IE910717A1 - Anti-smoking treatment kit - Google Patents

Abstract

An anti-smoking treatment kit comprises:- corticotrophin or a corticotrophin analogue, and an anxiolytic, and/or a sedative and/or an opiate withdrawal agent, e.g. clonidine.

Description

This invention relates to an anti-smoking treatment kit which includes the materials for treatment of a patient to reduce or eliminate the symptoms of smoking withdrawal syndrome in tobacco smokers and thereby make it easier for them to stop smoking.

Background of the Invention Known methods of treating tobacco addiction have met with limited success. Anti-smoking treatment clinics using a variety of methods report a long-term success rate of from 10 to 20% (Higenbottom T. and Chamberlain A. (1984) Thorax, 39, 641-646).

One of the reasons for this low success rate has been that the proposed treatments have not been based on an understanding of the physiological effects of nicotine. It is accordingly an object of the present invention to provide a treatment kit the contents of which reflect the physiological action of nicotine.

IE 91717 - 2 An immediate physiological effect of nicotine inhalation is a temporary rise in blood sugar which produces the ’lift’ experienced by smokers (Haggard H. and Greenberg L. (1934) Science, 79, 165-166). This rise in blood sugar is the result of an increased output of glucocorticoids by the adrenal cortex in response to stimulation by endogenous corticotrophin secreted by the anterior pituitary gland in response to stimulation with nicotine (Kershbaum A. et al. (1968) J.A.M.A., 203, 275-278). It would therefore appear that the ’lift’ associated with smoking is initiated by the secretion of corticotrophin.

It is possible that, in smokers, the capacity of the anterior pituitary gland to produce normal quantities of corticotrophin is impaired by repeated stimulation with nicotine. This would result in secondary hypoadrenocorticism and a consequent reduced output of glucocorticoids with a tendency to hypoglycaemia. The latter would result in a reflex increase in adrenalin production which would simultaneously tend to correct the hypoglycaemia and cause feelings of nervous tension. The hunger caused by the low blood sugar and the nervous tension caused by the extra circulating adrenalin may accordingly be the basis for smoking withdrawal syndrome. Relief of these symptoms by nicotine inhalation is believed to be the result of nicotine-stimulated secretion of endogenous corticotrophin.

It is accordingly an object of the present invention to provide an anti-smoking kit such as to enable a medical practitioner to carry out a more effective anti-smoking treatment which reduces or eliminates the symptoms of smoking withdrawal syndrome.

Summary of the Invention According to the present invention there is provided an anti-smoking treatment kit which includes corticotrophin or a corticotrophin analogue together with an anxiolithic and/or a night sedative and/or an opiate agonist.

The term ’’corticotrophin” is used hereinafter to refer to a corticotrophin or a corticotrophin analogue.

The corticotrophin is preferably administered by deep intramuscular injection and the kit accordingly preferably includes a hypodermic syringe for effecting the required injection(s). Any suitable form of corticotrophin can be used, for example, ACTH/CMC, Cortrosyn, Synacthen, Acthar Gel, Cortrosyn Depot and Synacthen Depot (Cortrosyn, Synacthen, Acthar Gel, Cortrosyn Depot and Synacthen Depot are Trade Marks). Ε 91717 - 4 If an anxiolithic is included in the kit it may be Buspar or Motival whilst, if a night sedative is included in the kit, it may be either Temazepam or Zopiclone. The preferred opiate agonist is clonidine.

The kit preferably also includes an instruction sheet for the patient containing information concerning the treatment and recommendations concerning the diet to be adopted to obtain maximum benefit from the treatment.

Hypoadrenocorticism is associated with a tendency to hypoglycaemia and the dietary recommendations are preferably such as to prevent hypoglycaemic reactions, i.e. by eating between meals, taking snacks at bedtime and eating less at meal times. Refined carbohydrate should be avoided because of its tendency to cause insulin-mediated rebound hypoglycaemia.

Cholesterol is an obligatory intermediary in the biosynthesis of corticosteroids, 60 to 80% of which comes from exogenous sources. The recommended diet should, therefore, contain regular amounts of exogenous cholesterol, e.g. meat, fish, nuts, eggs and dairy products. The diet should also be well-balanced and include fruit, vegetables, wholemeal products and unsaturated fats such as vegetable oils and olive oil. Stimulants such as alcohol and caffeine (in tea, coffee and cola) should be kept to a minimum.

Exhaustion tends to impair adrenocortical efficiency and tired patients may respond disappointingly to treatment. Such patients should accordingly be counselled to adjust their lifestyles to reduce worry and fatigue as well as alcohol and caffeine consumption. They should have wholesome meals, regular fresh air and exercise and be advised to go to bed earlier.

The results of clinical trials carried out using combination < of corticotrophin and clonidine are set out below: A B C D E F G H I J K L 1 10 8 5 - 0 0 - - - - 50 2 30 25 18 11 0 0 0 0 - - 75 3 25 15 6 - 8 0.4 0 0 - - 150 4 20 10 9 - 0 0 - - - - 0 5 20 18 14 11 6 0 0 0 0 0 100 6 30 15 8 20 1.5 1 0 0 - - 225 7 30 15 14 14 4 1 0.75 0 0 - 150 8 25 14 12 16 0 0 0 - - - 0 9 25 15 12 20 0.5 0 0 0 - - 75 10 60 59 40 - 2.5 3.5 0 0 0 0 300 11 20 6 6 7 0 0 - - - - 0 12 20 9 9 - 1 1 3 2 3 3 75 13 15 8 4 7 0 - - - - - (75) 14 12 10 6 9. 5 3 2 0 0 75.

IE 91717 - 6 A = Patient, B = Number of cigarettes previously smoked per day, C = Number of cigarettes smoked per day as a result of cutting down by willpower, D = Number of cigarettes smoked per day as a result of cutting down with the assistance of clonidine tablets, E = Number of cigarettes smoked per day after a placebo injection, Ό F = Number of cigarettes smoked per day after a first corticotrophin injection, G = Number of cigarettes smoked per day after a second corticotrophin injection, H = Number cigarettes ! smoked per day after a third corticotrophin injection, I = Number of cigarettes smoked per day after a fourth corticotrophin injection, J = Number of cigarettes smoked per day after a fifth corticotrophin injection, K = Number of cigarettes smoked per day after a sixth corticotrophin injection, and L = Daily dose of clonidine in micrograms. » Brief details of the patients . are as follows:- Patient 1, female aged 25 who had smoked for 15 years.

Patient 2, male aged 40 who had smoked for 28 years. Patient 3, female aged 45 who had smoked for 27 years. Patient 4, male aged 43 who had smoked for 5 years. The taking of clonidine tablets was found not to be helpful for this patient.

Patient 5, male aged 53 who had smoked for 38 years. Patient 6, male aged 42 who had smoked for 27 years. Patient 7, male aged 35 who had smoked for 20 years. Patient 8, male aged 25 who had smoked for 10 years taking of clonidine tablets was found not to be helpful for this patient.

Patient 9, female aged 53 who had smoked for 38 years. Patient 10, female aged 48 who had smoked for 34 years. Patient 11, female aged 20 who had smoked for 11 years.

The taking of clonidine tablets was found not to be helpful for this patient.

Patient 12, female aged 58 who had smoked for 31 years. She has not stopped smoking completely and continues to smoke 3 cigarettes a day. She says that, although smoking no longer gives her pleasure, she misses the pleasure that she used to get from smoking. She adds that she is weak-willed and that her husband smokes heavily. She also has much stress, both at home and at work.

Patient 13, male aged 40 who had smoked for 25 years. This patient stopped taking clonidine tablets because of unpleasant side effects (stomach bloating).

Patient 14, female aged 62 who had smoked for 44 years.

The corticotrophin is supplied as part of the kit in a 5 ml. vial which contains corticotrophin gelatin injection, 80 i.u./ml. for deep muscular injection. It is stored at between 2° and 8° C. at which temperatures it is a gel. It should be liquefied prior to administration by rotating the vial under warm running water.

The corticotrophin is drawn up into a 2ml. syringe using a large-bore needle and then administered by deep intramuscular injection using a small-bore needle into the lateral aspect or back of an upper arm of the patient. Deep intramuscular injection is recommended since subcutaneous injection has been found to be associated with bruising.

The corticotrophin injections should be given in the morning, between 7 a.m. and 12 noon after breakfast. This harmonises with circadian rhythms and it has been found that the administration of corticotrophin is of most benefit for subjects adhering to a schedule of diurnal activity and nocturnal rest when given at 7 a.m. rather than at 2 p.m. or at 9 p.m.

In clinical practice, patients are advised to attend as soon after breakfast as is practicable between 7 a.m. and 12 noon. Shift workers are advised to attend after they have slept and eaten.

On the first day of treatment, male patients receive an injection of 2 ml. (160 i.u.) while female patients receive an IE 91717 - 9 injection of 1.5 ml. (120 i.u.).0n the third or fourth day, they receive an injection of 1 ml. (80 i.u.). The first two injections constitute a primary course.

Mild insomnia may occur during the night following the first injection. This can be anticipated and treated with appropriate night sedation ( Temazepam 20 mg. which can be provided as one of the constituents of the treatment kit). In order to promote stress reduction, patients are advised to reduce alcohol and caffeine consumption. They should also be advised to go to bed earlier. An anxiolithic (Motival or Buspar), which can be provided as one of the constituents of the treatment kit, may also be prescribed.

Those patients who, after the corticotrophin injections, experience craving for tobacco, can benefit from clonidine tablets, 50 to 100 micrograms, taken on waking and before meals. The optimal dose is the highest dose which is well tolerated. If side effects, such as dry mouth, sedation or gastro-intestinal disturbance, occur then the dose should be appropriately reduced. Clonidine treatment may be tailed off a few weeks after complete cessation of smoking.

Patients who have completed a primary course and who then continue to have residual withdrawal symptoms, may be given additional 1 ml. (80 i.u.) injections at three day intervals, provided that:IE 91717 - ίο a) they have either completely stopped smoking or have reduced their daily rate by at least 90%, b) they are not under excess pressure or over-tired, and c) they are following the suggested dietary advice and, in particular, are having a wholesome breakfast and a snack at bedtime.

Additional 1ml. (80 i.u.) injections may also be given at intervals of from 3 to 6 days for control of exacerbations of withdrawal symptoms which can occur after completion of a primary course.

Patients who, after a primary course, fail to reduce their rate of smoking by 90% or more or who continue to experience intolerable withdrawal symptoms, should be advised to discontinue the injection treatments for at least two weeks. They should be permitted to smoke and should be counselled on stress reduction and dietary improvement. When this has been achieved, injection treatment may be recommenced with a primary course.

Patients who have successfully stopped smoking as a result of a course of treatment as outlined above but who subsequently relapse may similarly be treated with a repeat primary course.

IE 91717 - 11 The recommended contents of a kit for supply to a medical practitioner administering a course of treatment are as follows:a) corticotrophin BP for injection 80 i.u. per ml., one 5 ml. vial, b) clonidine fifty 25 microgram tablets, c) Buspar or Motival 15 tablets, d) Temazepam 6 capsules, e) 2 large-bore hypodermic needles, f) 2 small-bore hypodermic needles, g) two 2 ml. hypodermic syringes, h) cotton wool, plasters and swabs, i) 1 Doctor’s method sheet, j) 1 Doctor’s medical questionnaire sheet, k) 2 Patient instruction leaflets, one on stress and diet and the other on the treatment procedure, and l) 1 Patient agreement form.

The anti-smoking kit is for supply to a medical practitioner and is such as to offer him the maximum assistance in providing an overall treatment to his patient. The medical questionnaire sheet thus includes such questions as to ensure that all relevant aspects of the patient’s medical history are taken into account before any Injections are administered.

Claims (9)

1. Claims:1. An anti-smoking treatment kit which includes corticotrophin or a corticotrophin analogue together with an anxiolithic and/or a night sedative and/or an opiate agonist.

2. An anti-smoking treatment kit according to Claim 1, which includes a hypodermic syringe for use in effecting the required injection(s).

3. An anti-smoking treatment kit according to Claim 1, which includes an instruction sheet for the patient containing information concerning the treatment and recommendations concerning the diet to be adopted to obtain maximum benefit from the treatment.

4. An anti-smoking treatment kit according to Claim 1, which includes corticotrophin and clonidine.

5. An anti-smoking treatment kit according to Claim 1 or Claim 4, in which the corticotrophin is in the form of a gel contained in a vial. IE 91717 -136. An anti-smoking treatment kit according to Claim 4, in which the clonidine is in the form of tablets representing dosages of 25 micrograms.

6. 7. An anti-smoking treatment kit according to Claim 4, which includes both an anxiolithic and a night sedative.

7. 8. An anti-smoking treatment kit according to Claim 3, which includes a method sheet giving instructions to a medical practitioner for use of the kit, a questionnaire sheet for use by the practitioner in interviewing a patient, and a patient agreement or consent form.

8.

9. An anti-smoking treatment kit containing equipment and pharmaceuticals for use in the treatment of a patient, substantially as hereinbefore described and for use in the manner described herein.