
30
Q

Kinetics of Propofol?

A
  1. Initial redistribution half-life is between 2-4 mins
  2. About 98% protein bound
  3. It has the largest vD @ 4L/kg
  4. used in hepatic and renal impairment
  5. Risk of propofol related infusion syndrome (PRIS) in children
31
Q

CVS effect of Propofol?

A
  1. Marked fall in BP secondary to vasodilation.

2. Increase in HR

32
Q

Respiratory effect of Propofol?

A
  1. Respiratory depression

2. Reduces airway reflexes

33
Q

CNS effect of Propofol?

A
  1. Epileptiform movements
  2. Anticonvulsant
  3. It reduces CBF, ICP