The Pharmaceutical Industry

Butazolidin Orally effective compound  Has achieved great clinical success in treatment of rheumatoid disorders and other non-specific inflammatory conditions Side effects: majority are mild and serious incidents are exceedingly rare - Nevertheless, treatment should be suspended immediately signs of intolerance become apparent - Most frequently noted are gastrointestinal, e.g. epigastric distress, nausea or anorexia - Oedema, if it occurs, is usually slight and transitory, but special care is necessary in latent cardiac insufficiency - Rare adverse reactions include severe allergic reactions of skin, changes in blood pressure, even more rarely - Agranulocytosis

Phenylbutazone Not simple analgesic Potent drug; misuse can lead to serious results, many with potentially fatal consequences Recommended only for short-term use in treatment of attacks of acute gouty arthritis when colchicine isn't effective and poorly tolerated Poorly tolerated by many patients Principal adverse reactions: nausea, vomiting, epigastric discomfort, peptic ulcer, gastrointestinal bleeding, rash, aphthous stomatitis, aplistic anemia, leukopenia, agranulocytosis, thrombocytopenia, oedema - therapy shouldn't be continued beyond 3-4 days

Bateman's Pectoral Drops Immediate ease in all colds, coughs, agues, fevers, fluxes, pains in breast, limbs and joints; as also in all fits of gout, rheumatic pains, stone, grovel, cholick Patented 1723 Benjamen Okell Contents: tincture of castor, portions of camphor, opium, anise seed

Godfrey's Cordial Same types of conditions as above, apparently used for kids, "sleeping cordial" Use of opium in these sorts of mixtures not infrequent - indicators that kids were consequently poisoned

Dr Scott's electric corsets and belts"Gentle and pleasant support", aiding by vitalising properties of electricity the functions of the nervous organisation

Holman Liver and Stomach Pad Worn just below breast bone, over pit of stomach Properties absorbed through pores of skin, invigorating liver and stomach and purifying blood, thereby curing liver complaints, indigestion, dyspepsia, rheumatism, jaundice, gout, biliousness, diarrhoea, constipation

Dr

Dr Ricord's Essence of LifeRegenerating all important elements of human frame and enabling man to fulfil his most sacred obligations

Mariani WineCocaine wine...usually recommended 3 times a day for insomnia, anemia, impotence, melancholy

In early 20th c., drugs promoted with no regard to truthfulness of claims being made - Claims relate to effectiveness, side effects/adverse reactions, contraindications Late 1930s, first "antibiotics" became available - sulphanilamides usually sold as tablet - Demand for liquid form for kids - difficulty finding solvent - Diethylene glycol used as solvent - No trials conducted, no animal studies - 240 gallons made - 107 kids died

Thalidomide Discovered 1950s by German company Chemie Gruenthal No proper clinical trials Chemie Gruenthal marketed thalidomide under various names incl. "Contergan" - first marketed 1956 for respiratory infections; then in 1958 as sedative Side effects: sleepiness, drowsiness, constipation, skin rash, severe headaches, peripheral neuropathy, dizziness, nausea, depression/mood swings, shivering/buzzing in ears; absolute prohibition against use during pregnancy Now being prescribed for range of new indications - may well be effective in treatment of tuberculosis, leprosy, incurable bone marrow cancer (multiple myeloma), complications of AIDS (mouth ulcers); also being tested for other cancers incl. lung cancer

Contergan Marketed with Aspirin over counter Doctors asked to test drug Side effects: by 1959, reports of side effects received by company - e.g. Dr Ralph Voss observed case of polyneuritis on 3.1.59 - wrote to company asking if this could be due to drug - Dr Werner and Dr Sieners replied this had never been observed -- Claim was untrue - 5-20% incidence of side effects Side effects: mid-1960s, drug been sold for about 4 years Company without clinical head of its testing section - numerous reports of side effects By end of 1960, 1600 reports of side effects, with 100 cases of severe polyneuritis existed Late 1960, Dr Horst Frenkel (neurologist) wrote to company stating he was going to publish 20 observations of nerve damage - Reps of company visited Frenkel and journal editors to attempt to prevent publication - publication delayed By 4.5.61, reports both Britain and Germany of polyneuritis - critical reviews in German magazines  Company continued unrestrained marketing - To maintain maximum turnover, Dr Oswald and Dr Nowel visited superintendent of health departments of ministries of interior affairs and gave special prominence to "contergan as good as ataxic" and "side effects practically never occurred"

Key areas

Key areas Control of drug name (trade/genetic) Disclosure of side effects Limits of effectiveness

1960s Control of drug name: chemical name; generic name; trade/brand name; products more expensive if sold by trade name Disclosure of side effects: previous ads didn't require side effects to be states; now complete statement of side effects and contraindications are required Limits of drug's effectiveness: ; Fair Balance now bans drugs which ignore recent findings; ignore published articles detailing side effects; implies that study reflects greater experience with drug than it does in fact; fails to reveal that favourable studies conflict with other reliable studies; suggest (improperly) that animal studies have clinical significance

6 most widely prescribed antidepressants  Prozac (Fluoxetine) Paxil (Paroxetine) Zoloft (Sertaline) Effexor (Venlafaxine) Serzone (Nefazodone) Celexa (Citalopram)

In clinical trials the effect of the active drug is drug response minus placebo response For most clinical trials there are statistically significant differences between treatment and placebo groups

Most new drugs which are developed are rarely truly new treatments New drugs marketed as improved treatment Yet clinical trials almost always compare no treatment vs. new treatment Very rarely is comparison current treatment vs. new treatment

Advantage of placebo is that it produces no adverse side effects

Prescription drugs comprise large and growing proportion of all health care costs 2000, in USA, prescription drugs were 9-10% of all health care expenditures

Direct-to-consumer Ads for medications appear in non-medical journals; to persuade potential patients to ask doctor for med. USA permits DTC ads in TV; Aus doesn't Some evidence that ads increased sales of some pharmaceutical products

Profits can be made by persuading health people they're sick; e.g. baldness - International Hair Study Institute (IHSI) set upIHSI research finds that hair loss can lead to panic and other emotional problems; affect job prospects and mental wellbeingCompany can't directly advertise its medications but publishes ads with suggestion that those concerned should see doctor

Irritable Bowel Syndrome Common functional disorder Medical communication companies have stated they aim to create new image of IBS as "common and concrete" disease; aim is to promote Lotronex (treatment drug) Use strategy of educating doctors to view that IBS is significant and discrete disease Also aim to convince patients that IBS is medical problem Set up advisory board: develop best practice guidelines; develop patient support programs etc Program suspended because Lotronex found to lead to some deaths

Social Phobia Roche - promoting antidepressant Auronx for social phobia Roche claim that over 1 million Australians have undiagnosed "social phobia" (shyness) Roche worked with Obsessive Compulsive and Anxiety Disorders Foundation of Victoria to fund large conference on social phobia Raise awareness of shyness as disease; set up advisory groups, scientific meetings and publications

Erectile Dysfunction Public ads have claimed that "39% of men who visit GPs have erectile problems" Phizer provided grant to set up community group - Impotence Australia Other studies suggest that erection problems only affect about 3% of men in 40s; 64% in 70s

Serious drug reactions defined as those requiring hospitalisation, permanently disabling or leading to death

World medicine production Trends from 1985-1999 indicate that value of medicine production growth 4 times more rapidly than world's income Medicine production highly concentrated in industrialised countries Large volume markets of lower-price medicines exist in highly competitive domestic markets of China and India

Butazolidin; Phenylbutazone

18th and 20th C. Meds

Thalidomide and Contergan

US Legislation; Advertising

IBS; Social Phobia; Erectile Dysfunction