Adverse Effect

Causes of Adverse Effects Overdosage (A). The drug is administered in a higher dose than is required for the principal effect this directly or indirectly affects other body functions. 

For instance, morphine (p.208), given in the appropriate dose, affords excellent pain relief by influencing nociceptive pathways in the CNS.In excessive doses, it inhibits the respiratory center and makes apnea imminent. The dose-dependence of both effects can be graphed in the form of dose-response curves (DRCs). The distance between the two DRCs indicates the difference between the therapeutic and toxic doses. This margin of safety ( therapeutic index ) indicates the risk of toxicity when standard doses are exceeded. 

It should be noted that, apart from the amount administered, the rate of drug delivery is important. The faster blood levels rise, the higher concentrations will climb (p. 49). Rather than being required therapeutically, the initial concentration peak following i.v. injection of morphinelike agents causes side effects (intoxication and respiratory depression, p. 208). 

Increased sensitivity (B). If certain body functions develop hyperreactivity, unwanted effects can occur even at normal Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms 

Lack of selectivity (C). Despite appropriate dosing and normal sensitivity, undesired effects can occur because the drug does not specifically act on the targeted (diseased) tissue or organ. For instance, the anticholinergic atropine is bound only to acetylcholine receptors of the muscarinic type however, these are present in many different organs. Moreover, the neuroleptic chlorpromazine is able to interact with several different receptor types. Thus, its action is neither organ-specific nor receptor-specific. 

All of the examples discussed in Section 7.2.3, reveal the great potential of solid forms that can be exploited to achieve the desired pharmacokinetic properties. However, one has to also keep in mind the possibility that an increase in dissolution rate and solubility could sometimes even prove to be detrimental. It could lead to the accumulation of the drug, beyond the equilibrium solubility, creating a driving force for the nucleation and crystallization of some stable phases in the physiological medium. To avoid any such accumulation, the drug should possess a sufficient absorption rate for its optimal distribution in the body. 

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This might he worthwhile if the FEED-BYPRODUCT separation is expensive. To use a purge, the FEED and BYPRODUCT must be adjacent to each other in order of volatility (assuming distillation is used as the means of separation). Of course, care should be taken to ensure that the resulting increase in concentration of BYPRODUCT in the reactor does not have an adverse effect on reactor performance. Too much BYPRODUCT might, for example, cause a deterioration in the performance of the catalyst. 

Exposure limits (threshold limit value or TLV) are those set by the Occupational Safety and Health Administration and represent conditions to which most workers can be exposed without adverse effects. The TLV value is expressed as a time weighted average airborne concentration over a normal 8-hour workday and 40-hour workweek. 

Since the introduction of cortisone (1) (1948) and hydrocortisone (2) (1951), adrenal-cortical hormones have remained an important and unreplaced dmg class. Though not without adverse effects, these compounds have continued to be the dmg of choice in the treatment of afflictions ranging from the moderate skin rash to severe acute inflammatory disorders, and are included in many other therapeutic regimes. 

Health and Safety Factors. The following toxicides for acetonitrile have been reported oral LD q (lats), 3030—6500 mg/kg skin LD q (rabbits), 3884—7850 mg/kg and inhalation LC q (i ts), 7500—17,000 ppm (29). Humans can detect the odor of acetonitrile at 40 ppm. Exposure for 4 h at up to 80 ppm has not produced adverse effects. However, exposure for 4 h at 160 ppm results in reddening of the face and some temporary bronchial tightness. 

Pharmaceutical powder aerosols have more stringent requirements placed upon the formulation regarding moisture, particle size, and the valve. For metered-dose inhalers, the dispensed product must be deflvered as a spray having a relatively small (3—6 -lm) particle size so that the particles can be deposited at the proper site in the respiratory system. On the other hand, topical powders must be formulated to minimize the number of particles in the 3—6-p.m range because of the adverse effects on the body if these materials are accidently inhaled. 

Addition of approximately 40% of the halogen flame retardants are needed to obtain a reasonable degree of flame retardancy. This usually adversely affects the properties of the plastic. The efficiency of the halogens is enhanced by the addition of inorganic flame retardants, resulting ia the overall reduction of flame-retardant additive package and minimising the adverse effects of the retardants. 

Most of the bacteria, yeasts, molds, and higher fungi of interest for SCP production are deficient in methionine and must be supplemented with this amino acid to be suitable for animal feeding or human food appHcations. Also, lysine—arginine ratios should be adjusted in poultry rations in which yeast SCP is used (62). Human feeding studies have shown that only limited quantities of yeast such as Candida utilis can be added to food products without adverse effects on flavor (63). 

Oral LD q levels have been deterrnined in the mouse at 470 mg/kg (21) and the guinea pig at 7750 mg/kg (22). Several other studies (23—25) have shown that large quantities of both synthetic and natural glycerol can be adniinistered orally to experimental animals and humans without the appearance of adverse effects. Intravenous adniinistration of solutions containing 5% glycerol to animals and humans has been found to cause no toxic or otherwise undesirable effects (26). 

Rats showed no adverse effects from 5.0% dipropylene glycol in their drinking water for 77 days, but at a dose of 10.0% in the drinking water, kidney and Hver injury and some deaths occurred (35). A sufficient number of studies have not been carried out on tripropylene glycol to permit conclusions to be drawn regarding its chronic oral toxicity. 

An alternative process is electroslag remelting (ESR). More oxide inclusions are found in ESR steel than in VAR steel, but thek size and distribution are such that they normally have no noticeable adverse effect on properties (141). 

R53 may cause long-term adverse effects in the aquatic environment c... 

Materials of Construction. In choosing the proper materials of constmction for storing and using hydrazine, it is necessary to consider both the effects of the material on the stabiUty and quaUty of the hydrazine as well as the effect of the hydrazine on the material of constmction. Hydrazine is thermally stable, storable for years without adverse effects either to the product or the storage container provided the recommended materials are used, all systems are clean, and an inert gas, ie, nitrogen, is maintained over the system at all times. Table 10 is a brief listing of materials compatibiUty (125). 

D. Schmidt, Adverse Effects of Antiepileptics, Raven Press, New York, 1982. 

Adverse side effects of gold treatments include stomatitis, rash, and proteinuria. Complete blood counts and urinalysis should be performed before each or every other injection of gold compounds. Pmritic skin rash and stomatitis are more common adverse effects that may resolve, if therapy is withheld for a few weeks and then restarted cautiously at a lower dose. Oral gold causes less mucocutaneous, bone marrow, and renal toxicity than injectable gold, but more diarrhea and other gastrointestinal reactions appear. 

Penicillamine (29) can be effective in patients with refractory RA and may delay progression of erosions, but adverse effects limit its useflilness. The most common adverse side effects for penicillamine are similar to those of parenteral gold therapy, ie, pmritic rash, protein uria, leukopenia, and thrombocytopenia. Decreased or altered taste sensation is a relatively common adverse effect for penicillamine. A monthly blood count, platelet count, and urinalysis are recommended, and also hepatic and renal function should be periodically monitored. Penicillamine is teratogenic and should not be used during pregnancy. 

Cancer. Cancer is a cellular malignancy characterized by loss of normal controls resulting in unregulated growth, lack of differentiation, and the abihty to invade local tissues and metastasize. Most cancers are potentially curable, if detected at an early enough stage. The ideal antineoplastic agent would destroy cancer cells without adverse effects or toxicities to normal cells. No such dmg exists. 

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