Orthoform, methyl-para-amido-meta-oxybenzoic ester, is applied as a powder to painful ulcers, or in ointment form to projecting hemorrhoids or to the vulva in pruritus; or is used in suppositories in anal fissure or ulcer, or in the form of lozenges to be dissolved in the mouth to overcome dry cough, or in tuberculous laryngitis to permit swallowing. It may be taken internally for ulcer of the stomach. Dose, 5 grains (0.3 gm.) in suppository, lozenge, capsule, or powder. A 5 or 10 per cent. ointment is also employed. The author has seen a spreading dermatitis of the fingers and hands after the use of an orthoform ointment. It occurred twice in the same person and was doubtless due to idiosyncrasy.

Anesthesin, the ethyl ester of para-amido-benzoic acid, has the same uses and dosage as orthoform. It is slightly soluble in water, and more readily so in alcohol and the oils.

Propaesin, para-amido-benzoic-acid-propyl ester is a crystalline powder, slightly soluble in water and moderately so in alcohol. It is used in the same way as the last named, in doses of 5 grains (0.3 gm.) or in 10 per cent. ointment. Dipropaesin is a combination of one molecule of urea with two of propaesin. It is anesthetic in an alkaline medium.

Chloretone, chlorbutanol, is sometimes employed in the same way (see under Hypnotics), in powder, tablets, spray, etc., as a local anesthetic.

Holocaine, para-diethoxy-ethenyl-diphenyl-amidin chloride, is very soluble in water, but more irritant and more toxic than cocaine. In forty-five seconds a 1 per cent. solution produces an anesthesia of the eye which lasts ten or fifteen minutes, without any effect on pupil, accommodation, intra-ocular tension, or the arterioles.

Dionine, di-ethyl morphine chloride, is soluble in 7 parts of water, and is used in 5 per cent. solution to dilate the pupil, to lessen intra-ocular tension, and to abolish pain in the eye. Snyder prefers it to eserine in glaucoma. At first it causes great irritation and even chemosis, but this soon disappears. Its systemic effect is similar to that of codeine. (See Morphine.)

Yohimbine is an alkaloid yielded by a tree of the Apocynaceae of German West Africa. Its solutions decompose on boiling and deteriorate on keeping. It is less anesthetic than cocaine and dilates the pupil, but it so strongly dilates the vessels that to prevent hyperemia a 2 per cent. solution requires to be mixed with an equal quantity of epinephrine solution.

Taken by mouth, yohimbine is said to cause a dilatation of the cutaneous vessels, to stimulate the lower part of the spinal cord, to increase sexuality, and to induce erections of the penis which may or may not be accompanied by sexual desire. Dose, 1/8 grain (0.008 gm.), or in 2 per cent. solution hypodermatically 8 minims (0.5 c.c.). A number of veterinary writers have reported aphrodisiac effects in cows, pigs, and horses. Vasotonin, a preparation of yohimbin and urethane designed to lower arterial pressure, was found to have the opposite effect (Lawrence).

Schleich's infiltration anesthesia was famous at one time. He used solutions of the hydrochlorides of morphine and cocaine in three different strengths in 0.2 per cent. solution of sodium chloride. The strongest of his solutions contained 0.2 per cent. of cocaine and 0.025 per cent. of morphine.

Other local anesthetics are the ethyl chloride spray, which freezes the part, and is only momentary in its effects, and phenol, a 5 per cent. solution of which, kept in contact with the part, will slowly numb and anesthetize.

Eriodictyon (yerba santa) is an astringent, resinous, bitter drug, of which the fluid extract is official; dose, 30 minims (2 c.c.). It possesses the peculiar local action on the taste-buds of abolishing the taste for bitter, though not that for sweet, salt, or sour. If the mouth is rinsed with a little of the fluidextract diluted with water, a dose of quinine or strychnine taken three or four minutes later gives scarcely any bitter taste. It is sometimes made into a syrup and used as a vehicle for the administration of quinine to children; but in such admixture it has no time to act on the taste-buds, and really lessens the bitterness of the quinine salt by changing it to the tannate, an almost insoluble and therefore almost tasteless salt.

Intravenous Local Anesthesia

This method, introduced by Bier, gives complete anesthesia of a limb. The blood is squeezed out of the veins between two Esmarch bandages, and a 0.5 per cent. novocaine solution injected into a vein. The solution reaches all parts of the segment, and produces complete anesthesia of the segment in five minutes, so that even an amputation may be performed without pain. In an adult 50 to 100 c.c. of the solution are required for the arm, and somewhat more for the leg.

Quinine and urea hydrochloride has come into extensive use as a local anesthetic. It is mostly used hypodermatically and is described under "Quinine."

Some Peripheral Depressants Not Of Great Medicinal Importance

1. hydrocyanic acid and cyanides

Preparations

Diluted hydrocyanic acid, Hcn, a 2 per cent. solution; dose, 1 minim (0.06 c.c.). It rapidly deteriorates on keeping. Undiluted hydrocyanic (prussic) acid is not employed in medicine.

Potassium cyanide, Kcn; dose, 1/6 grain (0.01 gm.).

In addition, hydrocyanic acid is present in preparations of wild-cherry bark (Prunus virginiana), the oil of bitter almond (Amygdala amara), and cherry-laurel leaves (Laurocerasus). In these it does not occur in the crude drugs, but is developed in the presence of water by the action of the ferment emulsin on the glucoside amygdalin, both of which are present. (For the reaction, see Part I, Glucosides.) The official oil of bitter almond contains 2 to 4 per cent. hydrocyanic acid and 85 per cent. benzaldehyde; dose, 1 minim (0.06 c.c.). The preparations of these are:

Infusion of wild cherry, 4 per cent.; dose, 2 ounces (60 c.c.).

Syrup of wild cherry, 15 per cent.; dose, 1 dram (4 c.c.).

Fluidextract of wild cherry; dose, 30 minims (2 c.c.).

Bitter almond water (aqua amygdalae amarae), 0.1 per cent.; dose, 1 dram (4 c.c.).

Spirit of bitter almond, 1 per cent., 3 minims (0.2 c.c.).

Action

Cyanides are general protoplasmic poisons, highly toxic to all living things, and antagonistic to the action of the body ferments. Locally, they tend to depress the ends of the sensory nerves.

Poisoning

Large doses so affect the protoplasm of the body that it is unable to absorb oxygen from the blood. As a consequence, the venous blood is like the arterial blood, i. e., red and oxygenated. This is, so far as we know, due to inhibition of the activity of the oxidases (oxidizing ferments), through whose action the oxygen of the blood is utilized in the cells. This property of cyanides has been established by Richards as of value in the study of the action of certain oxidizable poisons.

After a toxic dose of cyanide there is a passing stimulation of the vagus, vasoconstrictor, and respiratory centers, followed by marked depression of these. There are widely dilated pupils, and vomiting from stimulation of the pupil-dilating and vomiting centers, then convulsions, probably of medullary origin, collapse, and death from failure of the respiraton. Very large doses taken when the stomach is empty are followed almost immediately by a few convulsive movements and death. The fatal dose is variable because of differences in the strength of preparations. Art amount of dilution equivalent to about 1 minim of pure hydrocyanic acid, or 2 1/2 grains (0.16 gm.) of potassium cyanide, is reckoned to be a lethal dose (Taylor). For an elephant in Central Park it required 9 ounces (180 gm.) of potassium cyanide to produce death. The poison may be detected by the characteristic odor, which is perceptible in the mouth or the emptied bottle, or at postmortem on opening the body.

Treatment

Prompt emptying of the stomach, and the administration by mouth of oxidizing antidotes, such as hydrogen peroxide, potassium permanganate, or, perhaps, much better, freshly prepared ferric hydroxide (the arsenic antidote). Intravenously 1 per cent. sodium hyposulphite, and 0.5 per cent, co-baltous nitrate have been recommended. In addition, are indicated artificial respiration and the general treatment for collapse.

Therapeutics

It has been employed locally to allay itching and to stop nausea and vomiting. It is also used to check cough. There is no evidence to justify its employment for these purposes, and it would seem that the medicinal use of hydrocyanic acid or potassium cyanide might with advantage be abandoned.

The syrup of wild cherry is much used as a flavor in cough mixtures. . Cherry-laurel water and the water and spirit of bitter almond are used as flavors.