Toxicity and adverse/side effects

Serotonin-Selective Reuptake Inhibitors. Since their introduction in the mid-1980s SSRIs have become the most widely used of all antidepressants. This is largely because of their improved safety and tolerability in clinical use. Although the SSRIs are no more efficacious or rapid in onset of action than the tricyclics, they lack most of the serious toxicity and adverse side effects associated with the first-generation drugs. The relative absence of cardiac toxicity makes the SSRIs relatively safe in overdose (36). Fatal overdose... 

Except for synthetic polynucleotides, tittle data are available on the structure-activity relationship in the induction of interferon by synthetic polymers. Unfortunately, synthetic polynucleotides exhibit inherent toxicity and adverse side effects if applied in vivo. 

Table 11.5 Software for prediction of toxicity and adverse side effects...

As indicated in Table 1, statins, which block cholesterol biosynthesis by inhibition of hepatic HMGCoA reductase, have been used extensively to reduce LDL-C levels. At most therapeutic doses, statins marginally increase HDL levels by 5-10% [3,16]. The HDL elevation observed with statins has been highly variable and not easily extrapolated from the effects on LDL. A recent study (STELLAR) demonstrated increased HDL elevation with the use of rosuvastatin compared to simvastatin, pravastatin or atorvastatin (10% vs. 2-6%) [16,24], Although the mechanism of HDL elevation by statins is not clearly understood, it is proposed that statins enhance hepatic apoA-I synthesis [25] and decrease apoB-containing lipoproteins [26]. A number of clinical trials have demonstrated that statins reduce the risk of major coronary events. However, it is not clear if the statin-induced rise in HDL levels is an independent contributor to the reduced risk of coronary events. The observed small increase in HDL and adverse side effect profile related to liver function abnormalities and muscle toxicity limits the use of statins as monotherapy for HDL elevation [27],... 

Originally used in the treatment of malaria, the drugs chloroquine (Aralen) and hydroxychloroquine (Pla-quenil) have also been used to treat rheumatoid arthritis. In the past, these drugs have been used reluctantly because of the fear of retinal toxicity (see Adverse Side Effects ).25 There is now evidence, however, that these agents can be used safely, but they are only marginally effective when compared to other DMARDs. These drugs are therefore not usually the first choice, but they can be used in patients who cannot tolerate other DMARDs, or in combination with another DMARD (e.g., methotrexate) for more comprehensive treatment. 

Very possibly, however, inhibitors for the previously mentioned enzymes may exist in the plant world, as distinguished from synthetic chemicals. And among these plant snbstances there will perhaps be some that do not have toxic or adverse side effects. 

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. 

The Class I agents have many similar side effects and toxicities. The anticholinergic side effects include dry mouth, constipation, and urinary hesitancy and retention. Common gastrointestinal (GI) side effects include nausea, vomiting, diarrhea, and anorexia. Cardiovascular adverse effects are hypotension, tachycardia, arrhythmias, and myocardial depression, especially in patients with congestive heart failure. Common central nervous system (CNS) side effects are headache, dizziness, mental confusion, hallucinations, CNS stimulation, paraesthesias, and convulsions. 

The adverse side-effects of the TCAs, coupled with their toxicity in overdose, provoked a search for compounds which retained their monoamine uptake blocking activity but which lacked the side-effects arising from interactions with Hj, aj-adreno-ceptors and muscarinic receptors. One of the first compounds to emerge from this effort was iprindole, which has an indole nucleus (Fig. 20.3). This turned out to be an interesting compound because it has no apparent effects on monoamine uptake and is not a MAO inhibitor. This, together with its relatively minor antimuscarinic effects, led to it commonly being described as an atypical antidepressant. Mechanisms that could underlie its therapeutic actions have still not been identified but, in any case, this drug has now been withdrawn in the UK. 

In CONCLUSION, lithium is universally accepted as a mood-stabilizing drug and an effective antimanic agent whose value is limited by its poor therapeutic index (i.e. its therapeutic to toxicity ratio). Neuroleptics are effective in attenuating the symptoms of acute mania but they too have serious adverse side effects. High potency typical neuroleptics appear to increase the likelihood of tardive dyskinesia. Of the less well-established treatments, carbamazepine would appear to have a role, particularly in the more advanced stages of the illness when lithium is less effective. 

Daptomycin can give quite a few adverse reactions. The primary toxicities associated with daptomycin use are myopathies. Significant rates of cardiovascular, central nervous system, dermatological, gastrointestinal and hematological side effects have also been reported. 

Adverse effects include sedation, ataxia, dizziness and extrapyramidal side effects, dry mouth, blurred vision and urinary retention hepatic damage, bone marrow depression, hypertension, left ventricular failure and cardiovascular collapse in toxic doses. 

Adverse Side Effects. Azathioprine is relatively toxic, with more frequent and more severe side effects than other DMARDs.97 The primary side effects include fever, chills, sore throat, fatigue, loss of appetite, and nausea or vomiting these effects often limit the use of this drug. 

Adverse Side Effects. Adverse effects are relatively common with gold therapy, with approximately one third of patients experiencing some form of toxic effect.84 The primary side effects caused by gold compounds are gastrointestinal distress (diarrhea, indigestion), irritation of the oral mucosa, and rashes and... 

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