General side effect profile

The general side effect profile from Caliper tvith 65 different targets. 

Clinically, GM-CSF or G-CSF have been used to accelerate recovery after chemotherapy and total body or extended field irradiation, situations that cause neutropenia and decreased platelets, and possibly lead to fatal septic infection or diffuse hemorrhage, respectively. G-CSF and GM-CSF reproducibly decrease the period of granulocytopenia, the number of infectious episodes, and the length of hospitalization in such patients (152), although it is not clear that dose escalation of the cytotoxic agent and increased cure rate can be rehably achieved. One aspect of the effects of G-CSF and GM-CSF is that these agents can activate mature cells to function more efficiently. This may, however, also lead to the production of cytokines, such as TNF- a, that have some toxic side effects. In general, both cytokines are reasonably well tolerated. The side effect profile of G-CSF is more favorable than that of GM-CSF. Medullary bone pain is the only common toxicity. 

P-Adrenoceptors have been subdivided into P - and P2-adrenoceptors. A third subset called nontypical P-adrenoceptors or P -adrenoceptors have been described but are stiU the subject of debate. In terms of the interactions with various subsets of P-adrenoceptors, some antagonists are nonselective in that they antagonize the effects of activation of both P - and P2-adrenoceptors, whereas others are selective for either P - or P2-adrenoceptors. P - and P2-adrenoceptors coexist in almost all organs but generally, one type predominates. The focus herein is on the clinically relevant P -adrenoceptor-mediated effects on heart and on P2-adrenoceptor-mediated effects on smooth muscles of blood vessels and bronchioles, the insulin-secreting tissue of the pancreas, and skeletal muscle glycogenolysis for side effects profile (36). 

The choice of an antibiotic agent for acute bacterial conjunctivitis is largely empiric. The initial treatment needs to include Staphylococcus coverage, but also may be chosen on the basis of cost and side-effect profile.13,14 In general, ointments are a good dosage form for children. Adults prefer drops because they do not interfere with vision.14... 

Toremifene is a recently marketed antiestrogen whose primary advantage is a lower estrogenic antiestrogenic ratio than tamoxifen (based on laboratory data).41 Toremifene (60 mg orally daily) has been found to have efficacy similar to that of tamoxifen in metastatic disease and a generally similar side-effect profile.42 Currently, toremifene is indicated as an alternative to tamoxifen in patients with metastatic breast cancer, but studies are ongoing that evaluate its safety and efficacy in the adjuvant setting. 

Regarding side-effect profiles, all three SSNRIs are generally well tolerated, most adverse events occurring early in treatment, with a mild to moderate severity and a tendency to decrease or disappear with continued treatment. Venlafaxine (1) seems to be the least weU-toIerated SNRI, combining a higher level of serotonergic adverse events (nausea, sexual dysfunction, withdrawal problems) with dose-dependent hypertension. In contrast, milnacipran (2) and duloxetine (3) appear better tolerated and essentially devoid of cardiovascular toxicity. 

In general, the SSRIs have a more tolerable side effect profile than the tricyclic antidepressants with their anticholinergic effects. Review of the rate that subjects in the controlled studies discontinued a SSRI because of adverse effects provides some perspective on how well tolerated the medications are, although the specifics may vary according to dosage and design (e.g., forced titration) and are not directly comparable. The rate of discontinuation was reported to be 12% (4/48) for fluoxetine (Emslie et ah, 1997), 9.7% for paroxetine (Keller et ah, 2001), 13% (12/92) for sertraline (March et ah, 1998), and 33% (19/57) (Riddle et ah, 2001) and 7.9% (5/63) for fluvoxamine (Walkup et ah, 2001). 

In summary, buspirone is an effective generalized anxiety treatment that differs from conventional antianxiety drugs in speed of symptom reduction and types of symptoms affected. Although buspirone might seem to be the drug of choice for treatment of chronic anxiety, it has not displaced the use of benzodiazepines in the treatment of anxiety, perhaps because of its side-effect profile [dizziness, sedation, nausea], slow onset of action, and the opinion of some clinicians that its anxiolytic efficacy is less robust than that of benzodiazepines. Buspirone is accepted as an anxiolytic treatment much more widely in the United States than in most other countries [Kunovac and Stahl 1995]. 

The commonly used classes of antidepressants are discussed in the following sections, and information about doses and half-lives is summarized in Table 2-1. The antidepressant classes are based on similarity of receptor effects and side effects. All are effective against depression when administered in therapeutic doses. The choice of antidepressant medication is based on the patient s psychiatric symptoms, his or her history of treatment response, family members history of response, medication side-effect profiles, and comorbid disorders (Tables 2-2 and 2-3). In general, SSRIs and the other newer antidepressants are better tolerated and safer than TCAs and MAOIs, although many patients benefit from treatment with these older drugs. In the following sections, clinically relevant information is presented for the antidepressant medication classes individually, and the pharmacological treatment of depression is also discussed. The use of antidepressants to treat anxiety disorders is addressed in Chapter 3. 

Opioid peptides have an action and side-effect profile identical to non-peptidic opioids, but in general have significantly less favorable physicochemical and pharmacokinetic properties. Considering the numerous attempts to overcome these drawbacks undertaken since the mid-1970s that have not resulted in a single opioid... 

Although the SSRIs clearly share the same mechanism of action, therapeutic profiles, and overall side effect profiles, individual patients often react very differently to one SSRI versus another. This is not generally observed in large clinical trials, where group differences between two SSRIs either in efficacy or in side effects are very difficult to document. Rather, such differences are seen by prescribers treating patients one at a time, with some patients experiencing a therapeutic response to one SSRI and not another and other patients tolerating one SSRI but not another. 

Adverse Effects. The most common side effects associated with tizanidine include sedation, dizziness, and dry mouth.40 As indicated, however, tizanidine tends to have a more favorable side effect profile than other alpha-2 agonists, and this drug produces less generalized weakness than oral baclofen or diazepam. Tizanidine may therefore be a better alternative to these other agents in patients who need to reduce spasticity while maintaining adequate muscle strength for ambulation, transfers, and so forth. 

Neuroleptics have been the group of drugs most widely recommended for delusional states. Of the first-generation neuroleptics, the sedative, cognitive impairing and extrapyramidal side effects are likely to be particularly prominent in the elderly. The introduction of the atypical neuroleptics should improve the treatment of these disorders as they are generally better tolerated due to their improved side-effect profile. 

Table 70-4 shows the relative potency and selectivity of the antidepressants for inhibition of NE and 5-HT reuptake and relative side-effect profiles. The selective serotonin reuptake inhibitors (SSRIs) inhibit the reuptake of 5-HT into the presynaptic neuron. They are generally chosen as first-line antidepressants because of their safety in overdose and improved tolerability compared to earlier agents. 

Tricyclic antidepressants are no longer generally considered a first-line treatment option for depression because of their side effect profile... 

Use of Oral CAIs in Clinical Practice. Use of oral CAIs is generally limited to the management of acute primary ACG or in cases where other efforts have been proven to be inadequate or contraindicated. In chronic use, methazolamide 25 or 50 mg three times a day generally carries a more favorable side effect profile than acetazolamide in any form. If acetazolamide must be used chronically, then 500 mg (at bedtime or twice daily) in a sustained-release form is preferred. This formulation may... 

---