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Canal of one of the patient's lower anterior teeth. During this procedure, the air tip was inserted into and held in the canal. Because of the emphysematous appearance of the face at autopsy, the pathologist tied off the great vessels and then, under water, opened into the right ventricle, from which a large quantity of air bubbled forth."40 The authors went on to document the phenomenon in anaesthetized dogs and were able to produce air embolism by inserting a 21-gauge blunt cannula into the root canal and blowing air through it at 40-45 psi. The air was uniformly fatal if backflow from the cannula could be prevented by sealing it with self-curing acrylic resin, although an incomplete seal also allowed fatal results. Although the surgeon had not "sealed" the cannon drill into the mandible, he had produced the same effect. Firstly, the drill was designed to cut a precise hole in the mandible. Secondly, the presence of the mucoperiosteal flap could have acted as a "cover" over the drill to trap air in the mandible. Rickles and Joshi went on to state that an older animal did not succumb, although it had "an extremely emphysematous tongue and floor of the mouth, " presumably because "the narrower apical foramen and the possibility of fewer vessels with thicker walls in the periapical region as compared with those of younger dogs prevented effective air embolization." This may explain why Patient 1 succumbed so quickly and fatally ; , why Patients 2 and 3 could be resuscitated, why Patient 5 recovered from his cardiovascular collapse, and why Patient 4 suffered only massive subcutaneous emphysema. In conclusion, patients undergoing dental surgery are at risk of cardiovascular collapse. This may result from an exaggerated autonomic nervous system response to anxiety, from hypoxia, or from dysrhythmias induced by general or local anaesthetics alone or mixed with epinephrine ; . Less often, as illustrated by these cases, the surgical procedure is the cause of the collapse. Anaesthetists should be aware of the complications of both the anaesthetic and the surgery and be prepared to recognise and treat them.
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There is relatively less action on the nigrostriatal pathway where extrapyramidal side effects are thought to originate. D. These drugs have a therapeutic dose range that allows for the antipsychotic effect without inducing significant extrapyramidal symptoms. 1. Clozapine is an antagonist of serotonin-2A, alpha-1, dopamine-1, 2, and 4 receptors. Clozapine also possesses significant antihistamine and anticholinergic properties, leading to a side-effect profile similar to that of the typical low-potency agents. 2. Aripiprazole is a unique atypical agent in that it is a partial dopamine agonist D2 receptor ; . It is serotonin 2A receptor antagonist but is also a partial serotonin 1A agonist. 3. Serotonin-dopamine antagonists include risperidone Risperdal ; , olanzapine Zyprexa ; , ziprasidone Geodon ; , and quetiapine Seroquel ; . E. Pharmacokinetics 1. After oral absorption, peak plasma levels of antipsychotics usually occur within 2-4 hours. Liquid preparations are absorbed more quickly. IM injections reach peak levels in 30-60 minutes. 2. Antipsychotic agents undergo extensive hepatic metabolism. Typically 50% of the antipsychotic is excreted via the enterohepatic circulation and 50% is excreted through the kidneys. 3. Antipsychotics are 85-90% protein bound and highly lipophilic. 4. Half-lives generally range from 5-50 hours. Steady state plasma levels are established in 4-10 days. 5. Switching: When changing to an atypical antipsychotic, switching should employ the cross-titration method. The new medication should be added while the former medication is usually tapered over time 2-3 weeks ; . III. Clinical Guidelines A. Choosing an Antipsychotic Agent 1. In general, the choice of neuroleptic should be made based on past history of neuroleptic response and side effects. 2. Atypical antipsychotics have gained acceptance as firstline drugs for treatment of psychosis. They provide a superior long-term outcome in treatment of schizophrenia compared to typical antipsychotics. At least two weeks of treatment is required before a significant antipsychotic effect is achieved. 3. Patients with tardive dyskinesia TD ; should be considered for treatment with an atypical agent to avoid progression of neurological impairment. a. Clozapine is not associated with tardive dyskinesia. b. Olanzapine Zyprexa ; , risperidone Risperdal ; , quetiapine Seroquel ; and ziprasidone Geodon ; have significantly reduced incidences of tardive dyskinesia. B. Efficacy 1. Positive Symptoms: With the exception of clozapine, no differences have been clearly shown in the efficacy of typical and atypical agents in the treatment of positive symptoms eg, hallucinations, delusions, disorganization ; . Clozapine is more effective than typical agents. 2. Negative Symptoms: Atypical agents may be more effective in the treatment of negative symptoms eg, affective flattening, anhedonia, avolition ; associated with psychotic disorders. 3. Treatment-Resistant Psychosis: Clozapine is the only antipsychotic with substantial data to support efficacy in treatment-resistant psychosis. Thirty percent of poor responders to typical agents show significant improvement when treated with clozapine. 4. Bipolar Disorder: Quetiapine, olanzapine, aripiprazole, ziprasidone, and risperidone are FDA-approved for the treatment of acute mania. Olanzapine and aripiprazole have an indication for maintenance treatment of bipolar disorder. IV.Adverse Drug Reactions A. Side Effects Primarily Associated with Typical Antipsychotics 1. The typical antipsychotics have traditionally been classified according to their potency. 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