Barbara R. Manno

Drug Excretion in Human Breast Milk

SummaryThe excretion of drugs in human breast milk is reviewed with regard to milk production, composition, feeding patterns and mechanisms of drug transfer into milk. Fundamental principles of breast milk excretion are used to construct a pharmacokinetic approach useful for the study of most drugs. An infant-modulated 3-compartment open model is proposed for drug distribution and elimination in the breast feeding woman. Milk/plasma drug concentration ratios are projected on the basis of pH partitioning. While some studies confirm these projections, other studies demonstrate a need to consider additional factors such as lipid solubility and protein binding characteristics of a drug in milk.Data are lacking for most drugs and hence dosing via milk or risk to the infant remains speculative. Very few pharmacokinetic studies of both milk and infant plasma were found. A review of selected drug classes cites available information as a basis for future studies. Few drugs are contraindicated in breast feeding women, but supportive data for either proscriptions or permissive statements are often lacking. A neglected but potentially serious infant risk — impaired behaviour and development — is discussed from the standpoint of emerging animal data.Conceptually valid and comprehensive studies on drug excretion in breast milk are needed if this valuable nutrient for infants is to be made available safely.

Toxicology of Ipecac: A Review

The general effectiveness and safety of Ipecac syrup, per se, has not been questioned, but rather an attempt has been made to consolidate pertinent literature dealing with the toxic manifestations of Ipecac fluid extract. Ipecac contains both emetine and cephaeline and the toxicity of Ipecac fluid extract is consistent with reports on the toxicity of both compounds. The majority of the work has involved emetine since it is in higher concentration in Ipecac fluid extract than is cephaeline. Comparison of the clinical picture presented in syrup or fluid extract of Ipecac overdose and emetine toxicity in amebiasis treatment permits us to summarize the general characteristics of Ipecac alkaloid toxicity as involving primarily gastrointestinal, cardiovascular, and neuromuscular foci.

Topographic quantitative EEG sequelae of chronic marihuana use: a replication using medically and psychiatrically screened normal subjects

In two previous studies it was reported that chronic marihuana (THC) use was associated with unique quantitative EEG features which were present in the non-intoxicated state. THC users, as contrasted with controls, had significant elevations of Absolute Power, Relative Power, and Coherence of alpha activity over the bilateral frontal cortex. Furthermore, a quantitative EEG discriminant function analyses permitted a 95% correct user versus non-user classification. However, because all of the THC users and 58% of the non-user controls were psychiatric inpatients, diagnostic and medication effects, if any, were uncontrolled. In the present study the same quantitative EEG methods were used to study daily THC users and non-user controls who underwent a rigorous screening process to insure that they were medically and psychiatrically healthy. The results of previous studies were replicated and an additional EEG correlate of chronic THC exposure (reduced alpha frequency) was identified.

Comparison of Efficacy of Ginger with Various Antimotion Sickness Drugs

UNLABELLED Ginger and several other medications were compared with scopolamine and d-amphetamine for effectiveness in prevention of motion sickness. METHODS Double-blind techniques were used. The subjects were given the medications two hours before they were rotated in a chair making head movements until a symptom total short of vomiting was reached. Standardized N.A.S.A. techniques were used for speed of rotation and end-point of motion sickness. RESULTS The three doses of ginger were all at the placebo level of efficacy. Amitriptyline, ethopropazine and trihexyphenidyl increased the tolerated head movements but the increase was not statistically significant. Significant levels of protection were produced by dimenhydrinate, promethazine, scopolamine and d-amphetamine. Protection was further increased by combination of these latter drugs with d-amphetamine. Efficacy was greatest as the dose was increased. CONCLUSIONS The medication of choice in this study was scopolamine 0.6 mg with d-amphetamine 10 mg. This combination provided good protection with acceptable side effects.

Acute Marihuana (THC) Exposure Produces a “Transient” Topographic Quantitative EEG Profile Identical to the “Persistent” Profile Seen in Chronic Heavy Users

In two published pilot studies and a controlled replication using screened normals, chronic marihuana (THC) use was associated with a unique topographic quantitative EEG profile, consisting of significant elevations of Absolute and Relative Power and Coherence of alpha activity over the bilateral frontal cortex as well as a significant decrease in alpha frequency. This report attempts to establish the causal influence of THC in the above findings by the transient production of this exact quantitative EEG profile in subjects who did not display it at the beginning. Using paced smoking of marihuana with high and low dose THC content and placebo marihuana in a counterbalanced design under double blind conditions, all four of the topographic features of chronic THC exposure were produced as transient effects by THC but not by placebo.

PURSUIT METER II, A COMPUTER-BASED DEVICE FOR TESTING PURSUIT-TRACKING PERFORMANCE

The Pursuit Meter II, a microcomputer-based device developed for the quantitative determination of human pursuit-tracking performance, is described. Computer-generated moving patterns are displayed on a high resolution color video monitor. For the subject the task is to attempt to superimpose a red line presented on the screen, the vertical location of which he controls with a steering device, over a blue line the computer generates as the problem. Both lines, each composed of 279 segments, are generated at the same rate, left to right on the monitor. The individual differences between the subjects response and the problem are summed and stored by the computer as an error score which correlates inversely to the subjects ability to perform the task. Three Pursuit Meter II problems were presented to 26 male college students. Our data demonstrated that different levels of performance to the problems resulted and that the Pursuit Meter II can be used to quantify human pursuit-tracking performance.

Determination of temazepam and temazepam glucuronide by reversed-phase high-performance liquid chromatography

A rapid and sensitive method for extracting temazepam from human serum and urine is presented. Free temazepam is extracted from plasma and urine samples using n-butyl chloride with nitrazepam as the internal standard. Temazepam glucuronide is analyzed as free temazepam after incubating extracts with beta-glucuronidase. Separation is achieved using a C8 reversed-phase column with a methanol-water-phosphate buffer mobile phase. An ultraviolet detector operated at 230 nm is used and a linear response is observed from 20 ng/ml to 10 micrograms/ml. The limit of detection is 15.5 ng/ml and the limit of quantitation is 46.5 ng/ml. Coefficients of variation are less than 10% for concentrations greater than 50 ng/ml. Application of the methodology is demonstrated in a pharmacokinetic study using eight healthy male subjects.

Analysis and Interpretation of the Cannabinolic Content of Confiscated Marihuana Samples

In the last decade marihuana consumption in the United States has increased dramatically. A recent government estimate suggested that sufficient illicit marihuana is available in this country to provide 10 cigarettes per capita. Criminal penalties for possession of marihuana in this country are assigned for possession of defined quantities of marihuana and its identification as Cannabis sativa by microscopic and/or chemical tests.

The effects of temazepam and ethanol on human psychomotor performance

SummaryWe have studied the effects of temazepam, alone and in combination with ethanol, on psychomotor performance in six healthy men and women using a battery of five microcomputer-based tasks before and 30, 90, and 150 min after treatment.The tests were pursuit tracking, divided attention, two four-choice reaction time tests and tapping rate. The entire battery required 25 min. The subjects also reported their mood at each testing time using a computerized bipolar mood scales test.Temazepam (15 mg) plus ethanol (peak blood concentration of 11 mmol·1−1) significantly impaired divided attention, tracking, and reaction time over a 3 h period. There was significant impairment versus placebo for each drug alone on some of the tests.Plasma and urine concentrations of temazepam and temazepam glucuronide were measured, but there was no significant temporal correlation between impairment and drug or metabolite concentration in either plasma or urine.The subjects knew when they had taken ethanol, but could not discriminate temazepam from ethanol whether alone or in combination. The subjects rated their performance similarly after each of the four treatment conditions.The performance on the tracking, divided attention, and PAB reaction time tasks used in this study was impaired by a combination of Tmazepam and ethanol in doses which may not cause impairment when each is given alone.

Validation of two devices for evaluation of human psychomotor performance

The Pursuit Meter III (PM III) and the Simultaneous Hand and Foot Tracking (SHAFT) task are microcomputer-based devices for the evaluation of human psychomotor performance. Both devices are pursuit-tracking tasks. The primary task (PM III) requires a subject superimpose a line over a computer-generated sine wave. The computer wave is black and the subjects wave is red. The vertical position of the subjects wave is determined by a joystick controller. The SHAFT adds a second simultaneous tracking task (FTT) that is operated by means of a foot control. Ten naive subjects performed either device for 5 sessions/day over a three-day period. Each session consisted of 5 sweeps of the sine wave pattern. Mean performance on both tasks generally improved over the assessment period, and differential stability was reached within 10 sweeps for each device.