Extrapyramidal reactions caused

When ondansetron is administered with rifampin, blood levels of ondansetron may be reduced, decreasing the antiemetic effect. Dimenhydrinate may mask the signs and symptoms of ototoxicity when administered with ototoxic drugp, such as the aminoglycosides (see Chap. 10), causing irreversible hearing damage. When lithium is administered with prochlorperazine, the risk of extrapyramidal reactions increases (see Chap. 32). 

When stimulation of Gl motility might be dangerous (eg, in the presence of Gl hemorrhage, mechanical obstruction, or perforation) pheochromocytoma (the drug may cause a hypertensive crisis, probably because of release of catecholamines from the tumor control such crises with phentolamine) sensitivity or intolerance to metoclopramide epileptics or patients receiving drugs likely to cause extrapyramidal reactions (the frequency and severity of seizures or extrapyramidal reactions may be increased). 

Extrapyramidal reactions include parkinsonism, acute muscular dystonias, akathisia, tardive dyskinesia and malignant neuroleptic syndrome. They can also cause hypersensitivity reaction including cholestatic jaundice, skin rash, urticaria, photosensitivity and contact dermatitis. There is also blue pigmentation of skin, lenticular opacities on prolonged use of drug. 

One common denominator of all antipsychotics is the biockade of centrai dopamine (DA) receptors. As a result, extrapyramidal reactions, particularly parkinsonian symptoms, are a major adverse effect of many of these drugs, as well as an important clue to their mechanism of action. True Parkinson s disease is caused by a DA deficiency in the nigrostriatal system. Further, crystallographic data have demonstrated that CPZ s molecular configuration is similar to that of DA, which could explain its ability to block this neurotransmitter s receptors. Drugs with similar structures that do not block DA receptors (e.g., promethazine, imipramine) do not have antipsychotic activity. Another example is the isomer of flupenthixol, which blocks DA receptors is an effective antipsychotic, but the isomer that does not is ineffective (7). The other family of dopamine receptors, D and Dg, have not yet been implicated in psychosis. 

Because the tardive syndromes that develop in adults are often irreversible and have no satisfactory treatment, care must be taken to reduce the likelihood of their occurrence. Antipsychotic medication should be prescribed only when necessary and should be withheld periodically to assess the need for continued treatment and to unmask incipient dyskinesia. Thioridazine, a phenothiazine with a piperidine side chain, is an effective antipsychotic agent that seems less likely than most to cause extrapyramidal reactions, perhaps because it has little effect on dopamine receptors in the striatal system. Finally, antimuscarinic drugs should not be prescribed routinely in patients receiving neuroleptics, because the combination may increase the likelihood of dyskinesia. 

Metoclopramide can cause adverse effects such as sedation, akathisia (motor restlessness), involuntary movements, diarrhea, and dizziness. The extrapyramidal reactions, which are more common in patients < 30 years old, can be relieved by intravenous or oral diphenhydramine or benztropine (Cogentin). 

Risperdal causes all the extrapyramidal reactions found with other neuroleptics, including tardive dyskinesia (Addington et al., 1995) and neuroleptic malignant syndrome (Mahendra, 1995 Singer et al., 1995 see chapter 4). It is too early to tell if the rate of tardive dyskinesia will differ from that of other neuroleptics. 

The so-called clinical effect of neuroleptics, their chemical loboto-mizing impact, is primarily caused by the blockade of dopaminergic nerves, especially the D2 receptors, in the ventral striatum, with their connections to the limbic system and frontal lobes (chapters 1 and 2). However, blockade of the same D2 receptors in the dorsal striatum is the probable cause of extrapyramidal reactions, including TD (Ethier et al., 2004 Seeman, 1995). Hence, as described in chapter 1, the so-called therapeutic effect is inextricably entwined with some of the worst adverse effects. 

SSRIs cause a wide range of neurological impairments. Spigset (1999) found the following neurological reports in order of frequency parethesias, headache, dizziness, tremor, seizures, acute dystonia, dyskinesia, muscle cramps, muscle weakness, parkinsonism, muscle stiffness, akathisia, myoclonus, extrapyramidal reactions, increased muscle tone, and migraine. There have been reports of irreversible tardive dyskinesia caused by SSRIs (see subsequent section). 

The risk of causing EPS, another SSRI-induced neurologist disorder, was apparent from early on. The FDA s Kapit (1986) warned, It is possible that a tardive syndrome related to fluoxetine may exist. It will be necessary to be on the lookout for such events (p. 32). By January 1993, more than two dozen reports of Prozac-induced tardive dyskinesia had reached the FDA (1993), but the profession has not taken much notice. Numerous case reports confirm that the SSRIs can produce persistent extrapyramidal reactions, including tardive dystonia with painful and disabling spasms of the neck and shoulder musculature. 

Acute extrapyramidal reactions occur more often after ingestion of high-potency drugs, such as haloperidol and fluphenazine these respond to parenteral benzatropine, but anticholinergic drugs should be used judiciously, so as not to worsen peripheral or central autonomic toxicity. Other serious, but less frequent, complications include paralytic ileus and hypothermia. Acute renal insufficiency has been very rarely reported, but is apparently reversible and can occur secondary to severe hypotension or other causes after acute ingestion (615). 

Atypical antipsychotics such as aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are effective as monotherapy or adjunctive therapy with lithium and valproate in the treatment of acute mania. Some antipsychotics have the potential to cause adverse effects such as extrapyramidal reactions, sedation, depression, emotional blunting, sexual dysfunction, weight gain, and orthostatic hypotension. Prophylactic use of antipsychotics may be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed because of long-term adverse effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). ... 

Metoclopramide is contraindicated in the presence of GI hemorrhage, mechanical obstruction, or perforation. Because it is a dopamine-receptor-blocking agent, it causes extrapyramidal reactions such as dystonia and parkinsonism. 

Overdosage with metoclopramide causes drowsiness, disorientation, extrapyramidal reactions, muscle hypertonia, irritability, and agitation. Diphenhydramine, possessing... 

Thioridazine (50 to 100 mg p.o. t.i.d.) is indicated in psychosis. Thioridazine has potent anticholinergic properties and causes heavy sedation. However, it produces a very low incidence of extrapyramidal reactions such as akathisia, dystonia, parkinsonism, tardive dyskinesia, and neuroleptic malignant syndrome. Thioridazine is metabolized to mesoridazine, which is an active antipsychotic (see Table 19). 

The authors of the report suggest that this reaction was possibly caused by the additive dystonic effects of the loxapine and sumatriptan, despite the presence of the benzatropine. Dystonia is not an uncommon extrapyramidal reaction associated with antipsychotics, and neck stiffness and dystonia are recognised adverse effects of sumatriptan, but of low incidence. This seems to be the first and only report of this apparent interaction, and therefore its general significance is unclear. 

The tricyclics also have antimuscarinic (sometimes referred to as anticholinergic or atropine-like) activity and can cause dry mouth, blurred vision, constipation, urinary retention and an increase in ocular pressure. Postural hypotension and cardiotoxic effects may also occur, but they are less frequent. CNS adverse effects include sedation, the precipitation of seizures in certain individuals, and extrapyramidal reactions. 

Both SSRIs and metoclopramide can cause extrapyramidal reactions metoclopramide by blocking dopamine D2 receptors in the basal ganglia, and SSRIs by inhibition of dopamine neurotransmission. Metoclopramide has also been reported to have intermediate affinity to certain serotonin receptors. ... 

May cause extrapyramidal reactions (EPSs) and abnormalities of liver function tests... 

Among the most significant adverse reactions associated with the antipsychotic dm are the extrapyramidal effects. The term extrapyramidal effects refers to a group of adverse reactions occurring on the extrapyramidal portion of the nervous system as a result of antipsychotic drains. This part of the nervous system affects body posture and promotes smooth and uninterrupted movement of various muscle groups. Antipsychotics disturb the function of the extrapyramidal portion of the nervous system, causing abnormal muscle movement. Extrapyramidal effects include Parkinson-like symptoms (see Chap. 29), akathisia, and dystonia (see Display 32-1). 

Extrapyramidal symptoms Extrapyramidal symptoms, manifested primarily as acute dystonic reactions, occur in approximately 0.2% to 1% of patients treated with the usual adult dosages of 30 to 40 mg/day. These usually are seen during the first 24 to 48 hours of treatment, occur more frequently in children and young adults, and are even more frequent at the higher doses used in prophylaxis of vomiting caused by cancer chemotherapy. If symptoms occur, they usually subside following 50 mg diphenhydramine IM. Benztropine 1 to 2 mg IM may also be used to reverse these reactions. 

Most antipsychotics and especially the piperazines and the butyrophenones can cause extrapyra-midal symptoms. Blockade of dopamine receptors mainly in the corpus striatum is held responsible for these extrapyramidal effects. They may become manifest as a variety of clinical symptoms and it should be noted that within 24 8 hours after the beginning of treatment acute dystonic reactions like torticollis, facial grimacing and opisthotonos may occur. Parkinsonism-like symptoms such as bradyki-nesia, rigidity and tremor occur after weeks or months of therapy and are more common in the elderly. Motor restlessness, i.e. akathisia, also mostly occurs not before weeks or months after starting therapy. The tendency of an antipsychotic agent to produce extrapyramidal symptoms appears to be inversely related to its ability to block cholinergic receptors. 

Side effects include fatigue, insomnia, and altered motor coordination. Parkinsonian side effects and acute dys-tonic reactions also have been reported. Metoclopramide stimulates prolactin secretion, which can cause galactorrhea and menstrual disorders. Extrapyramidal side effects seen following administration of the phenothiazines, thioxanthenes, and butyrophenones may be accentuated by metoclopramide. 

Ondansetron generally does not cause severe toxicity. Headache and constipation are the most frequent adverse effects. Light-headedness, dizziness, and transient increases in serum aminotransferase activity can occur. Extrapyramidal effects have occurred rarely, and anaphylactoid reactions have been reported. 

There is a more clear-cut cause-and-effect relation in the parkinsonian symptoms that occasionally occur with high-dosage tricyclic therapy in susceptible individuals (particularly elderly women). Because of its piperazine side-chain and structural resemblance to the phenothia-zines, amoxapine has antidopaminergic properties that appear to produce typical dystonic reactions (88), but other tricyclic antidepressants may also be implicated in producing the full range of so-called extrapyramidal syndromes, including akathisia, dystonic reactions, parkinsonism, and tardive dyskinesia. Case reports have been described before (SEDA-16, 9 SEDA-17, 18 SEDA-18, 18). In the reports of tardive dyskinesia the problem is often that these patients have taken many different drugs. 

Diphenhydramine can cause extrapyramidal symptoms as part of an acute dystonic reaction (SEDA-19,173). 

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