Novocaine

NOVOCAINE (Novocainum) ФУИ (Procaine amer. pharm.), hydrochloric para-amino-benzoyl-diethyl-amino-ethanol NH_aC_eH₄. .CO.OCH₂.CH₂N / ²**^S.HC1, mol. wt. 272.6. \c₂н₆ First obtained N. (synthetically) by Einhorn and Ulfelder (A. Einhorn, E. Uhl-felder; 1905); in the same year Biberfeld and Braun (Biberfeld, H. Braun) introduced it into medicine as a substitute for cocaine. N. consists of colorless crystals of an astringent bitter taste, odorless, melting at 156°, soluble in 1 part water, in 30 parts alcohol and almost insoluble in ether. Aqueous solutions (1:9) of neutral reaction, are thermally stable (even after 24-hour heating to 100° only a negligible loss in activity occurs) and therefore can be repeatedly sterilized by boiling. With prolonged storage, solutions of N. acquire a brown color, but their activity and toxicity change little (for at least several months). N. should be stored in well-sealed vessels, protected from light. When acted upon by alkalis, the base of N. is liberated in the form of colorless crystals, melting at 61-63°, insoluble in water but easily soluble in alcohol, ether and benzene, as well as in fatty oils (up to 10%) with slight heating. Action on the body. Similar to cocaine (see), N. when applied locally has the ability to selectively paralyze the endings of sensory nerves, but the character of N.'s action is still substantially different from that of cocaine. N. is free from irritating action on tissues; the cornea for example is not damaged even when a concentrated solution of N. or N. in substantia is applied to it; 10% solutions of N., injected under the skin, have no other effect on tissues than any hypertonic salt solution. Blood vessels N., unlike cocaine, does not constrict; has no effect on the pupil, intraocular pressure and accommodation. To obtain approximately the same degree of anesthesia, N. is required depending on the place of application either the same amount or significantly (2-3 times) more than cocaine. Experimental data show that the anesthetic strength of N. on the rabbit cornea is 16 times less than that of cocaine (Closson), whereas on the trunks of sensory nerves of frogs, as well as on their endings in rabbits, with intracutaneous injection both poisons act equally; the latter also applies to motor nerves on the frog nerve-muscle preparation; Closson showed that in frogs cocaine acts more strongly on nerve endings than on nerve trunks, whereas N. acts equally on both. Sollmann believes that the strength of the paralyzing action of both poisons is the same, and the difference in the degree of anesthesia they cause is explained by the much greater penetrating ability of cocaine, which is manifested when both poisons are applied to mucous membranes, whereas with direct contact with nerve endings or trunks, where penetrating ability plays no role, their strength of action is found to be the same. Confirmation of this view is also provided by the experiments of Copeland, who showed that Novocainum boricum, applied to the rabbit cornea, is 2 times stronger than cocaine, whereas hydrochloric N. under these conditions is 16 times weaker than cocaine; Clark explains the difference in the strength of action of these salts by the fact that salts with a low degree of dissociation (N. boricum) can penetrate through mucous membranes, whereas easily dissociating ones (N. hydrochloricum) do not possess this ability. The difference in the strength of anesthetic action of N. and cocaine is largely due also to the absence of vasoconstrictive action in N., thanks to which it more quickly leaves the site of introduction, being absorbed into the blood. When adrenaline is added to the solution of N., causing a sharp constriction of blood vessels, the absorption of N. is slowed down, and its anesthetic action is significantly enhanced and prolonged. It is possible that in addition to vasoconstriction, there is also a potentiation of N.'s action by adrenaline. In general, it can be considered that 1/2% and stronger solutions of N. with adrenaline have the same anesthetic strength as corresponding solutions of cocaine with adrenaline; while at weaker concentrations N. is always somewhat weaker than cocaine. In addition to enhancing the action of novocaine, the addition of adrenaline (1 drop of solution, 1:1,000 per 5-10 cm³ of N. solution) also significantly prolongs its action; for example, injection of 0.5 cm³ of 2% N. into the base of the finger causes anesthesia for approximately 20 minutes, whereas with N. with adrenaline the effect does not disappear completely even after an hour. The toxicity of N. is small; of all currently soluble in water local anesthetic agents it is perhaps the least poisonous. In an experiment on himself, Liebl (1906) received from a subcutaneous injection of 0.4 N. only a transient sensation of warmth; injected an hour after this dose of 0.75 N. gave mild poisoning symptoms, disappearing after 1½ hours. Subsequent observations on patients showed that toxic action was sometimes observed even from small doses (0.01 to 0.13), whereas in other cases up to 3.0 N. was used quite safely. Combination with adrenaline sharply reduces the toxicity of N., so that at present up to 1-1.5 N. is often injected under the skin. With accidental intravenous injection of N. (without adrenaline) to humans in an amount of 0.05, loss of consciousness and convulsions were noted. Experimental data show that the addition of adrenaline reduces the toxicity of N. even with intravenous injection; Hatcher and Eggleston attribute this to the stimulating effect of adrenaline on the heart. Compared with cocaine, N. is much less toxic. The quantitative ratios in experiments on animals were different depending on the routes and methods of administration of both poisons. Biberfeld found that with subcutaneous injection the lethal dose was approximately 5-6 times greater for N. compared to cocaine for dogs, cats, rabbits and frogs; for guinea pigs - 8 times. With intravenous injection to cats, the minimal lethal dose for N. was 3 times greater than for cocaine (Hatcher and Eggleston). In terms of toxic action on the heart, N. was weaker than cocaine by 10 times in rats and guinea pigs and by 1-1.4 times in frogs (Roth). With intradural injection to warm-blooded animals, the depressing effect on blood pressure and respiration were almost the same for both poisons (Roth). A comparative study of toxicity with subcutaneous and intravenous injection showed that for N. the ratio of minimal lethal doses in this case was greater than 5, whereas for cocaine it was less than 4. The addition of adrenaline reduces the toxicity of N. much more than that of cocaine. Under these conditions, N. in cats with subcutaneous injection was 10 times less toxic than cocaine (Hatcher and Eggleston). With repeated administration of N., in contrast to cocaine, phenomena of habituation and addiction to the poison do not develop, nor are phenomena of cumulation observed. The fate of N. in the body is apparently also different from that of cocaine, since unlike the latter N. is not found in urine in unchanged form. It is believed (Hatcher, Eggleston) that N. is rapidly destroyed in the liver, which does not happen with cocaine. Acute poisoning is relatively rarely observed in humans, since N. is usually used together with adrenaline. The following symptoms of poisoning have been described: dizziness, headache, nausea, vomiting, motor excitement, feeling of fear; in severe cases - amaurosis, pallor of the face, cold sweat, small pulse, loss of consciousness, collapse, paralysis of respiration. With prolonged repeated exposure of solutions of N. to the skin (in dentists due to leakage from the syringe), a purely local dermatitis often develops with increased sensitivity of the affected areas of the skin. Treatment of acute poisoning. In order to limit the entry of N. into the body, the limb should be tied with a tourniquet above the injection site. In cases of severe excitement - careful anesthesia with chloroform or chloral hydrate in enema, internally sodium bromide (1.0-2.0). In collapse - black hot coffee or tea, cognac, 70% alcohol (by teaspoon), mustard plasters on the heart area, warm baths with cold douches, under the skin - camphor, caffeine; rubbing hands and feet, wrapping them in warm sheets; bloodletting (300-400 cm³), infusion of physiol. solution. With severe respiratory disorders, artificial respiration is used. Application and dosage. Of all local anesthetic agents, N. and cocaine are currently used more often than others, with cocaine, due to its strong action on nerve endings, being an unsurpassed means for anesthesia of mucous membranes, while N., due to its low toxicity, is a valuable means for conduction anesthesia. (Application of N. - see Local anesthesia.) Many authors recommend adding adrenaline to N.

Adrenalini hydrochlorici 1:1,000); usually 1-2 drops are added per calculation for 5-10 cm³ of N. solution, but with larger quantities of the latter, proportionally less, so that in general no more than 15 drops of adrenaline are injected. Adrenaline should not be used for infiltration of the skin itself due to the possibility of gangrene. It is not advisable to add adrenaline before sterilizing N. solutions, since under the influence of temperature adrenaline easily decomposes, which is recognized by the pink color of the solution. According to some authors (Gross and Kochmann), adding 0.4% Kalii sulfurici to N. leads to a more rapid onset, enhancement (potentiation) and prolongation of anesthesia. The amount of K₂SO₄ added is so small that there is no question of any harmful effect. Kal. surf. can be combined with adrenaline, e.g., Rp. Novocaini 1.0, Sol. 2% Kalii sulfurici 20.0, Sol. 0.9% Natrii chlorati ad 100.0, Sol. 1:1000 Adrenalini hydrochlorici gtt XII. MDS for infiltration anesthesia (Hoffmann and Kochmann). Gross proposed adding Natrium bicarbonicum to novocaine (calculated ¼ part of the latter to 1 part N.), since in this case a larger part of N. is in the solution in the form of free base, the anesthetic power of which is higher than that of its salts. For stronger (over 3%) solutions of N., it is recommended to add less soda, otherwise precipitation of the base from the solution will occur. To create isotonicity, Gross recommends adding NaCl to N. solutions according to the following calculation per 100 cm³ of N. solution: for a 2% solution of the latter-0.5, for 3%-0.4, for 4%-0.3. Soda is more often added in about 1%. Preparations: 1. Novocainum (ФУП), seu Novocainum hydrochloricum; highest single dose under the skin 0.1, daily 0.3. 2. Novocainum nitricum, small, colorless and odorless crystals, melting at 100-102°, extremely soluble in water and alcohol; used like the previous one, but has the advantage that it does not cause precipitation of silver, and therefore is often used in 3% solution with Argentum nitricum in diseases of the urinary tract. 3. Novocaine-base, used in the form of solutions (up to 10%) in fatty oils in diseases of the ear and nose. 4. Novadrin, Novorenal and other commercial preparations, which are ready-made sterile solutions of N. with adrenaline in various concentrations (¼-½-1-2-5-10% solutions of N.) for dental practice and various types of anesthesia, 2% solution is also called Adrecam, it in combination with Magnesium sulfuricum-Optocain B. It should be borne in mind that in ready-made solutions, adrenaline is often significantly decomposed (pink color of the solution). 5. Letargin-commercial preparation in ampoules of 1.0 each, containing Extr. cort. Hamamelidis 0.5, Novocaini 0.015, Natrii chlorati 0.0092, Thymoli 0.0002, Aquae dest. 0.5 and 1 drop of Sol. 1:1,000 Adrenalini hydrochlorici. Used in dental practice. 6. Narkosia-commercial preparation in ampoules of 1.0 each, containing Extr. cort. Hamamelidis 1.0, Novocaini 0.015, Cocaini hydrochlorici 0.005, 1 drop of Sol. 1:1,000 Adrenalini hydrochlorici and physiological solution of Natrii chlorati.