Nurses role in disulfiram therapy

PREPARED BY:
M.VIJAYARANI

NURSES ROLE IN DISULFIRAM THERAPY


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:

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 o r 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, such that 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 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.
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 atlesat 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. This precaution is based on animal studies, which have suggested a possible toxic reaction between inhaled dibromide and ingested disulfiram. Rats exposed to this regimen have shown a higher incidence of tumors and mortality. Correlation of this finding in humans however has not been demonstrated.

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.

Carcinogenicity and mutagenicity data are not clearly established. In rats, simultaneous ingestion in the diet of disulfiram and nitrite for 78 weeks has been reported to cause tumors. It has been suggested that conversion of nitrite to nitrosamines in the stomach could be responsible for the development of the tumors. Disulfiram alone did not lead to tumor development. The relevance of these findings to humans is not known at this time.

In one study, disulfiram had deleterious effects on the reproductive cycle and reproductive capabilities of female rats, and the growth of their pups. In another study, no adverse effect on fertility was noted. Studies in the hamster, rat, and mouse have not produced any teratogenic effect in the offspring.

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.

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 case of DER induced by a challenge test, the resuscitation should be and is usually available but the occurrence of DER in an uncontrolled situation is likely to be fatal. Prompt treatment should be initiated to control fall in BP. In patients with moderate to severe DER, intravenous fluids and in some, dopamine infusion is necessary to control the severe hypo tension. Other measures such as the administration of oxygen or carbogen (95% oxygen, 5% carbon dioxide), massive i.v. Doses of vitamin C (1 g), ephedrine sulfate, or antihistamines i.v. might be indicated. Potassium levels should be monitored particularly in patients on digitalis since hypokalemia has been reported.

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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