Explain the solubility characteristics of nitrous oxide.

Nitrous oxide possesses low solubility in the blood, reaches high arterial tension rapidly, Rapid equilibrium in the brain and fast onset of action ( rapid onset-rapid recovery)

Pass: Bolded concept


Draw the arterial anaesthetic tension vs time for nitrous oxide vs halothane or Methoxyflurane.

nervous 1

Pass: curve


What's the mechanism of action of Rocuronium?
(Prompt: receptor level)

Non-depolarising NM blocker.
In low doses it predominantly acts as a competitive inhibitor of Acetylcholine at nicotinic receptors.

In larger doses it can enter the pore of the ion channel -> greater NM blockade.

It can also block prejunctional sodium channels-> interference with the mobilisation of AChI at nerve endings.

Notes: Non-depolarising NM blocker. Initially acts as competitive inhibitor for Ach at nicotinic receptors

Describe the pharmacokinetics of rocuronium.

Prompt: Describe rocuronium’s distribution and elimination.

Undergoes rapid distribution.

Highly ionized – so small Vd (80-140m1/kg).

Undergoes hepatic metabolism (75-90%) and renal excretion.

Duration of action is 20-35mins.
Notes: Rapid distribution. Short T1/2.


Describe the pharmacokinetics of sodium vaiproate.

Well absorbed PO, bioavailability >80%

Food may delay abs for several hours. Peak plasma levels 2 hrs if empty stomach

90% protein bound (fraction bound reduces as total dose increases). Highly ionized and highly protein bound, therefore

Small VD, essentially confined to extracellular water, approx. 0.15L/kg

95% hepatic metabolism, (some to active metabolites), 5% unchanged in urine

Clearance is low and dose dependent, T1/2 is approx. 15/24 (9-18) and reduced if taking other antiepileptic drugs

Highly protein bound and small Vd to pass

Describe the toxic effects of sodium vaiproate.

Mild : Transient GI inc anorexia, nausea and vomiting. Rash, alopecia and increased appetite.

Weight gain.

Major Overdose:

CNS: coma, cerebral oedema (potentially fatal)

Bone marrow depression

Metabolic effects: hyperNa, hypoCa, hyperammonaemia

CVS, renal effects

Severe and idiosyncratic

1. Hepatotoxicity — rarely fatal, usually in under 2 yo, or multiple meds. Elevation of LFTs in 40%. May be reversible

2. Thrombocytopaenia

CNS to pass


Give some examples of drugs used as anaesthetic induction agents?

Thiopentone, propofol, ketamine, fentanyl, midazolam, etomidate

Pass: 2

Describe the onset and recovery of propofol and ketamine?

Both have rapid, Ketamine has a slower recovery and is often associated with emergence phenomena.

Pass: Bold

Describe the cardiovascular effects of propofol and ketamine?

Propofol—marked decrease in BP during induction via decreased peripheral arterial resistance and venodilation. Also greater direct negative inotropic effects cf other induction agents

Ketamine — produces does-related CV stimulation, increased KR, BP and CO (by stimulating central symp nervous system +/-inhibiting NA reuptake at symp nerve terminals

Pass: Bold


How does Sumatriptan work in the treatment of migraine headache?

•             A selective agonist for 5HTID + 5HTB

•             These receptors are found on cerebral & meningeal vessels

•             It causes vasoconstriction

Serotonin agonist to pass

Please describe the pharmacokinetics of Sumatriptan.

•             Bioavailability 15% (other agents in the group have availabilities of 40- 70%)

•             T 1/2= 2-3 hours

•             Given SIC, nasally, orally

Notes: Poor bio-availability given sic

What are the pros and cons in using Sumatriptan for migraine?


•             Mild side effect eg tingling, dizziness, muscle weakness, neck pain, injection site reactions

•             Effective


•             Contraindicated in patients with IHD due to coronary spasm

•             Short duration of action (several doses required for prolonged attack)

•             Very expensive

Notes: Coronary spasm


How do benzodiazepines work at the receptor level?

  1. GABA receptor. Bind to varying subunits, mainly y or a. Separate site to GABA
  2. GABA opens CI channels and increases membrane polarisation
  3. Do not directly activate the receptor but facilitate the effect of GABA

What are the clinical effects of benzodiazepines?

Sedation Including disinhibition and amnesia

Hypnosis Decreased latency of onset Increased stage 2 NREM

Decreased REM

Anaesthesia (adjunct)

Anticonvulsant Variable

Particularly clonazepam, lorazepam, diazepam, nitrazepam

Muscle relaxation

Respiratory depression Respiratory centre depression usual cause of death

Cardiovascular depression if vulnerable or excessive dose

What is flumazenil? How does it work? Describe potential adverse effects from the use of it the management of benzodiazepine toxicity.

vomiting / seizures/ unmasking withdrawal


What benzodiazepines are commonly used in the ED?

Diazepam, lorazepam, midazolam, clonazepam, temazepam,

Pass: at least 2

What is the mechanism of action of benzodiazepines?
Prompt: describe how they interact with receptors.

Agonist at GABA A receptor which is chloride ion channel binding between alpha1 & gamma2 subunit (BZ site) – more selective than barbs. Low affinity for GABA B.
GABA inhibition enhanced.

Pass: Bold

What are the clinical effects of benzodiazepines?

Sedation, hypnosis, anticonvulsant, muscle relaxation, resp depression (esp if resp disease), CVS depression, decreased contractility, decr vasomotor tone (esp if CVS disease)

Pass: Bold


A 50 year old woman is brought to the ED with an amitriptyline overdose. Which factors determine the volume of distribution of a drug?

  • Drug factors
    • Lipid solubility (high in TCA)
    • pKa
    • pH
    • Protein binding (high in TCA)
  • Patient factors
    • Age
    • Gender
    • Comorbid disease e.g. oedema or ascites
    • Body fat
    • Blood flow to tissues

Pass Criteria:

  • At least 2 from each group

Describe the volume of distribution of tricyclic antidepressants. How does this influence their toxicity?

  • TCAs have a large Vd (5-30L/kg), tissue concentrations are high especially in well perfused organs such as the brain and heart.

Pass Criteria:

  • Bold to pass

What therapies for tricyclic toxicity might reduce their tissue distribution?

  • Alkalinisation (Bicarbonate or hyperventilation) increases plasma protein binding of the free drug removing it from the tissues reducing its toxicity

Pass Criteria:

  • Bold to pass


What are the possible pharmacodynamic mechanisms of sodium valproate?

PROMPT – What ion channels/neurotransmitters are most likely involved?

  • GABA increased presynaptically by reduced GABA breakdown to succinate (ABAT/GAT1)
    • >Cl- inh post synaptic GABR channel/possible increased production (GAD)
  • Direct inhibitory actions on post synaptic sodium channel, particularly high frequency gates and Ca+ (membrane stabilisation – reduces voltage gated outflow)
  • Blocked NMDA receptor activation effects?

Pass Criteria:

  • Bold to pass

What are the adverse effects of sodium valproate?

  • Nausea/vomiting/GI (very common)
  • Severe hepatotoxicity – liver failure (> young/other hepatotoxic drugs/liver damaged)
  • Marked fetal abnormality rates (8-9%)
  • Reduced IQ & other possible developmental effects
  • Thrombocytopaenia/bruising
  • Pancreatitis
  • Alopecia
  • Neuro – asthenia, tremor, nystagmus
  • Hypersensitivity reactions

Pass Criteria:

  • Bold and one other

What therapies for tricyclic toxicity might reduce their tissue distribution?

  • Alkalinisation (Bicarbonate or hyperventilation) increases plasma protein binding of the free drug removing it from the tissues reducing its toxicity

Pass Criteria:

  • Bold to pass



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

  • Neuro
    • Tremor
    • Choreoathetosis
    • Ataxia
    • Dysarthria
    • Hyperactivity
    • Confusion
    • Withdrawal
  • Thyroid
    • Reversible hypothyroidism
  • Renal
    • Polyuria
    • Polydipsia (nephrogenic diabetes insipidus)
    • Chronic interstitial nephritis
    • Nephrotic syndrome
  • Cardiovascular
    • Oedema
    • Worsening of sick sinus syndrome

Pass Criteria:

  • At least 3 bold

Describe the pharmacokinetics of lithium.

  • Oral absorption (peak 0.5-2 hours but complete 6-8 hours)
  • Distributes in TBW
  • Excreted unchanged in urine
  • Plasma half-life 20 hours
  • Therapeutic concentration 0.6-1.4 mmol/L

Pass Criteria:

  • Bold + some appreciation of longer half-life

How can you assess lithium toxicity and how do you treat it?

  • Measure levels (should be 10-12 hours after last dose)
  • > 2 mmol/L should be considered toxic
  • Treatment is supportive and haemodialysis (PROMPT – Lithium is an ion)

Pass Criteria:

  • Bold + some concept that levels should be measured well after last dose



How does metoclopramide cause a dystonic reaction?

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

Pass Criteria:

  • Bold to pass

You treat a dystonic reaction with benztropine. What is its mechanism of action?

  • Blocks the muscarinic cholinergic receptors; an anti-muscarinic agent

Pass Criteria:

  • Bold

What are the potential side effects of benztropine?

  • Tachycardia
  • Sedation
  • Mydriasis
  • Urinary retention
  • Dry mouth

Pass Criteria:

  • Knows 3

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