Anti-tussives
Mechanism of action:
Pholcodine is classified as a cough suppressant (anti-tussive agent). It
is termed a centrally-acting anti-tussive because of its ability to
suppress the cough reflex by depressing the medullary cough centre (Merck
Manual). By acting at the cough centre in the brain, pholcodine supposedly
reduces the discharge of nerve impulses to the muscles that cause coughing
(Mason, 2002)
Pholcodine has been found to have equivalent or greater anti-tussive
activity than codeine in animal test studies (Findlay, 1988). The cough
suppressant property of pholcodine seems to be apparent in man, however,
further efficacy studies need to support this supposition (Findley, 1988).
Contra-indications:
Looking at evidence-based literature, there are no compelling
contraindications that can be substantiated. However,
http://www.medicdirect.co.uk/med_cabinet/medicine states that pholcodine
should not be used in patients with active liver disease and respiratory
failure. In those with respiratory failure, it can exacerbate the
symptoms (AMH 2004).
Also it is advisable to avoid cough suppressants in patients with a
productive cough (NPS Pharmacy Letter, 2002)
Disease state information:
Literature suggests that pholcodine should be used in the treatment of an
acute cough associated with common cold or acute upper respiratory tract
infection (URTI) and chronic cough, however, there is little evidence to
support this claim (Chung and Chang, 2002).
Protocols for the use of Dextromethorphan:
Many over-the counter (OTC) cough suppressant preparations currently on
the market do contain pholcodine - Preparations such as Actuss, Duro-Tuss,
Linctus Tussinol and Logicin Cough Supressant to name a few (eAPP Guide,
2003). From the literature researched, however, there is little
evidence-based material, let alone recent evidence-based material,
available to support the use of pholcodine in the treatment of cough.
In the 1960’s, a ‘new’ opioid derivative, similar to codeine was
unearthed and this was when most relevant research was conducted. However,
since this time not many reviews were published with reference to
pholcodine.
A double-blind, controlled investigation was undertaken in the 1970’s to
elucidate the effectiveness of pholcodine, with and without an
antihistamine on cough. Twenty-four patients were involved in this trial,
which was conducted over five consecutive days. The pattern and
frequency of cough was then observed (Edwards et al, 1977).
Prior to this trial, previous work suggested that pholcodine might
suppress cough (Edwards et al, 1977). However, from this trial, the
only preparation that was able to significantly reduce the frequency of
cough was the combination preparation of pholcodine and phenyltoloxamine
(an antihistamine) and not pholcodine alone (Edwards et al, 1977).
Statistically, pholcodine with an antihistamine had a greater cough
suppressant effect when compared to control period (P<0.001), the placebo
period (P<0.001) and pholcodine periods (P<0.01) (Edwards et al, 1977).
The combined preparation reduced the frequency of cough by 50%
(Edwards et al, 1977). Pholcodine preparations alone did not produce any
statistically significant reduction of coughing compared with that of
the placebo.
This article was the only one that had any sort of trial conducted or
reviewed. Thus only one side of the story is told, that of lack of
efficacy of pholcodine as an anti-tussive agent.
Adverse Effects:
Due to their opiate derivation, common adverse effects of anti-tussives
such as pholcodine, are drowsiness, constipation, nausea and vomiting
(AMH 2004).
Preclinical toxicity studies suggest that pholcodine is safer than its
opiate derivate, codeine. This is because of the reduced respiratory
depressant and cardiovascular effects it has at therapeutic doses.
Unlike codeine, it is not metabolised to morphine, an attribute that
adds significantly to its safety profile. As well as producing fewer
adverse effects, pholcodine also seems to lack or have a lower abuse
potential than that exhibited by codeine (Findley, 1988 and Mason, 2002).
