Anaesthetic Drugs 1 to 10
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
- 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
- Rapid distribution
- Rapid elimination
What are the adverse effects of pancuronium?
- Minor tachycardia, hypertension, sl increased CO can occur
- Life-threatening anaphylaxis < 1:10,000
- A cardiac and allergy effect
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
- 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
- Knowledge of respiratory and cardiac effects of propofol
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
- Demonstrated understanding of CV effects of ketamine
What are the side effects of ketamine?
- Decreased RR
- Postoperative disorientation
- Sensory and perceptual illusions
- Emergence phenomenon
- Raised ICP– increases cerebral blood flow, oxygen consumption and ICP
- 2 bold + 1 other
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
- 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
- 3 bold to pass
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
What properties does Propofol have that make it a good IV anaesthetic?
- Rate of recovery is more rapid than other drugs i.e. thiopentone
- Antiemetic effect
- Short distribution 1/2 life (2-8 min)
- Does not cause cumulative effect (because of its short 1/2 life)
- 2 out of 4
Outline its pharmacokinetic profile of Propofol?
- Distribution 1/2 life: 2-8 min
- Elimination 1/2 life: 30-60 min
- Rapidly metabolised in liver by conjugation to glucoronide sulphate and excreted in urine
- <1% of drug is excreted unchanged
- Clearance of propofol > hepatic blood flow. Hence there is an extrahepatic route of elimination in addition to the liver enzyme metabolism
- 3 out of 5
Describe the adverse effects of suxamethonium?
- Paralysis and unable to secure airway
- 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
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
- 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.
- Rarely precipitates porphyric crisis by inducing ALA synthase in liver
Describe the actions of Dantrolene
- 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?
- 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?
What are the pharmacodynamic effects of lignocaine on the heart?
• 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?
• 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)