Ionisation Flashcards
(21 cards)
What structural features make a molecule hydrophilic?
Polarity—molecules need polar functional groups (especially nitrogen or oxygen) to disrupt hydrogen bonding in water and dissolve.
Why is ethanol soluble in water but dodecanol is not?
Ethanol has a small hydrocarbon chain and a polar –OH group; dodecanol has a longer hydrocarbon chain that reduces its solubility despite having an –OH group.
Define strong vs weak electrolytes
Full vs partial dissociation into ions in solution
What functional groups in drugs are commonly responsible for partial ionisation?
Carboxyl group (COOH) – weak acid
Amine group (NH₂) – weak base
What is the role of pKa in ionisation?
pKa is the pH at which 50% of a molecule is ionised and 50% is unionised. It helps predict how much of a drug will be in each form at physiological pH.
What is the formula for the acid dissociation constant, Ka?
Ka= [protonacceptor][H+]/[proton donor]
What is pKa?
The negative logarithm of Ka. It reflects the pH at which half the molecule is ionised.
What is the Henderson-Hasselbalch equation for a weak acid?
pH = pKa + log( [A-]/[AH] )
What is the Henderson-Hasselbalch equation for a weak base?
pH = pKa + log( [B]/[BH+] )
What does it mean if pKa = pH?
The concentration of ionised and unionised forms are equal (50:50).
What is the ionised:unionised ratio at pH 7.1 if pKa = 6.1?
10:1 (ionised to unionised)
What is the pKa of the carbonic acid–bicarbonate buffer system? And therefore what is the ratio of HCO3-:H2CO3 at pH 7.1
6.1. 10:1
Term: Buffer
A solution that resists changes in pH by neutralising added acid or base. Works best when pH ≈ pKa.
What are two major physiological buffering systems?
Bicarbonate system
Deoxyhaemoglobin buffering CO₂
What two key factors determine whether an anaesthetic reaches the brain?
Lipid solubility
pKa (determines proportion of unionised form)
Why must injectable drugs be soluble in water?
Ionised forms dissolve in water. However, if highly ionised, they may irritate veins due to extreme pH, requiring special solubilisation methods.
Name 3 formulation strategies for solubilising intravenous agents:
Propofol: lipid emulsion (egg phosphatide)
Etomidate: polyethylene glycol or intralipid
Thiopental: alkaline powder reconstituted with water
What factors contribute to a fast onset of CNS drugs?
Low pKa → more unionised at pH 7.4
High lipid solubility
Low protein binding
Why does alfentanil have a faster onset than morphine?
Alfentanil pKa = 6.4 (mostly unionised at pH 7.4)
Morphine pKa = 7.9 (more ionised)
Even though alfentanil is 90% protein bound, it’s less ionised and crosses BBB faster.
How does ionisation affect drug duration?
More ionisation = more drug retained in plasma = longer duration.
More unionised = faster BBB crossing but shorter duration due to redistribution into fat.
Compare fentanyl and propofol in terms of duration.
Fentanyl: pKa = 8.5 → more ionised → longer duration
Propofol: pKa = 11 → mostly unionised → faster onset, shorter duration due to redistribution
