Drug-related side effects

The costs associated with the treatment of a disease are categorized as direct costs and indirect costs. Those who are responsible for the payment of healthcare services are usually most interested in direct costs, or costs that are incurred directly as a result of the care of the patient s condition. These costs include hospitalization, physician visits, drugs, laboratory tests and procedures. They also include the treatment of drug-related side effects, the treatment of unfavorable drug drug interactions and the costs of switching from the current therapy to a new therapy. Direct costs may also include savings due to costs that are avoided inpatient days, outpatient visits, procedures and laboratory tests that do not occur. 

As a consequence of metered, localized drug delivery, controlled release devices generally equal or improve the therapeutic effects of conventional medications, while using a fraction of the drug. Thus, the problems of drug-related side effects are correspondingly lower. 

Discontinuation of self-treatment by the patient (= drop-out) is a critical point for the evaluation of studies. There are two dilferent types of drop-outs informative and non-informative. Non-informative drop-out means that no reason for the discontinuation is given this means that the patient stops taking medication by chance. Informative drop-out means that discontinuation occurs due to facts that give feedback for evaluation of the treatment, e.g. discontinuation due to drug-related side-effects. A comprehensive description of drop-out models can be found elsewhere [48]. 

Nesher R, Ticho U. Switching from systemic to the topical carbonic anhydrase inhibitor dorzolamide effect on the quality of life of glaucoma patients with drug-related side effects. Isr Med Assoc J 2003 5(4) 260-3. 

Table 3. Drug-related side effects reported (12 ) ...

Normally, 88% to 92% of phenytoin is bound to plasma protein, leaving 8% to 12% unbound. The unbound component is able to leave the blood to produce the clinical effect in the CNS, produce dose-related side effects in the CNS and at other sites, distribute to other peripheral sites, and be metabolized. Certain patient groups are known to have decreased protein binding, resulting in an increased percentage of drug that is unbound. These patient groups include ... 

Traditionally, the ideal extended-release product has been conceived as providing essentially stable blood levels over the whole dosing frequency interval. Thus, unlike the saw-edge blood concentration time profile of a non-controlled-release product that may show rather wild fluctuations between sub- and su-pratherapeutic blood levels, the ideal extended-release product avoids both nontherapeutic blood levels and those likely to have an increased frequency of dose-related side effects. However, in recent years con-trolled-release products that deliberately exploit a pulsatile drug release time profile have also attracted attention. 

Sulfasalazine is often associated with either dose-related or idiosyncratic adverse drug effects. Dose-related side effects usually include GI disturbances such as nausea, vomiting, diarrhea, or anorexia, but may also include headache and arthralgia. 

Rimonabant is an inverse agonist for the cannabi-noid receptor CBl. In 2006 rimonabant was approved in the European Union as an anti-obesity drug. The use of rimonabant after one year produces a modest weight loss of approximately 5%. However there are serious concerns over suicidality, depression and other related side effects associated with use of the drug. In Europe, rimonabant is now contraindicated for patients with severe depression. 

Type B effects are not related to the pharmacological properties of these drugs. Serious side effects may occur. Allergic skin and liver reactions to aspirin and paracetamol have been reported with risk of fibrosis, particularly in the retroperitoneal region for methysergide and hypersensitivity reactions with NSAID and pure analgesics. 

Dopamine agonists may produce adverse side effects such as nausea and vomiting. Postural hypotension is also a problem in some patients. With prolonged use, these drugs may cause CNS-related side effects such as confusion and hallucinations. 

Some common combinations of penicillins and specific beta-lactamase inhibitors are listed in Table 33-2. Administration of these drug combinations may produce side effects that are caused primarily by the penicillin component that is, penicillin-related side effects such as headache, gastrointestinal problems, and allergic reactions. Nonetheless, combining a beta-lactamase inhibitor with a penicillin can be an effective way of treating bacterial infections that might otherwise be resistant to traditional antibacterial therapy. 

Side effects. The common dose-related side effects of valproate include nausea, vomiting and gastrointestinal distress weight gain is frequent (estimated as high as 30%) and may be associated with a drug-induced decrease in the beta oxidation of fatty acids. Sedation is also frequent. Alopecia is an unusual side effect of valproate, possibly caused by an abnormal metabolite. Valproate has a number of metabolically linked side... 

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