James M. Dille

Comparison of the Effects of Marihuana and Alcohol on Simulated Driving Performance

The effects of marihuana, alcohol, and no treatment on simulated driving performance were determined for experienced marihuana smokers. Subjects experiencing a social marihuana high accumulated significantly more speedometer errors than when under control conditions, whereas there were no significant differences in accelerator, brake, signal, steering, and total errors. The same subjects intoxicated from alcohol accumulated significantly more accelerator, brake, signal, speedometer, and total errors than under normal conditions, whereas there was no significant difference in steering errors. Impairment in simulated driving performance does not seem to be a function of increased marihuana dosage or inexperience with the drug.

Vasopressor effects of topical epinephrine in certain dental procedures

Summary o 1. The use of epinephrine solutions for the control of bleeding in dental surgical procedures is attended, under certain circumstances, by absorption and a subsequent rise in blood pressure. 2. Generally, absorption and vasopressor effects are greater with greater vascular exposure and increase with increased concentration of epinephrine solutions. 3. The vasopressor effect of (locally) applied epinephrine is especially marked when the cortical plate of bone has been penetrated.

Elimination of Metrazol

Pharmacological and clinical evidence points to the fact that metrazol is very rapidly detoxicated in the body. The intravenous administration of a convulsive dose produces typical clonic convulsions from which the animal rapidly recovers. There is a possibility that the metrazol might be excreted by the kidneys, and so our first step consisted in eliminating this possibility. Chemical analysis of the urine of cats receiving convulsive doses of metrazol snowed none of the drug to be present in the urine. Bilaterally nephrectomized cats showed the same reaction to a convulsive dose of metrazol as they did before the performance of the nephrectomy. Hinsberg has shown that practically no metrazol is excreted by the intestinal route. It therefore seems logical that metrazol is not excreted but is detoxified. The liver has generally been assumed to be the locale for drug detoxication. We therefore administered phosphorus to cats. Cats treated in this way died from the administration of a dose of metrazol which formerly produced only slight convulsions. The role of the liver was further tested by a comparison of the dose required to produce convulsions when the drug was infused into the marginal ear vein or the portal vein of rabbits. In all cases a larger amount was required to produce convulsions when administered by the portal route. This evidence seems to establish the fact that metrazol is detoxified rather than excreted and that the liver plays an important role in the detoxication process.

AN EXPERIMENTAL INVESTIGATION OF THE CHANGE EFFECTED BY THE INGESTION OF CARISOPRODOL, ASPIRIN, CODEINE, AND A PLACEBO UPON THE THRESHOLD FOR DEEP PAIN INDUCED BY ULTRASONIC STIMULATION*

The analgesic properties of N-isopropyl-2-methyl-Zpropyl-l , 3-propanediol dicarbamate (carisoprodol) have been described by Berger el al. These investigators have indicated that carisoprodol has not shown any analgesic action when evaluated by some of the more commonly used pharmacological tests for analgesia such as the Woolfe and MacDonald2 hot-plate test, but that it was effective in relieving pain of the type produced by injection of silver nitrate in joints. They suggested that carisoprodol might modify the central perception of certain forms of pain, notably pain and spasm related to skeletal muscles and joints. Both Hardy el aL3 and Beecher4 have described comprehensively various methods for the study of pain thresholds. Although Beecher referred to high-frequency sound waves as a means of producing aching pain, he thought the possibility of tissue damage might exclude the technique from use for experimental pain purposes. While there is considerable literature on the use of ultrasonic stimulation as a therapeutic technique, we found no references indicating that the technique had been used previously for evaluating threshold changes related to the ingestion of analgesics. Ultrasound was chosen as the stimulus against which to test the analgesic action of carisoprodol, aspirin, codeine, and a placebo because the type of pain produced by high-frequency sound waves emitted from a supersonic oscillator has been variously described as deep pain, aching pain, and bone or periosteal pain. Ultrasonic stimulation produces an aching pain that is deep in both the subjective and objective senses: the subject reports the pain to be deep pain, not felt at the surface of the skin; tissue damage, if it results, occurs in such sites as subcutaneous tissue and muscles, as well as at the skin surface. Pohlman and his associatesbs6 have indicated that damage due to ultrasonic stimulation occurred in areas close to the bone more readily than in homogeneous tissue. They also indicated that periosteal pain always precedes damage and becomes unbearable after a very short time. They reasoned that this was due to standing waves that form between the bone and the sound source. Horvath7 has shown that a considerable temperature rise occurs between the tissue and bone. This is not to say that much of the ultrasound is not absorbed by the bone. Both Horvath and S~hliephake**~ have demonstrated considerable absorption even though the reflection from the bone may be relatively large. In sum, ultrasonic stimulation produces a deep, aching pain; the concern

AN EVALUATION OF ATROPINE AS AN ANTISIALOGOGUE IN DENTISTRY.

Abstract Atropine is an effective salivary-secretion suppressant and, therefore, useful in dentistry. Its value depends upon a careful selection of proper dosage in order to achieve maximum antisialogogic effects with a minimum of side actions. This dose would range between 0.4 mg. and 0.8 mg. of atropine sulfate (total dose) for an average adult. A proportional reduction should be made on the basis of body weight for children. It should probably not be used at all for dental procedures on children under 6 years of age. A liquid form of the drug is preferable, since with it the dose can be roughly proportioned to the body weight of the patient.

Antibiotics—Their mechanism of action and uses as anti-infective agents☆

Abstract Anti-infective agents of clinical usefulness for systemic administration act by inhibition of enzymatic processes important in the metabolic scheme of the pathogenic organism. This action may occur (1) at the cell wall, preventing the uptake of an essential metabolite or (2) within the cell where it may block catabolic energy-supplying mechanisms or anabolic protein-synthesizing processes. In any case the organism loses its ability to reproduce itself. Within the body this is tantamount to the destruction of the organism and recovery from the symptoms which it has been causing. The organisms against which a given antibiotic is effective is called its bacterial spectrum. Overlapping of the bacterial spectra of different antibiotics probably indicates that the organisms have a common enzyme capable of being blocked by the antibiotic; however, the variety of enzyme systems is so great and so varied that a bacterial species is capable of producing mutant strains resistant to a given antibiotic. These mutant strains make use of alternate pathways not blocked by the antibiotic. A desirable bacterial spectrum must have a minimum or no effects on the cells of the tissues of the host. This means that it must block metabolic pathways which are peculiar to bacteria and not present in tissue cells. This property is present in penicillin and probably to a large degree in chloramphenicol, aureomycin, and terramycin, and to a definitely lesser degree in streptomycin. Other antibiotics as tyrothricin are so harmful to the tissues that in spite of desirable bacterial spectra their use is confined to topical application.

The nature of pain and the action of analgesics.

Abstract Pain may be divided into two classes with corresponding groups of analgesic drugs: traumatic pain against which morphine and pharmacologically related agents are effective, and tension pain against which aspirin and related agents (as well as morphine, of course) are effective. Difficulties lie in the way of an objective study of the effectiveness of analgesic drugs because of the sensory nature of pain and its interpretation in the consciousness. Morphine, codeine, and similar analgesics are effective pain-relieving agents and there should be no hesitation in their use provided the agent is properly selected and the dentist is aware of the side effects which may occur. Acetylsalicylic acid is effective in tension or functional type pain, but little reliance can be placed on it for the relief of traumatic pain.

Observations of 3-Hydroxy-N-Methylmorphinan Hydrobromide (Dromoran®) on Fetal Respiratory Movements of the Rabbit.∗

Discussion and Summary Dromoran® passes without difficulty across the placental barrier and produces a decrease in the rate of respiratory movements of the fetuses. This passage across the placental barrier might be expected in view of the general principle stated by Needham(8) that the placental barrier is freely passed by practically all substances of low molecular weight. Thus in obstetrical analgesia one can assume that the agent will pass the placental barrier and the best analgesic will be one which will have high analgesic potency in the mother and a minimal effect on fetal respiration activity. The final evaluation of an analgesic must therefore be made under clinical conditions where the analgesic property can be evaluated in the patient. The doses of Dromoran® used in these experiments were much higher than would be used for human patients and there is no doubt but what satisfactory analgesia in humans can be obtained with lower doses. The question of whether these doses depress the respiratory function of the baby can be answered by clinical observation only with difficulty. On the basis of the parallelism shown in the rabbit experiments between the response of the maternal respiration rate and the rate of fetal respiratory movement it would appear safe to assume that if, in the human mother, respiratory function was depressed there would almost certainly be a corresponding effect on the respiratory function of the baby. Thus an obstetrician might make use of changes in the maternal respiration rate as an index to the respiratory function of the baby.