Pharmacology

Question 1

Which drugs have significant pulmonary uptake?

Answer 1

Basic amines with pKa greater than 8

Question 2

What are the types of adverse drug reactions?

Answer 2

Type A

Augmented or dose-dependent
E.g. worsening coagulopathy with heparin

Type B

Bizzare or idiosyncratic
E.g. agranulocytosis

Type C

Chronic exposure
E.g. long term side effects of steroids

Type D

Delayed effects
E.g. cancer development in adults after drug exposure as a child

Type E

End of treatment effects, such as withdrawal symptoms

Question 3

How does aldosterone exert its effects?

Answer 3

Binds to intracellular steroid receptors

Increases expression of sodium channels and the sodium-potassium ATPase in the distal tubule and collecting duct

Question 4

How does dexmedetomidine exert its effects?

Answer 4

Agonist of G-Protein coupled alpha 2 adrenoreceptors

Activity in the locus coeruleus in the brain stem is thought to mediate the sleep and sedative effects

The spinal cord is thought to be the site of its analgesic action

Question 5

How does fentanyl exert its effects?

Answer 5

Metabotropic Gi-coupled opioid receptor agonist

Question 6

How does midazolam exert its effects?

Answer 6

GABA receptor agonist

Question 7

How does Ketamine exert its effects?

Answer 7

Multiple targets but priniciply N-methyl-d-aspartate (NMDA) receptor antagonism

Question 8

In which cohort of patients might you use the Kataria model?

Answer 8

Propofol TCI infusion for paediatric patients

Three compartment model for propfol that compensates for the underdosing that occurs with Marsh model.

Question 9

What is the Maitre model?

Answer 9

A three compartment TCI model for alfentanil

Question 10

What is the Armitage regime?

Answer 10

Uses 0.25% bupivacaine for caudal injection in children

0.5ml/kg to achieve lumbosacral anaesthesia
1ml/kg for thoracolumbar
1.25ml/kg for mid-thoracic

No more than 20ml or 2ml/kg should be given

Question 11

What did the CRASH-2 trial conclude regarding tranexamic acid?

Answer 11

9% relative risk reduction for death following major trauma

NNT of 67

Question 12

How does tranexamic acid work?

Answer 12

It is a lysine derivative antifibrinolytic agent

Question 13

What receptor action does nitrous oxide have?

Answer 13

N-methyl-D-aspartate receptor antagonist

Question 14

What harm can nitrous oxide cause to the patient?

Answer 14

NO2 oxidizes Vitamin B12
It can cause sub-acute combined degeneration of the cord with chronic use or in patients with folate/B12 deficiency.

Question 15

Why is desflurane heated in the Tec 6 vaporiser?

Answer 15

To prevent fluctuation in vapour pressures

Desflurane has a low boiling point and a high vapour pressure, which requires a heated, pressurised Tec 6 vaporiser to safely administer

Question 16

What is the half life of amiodarone?

Answer 16

Very long

Between 20 and 100 days

Question 17

What is tautomerism?

Answer 17

This is a form of dynamic structural isomerism, exemplified by the keto-enol transformation of thiopentone
Soluble, ionised thiopental exists in an alkaline pH, hence the vial has added hydroxide to maintain solubility.
On injection into the blood, the pH drop causes the molecule to unionise into the thiol group, and then to rapidly convert to the pharmacologically active thiopentone

Question 18

What does midazolam do with regards to isomerism?

Answer 18

Midazolam undergoes pH-dependent ring closure above pH 4
Below pH 4, the open ring structure is ionised and therefore water soluble
Above pH 4 the ring closes to form a lipid soluble molecule that can cross the blood brain barrier
pKa is 6.5, meaning that in the blood approximately 90% is unionised
This is commonly discussed as a form of tautomerism, however technically speaking it isn’t, becausel a water molecule is lost when the ring closes, so the molecular formula is different

Question 19

Can you name some drugs that demonstrate stereoisomerism?

Answer 19

Warfarin
Ropivacaine
Bupivacaine
Halothane
Isoflurane
Etomidate
Ketamine