Lecture 11 - Chemistry of Medicines to treat Diarrhoea and Constipation Flashcards
Adsorbent and bulk forming diarrhoea treatment
kaolin, light (adsorbent and bulk forming)
Anti-motility treatment for acute diarrhoea
Diphenoxylate & atropine (co-phenotrope)
codeine (phosphate)
morphine (with kaoline)
loperaide (HCl)
racecadotril
What do antimotility drugs codeine and morphine work on?
mu opioid receptors on neuronal varicosities, decreasing ACh release
What does a decrease Ach cause?
decreased peristaltic activity
Why is codeine formulated as codeine phosphate?
formulated as the salt which makes it more water soluble and better for formulation and gives better absorption
How does diphenoxylate work?
similar to codeine
How does atropine work?
Inversely agonises the mAchR receptors
How is diphenoxylate formualted?
Diphenoxylate hydrochloride salt
How is atropine formulated?
Atropine sulphate (salt)
How does racecadotril work?
activation of delta opioid receptors decreases cAMP levels reducing water and electrolyte secretion
What type of drug is racecadotril?
a prodrug to give thiorphan
Why is racecadotril not formulated as a salt?
it is a neutral molecule with no ionisable groups (with the exception of the amide which we consider non-ionisable at physiological pH)
Why is thiorphan not formulated as a salt?
It could be, but it is sufficiently hydrophilic and has the right physiochemical properties when released in the body
Where does the cleavage of racecadotril take place?
in the blood or in the stomach
How does loperamide work?
similar to morphine, codeine and diphenoxylate
What else is there evidence of loperamide doing?
non selective Ca2+ channel blocking
How is loperamide formulated?
As the hydrochloride salt
to aid water solubility and absorption
Why is loperamide not absorbed in the stomach?
It would be ionised and therefor would not passively cross the membrane
What is the pKa and log P of loperamide?
pKa = 8.6
log P = 4.5
Constipation treatment?
Linaclotide and lubiprostone
How does linaclotide work?
guanylate cyclase activator - increases water/electrolyte secretion
it is a cyclic peptide
Physiochemistry of linaclotide?
MWt = 1526
Polar molecule
Does linaclotide satisfy lipinski’s rule?
NO
it is administered orally so there must be some form of active uptake
How does lubiprostone work?
a prostone class of molecle
CIC-2 calcium channel activator
increases water/electrolyte secretion
Does lubiprostone satisfy Lipinski’s rule?
YES
How is lubiprostone administered?
capsules
How is linaclotide administered?
hard capsules
What does the structure of a drug dictate?
dosage forms, formulation types and site of absorption
