EXCERPTS:

General Summary.

1. On account of the corrosive action of these substances on glass vessels their use in ordinary therapeutics seems beset by many difficulties. But by attending to a few precautions these obstacles can be so minimized as to be practically overcome.

2. The topical action of strong hydrofluoric acid differs from that of the other concentrated mineral acids in being attended by more acute pain. If allowed to remain in contact with the skin for a considerable time, by combination with the lime and other bases of the tissues it forms a hard horny sheath, under cover of which it continues to penetrate the deeper tissues till its energy is expended. On removal of the slough the resulting ulcer manifests a readiness to heal scarcely inferior to that produced by oil of vitriol.

3. In poisoning by the strong acid the treatment must be regulated on the same fundamental principles as in poisoning by any of the other strong mineral acids.

4. The fumes of the acid on inhalation provoke dyspnoea and spasmodic cough, and if concentrated, produce intense bronchial and laryngeal irritation, with spasm of the glottis, convulsive cough, and in some cases speedy death. After even a short exposure to the fumes death may result from the secondary inflammatory action in the larynx, finer bronchi or lung substance. The inflammatory action seems to have nothing distinctive in itself. These dangerous and even fatal effects offer a powerful argument against the treatment of diphtheria by inhalations of this acid, as advocated by M. Bergeron.

5. The alkaline fluorides are not absorbed through the skin.

6. The remote action of the alkaline fluorides is essentially similar to that of the dilute acid, the super-added effect of the base becoming apparent only when the salts are given in large doses. These salts, possessing as they do, the characteristic therapeutical properties of fluorine, are to be preferred to the acid for ordinary medicinal use, seeing that they have the material advantages of being more easily preserved and dispensed.

7. Fractional doses after a time slightly impair the appetite. Moderate doses induce nausea and tend to disorder the stomach. Large doses readily excite vomiting by direct irritant action on the gastric mucous membrane – no vomiting occurs on subcutaneous administration of the drug, and free dilution diminishes the emetic tendency. No purgative action ordinarily attends the use of the salts even in large doses.

8. Nutrition is impaired by the prolonged ingestion of small doses of the alkaline fluorides or the acid, and this atonic condition is accompanied by slight loss of body-weight – the slightly depreciated appetite may partly account for this condition. The extensive and constant presence of fluorine in infinitesimal quantities in most of the animal tissues and secretions need not necessarily imply that it is connected with the well-being of nutrition, for its wide diffusion throughout the vegetable and mineral worlds necessitates its ingestion with the food, and would thus account for its general presence within the animal body.

9. The amount of urea excreted in the urine is increased, implying increased destruction of tissue. That the excessive elimination of urea is not due to an increase in the general tissue waste, seems evident from the fact that the body-temperature is distinctly reduced, the pulse-rate somewhat slowed, and the arterial pressure slightly lowered. What then is the tissue which being destroyed in excess furnishes this increased ureal excretion?

10. Observation showed that the alkaline fluorides and the acid profoundly modify the constitution of the blood, producing an anaemia (oligocythaemia), the essential characteristic of which is that the red corpuscles suffer a decrease out of all proportion to the haemoglobin. The extent of this numerical reduction of the red corpuscles, even when small doses of the drug are given, is very great, but with large doses the corpuscular loss becomes enormous. Thus with the provers after a five-days’ course of the drug, the general loss averaged about one-fourth of the total red corpuscles, and the induced anaemia was visible to the unaided eye. As the blood becomes impoverished the rate of decrease becomes slower; and on stopping the drug the red corpuscles more or less rapidly approach their normal standard. The anaemia cannot be ascribed to anorexia, as an extensive reduction occurs under the use of doses so small as not perceptibly to derange the appetite. The haemoglobin is only slightly reduced in amount; and as at the same time the size of the red disc becomes slightly larger, it will thus be able individually to take up a greater amount of haemoglobin than normally.  In the relatively slight decrease of the haemoglobin under their use, lies the comparative safety of these substances as possible remedial agents ; for should the haemoglobin, on which the functional activity of the corpuscles so largely depends, have been diminished in ratio at all similar to the corpuscular decrease, a much more grave anaemic condition would be established, and one which would have opposed a serious obstacle to the advisability of their employment in medicine.

11. Having established the fact of there being an enormous numerical reduction of the red corpuscles under the use of these drugs, we were led to ascertain the probable cause of this reduction; and by a process of exclusion, in so far as dealing with this somewhat problematical subject permits, we seemed to find that the corpuscular loss resulted from the undue stimulation of the disintegrating function of the spleen.

This conclusion is supported by several circumstances, chiefly pathological, and although the lessons of pathology are necessarily less certain than experimental observation, in the absence of the latter they afford much valuable information. On these drugs being given in small doses to patients with malarially enlarged spleens a decided reduction in size occurs, and in many cases the enlargement disappears. A consideration of the nature of the chronic enlargement led to the belief that it is not a pure hypertrophy, but in great measure a congestion – the vascular areas being enormously distended with blood; and that the functions are generally diminished or inactive, and not, as is usually stated, increased. The reduction of the enlargement was found to be intimately associated with the corpuscular decrease, and occur- red most extensively and rapidly in cases of soft enlargement, that is to say, in cases where the increased volume in a great measure depends on simple distension with blood. While on the other hand, mere loss of blood per se would not account for the reduction, because in many cases complicated by piles and dysentery, large hemorrhage occur from the bowel without the slightest reduction in size of the enlarged viscus.

It seems therefore probable that in the malarially enlarged spleen, where the function of disintegration of the red corpuscles in common with the Mother functions is inactive or depressed, the exhibition of fluorine by stimulating this function reduces;the total volume of the contained blood, and by thus relieving the organ of a principal cause of the swelling enables the muscular fibres to regain their normal activity and so contribute towards the further reduction of the enlargement.

12. Toxic doses affect frogs in a generally similar manner to warm-blooded animals : experiments therefore on the former afford results of much practical value.

13. Circulatory depression is a constant and characteristic effect of fluorine compounds. The cardiac contractions are slowed and weakened, and with poisonous doses the heart is arrested in diastole. The contractions are found to be arrested a considerable time before the contractility of the cardiac muscle to mechanical stimuli is lost. Thus showing that fluorine acts more powerfully on the nervous mechanism which regulates the contractions than on the muscular tissue itself. Under full medicinal doses the sphygmograph shows after a time a distinct reduction of blood- pressure.

14. Increased frequency of the respiratory act follows the injection of poisonous doses of the drug. The respirations  soon become retarded, slightly irregular and evidently laborious. The respiratory difficulty increases, and the inspiratory efforts ultimately become convulsive (asphyxial) in character. The imperfect aeration of the blood thus induced appears to contribute to the cardiac paralysis which is the immediate cause of death.

15. Even in the largest medicinal doses no narcotic effect, nor even drowsiness results. In toxic doses the pupils at first become slightly, dilated, then afterwards markedly contracted. Voluntary movements cease only a few seconds before the final arrest of the respirations and general circulation. The medulla appears to be specially affected. The spinal reflex irritability persisted throughout unimpaired. The voluntary muscles retained their electric excitability for some time after death.

16. The salivary secretion is very slightly increased, especially after large doses which excite nausea. The absorbent glands do not appear to be stimulated. The bulk of the urine is slightly increased, the increase being most marked after the drug has been given for some time and in large doses.

17. Medicinally, large and even moderate doses are attended by such unpleasant symptoms as to render it difficult to prevail upon patients to persist for any length of time with the use of fluorine compounds in any but fractional doses.

18. In epilepsy these drugs are of no value; and in phthisis pulmonalis, mitral disease and aortic regurgitation they are positively hurtful.

19. In rickets the bones are found to be deficient in fluorides, and the administration of minute doses of fluorine salts is reported to be of benefit in this disease.

20. Fluorine has no sedative effect whatever on the articular pains of acute rheumatism. The reputed efficacy of potassium fluoride over the pains was entirely due to the basic element of the salt. As fluorine powerfully weakens the heart, its use in acute rheumatism is dangerous.

21. In soft vascular goitres fluorine is of use, if persisted in, but the reduction seems to be a consequence of the general anaemia induced by fluorine, rather than the result of any special action on the cervical sympathetic.

22. In plethoric states, such as gout, fluorine may be admissable; also, for relieving vascular fulness in the earlier stages of aortic aneurism.

23. In the chronically enlarged spleen of malaria, when of recent origin and soft consistency, reduction in size readily occurs under the fluorides ; but this is only effected at the expense of considerable anaemia. These drugs are powerless to prevent or hinder further enlargement resulting from fresh paroxysms of the intermittent. The fluoric anaemia must be carefully watched and prevented going too far. Iron fluoride is of no value. Quinetum or Quinine fluoride is best. Fluorine is contraindicated in every case where grave adynamic symptoms are present.

These observations in affording definite ideas as to the characteristic action of fluorine compounds, also indicate the direction in which these powerful drugs are likely to prove of service as remedial agents. It now remains for a more extended clinical experience of these substances to determine whether or not the peculiar disadvantages incidental to their medicinal use will prove insuperable obstacles to their ordinary employment in practical therapeutics.

---

*See attached full study