Pharmacology: Benzydamine is an anti-inflammatory analgesic agent structurally unrelated to the steroid group. Benzydamine differs chemically from other non-steroidal anti-inflammatory agents in that it is a base rather than an acid.
Animal models show that when administered systemically, benzydamine is effective against pain and oedema due to inflammatory conditions. It also inhibits granuloma formation.
At concentrations used for topical treatment, benzydamine possesses local anaesthetic action. Benzydamine does not cause erosion of the gastric mucosa when given orally to rats at doses of up to 100 mg/kg.
The analgesic activity of benzydamine was more pronounced in models involving an experimental inflammation rather than in non-inflammatory pain. In common with the aspirin-like drugs, benzydamine possesses an antipyretic activity. Peripheral reflexes were transiently inhibited after intravenous administration to cats.
Pholcodine is an opioid chemically related to morphine. Pholcodine is a cough suppressant and has a mild sedative effect which relieves local irritation of the respiratory tract.
Pholcodine has little or no analgesic action. Unlike, morphine, codeine and dihydrocodeine therapeutic doses of pholcodine to not cause depression of respiration, CNS excitation, constipation or other side effects associated with narcotics.
Pholcodine is not euphorigenic therefore psychological dependence is unlikely to be a problem. There is no evidence of physical dependence after prolonged administration of pholcodine so it is not likely to be habit forming.
Isomalt is a sugar-substitute. It is a disaccharide alcohol and is an approximately equimolar mixture of glucose-mannitol and glucose-sorbitol. Isomalt produces no measurable changes in blood glucose levels.
Pharmacodynamics: The mechanism of anti-inflammatory action of benzydamine is not related to stimulation of the pituitary-adrenal axis. Like other non-steroidal anti-inflammatory agents, benzydamine inhibits the biosynthesis of prostaglandins under certain conditions, but its properties in this respect have not been fully elucidated. The stabilising effect on cellular membranes may also be involved in the mechanism of action.
Pholcodine acts primarily on the CNS causing depression of the cough reflex which is due to partly to the direct effect on the cough centre in the medulla. Pholcodine has a selective effect on the cough centre without affecting the respiratory centre.
Pharmacokinetics: Absorption: Benzydamine is well absorbed following oral administration. Following topical administration of benzydamine hydrochloride in solution form, benzydamine is well absorbed into the inflamed oral mucosa where it exerts anti-inflammatory and local anaesthetic actions. Plasma benzydamine levels following use of benzydamine solutions are low and parallel the amount actually ingested.
Pholcodine is readily absorbed from the gastrointestinal tract and does cross the blood-brain barrier.
Excretion: Benzydamine and its metabolites are excreted largely in the urine.
Metabolism is largely by oxidative pathways, although dealkylation can be shown.
Benzydamine has been detected in blood and urine following gargling with Difflam solutions. Most of the absorbed dose was eliminated in the first 24 hours. Repeated administration for 7 days did not result in accumulation of benzydamine in plasma.
Pholcodine is metabolised in the liver and its action may be prolonged in hepatic insufficiency. Pholcodine is not metabolised to morphine in man, a fact which may contribute to its more favourable toxicity profile. The low metabolism of the rather lipophilic pholcodine is the reason for its very slow elimination.