Cinchona calisaya: Peruvian bark. N.O. Rubiaceae. Cinchona and Quinine. Preparations from the bark and derivatives.
QUININE, one of the alkaloids obtained from cinchona bark, affords a good example of how the primary and secondary effects of a drug may be utilized, on opposite principles, for therapeutic purposes.
(1) QUININE is primarily a stimulant of protoplasm in general, and secondarily it exhausts and paralyses it. The movements of lowly organisms are first stimulated as are those of cilia; subsequently they become slower, less vigorous, and finally cease. These effects are induced by the direct application of solution of 1 in 20,000. If the solution is stronger the primary stimulus is less marked and shorter, the paralysing effect rapidly ensuing; if weaker the converse occurs. In the ordinary doses used for experimenting it is the secondary or depressing influence which is conspicuous, and the same action is utilized (antipathically) in many cases in its therapeutic employment.
(2) Action on Cells of Blood and Body.-The leucocytes soon become spheroidal and motionless in contact with a solution of quinine. The usual diapedesis of the white corpuscles of the frog, seen when the mesentery is examined under the microscope, is checked by the subcutaneous injection of quinine, the cells become granular and motionless. “Suppuration” is thus said to be prevented. By the doses required to effect this the phagocytic and antidotal power of the leucocytes is lessened and the resisting power of the organism to sepsis is diminished. The other cells of the body are probably affected similarly.
(3) Muscle tissue, both plain and striped, is first stimulated and then depressed, that is, the contractions are first increased and then diminished, arterioles are first constricted and then dilated.
(4) Circulatory System.-The pulse-rate is first increased and then diminished. Blood-pressure becomes lowered, followed possibly by the death of the subject. Besides the effect on the blood-cells noted in paragraph 2, haemorrhages in various parts have been noted as due to quinine, e.g., purpuric spots, and bleeding from mouth and vagina occur, also haemoptysis, though the heart and lungs are healthy (C.D.P.).
(5) Metabolism.-Even here the same order is observed, the predominant effect, however, being depression. The effect on tissue change is best seen by urinary analyses; after a slight temporary increase the phosphates, sulphates, chlorides, urea and uric acid are all diminished. The total solids may be lessened by as much as 40 percent., and the effect of a single dose may be seen in a fall of nitrogen excretion lasting as much as three days. The absorption of oxygen and the elimination remain unchanged. Coincident with the changes in metabolism is the influence on the body temperature.
(6) Temperature.-Experiments on animals show that the temperature is first slightly raised and then considerably lowered. These experiments furnish an interesting confirmation of those of Hahnemann, who found that his own temperature was raised by taking doses of cinchona bark, and that a condition was induced resembling a malarial attack. This experiment was made deliberately by Hahnemann with the object of ascertaining the action of “bark” in ague, and as a deduction the action of drugs on disease in general. After confirmatory experiments Hahnemann re-affirmed the fact as a rule for the selection of drugs in disease, similia similibus curentur. The secondary effect of quinine, its most obvious effect in large doses, is not due to increased loss of heat but to diminished production. The depression of temperature is proportionate to the lessened excretion of nitrogen. The pyrexial effects of quinine, to which we have already alluded, are usually unaccompanied by inflammation of any particular organ or structure.
Definite lesions are, however, sometimes met with, which will be referred to presently.
Intermittence has been noticed without repetition of the dose, but this did not occur in Hahnemann’s experiments on himself. He had to repeat the dose to induce a fresh febrile manifestation. this recurrence of the febrile condition may be daily or every second day, commencing chiefly in the evening or afternoon. During the stage of shivering there is commonly no thirst, but headache, vertigo, nausea, feeling of fulness in the head, pallor of face and coldness of hands and feet are present.
In the hot stage there are the usual headaches of fever, with red, burning face, dryness of mouth and lips, full, quick pulse and possibly some wandering. The relationship of the thirst to the stages of the fever must be noticed. It is rarely felt during the heat and still less during the cold stage, but mostly before the chill starts and during the perspiration. There may not be the regular stages of an ague fit; perhaps only a chill with cold feet and hands, inability to get warm in bed, but with heat of the head-all worse in the evening. Or heat only may be pronounced, with headache, abdominal and hepatic symptoms, or cough and stitches in the chest; heat without thirst-a striking and unexpected symptom.
Respiratory System.-Hoarseness, from mucus in the larynx, soreness and raw feeling there; choking, paroxysmal cough in the evening or at night mark the influence of chinchona on the larynx. The cough may be worse after midnight, from cold air, on awaking, from talking or laughing, and better from sitting propped up in bed (hyoscy., puls. and lycopod.). Or the irritation may extend lower in the chest, when the cough my be accompanied by retching, wheezing and oppression on the chest, with expectoration of mucus or muco-purulent and bloodstained sputum. Haemoptysis without lung disease may also occur. The breathing may be loud and stertorous and only possible when sitting erect, worse after eating, drinking, moving about and trying to breathe deeply.
Pressure in the chest, as from a weight on it, may be felt after a meal.
Urinary Organs.-China causes frequent micturition and burning at the urethral orifice. The urine varies with the site of chief impact of the poison. It is turbid and scanty, depositing a yellowish or brick-dust sediment in gastric catarrh; if jaundice is present it will be dark and contain bile-pigment. It is also accused of producing albuminuria, haematuria and haemoglobinuria. “This haemoglobinuria so resembles.. blackwater fever… that it has been contended that blackwater fever is really quinine poisoning occurring in malarial subjects. But this view is now abandoned, the fact is that chronic malaria and quinine can both cause haemoglobinuria (a parallel of deep significance to the homoeopathist), and although quinine sometimes seems to provoke this symptom when given in chronic malaria, it can also cause it to disappear…” (Wheeler, op. cit.).
The chief importance of quinine is centred in its use in malaria. Here we do not propose to go into the question of the use of that drug in the routine treatment and prevention of malaria. Its nodus operandi may be twofold-that of a parasiticide and that of a stimulant of body resistance. Indeed, even its parasiticidal action may be via the body-resistance route, for it is stated that a strength of quinine which, given per os, will kill malarial parasites, will allow them in vitro to live and multiply. It is still a point, unsettled by experts, whether the daily prophylactic dose of 5 gr. is desirable or not. Some observers denounce it as useless or dangerous and liable to predispose to blackwater fever, others regard it as an essential in malarial countries. Experience seems to show that the regular use of quinine in doses of 5 gr. daily does in most cases ward off attacks of ague and may banish blackwater fever from districts where it is prevalent. Irregular dosing, with sudden large doses when an attack of fever is threatening, is to be deprecated. Quinidine, a cinchona alkaloid isomeric with quinine, reduces the conductivity of the heart’s muscle, especially of the auricle, and thereby increases the time of the “refractory period’ in the auricular pulsations. This property is made use of in the treatment of extrasystolic paroxysmal tachycardia and auricular fibrillation, all of which irregularities it controls.
The indications for the homoeopathic use of cinchona (“china”) in malaria may be summarized as follows. Immediately before the paroxysm there is much thirst and increased appetite, with restlessness, sneezing, palpitation and nausea. The chill is pronounced and is not accompanied by thirst, nor (and this a “keynote”) is the heat; the intense heat is worse from movement; the patient wants to throw off the clothing but he gets chilly if uncovered. There are general aching pains and irritating cough.
In the sweating stage thirst returns. The sweat is exhausting and is worse during sleep, on movement, when covered up, and on the parts lain upon.
In the interval there will be debility, yellowish skin, abdominal distension and probably enlarged spleen. The tongue is thickly coated, the taste is too acute, there are bitter taste and eructations, turbid, scanty urine and absence of thirst, except just before a paroxysm. General aggravation ensues from draughts, mental exertion and drinking milk, and improvement from rest and warmth. China is chiefly indicated (homoeopathically) in benign cases, it is usually a day-time attack. Absence of thirst during the heat is one of its outstanding indications.
Arising out of the acute malarial condition is a chronic state of anaemia and malnutrition. No parasites may be discoverable in the blood. Indigestion, looseness of the bowels, headaches, with occasional rises of temperature without the typical malarial stages or periodicity, are commonly present. For such a case to require china the following features should be present: a pale or sallow complexion, sweating on slight exertion, inability to digest fruit or acid things, sensitiveness to cold air, with susceptibility to taking cold, shooting pains about the body, causing restlessness, necessitating movement. A very characteristic china symptom is surface tenderness to a light tough, but relief from firm pressure.
The prevailing mental condition is one of nervous irritability, with hyperaesthesia of the special senses, or on the contrary apathy and indifference. In either case mental effort for such patients is difficult and aggravates his general and mental state.
Periodicity is another element in the china pathogenesy; in a patient it need not be malarial to be benefited by the remedy, but in that disease the recurrences (when china is called for) are chiefly diurnal, while in nonmalarial neuralgia, dyspepsia, headache, &c., the recurrences are often about midnight, either every nigh or every second night (“tertian”).
Of the china neuralgias, supra-orbital pain is one of the most frequent; the paroxysm is brought on by moving the part, ever so gently, or by a light touch, and the pain is of a gradual crescendo character, with midnight origin or aggravation. Trembling or twitching of the limbs or of single muscles, and numbness of the parts lain on occur; the temperature and movement aggravations mentioned above are a part of the picture. The pains for which this remedy is required are often due to excessive loss of fluids-normal or pathological.
Loss of Fluids.-This source of ailments ranks almost as a keynote for china, loss of blood (traumatic, menstrual, epistaxis, &c.), excessive perspirations, seminal losses in excess, diarrhoea, &c., all may bring about china symptoms.
Haemorrhages.-China is useful for a number for a number of passive haemorrhages from such sources as nose, throat, bowel, uterus-mostly venous. Of course, in any such cases a local source should be sought for and dealt with. When none is found there will generally be some general state of the patient which will guide to the remedy, whether that state is the cause or the result of the haemorrhage. Sometimes ailments such as nerve pains, cramps and spasms, even convulsions, also local inflammations such as pneumonia or metritis, seem to follow a comparatively slight haemorrhage. The explanation probably is that the bleeding suddenly lowers an already low bodily resistance, and facilitates the development of some toxic or septic condition. Previous to the haemorrhage the patient would be a frail senses (odours, noises, light, &c.), pale, cachectic and with cold hands and feet. These, rather than the local post- haemorrhagic condition, would be the indications for china.
Digestive System.- Voracious appetite is a prominent china symptom. Small doses, taken by provers or inhaled by workers in quinine factories, cause diarrhoea, often containing undigested food. Gastro-duodenal catarrh, causing jaundice, is also produced. It is also curative in such conditions. The diarrhoea requiring china may be acute or chronic. The former is often found in the summer, accompanied by colicky pains. The stools vary from pale colour to brown, with undigested particles, and they are evacuated noisily with offensive gas, which has accumulated and distended the abdomen. Flatulent intestinal distension is very distressing and is not relieved by eructations.
Such an attack will be likely to be followed by colourless, constipated stools, headache, and slight jaundice. China will follow the condition in this development.
The chronic diarrhoea of china is a watery, painless action, frothy, brownish or black, and liable to be worse at night. This drug has gained a reputation in biliary colic which it is claimed to cure radically. On what ground this use of it was not clear, and we have no experience regarding it.
Respiratory System.- Cinchona does not appear to cause any local pulmonary lesions. It has been used in some asthmatic conditions, especially where there is stridor from laryngeal spasm or oedema of the glottis. The cough modalities may occasionally lead to the use of china for chest complaints. It is worse lying with the head low and on the left side, worse from draughts of cold air, on waking, in the evening or about midnight, and from any muscular exertion-laughing, talking, breathing deeply and moving about; also from eating and drinking. Loss of fluids, again, may be a pre-disposing cause. Some of the parietal pains of cases of cough or asthma may be reflected in the china pathogenesis-stitches, pressure, cutaneous hypersensitiveness (cannot bear percussion). Palpitation occurs in connection with febrile attacks but is not pathognomonic of china.
Limbs and Back.- A constricted feeling in the limbs, as if the clothing or garters were too tight, may draw attention to this remedy. Pain in the back, like pressure inwards, or like cramp, worse from any movement; tearing pains extending from back to thighs; darting, tearing pains, especially in hands and feet, gradually increasing; pains around joints; all these are worse from cold air and from movement, except that prolonged pain (as in bryonia cases) may impel to restless movement, though that is painful.
Sleeplessness before midnight or towards morning, from over- activity of the mind (constantly making plans), or unrefreshing sleep may be present in a china case.
Sexual Organs.- In men : excitement, with or followed by functional weakness; general debility following excessive genital stimulation and nocturnal emissions; tearing pain in the left cord and epididymis; these are the leading indications in this sphere. In women : dysmenorrhoea, with early and profuse, dark, clotted flow; fainting or convulsions from menorrhagia of “flooding” during childbirth ‘ acrid leucorrhoea; ovaritis, with great sensitiveness of the parts; any of these may present themselves in a china case.
Headaches.- Head pains are common, affecting either the whole head (bruised feeling), or the occiput (from loss of fluids), or a shooting from temple to temple. The character of the pain is bruised, shooting, throbbing or bursting; none of these may be very valuable as indications for the remedy, for they are very common. Coupled with the china modalities already mentioned they will lead to a reliable prescription.
Vertigo and noises in the head (ears) are well-known phenomena of cinchonism or quininism. The noises are ringing and humming, associated with temporary deafness. In poisonings ocular and aural disturbances develop, such as photophobia, colour distortions, contracted field and even blindness (usually temporary) and (in the case of the ears) cochlear origin. These are more often useful as leading to a choice of remedy in headaches and debility than in local, aural or ocular disease. They may, however, be called for in some early cases of nerve deafness or of retinitis.
The modalities of china run through its pathogenesis with a considerable degree of consistency.
(1) Subjects.-Stout, pale, sallow, exhausted individuals who are anaemic and short of breath and very sensitive to cold air and liable to take cold.
(2) Surface Tenderness.-Sensitiveness to light touch but relief from firm pressure.
(3) Mental State.-nervous irritability with hyperaesthesia of special senses, or indifference and apathy; mental effort is difficult and aggravates the general and mental states; no wish to go on living.
(4) Periodicity. Daily or alternate days; recurrences near midnight, but in malarial cases paroxysms usually diurnal, tend to “anticipate.”
(5) Ailments due to or aggravated by loss of fluids, normal or pathological.
(6) Malarial Attacks.-For special homoeopathic indications, see p.359. These cover only a few malarial cases, whereas quinine in material doses is given for most acute cases.
(7) Haemorrhages and the [results of excessive or prolonged bleeding.
(8) Diarrhoea.-Acute, with colic; chronic, painless, with undigested food.
(9) Gastric symptoms from fish, sour things, wine, slow digestion and great flatulent distension not relieved by eructations.
(10) Neuralgias : supra-orbital, periodic; headaches; noises in the head and aural vertigo
(11) Tearing pains in bones or periosteum, causing restlessness and relieved by movement (exception to general modality).
(12) Febrile heat without thirst.
From movement (most symptoms, except bones, &c.); from draughts and cold air in general; from eating and drinking (respiration); during sleep (sweat); fruits and acids, touch or light pressure; at night (colic); evening (febrile chills); mental exertion.
Sitting upright (cough); from rest and warmth; firm firm pressure; bending double (colic.).