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SC Multidisciplinary > Anaesthesiology: Pharmacology of Anaesthesiology > Flashcards

Anaesthesiology: Pharmacology of Anaesthesiology Flashcards

1
Q

Induction agent

A
  • A drug which induces **loss of consciousness in **one arm-brain circulation time when given at an appropriate dose
  • BDZ, Opioids are sometimes used to induce anaesthesia
    —> but do NOT produce rapid LOC
    —> therefore not considered to be an induction agent

Exception: Ketamine

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2
Q

***Drugs for inducing GA

A
  1. Barbiturates
  2. Etomidate
  3. Propofol
  4. Ketamine

(Inhalation induction:

  • more difficult to perform on adults
  • slower than IV induction
  • patient will go through the “excitement” phase of anaesthesia induction with risk of coughing, breath holding and laryngospasm
  • for children / people with difficulty cannulation (e.g. IVDU))
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3
Q
  1. Barbiturates (e.g. Thiopentone)
A

MOA:
- Potentiate effect of GABA at inhibitory GABAA receptor

Pharmacokinetics:

  • Rapid brain uptake, rapid redistribution, hepatic elimination
  • ***Slow metabolism & prolonged elimination

Effects:

  • CVS: ↓ MAP, ↑ HR, Myocardial depression
  • Respiratory: Depression ventilator centre, retain some airway reflexes
  • CNS: ↓ CMRO2 (cerebral metabolic rate of oxygen), ↓ CBF (cerebral blood flow), ↓ ICP, anti-convulsant

Uses:

  • ***Obstetrics
  • ***Epilepsy / seizures
  • ***RSI (rapid sequence induction)
  • ***Neurosurgical emergency
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4
Q
  1. Etomidate
A

MOA:
- Potentiate effect of GABA at GABAA receptor

Pharmacokinetics:

  • Rapid onset & redistribution
  • Hydrolysed by plasma esterases & liver

Effects:

  • CVS: CVS stability, ***NO effect on contractility, SVR, HR
  • Respiratory: ***Minimal effect on respiration
  • CNS: ↓ CMRO2, ↓ CBF, ↓ ICP
  • Others: Inhibits 11-β hydroxylase —> ***Adrenocortical suppression

Uses:

  • ***Cardiac patients
  • ***Haemodynamically unstable patients
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5
Q
  1. Propofol
A

MOA:
- Potentiate effect of GABA at inhibitory GABAA receptor

Pharmacokinetics:

  • ***Rapid onset & redistribution
  • Metabolised in liver, ***high clearance

Effects:

  • CVS: ***↓ SVR, ↓ cardiac contractility, ↓ preload
  • Respiratory: Respiratory depression, obtunds laryngeal reflexes
  • CNS: ↓ CMRO2, ↓ CBF, ↓ ICP, burst suppression
  • Others: **fast clear headed wake-up, **anti-emetic, ***propofol infusion syndrome

Uses:
- Most suitable for ***infusion of induction agents

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6
Q
  1. Ketamine
A

MOA:

  • Inhibits excitatory NT glutamate at ***NMDA receptors
  • ***Dissociative anaesthesia rather than hypnosis

Pharmacokinetics:

  • Rapid onset, Slower redistribution
  • Hepatic metabolism to norketamine

Effects:

  • CVS: ↑ HR, ↑ SVR, ↑ CO by ***SNS activation
  • Respiratory: Little effect on RR, bronchodilator, salivation, reflexes preserved
  • CNS: ↑ CBF, ↑ ICP, ↑ CMRO2, ***hallucinations, amnesic
  • Others: ***analgesic

Uses:

  • ***Shocked patients
  • As ***analgesic
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7
Q

Length of action of an IV bolus

A
  • An IV bolus of an appropriately dosed induction agent (other than ketamine) will keep the patient asleep for **3-5 mins
    —> ∵ fall in **    effector site (brain) concentration + **plasma concentration as drug **redistributes to other parts of body (fat, muscle, skin)

Actual elimination t1/2 of most induction agents: Several hours

Ketamine:

  • onset time of 30s (slower than thiopentone)
  • effects last for 5-10 minutes
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8
Q

***GA maintenance

A
  1. Volatile anaesthetic agents (Inhalation)
  2. Nitrous oxide (Inhalation)
  3. Induction agent (IV)
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9
Q
  1. Volatile anaesthetic agents (Inhalation)
A

Mainstay of anaesthetic maintenance

  1. Sevoflurane
  2. Desflurane
  3. Isoflurane
  • Halogenated ether compounds (comes in liquid form)
  • Vaporiser: adds a known concentration of volatile agent to a ***gas mixture (usually N2O, O2 or air/O2) which patient inhales via a breathing circuit
  • Concentration can be adjusted to keep appropriate concentration of volatile in the lungs
  • When volatile is stopped, as the patient ***exhales it is eliminated
    —> when the alveolar concentration drops to a critical level
    —> patient wakes up

Sevoflurane:

  • ***Sweet + pleasant smelling
  • ***Non-irritant
  • Low blood/gas solubility —> quicker induction than other volatile agents

Desflurane:

  • ***Irritant
  • Lowest blood/gas solubility

Halothane

  • Pleasant smelling
  • Historical use (∵ risk of Inhalational hepatitis + long induction time)
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10
Q
  1. Nitrous oxide (Inhalation)
A
  • Given with O2 or air in a gas mixture to inhale
  • **Weak anaesthetic
    —> not suitable as a sole anaesthetic for maintenance
    —> used in **    combination with a volatile anaesthetic gas
    —> need to breathe 104% to achieve anaesthesia

Advantages:

  • Good ***analgesia
  • Reduces MAC (Minimum alveolar concentration: Alveolar concentration of inhaled agent which prevents movement in response to a standard painful stimulation in 50% of subjects)

Disadvantages:

  • ***PONV
  • Diffusion into gas filled spaces
  • Effects on bone marrow
  • Environmental issues
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11
Q
  1. Induction agent (IV)
A

In theory:
- ALL induction agents are suitable to maintain anaesthesia if given as **infusion or **regular boluses

Problems with maintenance with induction agent:
1. ***Accumulation
- All drugs accumulate on continuous or repeat dosing
—> Very prolonged duration of action
—> Thiopentone a good example: accumulates with repeated dosing

  1. Dose timing
    - Difficult to judge when to give another dose if using bolus technique
    - Could be a problem if patient is paralysed
  2. SE
    - Etomidate: **Adrenocortical suppression
    - High doses of Propofol: **    Propofol infusion syndrome
    - Ketamine: ***hallucinations
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12
Q

Queen Mary Hospital

A

Total Intravenous Anaesthesia:
- Use of ***Propofol as both induction & maintenance agent

  • Special pharmacokinetic syringe pumps with computer programs “models” incorporated calculate the concentration of propofol in plasma and the brain for that particular patient’s weight/ (sometimes age, sex, height too)
    —> adjusts over time for redistribution & elimination
  • All anaesthesiologist needs to do is determine what concentration of propofol is appropriate
  • Used with ultra-short-acting opioid ***Remifentanil: synergistic effect
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13
Q

SE of GA agents

A

Occur during recovery period:

  1. Hypoxia
  2. Hypotension
  3. Sedation
  4. Confusion and agitation
  5. N+V
  6. Headache
  7. Shivering
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14
Q

Hypoxia

A
  1. Hypoventilation
    - Airway obstruction: tongue, edema, laryngospasm
    - Respiratory depression
    - Residual NMJ blockade
    - Poor analgesia
  2. V/Q mismatch
    - ↓ CO & FRC
  3. Shunt
    - Small airways closure —> lung perfused but not ventilated
  4. Diffusion hypoxia
    - N2O more soluble than O2
    —> when N2O stopped, diffuses into alveoli from blood faster than N2 can diffuse in opposite direction
    —> concentrates N2O compared to other gases in alveoli
    —> ↓ FiO2
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15
Q

Hypotension

A

Multiple causes for hypotension:

  1. Vasodilator & cardiac depressant effects of anaesthetic drugs
  2. Hypovolaemia
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16
Q

Sedation

A 
Multiple causes for sedation:
1. Residual effect of anaesthetic/analgesic drugs
2. Hypoxia
3. Hypotension
4. Hypoglycaemia
5. Hypothermia
6. Electrolyte disturbance
7. Intracranial pathology
etc.
17
Q

Confusion and agitation

A

Multiple causes for confusion and agitation:

  1. Residual effect of anaesthetic/analgesic drugs
  2. Hypoxis
  3. Hypotension
  4. Hypoglycaemia
  5. Hypothermia
  6. Electrolyte disturbance
  7. Intracranial pathology
  8. Pain + disorientation
  9. Urinary retention
  10. Post-anaesthetic cognitive dysfunction
18
Q

Shivering

A

Multiple causes for confusion and agitation:

  1. ↑ Muscle activity
  2. ↑ O2 consumption —> bad for those with impaired myocardial O2 supply
19
Q

Local anaesthesia

A

Na channel blocker:
- LA enter the nerve in unionised lipid-soluble free base form
—> inside the nerve, it ionises
—> ionised form enters + blocks Na channels
—> once enough Na channels are blocked
—> drops below threshold of critical level
—> ***depolarisation is prevented
—> action potentials cannot be generated (∵ all or nothing)
—> nerve blockade

20
Q

Calculating safe dose for LA

A

Depends on:

  1. Drug
  2. Weight of patient
  3. Vasoconstrictor additive

Bupivacaine:

  • Max recommended dose: 2 mg/kg
  • Max recommended dose with vasoconstrictor: 2 mg/kg
  • **long-acting LA —> very suitable for **post-operative pain relief
  • can become very dangerous if toxic levels develop from overdose or inadvertent IV injection

Levobupivacaine:

  • Max recommended dose: 2 mg/kg
  • Max recommended dose with vasoconstrictor: 2 mg/kg
  • ***less cardiotoxicity in overdose situation than Bupivacaine
  • takes longer to take effect than Lignocaine, this will not be an issue if the block is used in combination with GA

Lignocaine:

  • Max recommended dose: 3 mg/kg
  • Max recommended dose with vasoconstrictor: 7 mg/kg
  • ***short-acting

Ropivacaine:

  • Max recommended dose: 3 mg/kg
  • Max recommended dose with vasoconstrictor: 3 mg/kg
  • ***less potent than Bupivacaine and potentially less toxic when overdose
  • ***less motor blockade than Bupivacaine
21
Q

LA toxicity

A

Neurological S/S:

  1. ***Lightheadness, Dizziness, Drowsiness
  2. ***Tingling around lips, fingers / generalised
  3. ***Metallic taste
  4. ***Tinnitus
  5. BOV
  6. Confusion
  7. Restlessness
  8. Incoherent speech
  9. Tremors / Twitching
  10. ***Full-blown convulsions with LOC / Coma

CVS S/S:

  1. ***Bradycardia (can Tachycardia)
  2. ***Hypotension
  3. CVS collapse
  4. Respiratory arrest
  5. ***QRS + PR prolongation
  6. ***AV block
  7. Change in T wave amplitude
22
Q

LA toxicity vs LA allergy

A

LA toxicity:
Causes:
1. Inadvertent IV injection (failure to aspirate before + during injection)
2. Overdosage of LA
3. High plasma levels (∵ IV injection / high dose given continuously over a prolonged period, rapid injection / absorption over a highly vascular site e.g. intercostal)
4. High risk injection sites
- Lumbar plexus
- Intercostal block
5. Narrow therapeutic window agents (e.g. Bupivacaine)

Effect:
- Initially CNS effect —> CVS effect

Management:

  1. ***Stop injecting drug
  2. Assess ABC + give ***high flow O2 simultaneously
    - Hyperventilation may help increase pH (if metabolic acidosis)
  3. Treat convulsions with ***BDZ (IV Midazolam / Diazepam / Lorazepam / Thiopental (barbiturate))
  4. Treat hypotension with ***Vasopressors (Ephedrine / Phenylephrine / NE / E)
  5. Call for senior help, declare medical emergency, get nurses to bring resuscitation trolley
  6. Immediate CPR if cardiac arrest
    - Advanced airway
    - IV access
    - Prompt defibrillation
  7. 20% ***Intralipid
  8. Prepare for protracted resuscitation

LA allergy:

  • True allergy to amide local anaesthetics is rare
  • Ester local anaesthetics are more likely to be associated with allergic reactions
23
Q

Anxiolytics

A

BDZ

MOA:
- Works by enhancing GABAA inhibitory neurotransmission

Effect:

  • Sedative
  • Hypnotic
  • Anti-convulsant
  • Amnesic
  • Muscle relaxation

Uses in anaesthesia:
- For sedation, premedication / anxiolysis, occasionally GA induction at high doses, anti-convulsant

SE:

  1. CNS
    - dose related depression
    - amnesia
  2. CVS
    - mild / minimal effects on CVS —> effects more marked in elderly
  3. Respiratory
    - loss of sensitivity to CO2 —> effect varies from no effect to apnoea, ↓ tidal volume

Midazolam:

  • Most commonly used BDZ in anaesthesia
  • Water-soluble due to imiazole ring structure —> becomes lipid-soluble inside body
  • More potent than Diazepam
  • Onset time: 30s
  • Peak action: in 3-5 minutes
  • t1/2: 2-4 hours
  • High affinity for BZ receptor
  • Action terminated by redistribution from brain to other sites

BDZ reversal agent: Flumazenil

24
Q

Antiemetics

A

N+V:

  • mediated by
    1. Afferents from gut / vagus
    2. Vestibular system
    3. Chemoreceptor trigger zone (CTZ)
  • in area postrema at floor of 4th ventricle outside of BBB

These mediate with ***ill-defined area of brainstem traditionally known as “vomiting centre” & nucleus tractus solitarius (NTS)

  • Implicated receptors:
    1. 5HT3
    2. D2
    3. H1
    4. ACh
    5. NK1

Drugs:

  1. Anticholinergics
  2. Antihistamines
  3. Antidopaminergics
  4. ***Antiserotonin (1st line)
  5. ***Steroids (1st line)
25
Q

PONV risk factors

A

Multifactorial

  1. Patient factors
    - **Female
    - **    Young
    - ***Non-smoker
    - History of PONV
    - Travel sickness
  2. Surgical factors
    - Surgery type: **ENT, eye, abdominal, gynaecological
    - Surgical technique: **    Laparoscopic
    - Surgical complication: Swallowed blood
  3. Anaesthetic factors
    - Pharmacological: **Opioid, **N2O, Volatile agent
    - Others: dehydration, poorly controlled pain, anxiety
    - Failure to give prophylaxis in high-risk patient
26
Q
  1. Anticholinergics
A
  • Antagonism of muscarinic ACh receptor
  • 2nd-line anti-emetic
  • Useful for ***motion sickness, opioid-induced vomiting
  • Use is limited by SE (e.g. sedation, dry mouth, confusion)

Example:
- Hyoscine

27
Q
  1. Antihistamines
A
  • Antagonism of H1 receptor
  • 2nd-line anti-emetic

Example:
- Cyclizine

28
Q
  1. Antidopaminergics
A
  • Antagonism of D2 receptor
  • 2nd-line anti-emetic

Examples:

  • Prochlorperazine
  • Metoclopramide
29
Q
  1. Antiserotonin
A
  • Antagonism of 5-HT3
  • ***1st-line anti-emetic
  • **Prolong QTc, risk of **torsades de pointes

Example:
- Ondansetron

30
Q
  1. Steroids
A
  • Unknown mechanism of action for anti-emetic effect
  • ***1st-line anti-emetic

Example:
- Dexamethasone

31
Q

Analgesics

A
  1. Paracetamol
  2. Opioid
  3. NSAID
32
Q
  1. Paracetamol
A

MOA:
- Unknown
- Traditionally thought to work via inhibition of central prostaglandn synthesis, possibly multi-receptor action
—> COX (but not COX1 or COX2)
—> Serotonergic
—> Endocannabinoid
- Now known to not have anti-inflammatory properties

PK:
- Hepatic clearance

Uses:

  1. Anti-pyretic
  2. Analgesic
    - Consistenly shown in studies to ↓ pain scores
    - Enhance analgesia when used in conjunction with other classes of analgesics —> **Opioid-sparing + **Anti-hyperalgesic
    - No effect on platelet adhesiveness
    - No gastric irritation, N+V
33
Q
  1. Opioid
A

SE:

  1. Respiratory depression
  2. Sedation
  3. N+V
  4. Bradycardia + Hypotension
  5. Constipation
  6. Histamine release
  7. Hormonal effects
    - suppression of ACTH, prolactin
  8. Tolerance + Dependence

Caution: Renal failure
- Morphine is metabolised by the liver to active metabolite morphine-6-glucuronide and inactive metabolite morphine-3-glucuronide. These are ultimately excreted by the kidney
—> patient will be more susceptible to SE of morphine, and it is important to monitor this patient carefully, particularly HR, BP, SPO2, RR, sedation score

PCA:
Advantages compared to PRN administration:
1. Intravenous administration
- no bioavailability issues

  1. Small drug doses given at intervals
    - less chance of sudden “high” plasma level, more likely to maintain a constant plasma level
  2. Patient titrates drug to their own desired effect
  3. Safety
    - too much drug —> sedated patient —> unable to press PCA button
  4. Psychological wellbeing
    - patient in control
  5. No waiting to obtain drug
    - opioids are controlled drugs, administering is onerous on nurses
  6. Research shows overall amount of opioid used generally less than with other methods of administration
34
Q
  1. NSAID
A

Cyclo-oxygenase (COX) blockers

SE (more common in the elderly):
1. Renal disease
- NSAIDs block prostaglandin (PG) synthesis
—> ↓ Renal blood flow, Na retention
—> Renal failure
- Also risk of interstitial nephritis + ↑ K

  1. Heart failure
    - Na + H2O retention worsen cardiac failure
  2. Gastric ulceration, GI bleed
    - PGs inhibit gastric acid secretion which have cytoprotective effects on mucosa
  3. Low platelets / bleeding
    - NSAIDs block ***Thromboxane A2 synthesis —> needed for aggregation, adhesion + vasoconstriction
  4. Asthmatics
    - blockade of COX pathway
    —> shunts arachidonic acid to be converted to ***leukotrienes via lipo-oxygenase pathway
  5. IHD
    - COX 2 associated with **thrombosis risk
    —> Inhibition of COX2 mediated **    PGI2 production in coronary wall
    —> Loss of **vasodilating + **anti-thrombotic properties
    —> combined unopposed COX1 production of Thromboxane A2 (vasoconstricting + prothrombotic)
35
Q

NMJ blockers

A

Types:

  1. Depolarising
  2. Non-depolarising

Use:
- Relax laryngeal / vocal cord muscles

36
Q
  1. Depolarising NMJ blockers
A

MOA:
**Agonist of ACh receptor
—> causes prolonged receptor activation / depolarization
—> receptor becomes **refractory + deactivated
—> until membrane potential is reset

Example: ***Succinylcholine (aka Suxamethonium)

Succinylcholine:
- Only depolarizing NMJ blocker in clinical use
- Structurally: 2 ACh molecules joined together
- Recovery by **diffusion of succinylcholine away from receptor
—> ultimately broken down by **plasma cholinesterase
- Profound block within 60s
- Recovery begins in 3 mins
- Full recovery 12-15 mins
- **Rapid onset (45s)
—> particularly suitable for rapid sequence induction (RIS) is important
—> minimise duration in which the patient has an unsecured airway
—> time from **induction of anaesthesia to **intubation is short
- **Rapid offset (5 mins)
—> if wear off
—> patient can spontaneously breathe
—> otherwise patient in apnea (∴ still have to ***preoxygenate patient in case cannot secure airway / ventilate patient —> able to tolerate 5 mins of apnea)

SE of Succinylcholine:

  1. ***Parasympathetic effects
    - Cardiac: activation of muscarinic receptors at SA node —> Severe bradycardia / AV nodal rhythm after repeated dosing (children esp. vulnerable)
    - ↑ Bronchial + Salivary secretions
    - ↑ Intra-gastric pressure
  2. **HyperK
    - rise in serum K: 0.5-1 mmol/l
    - **    MUST check K before administration
    - may cause dangerous hyperkalaemia in renal patients, muscular dystrophy, burns & paraplegic patients
  3. Muscle pain
  4. ***Malignant hyperthermia / hyperpyrexia
  5. Allergy
    - type 1 hypersensitivity + anaphylaxis
  6. ↑ IOP
  7. Prolonged paralysis
    - in those with abnormal variants of plasma cholinesterases
  8. Tachyphylaxis
    - ↓ response after repeated dosing, may precede development of NMJ blockade ~ to non-depolarisers + prolonged paralysis
37
Q
  1. Non-depolarising NMJ blockers
A 
Example:
- Benzylisoquinolinium
—> ***Atracurium
- Aminosteroid
—> Pancuronium
—> Vecuronium
—> ***Rocuronium

MOA:
Competitive inhibition of ACh receptor at post-synaptic membrane
—> act as ***antagonists at the ACh receptor (vs depolarizing neuromuscular blockers which act as agonists)
—> Depolarisation by ACh is progressively diminished ∵ ↓ number of available receptors
—> eventually failure to generate an AP
—> action terminated by drug being broken down / diffusing away from receptor / displacement of drug away from receptor (by increasing availability of ACh)

Rocuronium:

  • Fast onset time (when used in high doses)
  • Longer offset time but Sugammadex enable it to be quickly reversed

Reversal:
1. Neostigmine (AChE inhibitor)
—> ↑ concentration of ACh at synaptic cleft
—> displace non-depolarizing neuromuscular blocker from ACh receptors

  1. Sugammadex
    - chelating agent for NMJ blocker
38
Q

Maintain Neuromuscular blockade

A
  1. Atracurium
    - ~45% of atracurium broken down by a process called ***Hofmann degradation at standard body temperature & pH, the drug will spontaneously break down and degradation is not dependent on any intact liver or kidney function
  2. Pancuronium
    - long acting amino-steroid non-depolarizing NMJ blocker
    - broken down by kidney —> prolonged elimination time + duration of action in renal failure
  3. Vecuronium
    - non-depolarizing amino-steroid NMJ blocker
    - broken down in liver, but some undergoes renal excretion, leading to increased duration of action in renal failure
  4. Rocuronium
    - mainly liver excreted but elimination t1/2 is increased 37% in renal failure

SC Multidisciplinary (10 decks)

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