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ACEM Primary VIVA > VIVA: Pharmacology - Nervous system > Flashcards

VIVA: Pharmacology - Nervous system Flashcards

1
Q

What is the mechanism of action of benzodiazepines?

A
  • Binds to molecular components of GABA(A) receptor* in neuronal membranes in CNS* (gamma subunit of pentamer)
  • This receptor is a chloride ion channel* and causes hyperpolarisation of the membrane
  • The benzodiazepines do not substitute for GABA (major inhibitory neurotransmitter in the CNS), but appear to potentiate GABA’s effects without directly activating GABA(A) receptors or opening the chloride channels
  • Causes an increase in the frequency (but not duration) of channel-opening events

*needed to pass

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2
Q

What are the organ level effects of diazepam?

A
  1. CNS:
    - Sedation*
    - Anxiolysis*
    - Amnesia and psychomotor and cognitive depression at lower doses
    - Hypnosis*
    - Anaesthesia* at higher doses
    - Anticonvulsant effect*
    - Muscle relaxation*
  2. Respiratory depression*
  3. Cardiovascular depression* (at higher doses and when hypovolaemic/CCF/chronic heart disease)

*3 to pass

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3
Q

What are the clinical uses of diazepam in the ED?

A

2 to pass:
- Anticonvulsant
- Sedation of agitated patient
- EtOH or benzodiazepine withdrawal
- Various toxidromes

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4
Q

What receptors do carbamazepine effect?

A
  • Sodium channel blocker*
  • Adenosine receptors antagonist
  • Anticholinergic (antimuscarinic)

*needed to pass

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5
Q

What are the most common dose-related adverse effects of carbamazepine?

A
  1. CNS effects:
    - Cerebellar effects: nystagmus, diplopia, ataxia
    - Drowsiness
  2. Anticholinergic effects:
    - Dry mouth
    - Tachycardia
    - Blurred vision
    - Delirium
  3. Cardiovascular effects:
    - Hypotension
  4. GIT:
    - GIT upset (nausea, vomiting)
    - Hepatic dysfunction
  5. Metabolic:
    - Hyponatraemia, water intoxication
  6. Haematological:
    - Blood dyscrasias, including leukopaenia commonly
    - Aplastic anaemic and agranulocytosis rarely
  7. Dermatological:
    - Erythematous skin rash
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6
Q

What important drug interactions does carbamazepine have?

A
  • Induces CYP450 enzymes / hepatic drug metabolising enzymes* and P-glycoprotein, resulting in increased clearance of some drugs and reducing their therapeutic blood levels (e.g. OCP, warfarin, phenytoin, valproate, lamotrigine, diazepam, phenobarbitone, carbamazepine itself)
  • As it induces its own metabolism, can result in breakthrough seizures
  • Valproate and phenytoin may inhibit carbamazepine elimination

*needed to pass + 1 other

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7
Q

Outline the clinical uses of carbamazepine

A
  • Anticonvulsant (partial and generalised tonic-clonic seizures)*
  • Treatment of bipolar mood disorder
  • Trigeminal neuralgia
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8
Q

Describe the mechanism of action of carbamazepine’s anticonvulsant activity

A

Blocks sodium channels:
- Inhibits high-frequency repetitive firing of neurons
- Presynaptic blocker of synaptic transmission (similar to phenytoin)

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9
Q

What are the pharmacokinetics of midazolam?

A
  1. Absorption:
    - Water-soluble*
    - Can be given PO, intranasal, buccal, PR, IV/IM/subcut
    - Poor oral bioavailability*
  2. Distribution:
    - Highly protein bound*
    - Crosses BBB easily at body pH
  3. Metabolism:
    - Hepatic metabolism
    - Short elimination half-life* 1.5-2.5hrs
  4. Excretion:
    - Renal excretion

*2/4 to pass

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10
Q

What are the clinical effects of midazolam?

A
  • Strong amnestic effect
  • Anticonvulsant*
  • Anxiolytic
  • Sedative-hypnotic
  • Antiemetic
  • Reduced sensitivity to CO2 (respiratory depression)

*needed to pass + 2 others

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11
Q

What are the clinical indications for the use of midazolam?

A
  • Anxiolysis
  • Sedation*
  • Anticonvulsant*
  • Antiemetic

*needed to pass

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12
Q

What are the adverse effects of midazolam?

A
  • Excess sedation*
  • Respiratory depression*
  • Decreased motor skills
  • Impaired judgement
  • Hypotension (particularly in hypovolaemic/CCF/chronic heart disease patients)
  • Occasionally rash

*needed to pass

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13
Q

What is the mechanism of action of phenytoin?

A
  • Sodium channel blockade* / reduced neuronal sodium conductance and prolongation of inactivated state of the sodium channel
  • Reduces Ca2+ influx into cells to decrease glutamate release
  • Enhances GABA release
  • Inhibits generation of rapidly repetitive action potentials

*needed to pass

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14
Q

Describe the elimination pharmacokinetics of phenytoin and how it affects toxicity

A
  • Phenytoin has dose-dependent elimination*
  • At low serum concentration it has first order kinetics*
  • Elimination becomes zero-order as serum concentration rises* with prolonged elimination and greater chance of toxicity with recurrent dosing and with even small increases in dose

*needed to pass

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15
Q

What are the adverse effects of phenytoin?

A
  1. Neurological (dose-related)*:
    - Ataxia
    - Drowsiness
    - Dizziness
    - Blurred vision
    - Hallucinations
    - Slurred speech and confusion
    - Peripheral neuropathy (idiosyncratic)
  2. Skin/soft tissue:
    - Hirsutism
    - Gingival hypertrophy
    - Acne
    - Facial coarsening
  3. Cardiovascular*:
    - Hypotension and arrhythmias with rapid IV administration

*1 of each to pass

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16
Q

Describe the pharmacokinetics of phenytoin

A
  1. Absorption:
    - High oral bioavailability (90%), poor IMI
    - Peak serum concentration 3-12hrs
  2. Distribution:
    - Highly plasma protein bound (90%)*
    - Vd 45L/70kg and widely distributed (brain, liver, skeletal muscle, fat)
  3. Metabolism:
    - Metabolised to inactive metabolites by the liver*
    - Dose-dependent: first order kinetics at low concentrations, zero order kinetics at higher concentrations due to saturation of hepatic enzymes (slows elimination)*
    - Half-life variable (12-36hrs) dependent on serum concentration as above
  4. Excretion:
    - Renal (<2% unchanged)

*needed to pass

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17
Q

What is the rationale for using a loading dose of phenytoin?

A

Reaches target concentration dose more quickly (otherwise it takes 4 half-lives to get to steady state)

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18
Q

What are the risks associated with IV phenytoin administration?

A
  1. Hypotension and bradycardia with rapid infusion* (due to diluent):
    - Limit rate of infusion to 50g/min maximum (30-60mins for full dose)
    - Less likely with fosphenytoin
  2. Allergic reactions
  3. Local necrosis if extravasation

*needed to pass

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19
Q

Describe the pharmacokinetics of valproate

A

4 to pass:

  1. Absorption:
    - Can be administered IV or PO
    - Well-absorbed orally with bioavailability >80%
    - Peak blood levels within 2hrs
  2. Distribution:
    - Highly protein bound
    - Low volume of distribution 0.15L/kg
  3. Metabolism:
    - Extensively metabolised in the liver
    - Long half-life 9-18hrs
  4. Excretion:
    - Excreted as glucuronide conjugate in urine (30-50% of dose)
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20
Q

What are the adverse effects of sodium valproate?

A
  1. GIT*:
    - Nausea, vomiting
    - Abdominal pain
    - Reflux
    - Asymptomatic LFT derangement
    - Weight gain, increased appetite (less commonly)
    - Idiosyncratic hepatic failure (rare; risk highest <2yrs old)
    - Pancreatitis
  2. CNS*:
    - Fine tremor
    - Ataxia
    - Sedation
    - Fatal encephalopathy if there is also a genetic abnormality of urea metabolism
  3. Skin/soft tissue:
    - Alopecia
    - Rash
  4. Haematological:
    - Idiosyncratic thrombocytopaenia
  5. Metabolic:
    - Hypernatraemia
  6. Reproductive:
    - Teratogenic if given in 1st trimester (e.g. neural tube defects, cardiovascular/facial/digital abnormalities)
  7. Hypersensitivity reactions

*1 of each to pass + 2 others

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21
Q

Sodium valproate exhibits capacity-limited protein-binding kinetics. What is this?

A
  • Sodium valproate is highly bound to plasma proteins (90%) at lower concentrations (75mg/L)
  • This mechanism is saturated at higher concentrations (150mg/L) leading to an increase in free drug (70% protein bound)
  • Results in apparent increased clearance of drug at higher doses and reduction in half-life: variable clearance
  • Thus dosage is preferred as a sustained release preparation
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22
Q

What are the possible pharmacodynamic mechanisms of sodium valproate?

A
  • GABA increased presynaptically by reduced GABA breakdown to succinate (ABAT/GAT1), possibly increased production (GAD)
  • Direct inhibitory actions on post-synaptic sodium channel, particularly high frequency gates, and Ca2+ (membrane-stabilisation - reduced voltage-gated outflow)
  • Possible blocked NMDA receptor activation effects
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23
Q

Describe the pharmacodynamics of amitriptyline

A
  • Blocks reuptake of serotonin and noradrenaline*
  • Blocks muscarinic, sympathetic a1, GABA(A), Na+ channel and histamine receptors
  • Monoamine vs neurotrophic vs neuroendocrine theories

*needed to pass + 2 other receptors

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24
Q

What are the toxic effects of amitriptyline and how are they mediated?

A

3 effects + receptor responsible:
1. Anticholinergic:
- Blurred vision
- Dry mouth
- Tachycardia
- Urinary retention
- Delirium
2. Antihistamine:
- Sedation
3. Alpha adrenergic blockade:
- Hypotension
4. Na+ channel blockade:
- Widened QRS
- Bradycardia
5. Direct central effects:
- Seizures

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25
Q

What are the adverse and/or toxic effects of lithium?

A
  1. Neurological:
    - Tremor
    - Choreoathetosis
    - Ataxia*
    - Dysarthria
    - Hyperactivity
    - Confusion*
    - Withdrawal
  2. Endocrine:
    - Reversible hypothyroidism*
  3. Renal:
    - Nephrogenic diabetes insipidus (polyuria, polydipsia)*
    - Chronic interstitial nephritis
    - Nephrotic syndrome
  4. Cardiovascular:
    - Oedema
    - Worsening of sick sinus syndrome
  • 3/4 to pass
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26
Q

Describe the pharmacokinetics of lithium

A
  1. Absorption:
    - Oral absorption* peaks at 0.5-2hrs, complete at 6-8hrs
  2. Distribution:
    - Distributes in TBW*
    - Therapeutic concentration 0.6-1.4mmol/L
  3. Metabolism:
    - Half-life 20hrs*
  4. Excretion:
    - Unchanged in urine*

*needed to pass

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27
Q

How can you assess lithium toxicity and how is it treated?

A
  • Measure levels 10-12hrs post last dose*
  • > 2mmol/L should be considered toxic
  • Treatment is supportive and haemodialysis
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28
Q

What is the mechanism of action of tricyclic antidepressants?

A
  1. Inhibition of serotonin and noradrenaline reuptake*:
    - Increases amount of serotonin and noradrenaline in certain parts of the brain (cortex and limbus; “monoamine hypothesis” for depression”) and spinal cord (ascending corticospinal tract - useful in neuropathic pain)
  2. Also blocks:
    - Na+ channels
    - K+ channels
    - Muscarinic (M1) receptors (anticholinergic)
    - Histaminic (H1) receptors
    - Alpha-1 adrenergic receptors (peripheral post-synaptic)

*needed to pass + 1 other

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29
Q

What clinical manifestations would be seen in an overdose of tricyclic antidepressants?

A
  1. Cardiovascular*:
    - Tachycardia
    - Hypotension (due to alpha blockade, impaired contractility)
    - ECG changes: PR prolongation, QRS widening (Na+ blockade), prolonged QT (K+ blockade), VT, VF
  2. CNS*:
    - Drowsiness
    - Delirium (anticholinergic)
    - Seizures
    - Coma
  3. Anticholinergic*:
    - Agitation, delirium
    - Mydriasis
    - Dry, warm, flushed skin
    - Urinary retention
    - Ileus
  • 1 example from each
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30
Q

What factors determine the volume of distribution of a drug?

A
  1. Drug factors*:
    - Lipid solubility
    - pKa
    - pH
    - Protein binding
  2. Patient factors*:
    - Age
    - Gender
    - Comorbid disease (e.g. oedema, ascites)
    - Body fat
    - Blood flow to tissues
  • 2 from each group
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31
Q

What therapies for tricyclic toxicity might reduce their tissue distribution?

A

Alkalinisation (e.g. with bicarbonate or hyperventilation) increases plasma protein binding of free drug, removing it from the tissues and reducing its toxicity

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32
Q

Describe the volume of distribution of tricyclic antidepressants. What factors contribute to this, and how does their volume of distribution influence their toxicity?

A

TCAs have a large Vd* (5-30L/kg), with high lipid solubility and high tissue protein binding
Tissue concentrations are high* in toxicity especially in well-perfused organs such as the brain and heart*

  • needed to pass
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33
Q

By what routes can olanzapine be administered?

A
  • PO*, sublingual
  • Parenteral* (IV, IM, depot IM)

*needed to pass

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34
Q

What dose and what route of olanzapine would you use for sedation in an agitated patient?

A

Dose 10-20mg regardless of route

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35
Q

What are the advantages of olanzapine over older “typical” antipsychotics?

A
  • Less extrapyramidal effects*
  • Less hypotension
  • Less tachycardia
  • Less effect on prolactin
  • More effective for both negative and positive psychotic symptoms, and cognition
  • Multiple routes of administration
  • High clinical potency

*needed to pass

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36
Q

What are the some of the clinical disadvantages of olanzapine?

A

2 to pass:
- Anticholinergic effects
- Lowered seizure threshold
- Weight gain
- Diabetes mellitus
- Hyperlipidaemia
- Expense

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37
Q

What are the pharmacodynamics of haloperidol?

A

Butyrophenone:
- High potency D2 receptor effects (dopamine antagonist)*
- High extra-pyramidal side effects*
- Low sedative effects*
- Minimal anticholinergic effects
- Minimal 5HT and H1 blockade effects

*2/3 to pass

38
Q

How do the pharmacodynamics of olanzapine differ from haloperidol?

A

Thienobenzodiazepine:
- Less D2 receptor effects
- High 5HT receptor blockade effects*
- Low extra-pyramidal side effects*
- Medium sedative effects*
- Low hypotensive and anticholinergic effects
- Low H1 blockade effects

*2/3 to pass

39
Q

Describe the pharmacokinetics of adrenaline

A

3 to pass:
1. Absorption:
- Poorly absorbed orally
- Routes of administration: subcut, IM, IV, nebulised
2. Distribution:
- 50% protein bound
- Does not cross BBB but crosses placenta
- Onset in seconds, duration of action 2mins
3. Metabolism:
- Terminated in synaptic nerve terminals, metabolised by catechol-O-methyltransferase and MAO with metabolites of VMA/MOPEG
4. Excretion:
- Metabolites in urine

40
Q

What are the pharmacodynamic effects of adrenaline?

A
  • Agonist effects for both alpha and beta receptor to the same degree
  • Low dose mainly beta, higher dose more alpha
  • Alpha*: vasoconstriction
  • B1*: positive inotropy and chronotropy
  • B2*: smooth muscle relaxation -> bronchodilatation, skeletal muscle vasodilatation (this may cause fall in TPR reflected in fall in diastolic BP sometimes seen)

*1 alpha and 1 beta effect to pass

41
Q

Describe the effects of adrenaline on other organs besides the heart

A

3 effects (from different systems) to pass:
1. Respiratory:
- Bronchodilation
2. Neurological:
- Pupillary dilatation
- Decreased IOP
3. GIT:
- Relaxation of gastric smooth muscle
- Increased glycogenolysis in the liver
4. Genitourinary:
- Uterine smooth muscle relaxation
- Bladder relaxation
- Bladder sphincter contraction
5. Salivary glands:
- Dry mouth
6. Metabolic:
- Metabolic acidosis
- Lipolysis (increased FA and glycerol in circulation)

42
Q

What is the mechanism of action of atropine?

A
  • Competitive reversible muscarinic ACh receptor antagonist*
  • Binds to muscarinic receptors, preventing the release of IP3 (inositol triphosphate), DAG (diacylglycerol) and inhibition of adenylyl cyclase caused by muscarinic agonists
  • Anticholinergic agent, equipotent at M1/M2/M3 receptors

*needed to pass

43
Q

Describe the organ effects of atropine

A

3 organ systems with an example of each to pass:
1. CNS:
- Delirium
- Decreased tremor in Parkinson’s disease
- Mydriasis
- Cycloplegia
2. Cardiovascular:
- Tachycardia
3. Respiratory:
- Bronchodilation
- Decreased secretions
4. GIT:
- Decreased saliva secretion
- Decreased gastric acid secretion
- Decreased mucin production
- Decreased gastric emptying and gut motility (increased intestinal transit time)
5. Genitourinary:
- Relaxes ureteric and bladder wall smooth muscle
- Urinary retention
6. Skin:
- Decreased sweating

44
Q

What is atropine used for clinically?

A
  1. Symptomatic bradyarrhythmias/bradycardia*
  2. Ophthalmology (used as mydriatic and cycloplegic)
  3. Occasionally in paediatric RSI using suxamethonium, especially 2nd dose
  4. Drying of secretions (e.g. in cholinergic nerve agent / organophosphate poisoning, or in palliative care)
  5. Traveler’s diarrhoea

*needed to pass + 1 other

45
Q

Describe the pharmacokinetics of atropine

A
  1. Absorption:
    - Route of administration: IV, PO, nebulised, topical
    - Well absorbed orally
  2. Distribution:
    - Wide Vd (including CNS)
  3. Metabolism:
    - 40% undergoes phase I and phase II hepatic metabolism
    - Half-life 2hrs
  4. Excretion:
    - Renal (60% unchanged)
46
Q

How does metoclopramide cause a dystonic reaction?

A

Metoclopramide is a dopamine antagonist* and causes an imbalance in the anticholinergic/dopamine transmission in the basal ganglia

*needed to pass

47
Q

What is the mechanism of action of benztropine in the treatment of dystonia?

A

Blocks muscarinic cholinergic receptors

48
Q

What are the potential side effects of benztropine?

A

3 to pass:
- Tachycardia
- Sedation
- Mydriasis
- Urinary retention
- Dry mouth

49
Q

What is the mechanism of action of metaraminol?

A

Direct a1 receptor agonist
Some indirect effect through increased noradrenaline

50
Q

What are the effects of metaraminol on the cardiovascular system?

A
  • Vasoconstriction (increased BP)
  • HR slows due to vagal feedback
  • CO unchanged or slightly decreased
  • Direct cardiac effects less important
51
Q

What role do sympathomimetics have in management of shock?

A
  • Temporising only* while other treatment instituted (fluids, etc)
  • Efficacy not proven
  • Useful in “failure” of sympathetic nervous system (e.g. in spinal injury or anaesthesia)

*needed to pass

52
Q

What receptors does noradrenaline act on?

A
  • Predominantly a1 receptor* to induce vascular smooth muscle constriction
  • Also active at a2 receptor (presynaptic), inhibiting noradrenaline release via negative feedback
  • Some effect on B1 and B2 receptors (more potent effect on B1)

*needed to pass + 1 other

53
Q

How does noradrenaline increase blood pressure?

A
  • Increased a1 activity -> vasoconstriction -> increased TPR* -> increased DBP
  • Increased B1 activity -> increased myocardial contractility* -> increased SBP
  • Overall rise in both SBP and DBP

*needed to pass

54
Q

How does noradrenaline affect the heart rate?

A
  • B1 activity increases HR
  • However compensatory baroreflex causes reflex bradycardia -> therefore minimal change in HR*

*needed to pass

55
Q

Describe the pharmacokinetics of ethanol

A
  1. Absorption:
    - Rapid from GIT, with peak levels in 30mins
  2. Distribution:
    - Rapid
    - Volume of distribution approximates TBW (0.5-0.7L/kg)
  3. Metabolism:
    - Predominantly hepatic*
    - Mainly by alcohol dehydrogenase* and less by microsomal ethanol oxidising system (MEOS)
    - Zero-order kinetics*
  4. Excretion:
    - Lungs, urine (small amounts)
56
Q

What does zero-order kinetics mean?

A

Elimination occurs at a constant rate independent of drug concentration

57
Q

What drugs other than ethanol have zero order kinetic metabolism?

A

1 to pass:
- Phenytoin
- Theophylline
- Warfarin
- Salicylate
- Heparin
- Paracetamol

58
Q

What are the pharmacodynamic effects of ethanol?

A
  1. CNS*:
    - Sedation
    - Disinhibition
    - Impaired judgement
    - Impaired motor skills
    - Ataxia
    - Slurred speech
    - Respiratory depression
    - Coma
  2. Cardiovascular:
    - Depressed contractility
  3. Smooth muscle:
    - Vasodilator -> hypothermia
    - Uterine smooth muscle relaxation

*3/8 to pass + 1 other

59
Q

Describe the pharmacodynamics of ketamine

A
  • Complex, but major effect is probably produced through the inhibition of the NMDA receptor complex* (with blockade of excitatory neurotransmitter glutamate)
  • Inhibits reuptake of catecholamine and serotonin
  • Potent short-acting sedative, amnestic, analgesic and anaesthetic

*needed to pass

60
Q

What are the systemic effects of ketamine?

A
  1. CNS:
    - Dissociative anaesthesia* (cataleptic state)
    - Profound analgesia*
    - Cerebral vasodilator and increases cerebral blood flow and cerebral metabolic rate (increases ICP, but not clinically significant)
    - May have anticonvulsant properties
    - Myoclonus
  2. Cardiovascular:
    - Haemodynamically stable*
    - Increases HR, BP and CO
    - Increases cardiac workload and myocardial oxygen consumption
  3. Respiratory:
    - Intact airway reflexes*
    - Minimal respiratory depression
    - Causes lacrimation and salivation that may cause laryngospasm in children
    - Bronchodilator
  4. Ocular:
    - Nystagmus

*needed to pass + 1 other

61
Q

What are the adverse effects of ketamine?

A

1 to pass:
1. CNS:
- Emergence phenomena (dysphoria)
- Hallucinations
- Seizures
2. GIT:
- Vomiting
3. Respiratory:
- Laryngospasm
- Increased salivation

62
Q

Besides the anaesthetic effect, what are the other indications for ketamine?

A

2 to pass:
- Analgesia
- Bronchodilator effect in asthma
- Acute behavioural disturbance
- Procedural sedation

63
Q

In what conditions might you avoid using ketamine?

A

1 to pass (excluding allergy):
- Allergy
- Raised ICP
- Raised IOP
- Recent or current URTI
- Shock

64
Q

Describe the pharmacokinetics of ketamine

A
  1. Absorption:
    - Highly lipid soluble, hence rapid onset*
  2. Distribution:
    - Low protein binding (12%)
    - Effect terminated by redistribution to inactive tissue sites*
  3. Metabolism:
    - Metabolised in liver* (N-demethylation by cytochrome P450) to norketamine, which has 1/3-1/5th the potency of ketamine
    - Norketamine then hydroxylated and conjugated into water-soluble inactive metabolites
  4. Excretion:
    - Metabolites excreted in urine*

*needed to pass

65
Q

Give an appropriate route and dose for ketamine for use in procedural sedation of a child

A

Either to pass:
- 1-2mg/kg IV
- 4-10mg/kg IMI

66
Q

Please describe the pharmacokinetics of propofol

A
  1. Absorption:
    - IV administration only
  2. Distribution:
    - Distribution half-life 2-4mins*
    - Rapid onset and recovery due to redistribution* from brain to skeletal muscle and fat, rather than metabolism
  3. Metabolism:
    - Duration of action 3-8mins, elimination half-life 4-23mins
    - Metabolised rapidly in the liver, some extra-hepatic metabolism (lung) when total body plasma clearance exceeds hepatic blood flow
  4. Excretion:
    - Urinary as glucuronides and sulphates, <1% unchanged

*needed to pass with reasonable understanding of drug distribution

67
Q

What are the adverse effects of propofol?

A
  1. Cardiovascular:
    - Hypotension* (due to vaso- and veno-dilation)
    - Negative inotropy
  2. Respiratory:
    - Apnoea*
    - Dose-related central depression of respiratory drive
  3. Pain on injection
  4. Hypersensitivity:
    - Allergy (due to soy/egg constituents)

*needed to pass

68
Q

How can you limit adverse effects when using propofol?

A

2 to pass:
- Caution with simultaneous co-administration of opiates/benzodiazepines
- Titrate small doses (10-20mg aliquots) slowly to effect
- Reduce doses in the elderly or with poor cardiovascular reserve
- Caution with haemodynamically unstable patients
- Give IV fluid bolus alongside

69
Q

What dose of propofol is used for induction of general anaesthesia? How does this differ from a procedural sedation dose?

A

Induction dose: 1-2.5mg/kg* (adults), 2.5-3.5mg/kg (children)

Procedural sedation: 0.5-1.0mg/kg single bolus dose or titrate in 10-20mg aliquots particularly in conjunction with morphine

*needed to pass

70
Q

What clinical effects should be anticipated when using propofol?

A
  1. CNS:
    - Anaesthesia
    - Sedation
    - NO analgesia
  2. Cardiovascular:
    - Hypotension* (due to vaso- and veno-dilation)
    - Negative inotropy
  3. Respiratory:
    - Apnoea*
    - Dose-related central depression of respiratory drive
  4. GIT:
    - Antiemetic properties
  5. Pain on injection
  6. Hypersensitivity:
    - Allergy (due to soy/egg constituents)
  7. Metabolic:
    - Metabolic acidosis when given as an infusion
  8. Propofol-related Infusion Syndrome
    - Acute refractory bradycardia progressing to asystole
    - Metabolic acidosis
    - Rhabdomyolysis
    - Hyperlipidaemia
    - Fatty or enlarged liver

*needed to pass + 2 others

71
Q

What type of drug is rocuronium?

A
  • Non-depolarising* muscle relaxant
  • Steroid derivative

*needed to pass

72
Q

What are the pharmacokinetics of rocuronium?

A
  1. Absorption:
    - Given IV
    - Onset 45-60secs
    - Dose 1.2mg/kg
  2. Distribution:
    - Duration of action 20-75mins
  3. Metabolism:
    - Hepatic
  4. Excretion:
    - 75-90% enterohepatic, the rest renal
73
Q

How does suxamethonium differ from rocuronium?

A
  • Duration of action is much shorter* (suxamethonium 5-10mins)
  • Different side effects and contraindications
  • Suxamethonium is metabolised by plasma pseudocholinesterase
  • Suxamethonium is a depolarising muscle relaxant with two phases of action: phase I is augmented by cholinesterase inhibitors
  • Rocuronium has an antidote (sugammadex)

*needed to pass + 2 others

74
Q

What is the mechanism of action of suxamethonium?

A

Depolarising neuromuscular blocker*

Phase I (depolarising):
- Binds to nicotinic receptor and opens channel, causing depolarisation of motor end plate
- Spreads to adjacent membranes causing contractions of muscle motor units (fasciculations)
- Depolarised membrane remains depolarised (and unresponsive to subsequent impulses) causing flaccid paralysis*

Phase II (desensitising):
- With continued or repeated exposure to suxamethonium, the initial endplate depolarisation decreases and membrane becomes repolarised
- Membrane cannot be depolarised
again as it is desensitised (mechanism unclear, however ? due to channel block becoming more important than agonist action at receptor)

*needed to pass + understanding of concept

75
Q

What are the pharmacokinetic properties of suxamethonium?

A
  1. Absorption:
    - Rapid onset (30-60secs)*
  2. Metabolism:
    - Short duration of action (2-8mins)
    - Hydrolysed rapidly by plasma pseudocholinesterase

*needed to pass

76
Q

What are the adverse effects of suxamethonium?

A
  1. Musculoskeletal:
    - Muscle pain from fasciculation
    - Malignant hyperthermia
    - Prolonged paralysis (due to reduced or absent pseudocholinesterase)
  2. Cardiovascular:
    - Bradycardia* (especially with repeated doses)
    - Other cardiac arrhythmias (e.g. if given with halothane)
  3. Metabolic:
    - Hyperkalaemia* (risk increased with burns, closed head injury, trauma, stroke)
  4. CNS:
    - Raised IOP
  5. GIT:
    - Raised intragastric pressure

*needed to pass + 2 others

77
Q

What is suxamethonium?

A
  • Depolarising neuromuscular blocker* producing rapid neuromuscular blockade at motor endplate nicotinic receptors
  • Structurally two acetylcholine molecules linked end to end
78
Q

What is the mechanism of action of vecuronium?

A
  • Non-depolarising neuromuscular blockade*
  • Competitive antagonist for acetylcholine at nicotinic receptors of neuromuscular junction*
  • Large doses will enter ion channel’s pore directly to produce more intense blockade
  • Also blocks pre-junctional Na+ channels to interfere with acetylcholine mobilisation at nerve endings

*needed to pass

79
Q

Describe the pharmacokinetics of vecuronium

A
  1. Absorption:
    - Highly polar
    - Poorly absorbed from GIT
    - Given IV
    - Onset within 1min, maximum effect at 3-5mins
  2. Distribution:
    - Rapidly distributed to extracellular space
    - Small volume of distribution (approximates blood volume)
    - Plasma protein 60-90%
  3. Metabolism:
    - Duration of action 20-35mins
    - Short half-life
  4. Excretion:
    - 75-90% by liver, rest by kidney
80
Q

Describe the mechanism of action of bupivacaine

A

Amide local anaesthetic:
- Blocks voltage-gated Na+ channels* in nerve
- Threshold for excitation increases, conduction slows, action potential rise declines, and action potential generation is abolished
- If Na+ current is blocked over the length of the nerve, propagation is ceased

*needed to pass

81
Q

Describe the pharmacokinetics of bupivacaine

A
  1. Distribution:
    - Distribution half-life 28mins
    - Large Vd (72L)
    - 95% protein bound
    - Lipophilic
  2. Metabolism:
    - Metabolised by the liver*
    - Duration of action 4-8hrs* (longer than lignocaine or ropivacaine)
    - Elimination half-life 3.5hrs

*needed to pass

82
Q

Give examples of clinical uses of bupivacaine

A

Nerve block (in low concentration 0.25%) for local infiltration*:
- Digital ring block
- Femoral
- Intercostal
- Intrapleural
- Epidural (post-op)
- Brachial plexus
- Sciatic nerve
- Intra-articular

*2 to pass

83
Q

List some toxic effects of bupivacaine

A
  1. Cardiovascular:
    - Cardiac arrhythmia*
    - Hypotension
    - Cardiac arrest
  2. CNS:
    - Sedation
    - Visual and auditory disturbance
    - Seizure*

*needed to pass

84
Q

How long will a bupivacaine block last?

A

3-6hrs

85
Q

What are the potential adverse effects of bupivacaine?

A
  1. Neurological*:
    - Sedation
    - Light-headedness
    - Visual and auditory disturbance
    - Tongue and mouth numbness
    - Metallic taste
    - Nystagmus
    - Restlessness
    - Muscle twitches
    - Seizure
  2. Respiratory:
    - Respiratory depression
  3. Cardiovascular*:
    - Arrhythmias
    - Cardiovascular collapse
    - Cardiac arrest
  4. Local toxicity:
    - Trauma
    - Neurotoxicity
  5. Allergy

*needed to pass

86
Q

How can the risk of the adverse effects of bupivacaine be minimised in the ED?

A
  • Ask about Hx of allergy
  • Use safe maximum dose (<2mg/kg)
  • Withdraw pre-injection
  • Avoid vessels (anatomical consideration, e.g. above rib below in intrapleural block)
  • Use US guidance
  • Ask patient to flag symptoms (e.g. metallic taste, tongue numbness)
  • Avoid hypoxia/acidosis
87
Q

What is the maximum safe dose of lignocaine for local anaesthesia?

A

Plain: 3mg/kg* (to maximum 300mg)
With adrenaline: 5mg/kg* (to maximum 500mg)

*needed to pass

88
Q

What factors affect absorption of lignocaine after local infiltration?

A

3 to pass:
- Dose
- Site of injection
- Drug-tissue binding
- Tissue blood flow
- Vasoconstrictors (combined preparation)

89
Q

What are the toxic effects of lignocaine?

A
  1. CNS*:
    - Early/mild: circumoral/tongue numbness, metallic taste, paraesthesia, sedation
    - Moderate: nystagmus, muscle twitching, nausea and vomiting, tinnitus, visual disturbance
    - Severe: seizures, sedation
  2. Cardiovascular*:
    - Cardiovascular collapse
    - Hypotension
    - Bradycardia
    - Rarely other arrhythmias
    - Worsen CCF or conduction blocks
  3. GIT:
    - Anorexia
    - Nausea and vomiting (through CNS effects)
  4. Haematological:
    - Methaemoglobinaemia
  5. Allergy:
    - Rare with amides

*2 of each to pass

90
Q

Describe the mechanism of action of lignocaine

A
  • Na+ channel blocker, class 1b (fast dissociation)
  • Blocks activated and inactivated Na+ channels to block nerve conduction
  • Less effect in infected tissue
91
Q

Describe the pharmacokinetics of sodium valproate

A

4 to pass:
- Can be administered IV or orally
- Well-absorbed orally with bioavailability of >80%
- Peak blood levels within 2hrs
- Highly protein bound and low volume of distribution 0.15L/kg
- Extensively metabolised in liver and excreted as glucuronide conjugate in urine (30-50% of dose)
- Long half-life 9-18hrs

ACEM Primary VIVA (45 decks)

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