Drug additives

Nephrotoxicity (damage to the kidneys) and ototoxicity (damage to the organs of hearing) may be seen with the administration of this drug. Additional adverse reactions include nausea, chills, fever, urticaria, sudden fall in blood pressure with parenteral administration, and skin rashes. 

Simon RA Adverse reactions to drug additives. J Allergy Clin Immunol 1984 74 623-630. 

Another approaeh to the problem of providing an intravenous drug additive serviee is to add the drug to a small-volume (50-100 ml) infusion in a eollapsible plastie eontainer and store the preparation at -20°C in a freezer. The infusion ean be removed when required and thawed rapidly by microwave. Many antibiotics are stable for several months when stored in minibags at -20° C and are unaffected by the thawing process in a suitable microwave oven. Other antibiotics, e.g. ampieillin, are degraded when frozen. 

While brain serotonin systems may play a key role in mediating some of the effects of MDMA on analgesia and body temperature as well as in the reported anxiolytic-like and mood-altering subjective effects of the drug, additional neurotransmitter systems may contribute to some of the unique subjective experiences reported for MDMA and other drugs in this class. 

There is still debate whether oral antihistamines control ocular allergy as well as topical antihistamines. Topical antihistamines are recommended before oral agent in step therapy because of the increased risk of systemic side effects with oral drugs. Additionally, topical antihistamines provide faster relief of ocular symptoms. Consider oral antihistamines... 

T. Oguchi, Freezing of drug/additive binary systems II. Relationship between decarboxylation behavior and molecular states of p-aminosalicylic acid, Chem. Pharm. Bull., 37, 3088-3091 (1989). 

The most serious disadvantage of the prodrug approach to controlled sustained delivery is that extensive development must be undertaken to find the correct chemical modification for a specific drug. Additionally, once a prodrug is formed, it is a new drug entity and, therefore, requires extensive and costly studies to determine safety and efficacy. 

Fig. 5. Zn2+ enhances amphetamine induced release of [3H]MPP+. HEK-293 cells stably expressing the hDAT were preloaded with [3H]MPP+ and superfused upon reaching a stable baseline (basal efflux mean of the three fractions before drug addition hDAT wt (A) basal efflux 0.247 0.004% min T, i.e., 245.6 + 6.7 dpm min, n = 60 observations of randomly chosen experiments performed on different days hDAT-H193K (B) basal [3H]MPP+ efflux 0.433 0.08% min-1, i.e., 181.2 + 7.1 dpm min-1, n = 47. The experiment was started with the collection of 4-min fractions. After three fractions (12 min) of basal efflux, cells were exposed to Zn2+ (101iM), or left at control conditions as indicated. After six fractions (from 24 min and onward), amphetamine (10 pM) was added to all superfusion channels. After nine fractions (from 36 min and onward), all channels were switched back to control conditions. Data are presented as fractional efflux, i.e., each fraction is expressed as the percentage of radioactivity present in the cells at the beginning of that fraction. Symbols represent means + S.E. of 6-12 observations (one observation equals one superfusion chamber all experiments were performed in triplicate). Reproduced with permission from ref. (83).

FDA, food and drugs additional safeguards for children. Code of Federal Regulations, Title 21, Part 50, Subpart D, Rev. April 2003, p. 293. 

The current development plan for BioPrint calls for information-rich compounds, compounds which have human clinical data available. In 2005, 50 new compounds were added to the database, including 41 recently marketed drugs. Additional information-rich compounds are compounds with available animal data. 

Diluents - Sodium chloride injections are also indicated as pharmaceutic aids and diluents for the infusion of compatible drug additives. 

Pentazocine (Talwin) Narcotic analgesic that causes more CNS adverse effects, including confusion and hallucinations, more commonly than other narcotic drugs. Additionally, it is a mixed agonist and antagonist. High... 

Pharmaceutical Research and Manufacturers of America (PhRMA) The association s sixty-seven member companies are involved in the discovery, development, and manufacture of prescription drugs. Additionally, twenty-four research affiliate companies conduct research related to the development of biopharmaceuticals and vaccines. PhRMA, previously known as the Pharmaceutical Manufactures Association (PMA), provides its technical input to ICH. 

Chronic alcoholism results in enzyme induction. Acute alcoholic intoxication tends to inhibit drug metabolism (whether person is alcoholic or not). Severe alcohol-induced hepatic dysfunction may inhibit ability to metabolize drugs. Disulfiram-like reaction in the presence of certain drugs. Additive central nervous system depression with other central nervous system depressants. 

NDA applicants are required to submit a list of all excipients (as well as other drug components), used in the manufacture of a proposed new drug. Additionally, the applicant must provide sufficient information to establish that the use of each excipient is safe for its intended use, at its intended quantity. This information includes safety data, a statement of the composition, specifications, and any analytical methods used for the excipient. When a USP/NF monograph exists for an excipient, the applicant may state that the excipient in the drug will comply with the standards in the monograph instead of providing composition, specification, and analytical method information. The required safety information includes... 

An aqueous medium, either water or a buffered solution preferably not exceeding pH 6.8, is recommended as the initial medium for development of an IVIVC. Sufficient data should be submitted to justify pH greater than 6.8. For poorly soluble drugs, addition of surfactant (e.g., 1% sodium lauryl sulfate) may be appropriate. In general, nonaqueous and hydroalcoholic systems are discouraged unless all attempts with aqueous media are unsuccessful. Appropriate review staff in CDER should be consulted before using any other media. 

CCRF-CEM T-lymphoblastoid cells (ATCC CCL 119) were cultivated in RPMI 1640 medium supplemented with L-glutamine (0.3 g/L) containing 10% bovine serum using 24-well tissue culture plates. The cells were seeded at 10s mL 1 and after a 24-h incubation period (C02 atmosphere, 37 °C) tested compounds were added at five different concentrations. The endpoint of the cell growth was 72 h following the drug addition. An appropriate aliquot from every dish was then counted (cell counter Serono 150+). The inhibitory potency of the compounds tested was expressed as IC50 values. 

Carbamazepine + antiarrhythmic drugs —> additive effect on cardiac conduction time can cause increased cardiotoxicity. 

F- food color, D - drug additive, C-cosmetic coloring ... 

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