Q1

What is pancuronium?

  • Non-depolarising NM blocker
  • Quaternary ammonium compound
  • Potent competitive antagonist of ACh at nicotinic receptors skeletal muscle motor end-plate
  • Interruption of transmission requires > 70% occupancy; blockade requires > 95% occupancy

Pass Criteria:

  • Nondepolarising NM blocker

Describe the pharmacokinetics of pancuronium?
Prompt: Describe its distribution and elimination

  • Poorly absorbed after oral admin
  • Rapidly and widely distributed after iv
  • Rapid elimination (T1/2 30min) by urinary excretion unchanged drug (highly water soluble), and hepatic metabolism with biliary excretion


Pass Criteria:

  • Rapid distribution
  • Rapid elimination

What are the adverse effects of pancuronium?

  • Uncommon
  • Minor tachycardia, hypertension, sl increased CO can occur
  • Life-threatening anaphylaxis < 1:10,000


Pass Criteria:

  • A cardiac and allergy effect

Q2

Describe the pharmacokinetics of propofol?

  • Intravenous administration
  • Distribution t1/2 2-8 min, redistribution t1/2 30-60 min
  • Metabolism- rapidly in liver; total body clearance is greater than hepatic blood flow, suggesting extrahepatic mechanisms
  • Excretion- urine as glucuronides and sulphates- <1% unchanged


Pass Criteria:

  • Must get bolded point to pass

What are the side effects of propofol?

  • Respiratory- dose-related depression of central ventilatory drive, apnoea,
  • Cardiac- Marked decrease in blood pressure through decreased peripheral arterial resistance and venodilatation, and direct negative inotropic effect.
  • Soy/egg allergy,
  • Pain on injection


Pass Criteria:

  • Knowledge of respiratory and cardiac effects of propofol

Q3

How does ketamine affect the cardiovascular system?

  • HR, BP and cardiac output increase
  • Stimulate central SNS, and inhibits re-uptake of noradrenaline at sympathetic nerve terminals


Pass Criteria:

  • Demonstrated understanding of CV effects of ketamine

What are the side effects of ketamine?

  • Sialorrhoea
  • Decreased RR
  • Postoperative disorientation
  • Sensory and perceptual illusions
  • Emergence phenomenon
  • Vomiting
  • Raised ICP– increases cerebral blood flow, oxygen consumption and ICP
  • Rash


Pass Criteria:

  • 2 bold + 1 other

Q4

Describe the mechanism of action of suxamethonium?

  • Phase I (depolarising)
    • Reacts with Nicotinic receptor, opens the channel, causing depolarisation of the motor end plate, not metabolised at the synapse, and so membranes remain unresponsive to subsequent impulses- lack of “repriming” leads toflaccid paralysis.
  • Phase II (desensitising)
    • Unclear, but channel block may be more important than agonist action.
    • Action is terminated by diffusion away from the end plate into the extracellular fluid, where it is metabolised by plasma cholinesterase


Pass Criteria:

  • Demonstrated understanding of mechanism of action

What are the side effects of suxamethonium?

  • Bradycardia– negative inotropic and chronotropic effects (inc. second dose bradycardia)
  • Hyperkalaemia (esp burns, nerve damage, NM disease, closed head injury)
  • Increased intra-ocular pressure
  • Increased intragastric pressure (inc. aspiration)
  • Muscle pain (in up to 20%)
  • Malignant hyperthermia (when combined with volatiles)
  • Sux apnoea in susceptible patients

 

Pass Criteria:

  • 3 bold to pass

Q5

What type of anaesthesia does ketamine produce?

  • Dissociative anaesthetic: analgesia, amnesia, catatonia +/- LOC

Which receptor action produces the anaesthesia?

  • Blockade of glutamic acid (excitatory neurotransmitter) at NMDA receptor

What are the cardiorespiratory effects of ketamine?

  • CVS: HR, BP, CO increase central SNS excitation
  • Resp: decreased rate, airway reflexes remain intact, bronchodilator

Q6

What properties does Propofol have that make it a good IV anaesthetic?

  1. Rate of recovery is more rapid than other drugs i.e. thiopentone
  2. Antiemetic effect
  3. Short distribution 1/2 life (2-8 min)
  4. Does not cause cumulative effect (because of its short 1/2 life)

 

Pass criteria

  • 2 out of 4

Outline its pharmacokinetic profile of Propofol?

  1. Distribution 1/2 life: 2-8 min
  2. Elimination  1/2 life: 30-60 min
  3. Rapidly metabolised in liver by conjugation to glucoronide sulphate and excreted in urine
  4. <1% of drug is excreted unchanged
  5. Clearance of propofol > hepatic blood flow. Hence there is an extrahepatic route of elimination in addition to the liver enzyme metabolism

 

Pass criteria

  • 3 out of 5

Q7

Describe the adverse effects of suxamethonium?

  • Paralysis and unable to secure airway
  • Bradycardia
  • Hyperkalaemia
  • Increased intra-ocular pressure
  • Increased gastric pressure
  • Muscle pain
  • Interactions with other drugs
  • Prolonged block if abnormal plasma cholinesterase

How do these compare to the non-depolarising agents?

  • Paralysis same but longer
  • Interactions with other drugs more prominent with non depolarising
  • Others not occur

Q8

Describe the pharmacokinetics of thiopentone.

  • After IV bolus, rapidly crosses the blood-brain barrier.
  • Plasma: brain equilibrium occurs < 1 min because of high lipid solubility.
  • Rapidly diffuses out of the brain and highly vascular tissues, and redistributed to muscle and fat.
  • Metabolized at rate of 12–16% per hour. <1% of the administered dose excreted unchanged by kidney

 

Pass Criteria:

  • 2 phase concept

What adverse effects does it cause when used as an anaesthetic induction agent?

  • Hypotension: Drops BP, SV, CO due to myocardial depressant effect and increased venous capacitance.
  • Apnoea.
  • Rarely precipitates porphyric crisis by inducing ALA synthase in liver

Pass Criteria:

  • Hypotension

Q9

Describe the actions of Dantrolene

ACTIONS:

  • Interferes with release of CC from SER, by binding to the SER CC channel (“ryanodine receptor”), hence reducing excitation coupling.
  • Motor units that contract rapidly are more sensitive (hence only slight depression of cardiac and smooth muscle

What are the uses?

USES:

  • Spasmolysis (cerebral palsy, MS, stroke)
  • Malignant hyperthermia (hereditary impairment of SER to sequester/reuptake calcium that has been released into the cell)

What is the dose for acute management of malignant hyperthermia?

DOSE for MI-I: 1 mg/kg IV, repeat as needed to 10 mg/kg


Q10

What are the pharmacodynamic effects of lignocaine on the heart?

• Selectively blocks the fast Na channels of the depolarised cells, increasing their refractory period,

• Decreases pacemaker activity,

• May cause hypotension by depressing myocardial contractility in those with heart failure.

 

Pass: bold + 1

NOTES: Type 113 antiarrhythmic. Affects cells with the longest APs, such as purkinje and ventricular cells as opposed to the atrial cells.

What features distinguish lignocaine from other Class I Antiarrythmics?

•             Does not prolong the duration of the AP.

•             Dissociates from the channel with rapid kinetics

•             Has no effect on normal cells.

 

Pass: (1 of 3)

What are the clinical uses of lignocaine?

  • Type 1B Antiarrhythmic
  • Local Anaesthetic
  • Post herpetic neuralgia

Pass: (2 of 3)


Questions 11 to 20