Effect unwanted

Caffeine is considered by pharmacologists to be a mild stimulant of the central nervous system. It has been shown to promote feelings of well being and increased abiUty to perform certain mental tasks efficiently. There are people who are oversensitive to the effects of caffeine overindulgence by these individuals, eg, intake of more than 600 mg caffeine/d, can bring unwanted effects such as anxiety, restlessness, sleeping difficulties, headache, or palpitations of the heart (54). 

Change in feed composition. This may happen due to change in suppliers or due to introduction of reworked material. Unwanted effect on reaction products, by-products. Varying inhibitor concentrations in monomers from different vendors. Potential for runaway reaction. 

Qualitative difference in pharmacological effect Opposite enantiomer may cause unwanted effects... 

For fibres and filaments such orientation is desirable, but for solid objects where impact strength is often more important than tensile strength such orientation is usually unwelcome. It can also have further unwanted effects. This arises from the fact that oriented molecules are basically unstable and will at the first opportunity try to coil up. Thus on heating samples up to temperatures near severe distortion can occur leading to warped mouldings. 

FIGURE 8.3 Examples of chemical modification of active drags that have either unwanted effects (cocaine, norepinephrine) or suboptimal effects (penicillin, progesterone) to molecules with useful therapeutic profiles. 

Taxanes (paclitaxel, docetaxel) are derivatives of yew tree bark (Taxus brevifolia). They stabilize microtubules in the polymerized state leading to nonfunctional microtubular bundles in the cell. Inhibition occurs during G2- and M-phases. Taxanes are also radiosensitizers. Unwanted effects include bone marrow suppression and cumulative neurotoxicity. 

Epipodophyllotoxins (etoposide, teniposide) are derived from mandrake root (Podophyllum peltatum). They inhibit topoisomerase H thus causing double strand breaks. Cells in S- and G2-phases are most sensitive. Unwanted effects include nausea and vomiting, myelosuppression, and hair loss. 

Camptothecins (irinotecan, topotecan) are derived from the bark of the Chinese tree Xi Shu (Camptotheca accuminata). They inhibit topoisomerase I thus effecting double strand breaks. Unwanted effects include diarrhea and reversible bone marrow depression. 

Local anaesthetics are more consistently effective than other therapies, but their use is controversial. High concentrations are needed for therapeutic benefit, but this also increases the amount crossing the blood brain barrier and entering the brain producing unwanted effects. Topical administration to the airways can reduce this. 

Emetogenic drugs may be of value in treating cases of acute poisoning but usually nausea and vomiting induced by a drag are unwanted effects occurring in addition to its therapeutic action. 

UDP-Glucuronyl Transferase Ultrarapid Metabolizer Unstable Angina Unwanted Effects UPR... 

There is some evidence of a synergistic effect on reinforcement with concurrent administration of benzodiazepines and opioids (Walker and Ettenberg 2003). Cocaine abusers are less likely than opioid abusers to abuse benzodiazepines, preferring alcohol and opioids as secondary drugs of abuse. The most common pattern of benzodiazepine misuse in these individuals is intermittent use of therapeutic or supratherapeutic doses to counter unwanted effects of cocaine. 

The most common unwanted effects of the barbiturates are oversedation and psychomotot impaitment, which may petsist well into the next day following a hypnotic dose. Patadoxical excitement, hypersensitivity reactions, and muscle or joint pain may occur in rare cases. Drug-drug interactions occur with the CNS sedatives, and a number of drugs have enhanced metabolism when co-administered with barbiturates (Barnhill et al. 1989). 

The best-understood sites of action of morphine are at spinal and brainstem/ midbrain loci, producing both the wanted and unwanted effects of the opioid. The spinal actions of opioids and their mechanisms of analgesia involve (1) reduced transmitter release from nociceptive C-fibres so that spinal neurons are less excited by incoming painful messages, and (2) postsynaptic inhibitions of neurons conveying information from the spinal cord to the brain. This dual action of opioids can result in a... 

The relative extent of the unwanted effects caused by selective agonists at the different opioid receptors is of great importance in determining if non-mu opioids will have better spectra of actions as compared to morphine. However, there are good indications that the kappa and delta receptor agonists cause less respiratory depression than mu... 

Even though the drug is used for non-medical reasons, there will still be sought-after and unwanted effects. 

Hydrate control is not included in this chapter, but is discussed in Chapter 13 because of the relative importance and difference in chemical mechanism. Many chemicals added to water will result in a depression of the freezing point. The practical application is restricted, however, because of some other unwanted effects, such as corrosion, destruction of rubber sealings in engine parts, or economic aspects. 

Another unwanted effect of smoothing is the alteration of the frequency characteristics of the noise. This calls for caution. Because low frequencies present in the noise are not removed, the improvement of the signal-to-noise ratio may be limited. This is illustrated in Fig. 40.23 where one can see that after smoothing with a 25 point window low-frequency noise is left. In Section 40.5.3 filtering... 

An early effort using this approach in Guinea-pigs reported variable results — attributable to incomplete nerve sectioning (Planel, 1953). Sectioning procedures may also produce some unwanted effects as intracranial nerve section will remove part of the animal s N. terminalis sensory capability (Devitsina and Cherova, 1992). 

Albuterol (also known as salbutamol outside the United States), the most commonly used inhaled short-acting 132-agonist, is a racemic mixture (50 50) of albuterol enantiomers. The R-enantiomer is the active component whereas the S-enantiomer is inactive or may be associated with unwanted effects. Levalbuterol, the pure R-enantiomer of albuterol, is available as a solution for nebulization and as an MDI dosage form. Comparative studies show similar efficacy and safety between levalbuterol and albuterol, but the acquisition cost of levalbuterol is substantially higher. 

The ultimate fate of drugs and their metabolites is a major concern. If they are not cleared in a reasonable time, they could promote undesirable side effects. Polymer drug carriers are usually nonbiodegradable, and if their size is greater than 40,000 daltons, they could accumulate in the host with the potential of future unwanted effects. 

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