C4 The chemical basis of drug action 1 Flashcards
what does normality describe?
- the number of equivalents per litre
- it is now rarely used as a unit
- for hydrochloric acid: 1M HCl = 1N HCl (it produces 1 equivalent of protons per L)
- for sulphuric acid: 1M = 2N (it produces 2 equivalents of protons per L)
state some examples of antacids
aluminium hydroxide
sodium bicarbonate
calcium carbonate
magnesium carbonate
magnesium hydroxide
magnesium triplicate
magnesium and aluminium hydroxides
magaldrate
state the ideal characteristics of an antacid
- acts locally (therefore insoluble in water and not absorbed into the circulation)
- maintains pH in the range 3-6
- exerts its effect swiftly and with a good duration of action
- does not produce large volumes of gas when reacting with HCl
- does not cause laxative effects or constipation
what can combining a number of antacids in one medicine do?
- can optimise the rate of onset of action, duration of action, range of pH reached
- perhaps moderate constipation and laxative effects
which metal salts have constipating and laxative effects?
- calcium and aluminium salts have constipating effect
- magnesium has laxative effect
what do most raft-forming agents contain?
2 main ingredients
- alginate
- gas-forming agent
active ingredients in Gaviscon double action
sodium alginate
sodium bicarbonate
calcium carbonate
describe alginic acid
- extracted from brown seaweeds
- polymer composed of sugar monomer units repeated (polysaccharide)
- can be 80 residues or more in length, molecular weight over 150 000 Daltons
- alginic acid and most metal alginates insoluble in water
- alkali metal salts of alginates are water soluble
action use of alginic acid
treatment of GORD
excipient
thickening agent
definition of alginic acid
- mixture of polyuronic acids composed of residues of D-mannuronic and L-guluronic acids
- obtained mainly from algae belonging to the Phaeophyceae
- a small proportion of the carboxyl groups may be neutralised
describe the structure of alginic acid
- lots of carboxylic groups on the above polymer
- pKa is therefore around 3.5 and this is important for its chemical mode of action
describe the alginic acid raft
- if pH drops below 3.5 (the approximate pKa) alginic acid precipitates as a gel
- the precipitate / gel swells and absorbs water
- the raft is formed
what do alginate based medicines contain and what do these ingredients do in acid?
- many alginate based medicines contain bicarbonate or carbonate
in acid:
- the bicarbonate or carbonate produces carbon dioxide
- the soluble alginate reacts to form an insoluble alginic acid precipitate / gel
- the precipitate / gel traps the carbon dioxide gas, to produce a low density raft (viscous foam) that can float on the stomach contents
what happens to calcium cations in alginates?
- calcium cations interact with the alginate / alginic acid and aid cross-linking in the polymer (chelate with non-metal ions)
- this increases the viscosity of the gel / raft
what is there evidence of regarding the presence of calcium cations in rafts?
calcium cations increase the raft strength (in vitro) via chelation crosslinks
describe the behaviour of oxygen atoms in chelation with calcium cations
- oxygen atoms behave as Lewis bases (electron pair donors) via their lone pairs
- 2 oxygen atoms able to chelate to one calcium cation
what possibilities of cross linking are there for chelation of oxygen and calcium in rafts?
draw an image to show the possibility of cross linking between chains
what is simeticone? what does it do?
- dimethicone (polydimethylsiloxane) and silica, and is also known as activated dimethicone
- silicone polymer
- believed to alter (lower) the surface tension of small gas bubbles so they co-join, to form larger bubbles
- allows gas in stomach to be more easily lost
- evidence that this relieves trapped wind and bloating in dyspepsia
action and use of simeticone
- silicone dioxide analogue
- defoaming agent
