ILA 3 - Pharmacokinetics/dynamics

Question 1

In order to induce anaesthesia what characteristics should a drug have?

Answer 1

• Low protein binding (protein binding lowers free concentration of a drug. If protein binding is low, it will allow a high plasma concentration, keeping the patient asleep.)
• High lipid solubility (Should have high lipid solubility to cross the blood brain barrier and reach site of action)

Question 2

Given the IV drug’s distribution, why might an additional volatile drug need to be given once the patient is asleep?

Answer 2

With IV there is high initial plasma concentration. But high lipid solubility means it reaches less perfused tissue quickly, lowering plasma concentration. Concentration decreases, patient will wake up.

This action is helpful in cases where short lived anaesthesia may be indicated but not here.

Patient needs extra dose to maintain plasma concentration enough to keep patient asleep.

Question 3

Define agonist and antagonist with an example of each

Answer 3

Agonist - ligand binds to receptor and produce appropriate response. Have high affinity and equity.
E.g. adrenaline is a beta agonist.

Antagonist - Ligand prevents binding of agonist, preventing its effects. Can be competitive (EC50 same) or non competitive (EC50 decreased).
Have affinity but no efficacy.
E.g. Propanolol is a beta blocker

Question 4

Competitive vs non competitive antagonism. With an example of each

Answer 4

Competitive antagonist - binds to same site as agonist, but does not activate it, blocking agonists action.
E.g. Naloxone, blocks opioid receptors (used in overdose)
Is reversible and surmountable (can be reversed by increasing agonist dose)

Non competitive antagonist - Binds to allosteric site, prevents activation of receptor. Irreversible and insurmountable.
(Ketamine at NDMA-glutamate receptor)

Question 5

What are the 4 drug targets

Answer 5

Receptors - Beta blockers
Enzymes - ACEi
Transporters/carrier proteins - PPI (omeprazole)
Ion channels - CCB (amlodipine)

Question 6

Define bioavailability

Answer 6

Amount of drug that reaches systemic circulation unaltered. IV have 100% bioavailability. Oral have <100% so may need higher doses than IM or IV.

E.g. morphine has a bioavailability of 50% orally, so dosage must be doubled.

Question 7

Define first pass metabolism (first pass effect)

Answer 7

Rapid uptake and metabolism of an agent into inactive compounds by the liver immediately after enteric absorption, before it reaches it systemic circulation. This reduces concentration of the drug before it can reach circulation.

Not all drugs undergo first pass metabolism, some have more effect than others.

Question 8

Why must a patient with renal failure be prescribed less morphine.

Answer 8

Morphine metabolised into morphine 6 glucuronide, which is excreted by kidney. If kidney function bad, wont be as steadily excreted, can lead to respiratory failure. (must be reversed by naloxone)

Question 9

Ideal IV anaesthetic properties

Answer 9

Physical
- Long shelf life
- Cheap
- No pain on injectino

Pharmacokinetic
- Rapid onset - low protein binding and high solubility
- Rapid clearance and metabolism
- No active metabolites.

Pharmacodynamic
- Minimal CVD and resp effects.
- No histamine/allergy/hypersensitivity
- No hang over effect