DISULFIRAM

INTRODUCTION:

Disulfiram is the medicine used for long-term treatment of patients with alcohol misuse. It
produces extremely unpleasant reactions in a person who ingests even a small amount of alcohol
while taking disulfiram. This effect is used in the treatment of patients with alcohol problems
.The knowledge that taking alcohol will be unpleasant serves as a reinforcement or additional
support to their decision not to drink. It also protects them from giving into sudden urges to
drink, or pressure from friends.

TYPES OF ALCOHOL DEPENDENCE:

TOLERANCE:
It refers to the decreased psychoactive effect of drug resulting from repeated exposure. It is also
possible to develop cross – tolerance to other drugs in the same category.

PSYCHOLOGICAL DEPENDENCE:
refers to a compulsive need to experience pleasurable responses from a substance.

PHYSICAL DEPENDENCE:
refers to altered physiological state resulting from prolonged substance use: regular use is
necessary to prevent withdrawal.

WITHDRAWAL SYNDROME:
refers to symptoms occurring a period after the discontinuance of an addictive substance,
frequently characterized by painful physical / or psychological symptoms.

HARMFUL USE:
Clear evidence that the use of a substance was responsible for causing actual psychologic or
physical harm to the user.

DEPENDENCE SYNDROME:
A definite diagnosis of dependence should usually be made only if three or more of the following
have been experienced or exhibited at some time during the previous year.
A strong desire or sense of compulsion to take the substance.
Difficulties in controlling substance-taking behaviour in terms of its onset, termination, or levels
of use.

A physiological withdrawal state when substance use has caused or been reduced, as evidenced
by the characteristics withdrawal syndrome for the substance, or use of the same (or a closely
related) substance with the intention or relieving or avoiding withdrawal symptoms:

EVIDENCE OF TOLERANCE

 increased doses of psychoactive substance are required in orders to achieve effects

originally produced by lower doses.
 Progressive neglect of alternative pleasures or interest because of psychoactive substance
use, increased amount of time necessary to obtain or take the substance or to recover
from its effects.
 Persisting with substance use despite clear evidence of overtly harmful consequences,
e.g., physical health, mood, cognitive functioning: efforts should be made to determine
that the user was aware of the nature and extent of the harm.

ETIOLOGY OF DEPENDENCE:

The main predisposing factors are:

*Genetic factors
*Personality factors
*School
*Peer influence
*Community settings
*Culture
*Youth subculture
*Modeling
*Economics
*Social environment

DEFINITION:
Disulfiram is used to sensitize an individual to alcohol by inducing an unpleasant alcohol –
disulfiram reaction.

PRINCIPLE OF DISULFIRAM THERAPY:

Disulfiram therapy works on the classical conditioning principle of inhibiting impulsive drinking
because the client tries to avoid the unpleasant physical effects from the alcohol disulfiram
reaction.

AIMS OF DISULFIRAM THERAPY:

Disulfiram helps a person

§ To start a period of being SOBER

§ To give cover over a HIGH RISK PERIOD
§ To RESIST IMPULSE to drink
§ To REDUCE DRINKING days
§ To help the organs recuperate and the individual to CHANGE HIS LIFE STYLE. (By
prolonged abstinence a person can learn new coping skills and damaged organ can return to
normal state)

BENEFITS OF DISULFIRAM:

Supervised disulfiram, especially when combined with psychosocial management aids in

abstinence.

Disulfiram helps the patient as an additional support in his decision not to drink. it also protects
the person from giving in to sudden urges to drink ,or to give in to pressure from friends.

PHARMACOKINETICS:

It has been shown that 80 to 95% of an ingested dose is absorbed from the gastrointestinal tract
and rapidly distributed to tissues and organs: liver, spleen, adrenals, fatty tissues, and brain. It is
then metabolized to diethyldithiocarbamate or mixed disulfides, one of the end products being
carbon disulfide. The unabsorbed fraction is excreted in the feces; the intermediate and final
metabolites are excreted in the urine, and the volatile metabolites in the breath.
INDICATIONS:

Disulfiram is used on motivated clients who have shown the ability to stay sober. As an aid in
the management of selected chronic alcoholic patients who want to remain in a state of enforced
sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage.
Used alone, without proper motivation and without supportive therapy, disulfiram is not a cure
for alcoholism, and it is unlikely that it will have more than a brief effect on the drinking pattern
of the chronic alcoholic.

DOSAGE:

INITIATION OF THERAPY:

A maximum of 500 mg daily in a single dose should be given for 1 to 2 weeks, preferably taken
in the morning. Patients experiencing a sedative effect may take the drug at bedtime or, if
necessary, dosage may be adjusted downward. Average maintenance dose is 250 mg daily (range
125 to 500 mg) but should not exceed 500 mg daily.

INDIVIDUAL DIFFERENCES:

Some patients, while seemingly on adequate maintenance doses, report that they are able to drink
with impunity. Such patients must be presumed to be disposing of their tablets in some manner
without actually taking them. Until it has been reliably confirmed that these patients have been
taking their daily tablets (preferably crushed and well mixed with liquid), it cannot be concluded
that disulfiram is ineffective.

DURATION OF EFFECT:

The action of the drug can last from 5 days to 2 weeks after the last dose.

ETHANOL DISULFIRAM REACTION:

The constellation of side effects caused by alcohol plus disulfiram therapy is referred to as the
‘acetaldehyde syndrome’. This syndrome can be very dangerous and even fatal. Accumulation of
acetaldehyde in the blood produces a complex of highly unpleasant symptoms referred to as the
disulfiram-alcohol reaction. This reaction, which is proportional to the dosage of both disulfiram
and alcohol, will persist as long as alcohol is being metabolized. Disulfiram does not appear to
influence the rate of alcohol elimination from the body.

DISULFIRAM – ETHANOL REACTION:

It includes the following

-Throbbing head ache

-Nausea and vomiting

-Sweating
-Facial flushing
-Thirst
-Confusion
-Tachycardia
-Blurring of vision
-Drowsiness
-Giddiness
-Bloodshot eyes
-Chest pain
-Low BP and shock
-Respiratory distress
-Syncope
-Neck pain
-Marked uneasiness
-Vertigo

In severe reactions: There may be respiratory depression, cardiovascular collapse, arrhythmias,

myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death.
The intensity of the reaction may vary with each individual but is generally proportional to the
amount of disulfiram and alcohol ingested. In the sensitive individual, mild reactions may occur
when the blood alcohol concentration is increased to as little as 5-to 10-mg/100 mL. At a
concentration of 50 mg/100 mL symptoms are usually fully developed, and when the
concentration reaches 125 to 150 mg/100 mL unconsciousness may occur.

Duration of the reaction:

The duration of the reaction is variable, from 30 to 60 minutes in mild cases, up to several hours
in more severe cases or as long as there is alcohol remaining in the blood. In severe reactions,
supportive measures to restore blood pressure and treat shock should be instituted Disulfiram is
slowly absorbed from the gastrointestinal tract and is slowly eliminated from the body. Ingestion
of alcohol may produce unpleasant symptoms 1 or even 2 weeks after a patient has taken his last
dose of disulfiram.

ADVERSE EFFECTS OF DISULFIRAM IN THE ABSENCE OF ALCOHOL:

In the absence of alcohol, disulfiram causes significant effects. Drowsiness and skin eruptions
may occur during initial use, but they diminish with time.

DURATION OF THERAPY:

For long-term recovery and to learn new ways of coping with life, a period of abstinence needs
to at least one and probably two years. So it is appropriate to take disulfiram tablet for atleast six
months and probably up to 2 years. Daily, uninterrupted administration of

disulfiram must be continued until the patient has established a basis for permanent self-control.
Depending on the individual patient, maintenance therapy may be required for months or even
years.

CONTRA INDICATIONS:

Generally disulfiram is not used in

· Children
· Pregnant women
· Recent ‘ heart attack’, coronary occlusion
· Liver damage (Cirrhosis of liver and acute hepatitis)
· Epilepsy
· Psychosis
· Major depression
· Recent ‘stroke’
· Hypothyroidism
· Cerebral damage
· Chronic and acute nephritis
· Mental illness (psychosis, major depression)
· Hypersensitivity to disulfiram or thiuram derivatives (used in manufacture of pesticides and
vulcanized rubber)
· Patient unwilling to take, or those who do not know that they being given
· Should never been given to patients until the patient has abstainer from alcohol for 12 hours.

THINGS TO BE AVOIDED DURING DISULFIRAM:

Even the small amount of alcohol will bring on the unpleasant disulfiram reaction. The person
taking disulfiram should not use or have the alcohol containing preparation such as

§ Cough syrups

§ Vitamin tonics

§ Ayurvedic tonics

§ After shave lotion

§ Perfumes

§ Sprits

§ Sprit based paints, glues, thinners etc

§ State and fermented food

§ Some preparations applied to the skin

The disulfiram and alcohol reaction may occur as long as one or two weeks after the best
dose of disulfiram.

CONSENT:

Disulfiram should always be prescribed with the full knowledge and consent of the client .the
clients needs to be told about the side effects and must west be well aware that any substances
that contain alcohol can trigger an adverse reaction.

SIDE EFFECTS:

In some people disulfiram in the absence of alcohol produces:

*Lethargy, drowsiness (45%)

*Decreased memory (40%)

*Headache (35%)
*Itching (33%)
*Decreased sleep (33%)
*Dizziness (22%)
*Sexual problems (10%)

*Peripheral neuropathy – tingling and numbness of hands and legs

Worsening depression and psychosis in some patients

*Less than 10 patients out of a 100 taking disulfiram, develop serious side effects, which
require withdrawal of the drug.

*Optic neuritis, peripheral neuritis, polyneuritis may occur following administration of

disulfiram. Multiple cases of both cholestatic and fulminant hepatitis have been reported
following administration of the drug.

*Occasional skin eruptions have been reported. In a small number of patients, a transient mild
drowsiness, fatigue, impotence, headache, acneiform eruptions, allergic dermatitis, or a
metallic or garlic-like aftertaste may be experienced during the first 2 weeks of therapy.

These complaints usually disappear later during therapy or with reduced dosage. Psychotic
reactions have been noted, in most cases attributable to high dosage, associated toxicity with
other drugs

(metronidazole or isoniazid), or the unmasking of underlying psychoses in patients stressed by

withdrawal of alcohol. Hepatotoxicity has been observed in a few patients.

OVERDOSE:

Severe cases of disulfiram poisoning have been reported mainly in children. Within a few hours
of ingestion of a large amount, drowsiness followed by coma develops accompanied by
persistent nausea, vomiting, aggressive and psychotic behavior, and ascending flaccid paralysis,
which can reach the cranial nerves. Treatment consists of administration of oxygen therapy,
glucose 5% i.v. and sodium ascorbate 1 g i.v. Patient should be kept in bed and as quiet as
possible with appropriate symptomatic treatment.
PRECAUTIONS:

*Patients having a history of industrial contact dermatitis who currently work or have previously
worked in the rubber industry should be evaluated for hypersensitivity to thiuram derivatives
before receiving disulfiram.

*Patients exposed to organic solvents, which may contain alcohol, acetaldehyde, paraldehyde or
structural analogues are at risk of experiencing disulfiram alcohol reactions. Such exposure
should be eliminated prior to treatment.

It is suggested that every patient under treatment carry an identification card stating that he is
receiving disulfiram and describing the symptoms most likely to occur as a result of the
disulfiram-alcohol reaction. In addition, this card should identify the attending physician or
institution to be contacted in emergency. Alcoholism may be associated or followed by
dependence on narcotics or sedatives. Barbiturates have been administered concurrently with
disulfiram without untoward effects, but the possibility of initiating a new dependence should be
considered. Patients taking disulfiram should not be exposed to ethylene dibromide or its vapors.

Since disulfiram-alcohol reactions could aggravate some medical conditions such as diabetes
mellitus, hypothyroidism, epilepsy, cerebral damage, chronic and

acute nephritis, hepatic cirrhosis or hepatic insufficiency, disulfiram should be used with extreme
care in patients having such a medical history. Baseline and follow-up transaminase tests (10 to
14 days) are suggested to detect any hepatic dysfunction that may be associated with disulfiram
therapy. In addition, a complete blood count and a sequential multiple analysis-12 test (SMA-12)
should be carried out every 6 months.

Disulfiram inhibits enzyme induction and may thus interfere with the metabolism of drugs taken
concomitantly. It enhances the effects of the coumarin anticoagulants and phenytoin.
Consequently, in patients on oral anticoagulants, such dosage should be adjusted. In patients on
phenytoin therapy, a baseline phenytoin serum level should be obtained before initiation of
disulfiram therapy. After initiation of therapy, serum levels should be reevaluated on different
days for evidence of an increase or continuing rise in levels. Appropriate dosage adjustment
should be made, if elevated levels are found. Disulfiram should be discontinued in patients
taking isoniazid if an unsteady gait develops or there are marked changes in mental state.
PATIENT SELECTION:

Because of the severity of the acetaldehyde syndrome, candidates must be carefully chosen.
Alcoholics who lack the determination to stop drinking should not be given disulfiram. In other
words, disulfiram must not be administered to alcoholics who are likely to attempt drinking
while undergoing treatment.

MODE OF USE:

Before prescribing, a physical examination and baseline liver function tests are performed .The
patients is encouraged to ask the partner, a nurse or welfare officer at work or at the health
center, or a pharmacist to see that the disulfiram is taken. This can be daily, or three times a
week, provided that the total weekly dose is sufficient .The product is in a dispersible form to be
taken in water so that it can be seen to be swallowed.

There should be medical follow up, but there is no consensus as to whether monitoring of liver
function tests should be carried out. However, monthly follow-up is appropriate to check for
signs of drinking and of other liver disease.

It is common to prescribe disulfiram for 6 months, but many patients ask to continue for longer
and there may be slips when disulfiram is withdrawn, even after long periods of abstinence. The
taking of disulfiram may reestablish an employer’s confidence, so that the patient may be
reinstated.

EFFICACY OF DISULFIRAM THERAPY:

Although disulfiram has been employed for over 50 years, its efficacy is only moderate. Given
the limited efficiency of disulfiram for the prevention of relapse, it should not be used as a first
line treatment of alcohol dependence. In clinical trials, the drug is no better than placebo at
maintaining abstinence: the proportion of patients who relapse and the time to relapse are the
same as with plecebo. However, although doesn’t prevent drinking, it does decrease the
frequency of drinking after relapse has occurred – presumably because of the unpleasant reaction
that the patient is now familiar with.

TIME FOR TAKING DISULFIRAM:

1. It is convenient to take disulfiram in the morning hours after coffee or breakfast.

2. Good outcome can be expected if:
  The person is highly motivated
 Daily use of disulfiram under supervision
 Abstinence prior to treatment
 Regular contact with the doctor or treating team.

MYTHS REGARDING ALCOHOL RECATION:

Some patients hear false information regarding the alcohol disulfiram reaction. It does not cause:

 Vomiting blood
 Passing blood in urine and stool
 Swelling all over the body
 Going mad
 Going blind

TREATMENT OF DISULFIRAM- ALCOHOL REACTION:

The patient should always carry identification cards describing the

disulfiram – alcohol reaction. If any person develops disulfiram– alcohol reaction:

Stop disulfiram

Immediately go to the near by doctor and show the card.

If disulfiram – alcohol reaction is severe, the person might need admission to hospital or nursing
home so that his pulse and BP can be monitored and symptomatic treatment with intravenous
fluids may be given. Inj. Avil for the allergic reaction and dopamine to elevate the BP may be
required according to the patient’s symptoms.

NURSING MANAGEMENT OF PATIENT WITH DISULFIRAM THERAPY:

Responsibilities Of A Nurse Before Prescribing Disulfiram:

· Obtain informed consent for disulfiram therapy.

· Explain the ingestion of even small quantities of alcohol may produce DER reaction

· Warn against consuming alcohol preparation like cough syrups, tonics, and ayurvedic
medicines.
· Collect the base line values of hemoglobin and liver function test.

· Administer disulfiram 250 mg daily orally a period of sobriety (at least 24 hours). The dose
may have to be increased to 500 mg / day in patients who do not develop DER on disulfiram 250
mg daily

· Explain clearly the symptoms of DER and suggest to measure to be taken in DER situation.

· Some clinicians prefer to demonstrate DER in a controlled environment. However, this

procedure is not advisable.

· Warn patient that DER may occur even one to two weeks after the last dose of disulfiram.

· Monitor haemogram and liver function test every 3 months.

· Look for signs of peripheral neuropathy.

ASSESSMENT:

Because of the unpleasant reaction patient would experience with the ingestion of alcohol, the
nurse reviews his level of understanding of the purpose, procedure, and consequences of
disulfiram therapy before he makes a decision about drug therapy. Patient’s health history is
reviewed for cardiovascular disease, diabetes mellitus, and epilepsy as a disulfiram alcohol
reaction may worsen these conditions: there is a higher rate of hepatotoxicity in clients with
existing hepatic dysfunction. It must be ascertained that the client has not ingested alcohol in any
form or been treated with paraldehyde in the 12 hours before beginning a disulfiram regimen to
prevent an interaction between the alcohol and disulfiram.

Patients concurrent drugs are also reviewed for significant drug interaction if he were to begin
disulfiram therapy: such as with anticoagulants, ant epileptic drugs, benzodiazepines, isoniazid
(INH), and metronidazle. The nature of the client’s support services should also be determined.

NURSING DIAGNOSIS:

1) Risk for injury related to a disulfiram alcohol reaction (nausea and vomiting, blurred vision,
tachycardia, flushing of the face, sweating, headache, dyspnoea, and rarely, seizures, loss of
consciousness, and death):

2) Disturbed sleep pattern related to the CNS effects of the drug (drowsiness): and

3) Potential complications of peripheral neuritis (numbness, tingling, or weakness of the hands

and feet), optic neuritis (change of vision), encephalopathy (mental changes) and hepatitis
(abdominal discomfort, anorexia, jaundice, dark urine, light stools).
PLANNING:

Patient will not drink alcoholic beverages and not experience adverse effects of the drug which
on and after the completion of disulfiram therapy.

IMPLEMENTATION:

Monitoring:

the effectiveness of disulfiram therapy is monitored by assessing the client abstinence from
alcohol use. Observe the client for visual disturbances and eye pain, which might indicate optic
neuritis. Tingling or numbness of the hands or feet may indicate the development of peripheral
neuritis. Jaundice may indicate a drug – induced hepatotoxicity.

INTERVENTION:

Written consent should be obtained from the patient before beginning disulfiram therapy.

Patient Education:

Patient education is an extremely important component of disulfiram therapy. Patients must be

thoroughly informed about the potential hazards of treatment. This is, they must be made aware that
consumption of any alcohol while taking disulfiram may produce a severe, potentially fatal, reaction.
Patients must be warned to avoid all forms of alcohol, including alcohol found in sauces and cough
syrup, and alcohol applied to the skin in after shave lotion, colognes and liniments. Patients should be
made aware that the effects of disulfiram will persist for about 2 weeks after the last dose is taken:
hence, continued abstinence is necessary. Individuals using disulfiram should be encouraged to carry
identification indicating their status.

EVALUATION:
Patient will abstain from alcohol without experiencing adverse effects of disulfiram. Patient will
effectively manage his therapeutic regimen, including stating food and medication sources of alcohol,
wearing a medic alert bracelet, and maintaining scheduled appointments with prescriber for monitoring
and treatment
CONCLUSION:

The drug disulfiram is used in conjunction with other alcohol dependency treatment methods. The
chemotherapeutic purpose of the drug is to assist the client to control or to not act on the impulse to
drink.

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