Indian Tobacco, Lobelia inflata. Generally official except in Russia and Spain.

Pharmacology

Nicotine, lobeline, and cytisine are classed together pharmacologically. The latter alkaloid is derived from Cytisus laburnum. Piturine, from Duboisia Hopwoodi, acts similarly to nicotine; and the synthetic quarternary ammonium basis produced by completely methylating the nitrogen of members of the adrenine series are also similar in influence.

The actions of the nicotine alkaloids differ only in minor details. Injected into the circulation in small doses, they stimulate the ganglion cells, the heart action being first inhibited and then accelerated. The blood-pressure is raised through stimulation of the vasomotor cells in the sympathetic ganglia; but this pressor effect is evanescent. The cardiac acceleration is due to the fact that small doses of nicotine and lobeline increase the secretion of adrenalin.

In large doses the blood pressure is low, and the heart-beat becomes slow and feeble, due to a direct toxic action on the heart muscle and, when taken by mouth, to the collapse resulting from gastrointestinal irritation and emesis.

Small doses injected excite the salivary and sweat glands, as well as the mucous glands of the trachea and bronchi. Lobeline, more particularly, but also the other alkaloids, produce dilatation of the bronchi through a sympathetic effect. Large doses, either injected or by mouth, paralyze all of the structures initially stimulated, with a cessation of spontaneous secretion; respiration becomes slow, dyspnea and asphyxia supervene, and death is from respiratory failure.

Violent vomiting is produced both by injection and ingestion. When injected, this is due to stimulation of the central nervous system, especially the medullary centers; and it is followed by great depression and prostration, with or without purgation. The movements of the intestines show only a brief augmentation, as do the involuntary muscles generally; but the later ganglionic paralysis blocks all tonic impulses from the central nervous system to the involuntary muscles. Plain muscle also loses tone.

Nicotine and lobeline have a powerful stimulating action on the central nervous system, injection causing muscular twitching, hurried respiration and vomiting; this quickly followed by depression. It is the ganglion cells that are first stimulated; and the later coma and convulsions are partly the result of asphyxia.

The pupil is influenced, usually being first contracted and then dilated.

The toxic action of lobelia so closely parallels what is said regarding the nicotine alkaloids that it needs little separate consideration. There have been many fatalities from lobelia.

The question of tolerance to nicotine and lobeline was worked out by Edmunds. See Jour. of Phar. and Exp. Ther., June, 1909. He proved that no true tolerance was gained to either alkaloid. On the contrary, sensitization occurred in some of the animals used. Tolerance in man is a very variable factor. No one definitely knows how or why it is established in the case of the tobacco-user, though it is probable the adrenal function is a factor.

Therapeutics

Permit some preliminary considerations. While I believe every word to be true that was stated under the pharmacology, and while I have personally known lobelia to induce most distressing and even dangerous symptoms, yet it seldom does, as a matter of fact, act as an energetic poison. Of course I am speaking of the whole drug, not of the energetic alkaloid. One reason for this is that full doses are nearly always promptly emetic in action. Most cases of dangerous toxic action are due to delayed emesis. Another reason is the notorious variation in alkaloidal strength of the drug, whether from the plant containing little lobeline, or heat or other destructive agencies disintegrating the alkaloid, is hard to say. At all events, many specimens of the crude drug and its preparations are quite inactive. Then, too, lobelia is not always readily absorbed; indeed, sometimes quite large doses seem to be less readily absorbed than are small ones. There are many people who will have more violent emesis from a few relatively small doses than they will from one large one, the latter seeming to set up a violent irritation almost purely local; but the drug may, later, be absorbed from the intestinal tract and give rise to dangerous symptoms.

I have often wondered why Cytisus laburnum has not largely displaced lobelia. The seed carries a rather definite and constant content of cytisine, which has the same action as lobeline. Cytisine is easily obtained pure in colorless crystals readily soluble in water. There is no uncertainty in the action of laburnum; a full dose of it is invariably toxic, as it is always absorbed. Yet I can find no recorded instances of fatal poisoning from it. Caffeine is an almost certain antidote to it. Baptisia, q. v., is active from essentially the same alkaloid, yet it is not considered a dangerous drug. Cytisine may be given in doses of 1-8 to 1 grain, it is said. If lobelia was as definite and constant in action as is laburnum there would be less confusion concerning it.

Here I wish to emphasize the fact - for it is a fact - that a whole drug may not be nearly so toxic as is its separated alkaloids. Especially is this true of a complex drug like lobelia.

Long ago, before the pharmacologists were active, Scudder, an Eclectic, said that lobelia is "a vital stimulant, by its influence upon the sympathetic nervous system giving increased activity of all the vegetative functions. These influences come from minute doses, one drop or less" - of the tincture. Reference to the pharmacology of lobelia shows considerable justification for his statement. Add to this the stimulation of the adrenal function, and one can see wherein small doses of lobelia may be valuable in stimulating digestion, secretion, and poor circulation due to innervated states. Certainly small doses of lobelia are just as rationally given as are small doses of ipecac; and they do no harm, at least.

As an emetic, lobelia is certainly effective; but, when we have so much safer emetics, why use lobelia?

In asthma lobelia is a well-established drug, due, probably, to two things: its stimulation of the suprarenal function, and its dilating the bronchi. This latter effect is probably due to the drug depressing the endings of the broncho-constrictor nerves in the muscle fibers of the bronchioles. Adrenaline stimulates the broncho-dilator nerve endings; so, if lobelia stimulates the adrenal function, we have here a beautiful illustration of the broncho-constrictors being depressed at the same time that the broncho-dilators are being stimulated.

In my experience, lobelia acts rather slowly in spasmodic asthma, as ordinarily administered; so I use it hypodermatically in non-alcoholic ampoules adjusted to a lobeline standard of 0.2 per cent and carrying antiseptics to render the solution stable. This solution I find to act purely as does lobelia, with two exceptions: it is prompt, and emesis is not very readily induced by full therapeutic dosage, one ampoule containing such a dose in a bulk of 1 cc. of solution.

As an antispasmodic lobelia is not alone of value in asthma. Jackson, The Jour. of Lab. and Clin. Med., Nov., 1915, contends that there are two forms of spasmodic bronchial asthma, the one of nervous, the other of muscular origin. I believe both factors prevail in some cases, as also in certain other spasmodic affections. In respiratory diseases we often need an antispasmodic affecting both nerve and muscle. Lobelia is such an agent.

An antispasmodic is purely a symptomatic remedy; but in spasmodic cough, spasmodic croup, bronchitis with a spasmodic element involved (as well as a nauseant expectorant), lobelia often serves very well. But in no other respiratory affection is its action so definite as in spasmodic bronchial asthma. In these indications moderate, not large, doses are indicated.

In a number of cases of rigid os in the first stage of labor, lobelia, gradually pushed to the point of nausea, has acted well in my hands. In relaxing strangulated hernia it is not used so much now as it formerly was, though it may be effective in some cases.

Ground lobelia seed may be incorporated in a poultice and applied externally in painful and oppressed respiratory affections.

During the last few years some very fantastic claims have been made for lobelia. Used conservatively, it is a useful drug with adults. Children do not tolerate it very well. One can readily become enthused over lobelia, especially in the treatment of respiratory affection. It is assuredly a good nauseating expectorant; but why derange digestion with any agent of this class in the routine treatment of respiratory affections? When such an agent is needed, ipecac is to be preferred. Modern books on the practice of medicine lay stress upon supportive treatment, and the old expectorant syrups are, very properly, going out. Don't overdo expectorants - lobelia or any other one.

Lobelia, except for its possible and certainly harmless indication in small doses, is an emergency remedy, not a routine one. In severe attacks of spasmodic asthma, in spasmodic croup (very carefully to small children), and in rigid os - such are the indications for lobelia. It is not a cure-all, and some of the claims made for it are so ridiculous that the profession is apt to drop the drug entirely, thus robbing therapy of an agent of definite usefulness within a narrow field.

Dosage

The leaves: average, 7 1/2 grains; maximum therapeutic, 30 grains. The fl.:1 to 30 minims; average, 8 minims. The tr.: emetic, 1 fluidrachm; expectorant, 5 to 15 minims. Better err on the side of small, rather than large, dosage.

Lobo-toxin and Subculoyd Lobelia are two lobelia products for hypodermic use.