Antipsychotics adverse effects

Abidi S, Bhaskara SM. From chlorpromazine to clozapine—antipsychotic adverse effects and the clinician s dilemma. Can J Psychiatry. 2003 48 749-755. 

Schizophrenia is perhaps the most debiUtating psychiatric illness in modem medicine, affecting about 1% of the general population. Many of those affected require institutionalization (180). Unfortunately, the compounds available to treat this disorder are not hiUy effective in treating the spectmm of symptoms in all patients. Adverse effects are also a problem (181). In addition, available antipsychotic (neuroleptic) dmgs (Table 5) can at most only provide symptomatic rehef. 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

It is not surprising that a DA antagonist (especially those acting primarily on Di receptors) should produce the symptoms of Parkinsonism, a disorder caused by inadequate DA function (see Chapter 15), nor that its intensity or rate of onset over some weeks or months should increase with Dj antagonistic potency. Tolerance to this adverse effect can develop without affecting antipsychotic activity but the speed with which Parkinsonism resolves after stopping therapy may be from 3 to 12 months and can persist indefinitely in some cases. 

Sprinkle capsule 15, 25 mg Atypical Antipsychotics FDA approved for use in bipolar disorder Aripiprazole Abilify Tablets 5, 10, 15, Dosage should be slowly increased to minimize adverse effects (e.g., 25 mg at bedtime for 1 week, then 25-50 mg/day increments at weekly intervals) 10-30 mg/day once daily acute treatment of mania or mixed episodes due to lack of efficacy used as an adjunctive agent with established mood stabilizers Use as monotherapy or in... 

Extrapyramidal symptoms (EPS) Adverse effects of medications such as antipsychotics. EPS include dystonia (involuntary muscle contractions), tardive dyskinesia (repetitive, involuntary movements), parkinsonian symptoms (akinesia and tremors), and akathisia (motor restlessness or anxiety). 

The answer is d, (Katzung, p 482.) Although many antipsychotic agents can cause orthostatic hypotension, chlorpromazine is the most likely choice of the agents above for causing this adverse effect. 

There is an increased risk of sedation and delirium with increased age. There is also an increased risk of antidopaminergic effects such as parkinsonism due to antipsychotic drugs. Many other drugs that pass the blood-brain barrier may cause adverse effects in the elderly. The response of opioids may be increased in the elderly, resulting in oversedation (Turnheim 1998). 

Gerlach J. (1991). New antipsychotics classification, efficacy, and adverse effects. Schizophr Bull. 17(2) 289-309. 

Clozapine and olanzapine are atypical antipsychotic drugs used in the treatment of schizophrenia. Their strnctnres are depicted in Scheme 2.36. The use of clozapine and olanzapine, which are more effective than standard neuroleptic drugs in the treatment of refractory schizophrenia, is, however, limited becanse of their adverse effects. These adverse effects are ascribed to the formation of the corresponding cation-radicals in living organisms under oxidation by bone marrow cells. These cation-radicals eliminate protons from the NH fragments and generate their nitrenium cations. The nitreninm cations are covalently bonnd to the life-important proteins. This results in the toxic effects of clozapine and olanzapine (Sikora et al. 2007). 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Neuroleptic activity profiles. The marked differences in action spectra of the phenothiazines, their derivatives and analogues, which may partially resemble those of butyrophenones, are important in determining therapeutic uses of neuroleptics. Relevant parameters include antipsychotic efficacy (symbolized by the arrow) the extent of sedation and the ability to induce ex-trapyramidal adverse effects. The latter depends on relative differences in antagonism towards dopamine and acetylcholine, respectively (p. 188). Thus, the butyrophenones carry an increased risk of adverse motor reactions because Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and oonditlons of lloense. 

These antihistamines infreguently cause typical phenothiazine adverse effects. See the Antipsychotic Agents monograph for a complete discussion. 

Agranulocytosis Because of a significant risk of agranulocytosis, a potentially life-threatening adverse reaction, reserve clozapine for use in the treatment of severely ill schizophrenic patients who fail to show an acceptable response to adequate courses of standard antipsychotic drug treatment because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Consequently, before initiating treatment with clozapine, it... 

Pimozide, penfluridol and fluspirilene are di-phenylbutylpiperidine derivatives. Pimozide and penfluridol are antipsychotics with high potency but they give relatively few extrapyramidal problems and exhibit minimal other adverse effects. Fluspirilene has similar pharmacological activity although the risk for extrapyramidal reactions seems to be somewhat higher. 

Haddad PM, Sharma SG. Adverse effects of atypical antipsychotics differential risk and clinical implications. CNS Drugs 2007 21(ll) 911-36. 

Owens DG. Adverse effects of antipsychotic agents. Do newer agents offer advantages Dmgs 1996 51(6) 895-930. 

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