Dose-related side effects

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. 

Dose-related side effects include dizziness, sedation, headache, ataxia, fatigue, vertigo, abnormal vision, diplopia, nausea, vomiting, and abdominal pain. It causes more hyponatremia than carbamazepine. 

The most frequent dose-related side effects of valproate are GI complaints, fine hand tremor, and sedation. A /1-blocker may alleviate tremors. Other... 

Dosage adjustments Side effects noted during the initial cycles may be transient if they continue, dosage adjustments may be indicated. Many side effects are related to the potency of the estrogen or progestin in the products. The following table summarizes these dose-related side effects. 

Recent reports recognize pediatric alopecia as one of the more common dose-related side effects specific to DVP (Devilat and Blumel, 1991). It usually does not... 

Indomethacin Indocin Relative high incidence of dose-related side effects problems occur in 25°/o-50°/o of patients. 

The well-known dose-related side effects include gingival hyperplasia (due to altered collagen metabolism), cerebellar-vestibular effects (nystagmus, vertigo, ataxia), behavioural changes (confusion, drowsiness, hallucinations), increased seizure frequency, gastrointestinal disturbances (nausea, anorexia), osteomalacia (due to reduced calcium absorption and increased vitamin D metabolism) and megaloblastic anaemia (due to reduced folate absorption). 

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... 

Dose-related side effects nausea, insomnia, diarrhea. 

Unfortunately, potentially fatal agranulocytosis appears in 1-2% of patients treated with clozapine (7). This necessitates frequent blood monitoring, which can be inconvenient and expensive. Furthermore, despite its low potential for causing EPS and TD, clozapine causes other, dose-related side effects that can limit its effectiveness in some patients. The precise pharmacological actions of clozapine responsible for its clinical effectiveness are still being debated. Attempts to duplicate elements cf its complex pharmacological profile have led to the discovery of several new atypical antipsychotic drugs that have been approved in the United States for the treatment of schizophrenia. 

For patients who are unable to swallow capsules, the contents may be emptied into applesauce, jelly, or some other nonalkatine vehicle, provided that the patient does not chew the microencapsulated beads. Side effects of pancreatic enzyme products are uncommon. Perianal irritation resembling diaper rash may occur in infants fed excess quantities of enzyme powders. Hyperuricosuria also has been reported to occur secondary to pancreatic enzyme use, apparently related to their high purine content. Proximal colonic stricture (fibrosing colonopathy) is a dose-related side effect associated with lipase doses in excess of 24,000 units/kg per day. ... 

TOXICITY Common dose-related side effects are G1 complaints (nausea, vomiting, and anorexia) and CNS effects (drowsiness, lethargy, euphoria, dizziness, headache, and hiccups) some tolerance to these effects develops. Parkinson-like symptoms and photophobia also have occurred. Restlessness, agitation, anxiety, aggressiveness, inability to concentrate, and other behavioral effects have occurred primarily in patients with a history of psychiatric disturbance. Urticaria and other skin reactions, including Stevens-Johnson syndrome, as well as systemic lupus erythematosus, eosinophilia, leukopenia, thrombocytopenia, pancytopenia, and aplastic anemia have been attributed to the drug, and deaths have resulted from bone marrow depression. 

Duff HJ, Roden D, Primm RK, Oates JA, Woosley RL. Mexiletine in the treatment of resistant ventricular anhythmias enhancement of efficacy and reduction of dose-related side effects by combination with quinidine. Circulation (1983) 67,1124-8. 

Therapeutic drug management (TDM) of most antidepressants is not widely available or widely utilized, for any clinical indication. The primary benefits of TDM in the management of antidepressant therapy could include assessment of patient compliance, detection of drug-drug interactions or altered pharmacokinetics, and evaluating the concentration relationship of individual patient response and/or thresholds for dose-related side effects. Of all the classes of antidepressant drugs, TDM of TCAs is most common. 

In the long-term NIH study involving 116 patients treated for up to 9.5 years [10], omeprazole caused no dose-related side-effects or idiosyncratic reactions in any patient, and no patient had to stop taking it because of an untoward effect. These results are similar to those of a number of other long-term treatment studies in patients with ZES [6, 8]. 

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