Reztiew Article

Antabuse (disulfiram)- a useful tool in General Practice

- Dr Svlvain de Miranda

SummaryIt is conse-*atiarly estimated thatl0% of patients seen in a busy generalpractice, are suffering from alcoholrelated problems. Much can howeaerbe done in family practice, as thisarticle emph,asises. It reaiews thepractical application of Antabuse-therapy in the ffictiae managementof this problem'

s Afr Fam pract rese; r0t2r4

Dr Sylvain de Miranda, MBBChThe Johannesburg Society of the National Councilon Alcoholism and Drug Dependence52 Pritchard StreetJohannesburg200r

Curriculum vitaeDr Sylvain de Miranda was born in Holland and came toSouth Africa during the Second World War. He graduated atthe University of the Witwatersrand in 1949 (MB BCh) andhas been involved with alcohol programmes since 1951. He ispresently Director and Head of Clinical Services of the SANational Council on Alcoholism and Drug Dependence,Johannesburg Society and part-time lecturer at both theUniversity of the Witwatersrand and RAU. He is the authorof many articles on alcohol and drug dependence and hasreceived several awards for his dedicated humanitarianservices in this field. He is married with two adult children.

t is conservatively estimated that I0To ofpatients seen in busy general practice aresuffering from alcohol related problems,

either due to irresponsible excessive drinking orto alcohol dependence per se.rSome general practitioners prefer not to managealcohol related problems and shy away fromgetting involved. Frequently we tend to gloss overthe problem stating "you should cut down a bit

KEY$7ORDS: Alcohol drinking; DrugTherapy

on your booze" or else recommend referral toa psychiatric consultant or an alcohol specialistagency.

The reasons for this are usually attributed toinsufficient time to devote to these people or thedifficulty in monitoring them adequately, or tothe high rate of non-compliance which makes thewhole operation seem to be a waste of time.

Much can however, be done in family practice.In order to assist the family practitioner in theeffective management of his alcohol-relatedproblem patients, this article will review thepractical application of "Antabuse" therapy.

Rationale

The properly supervised administrat ion ofAntabuse, is one of the very few methods availableto the practitioner to ensure the discontinuationof the patient's drinking pattern and therebyensure a prolonged period of alcohol- free

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stabilisation, during which rhe necessary suppor-tive counselling, psycho-therapy and fimitytherapy can be successfully applieci.

Method of administrationL Antabuse exerts its action over a minimumperiod of 36-48 hours (usually longer). Thereforethe administration of I tablet on alternate days isadvocated.22. To ensure compliance, initially arrange for thepatlent to report to your rooms on alternate days,where your nursing sister will:- administer rhe Antabuse in solution. underdirect supervision;- maintain an attendance register;- monitor the patient for any adverse effect (iealcohol-Antabuse reaction).3. After 6-8 weeks, the patient,s frequency ofattendance is lessened - depending oh generalprogress. The patient conrinues taking I Antabusetablet on alternate days, which is supplied byordinary prescription.

Precautionsl. Patient must be alcohol free for * 36 hours!.Qr. commencing Antabuse therapy.2r. .The full implications of the consequences ofdrinking alcohol whilst on Antabuse rherapy mustbe fully explained to the patienr.NB Never allow Antabuse to be used withoutthe patient's full knowledge (the method ofsurreptitiously administering Antabuse in theunsuspecting patient's food or beverage is oftenresorted to by desperate spouses!)3. Advise the wearing of a "medic-alert".

Mode of ActionAntabuse blocks the oxidation of alcohol at theacetaldehyde level, by inactivating the enzymeacetaldehyde dehydrogenase. The iesulting frighlevel of blood acetaldehyde accounts for the sig-nsand symptoms of the alcohol-Antabuse reactio;.3

Signs and symptoms of the a lcohol -Antabuse reactionO flishing of the skinO throbbing in head and neckO throbbing headachesO difficulty in breathing, with ,,tightness in thechest"O nausea and vomitingO sweatingO palpitations; rapid heart rarel drop in blood-pressure and fainting attacks

O in severe reactions there may be respiratorydepression and cardio-vascular collapse.The duration of this reaction can vary from 30minutes to several hours.

Treatment of the alcohol-Antabuse reactionO Treat for shock and restore blood-pressureO Oxygen administration; glucose drinks andkeeping foot of bed raisedO Intravenous injections of Vitamin C (500milligrams) and anti-histamines (eg2 ml Anthi-sanr 25 milligrams) can be most effective.

Contra-indications to the use of AntabuseAs in all medical applications of drugs, thephysician must be guided by the folowingconsiderations:l. absolute contra-indications;2. rclativ e contra-indications:3. clinical evaluation (the so-called ,,calculatedrisk").In my opinion, the only absolute contra-indicationto the use of Antabuse is proven sensitivity orallergy to the substance.

Manyu;ith

inaolzsedalcohol

Relative contra-indications, which are self-evidentfrom some of the above discussions, are:O cardio-vascular disease (especially coronaryartery disease and cardiac failure)O severe hypertensionO chronic, severe respiratory diseaseO pregnancyO severe hepatitis or cirrhosis of the liver.It is incumbent on the physician to be fully awareof, and to establish and assess, the existbnce ofthese conditions prior to treatment.Whilst always urging a different approach whenthese relative contra-indications exist, it is mycontention that if alternative tr.at-.nt methodiprove unsuccessful, the continued, severe abuseof alcohol will have far more disastrous effectson those conditions than the controlled, successfulexhibition of Antabuse. \Although the teratogenic effect of Antabuse is notknown, I have successfully administered Antabuseto a number of pregnant women, where theiruncontrolled drinking gave real rise to fears of

GPs prefer not to geta patient who has an

problem

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foetal alcohol damage. Low grade alcoholconsumption by these pregnant mothers treatedwith Antabuse, raises the spectre of abnormallyhigh blood acetaldehyde levels. Acetaldehyde isknown to be severely toxic to the foetus. However,no Antabuse related foetal damage has beenobserved in these babies after birth - againhighlighting the need for strict monitoring inAntabuse therapy.Suffice it to state, that all these cases provide areal test of clinical acumen and above all, athorough, sound knowledge of all aspects of thepathology of alcohol dependence is required.

Other adverse reactions1. Drug InteractionDisulfiram can interfere with the metabolism ofother drugs, thereby prolonging or altering theireffect, or producing side effects. Commonexamples are:all medication, foods or any substance containingalcohol or alcohol-like chemicals, eg- many anti-cough preparations- substances containing vinegar- fermented foodstuffs (NB: the use of sourporridge in Black South African communities)- certain cosmetic alcohol containing lotions (egaftershave lotions, astringents).Of special interest are those workers (on Antabusetherapy) at alcohol, chemical, industrial and fuel-energy plants, where the inhalation of fumes cancause severe alcohol-Antabuse reactions.

Pr operly superuis e d admini str ationof Antabuse is one method aaailableto the GP to ensure discontinuation

of drinking.

Special DrugsO Phenytoin (anti-convulsant) - administrationof Antabuse can cause severe phenltoin toxicitydue to the interference with phenytoinmetabolism.O Metronidazole (Flagyl) - has similar effectson alcohol metabolism as Antabuse. Theircombined use may give rise to overdosage"encephalopathy".O Isoniazid (INH and Rifamate) - usedextensively in the treatment of tuberculosis,

should not be administered concurrently withAntabuse.O Anti-coagulants - dosage may need adjust-ment as Antabuse enhances the anti-coagulanteffect.2. Toxic Reactions Per Se (In absence of anyofthe above factors)Antabuse has been blamed for a multitude of side-effects ranging from headaches and conjunctivitis,to loss of libido and impotence, to psychotic states.Having used and studied Antabuse in thetreatment of alcohol dependence in some 35 000cases since 1952, it may be pertinent here toexpress my views and findings on some of thecommonest allegations:

Never allow a desperate spouse toput Antabuse in the food of an

unsuspecting partner

O General Somatic Symptoms - such as head-aches, fatigue, palpitations, etc, are invariablypsychological manifestations of the patient'sprojection, directing his anger at Antabuse as thedirect cause for his inability to drink. (Similarprojections against spouse, nursing sister, doctorand therapist are often observed and must berecognised and dealt with as part of the prevailingpsycho-dynamics of alcohol dependence). Lowgrade consumption of alcohol or alcohol-likesubstances should always be remembered,however, when such vague symptoms occur.O Loss of Libido and Impotence - It has beenmy experience that this frequent complaint isstrongly psycho-dynamically rooted rather thanAntabuse related. Not many studies, using doubleblind trails, have been conducted. Those studiesthat have been reported, tend to prove that thereseems to be no difference in side effects reportedto disulfiram (Antabuse), calcium carbimide(Dipsan) or placebo. In fact, there appeared moresexual problems reported to placebo than toAntabuse and Dipsana.O Allergy or Sensitizsity - There is a definitepercentage incidence of Antabuse sensitivity. Alldegrees of dermatitis, from urticaria to exfoliativedermatitis have been observed. Intense pruritisand angioneurotic oedema often occur in thesecases. All observed cases responded totally toantihistamine therapy and discontinuation ofAntabuse.

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NB: - History of contact dermatitis toleather should alert the clinician topossib le antabuse sensi t iv i ty (seehistorical, original use of disulfiram toprevent oxidation in leather).

- A number of our nursing personnel,handling large volumes of Antabusetablets, have exhibited varying degreesof allergic dermatitis. In these cases, theuse of rubber gloves and face maskswhen handling Antabuse tablets, isindicated.

C Effects on Cennal and Peripheral NeroousSystem - Although the literature describesreported cases of psychotic states, confusionalstates; peripheral neuritis and optic neuritis, ithas been our observation, clinically, that in mostof these cases there was a history of repetitivelow alcohol or alcohol-like consumption, surrep-titiously or inadvertently. However, severe centralnervous system encephalopathy-like syndromeshave been reported as a result of severe over-dosage in both adults and children, in the absenceof alcohol intake.5'6

Patients may project their anger withAntabuse against their spouses or

doctors - but it should be dealt withas part of the psycho-dynamics of

alcohol dependence

3. The ImplantDistrlfiram has been manufactured in the formof slow-release pellets to be implanted under theskin as a once-only operation lasting 6-12 months("Esperal"). Unfortunately, its use has becomethe subject of much misguided media pronounce-ments, almost equating the use of the implantwith the absolute cure for alcohol dependence (thiscertainly is not the claim of the manufacturers).Except for some very few, highly selected cases,I am not in favour of routine use of disulfiramimplants for the following reasons:l. In spite of many years of existence, it has notobtained approval of the South African Medi-cine's Control Council (it can only be used forexperimental purposes).2. Bio-availability of implants is erratic.

3. Frequently, adequate supervision and controlis abandoned because daily administration isunnecessary. This often leads to uncontrolledalcohol-disulfi ram reactions.NB: The administration of these substances doesnot cure alcohol dependence but only assists inthe successful treatment thereof.

4. Being a "foreign body", often leads to "sepsis"as a result of "rejection reaction".

4. Additional Use of AntabuseRecently, our Johannesburg Clinics have success-fully applied the use of Antabuse in the treatmentof the common cough-mixture addictions. Thishas been developed because of the presence ofalcohol in many of these cough mixtures.

ConclusionDespite the many detractors, the moral andphilosophical opponents and a host of well-meaning ignorami, I strongly advocate thesupervised administration of Antabuse as anindispensable concommitant of successful treat-ment for the alcohol dependent. In fact, today,at our Johannesburg Clinics, the acceptance ofAntabuse has become part of the patient/clinictreatment contract.

Antabuse is zor used in terms of applying aversivetherapy, but simply and solely as an additional,mechanical safeguard to break the vicious cycleof alcohol addiction. In other words, it will notprevent the "craving for alcohol" so that on-goingsupportive therapy is an essential component ofthe successful treatment programme.The above approach is strongly recommended tofamily practitioners; especially those practising inareas where no proper special ised alcoholtreatment facilities exist.

References:l. Thomson P. Presentation of Alcohol Problems inGeneral Practice. Med International (SA Edition)1985;2: 1395-7.2. Brewer C. Supervised Antabuse Therapy. Brit JClin Pract 1984; (Supp 36) 38 (10): 5-9.3. Cox, Jacobs, Leblanc, Marshaman. Drugs and DrugAbuse; Addiction Research Foundation, Toronto,1983;243-8.4. Christensen J K. Side effects after Antabuse -myth or reality? Brit J Clin Pract 1984; (Suppl 36) 38(10): 21-6.5. Mokri B, Ohinshi A, Dyck P J. Disulfiramneuropathy. Neurology (NY) l98l; 3l:730-5.6. Benitz W, Tatro D S. Disulfiram intoxication in achild. J Paediatr 1985;3: 105.

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