Canonical Question
NeuroPharm – Sedatives
Master answer
(Please note Propofol was not asked in this paper)
PHARMACEUTIC
| IDEAL SEDATIVE | MIDAZOLAM Y/N | PROPOFOL Y/N |
|---|---|---|
| long shelf life | Y | Y |
| stable when drawn up and on exposure to light | Y | Y |
| water soluble | Y | N |
| no refridgeration | Y | Y |
| cheap | Y | Y |
| mixes well with other agents in the central line lumen | Y | Y |
| Bacteriostatic | Y | N |
PHARMACODYNAMIC
| IDEAL SEDATIVE | MIDAZOLAM Y/N | PROPOFOL Y/N |
|---|---|---|
| Known MOA | Y | N |
| Affects only CNS | N | N |
| No excitatory or emergence phenomenon | Y | N |
| No pain on injection | rare | N |
| Safe on Intra-arterial injection | N | N |
| No trigger for MH or porphyria | Y | N |
| Safe in pregnancy | N | Y |
| Reliable dose – effect curve with little inter- individual variation in effect | N | Y |
| Anxiolysis | Y | Y |
| Analgesic properties | N | N |
| Amnesia | Y | Y |
| No effect on cardiovascular performance | N ↓MAP, ↓SVR, ↓HR | N ↓MAP, ↓SVR, ↓HR |
| Does not depress respiratory drive | N Significant, Dose-dependent | N Mild, dose-dependent |
| Rousable sedation | Y | Y |
| Minimal side effects | N | N |
| No incidences of allergy / anaphylaxis | Y rare | Y rare |
| No idiosyncratic reactions | N | N |
| No tachyphylaxis | N | Y |
PHARMACOKINETIC
| IDEAL SEDATIVE | MIDAZOLAM Y/N | PROPOFOL Y/N |
|---|---|---|
| Low volume of distribution | Y 0.8-1.5L/kg | N 2-10 L/kg |
| rapid onset | Y 2 mins | Y 30sec |
| low protein binding | N 96% PB | N 98% PB |
| Largely unionized (high pKa) | Y pKa=6.5 (85% ionized at 7.4) | Y pKa=11 (99% unionized at 7.4) |
| Lipophilic | Y Highly lipophilic with closed ring | Y |
| inactive metabolites | N | Y |
| non-toxic metabolites | Y | Y |
| rapid clearance (context-sensitive half-life) | Y/N (CSHT 40mins at 2hrs) | Y (CSHT 20mins at 2hrs) |
| clearance not affected by either renal or hepatic dysfunction | Y | N |
| Little inter-individual variation in pharmacokinetics | N | Y |
| Availability of an antagonist | Y Flumazenil | N |
Propofol infusion syndrome:
When used at >4mg/Kg/Hr for more than 24 hours
- Metabolic acidosis,
- Lipaemia,
- rhabdomyolysis
- Cardiac failure
- arrhythmias and death
Gladwin / JC 2020
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2008B Q10 | Outline the pharmacological properties of an ideal agent for sedating patients undergoing mechanical ventilation in intensive care (50% of marks). Describe how propofol compares to the ‘ideal’ agent (50% of marks). | historical_member | — |
| 2016A Q24 | Describe the ideal sedative agent for an Intensive Care patient (50% of marks). How does midazolam compare to this (50% of marks)? | historical_member | — |