Antipsychotics phenothiazines

The answer is c. (Hardman, pp 414-4163) Unwanted pharmacologic side effects produced by phenothiazine antipsychotic drugs (e.g., perphenazine) include Parkinson-like syndrome, akathisia, dystonias, galactorrhea, amenorrhea, and infertility. These side effects are due to the ability of these agents to block dopamine receptors. The phenothiazines also block muscarinic and a-adrenergic receptors, which are responsible for other effects. 

Chlorpromazine is an aliphatic phenothiazine antipsychotic used in schizophrenia and which may exacerbate parkinsonism. Co-careldopa is a combination of levodopa and the peripheral dopa-decarboxylase inhibitor, carbidopa. Co-careldopa, amantadine, entacapone and bromocriptine are all indicated in the management of parkinsonism. 

Prochlorperazine is a potent phenothiazine antipsychotic drug that is associated with a high risk of extrapyramidal side-effects, a low degree of sedation and of antimuscarinic side-effects. Chlorpromazine is less likely to induce extrapyramidal side-effects but has increased risks of inducing sedation and antimuscarinic side-effects. Olanzapine is classified as an atypical antipsychotic having characteristically much fewer incidences of extrapyramidal... 

Tricyclics—compounds which differ from the phenothiazine antipsychotics in the ring-snbstitntion and chain characteristics— promethazine, trimeprazine, cyproheptadine,... 

Pharmacology The tricyclic antidepressants (TCAs), structurally related to the phenothiazine antipsychotic agents, possess 3 major pharmacologic actions in varying degrees Blocking of the amine pump, sedation, and peripheral and central... 

Bromocriptine (Parl el) [Antiparkinsonian Agent/Dopamine Receptor Agonist] Uses Parkin on Dz, hyperprolactinemia, acromegaly, pituitary tumors Action Direct-acting on the striatal dopamine receptors X prolactin secretion Dose Initial, 1.25 mg PO bid titrate to effect, w/ food Caution [B, ] Contra Severe ischemic heart Dz or PVD Disp Tabs, caps SE X BP, Raynaud phenomenon (vasospastic disorder resulting in discoloration of the fmgers/toes), dizziness, N, hallucinations Interactions T Effects W/ erythromycin, fluvoxamine, nefazodone, sympathomimetics, antihypertensives X effects W/ phenothiazines, antipsychotics EMS Monitor BP may cause intolerance to EtOH OD May cause NA, severe hypotension give IV fluids symptomatic and supportive... 

Fluphenazine (Prolixin, Permitil) [Antipsychotic/ Phenothiazine] Uses Schizophrenia Action Phenothiazine antipsychotic blocks postsynaptic mesolimbic dopamin gic brain receptors Dose 0.5-10 mg/d in % doses PO q6-8h, av age maint 5 mg/d or 1.25 mg IM, then... 

Phenothiazine antipsychotics can be divided in the aliphatic phenothiazines with a dimethylamino-propyl group, those with a piperazine structure and agents with a piperidine structure. 

This study also found that new schizophrenic symptoms often emerged during the 6 weeks of placebo treatment, whereas worsening of symptoms was prevented by antipsychotics. Heinz Lehmann (33) coined the term psychostatic to describe the ability of phenothiazine antipsychotics to prevent the reemergence of symptoms. 

The first phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, proved to have a wide variety of central nervous system, autonomic, and endocrine effects. Although efficacy of these drugs is primarily driven by D2-receptor blockade, their adverse actions were traced to blocking effects at a wide range of receptors including a adrenoceptors and muscarinic, Hi histaminic, and 5-HT2 receptors. 

In 1943, the best antidote that Hofmann could come up with was milk, but milk is a no more effective antidote to LSD than it is against insomnia. By 1980, it was clear that chlorpromazine, the phenothiazine antipsychotic that began the psychopharmacologic revolution in psychiatry in 1955, could ameliorate LSD psychosis as well as schizophrenia. And this closes the dopamine circle. Because chlorpromazine blocks dopamine receptors, its therapeutic efficacy in LSD psychosis gives further credence to our hypothesis of its dopaminergic mediation. 

Prochlorperazine Maleate. 2-Chloro-10-[3-(4-methyl-l-piperazinyl)-propyl]-10 H-phenothiazine maleate [84-02-6] (Compazine) (22) is a white or pale yellow crystalline powder. It is almost completely odorless, its saturated solution is acidic to litmus, it is practically insoluble in water and ethanol, and it is slightly soluble in warm chloroform. It may be made by the synthesis described in Reference 18. Prochlorperazine maleate [84-02-6] is an effective antiemetic and tranquilizing agent. It is not particularly effective for motion sickness. Adverse reactions that may occur include extrapyramidal reactions, motor resdessness, dystonias, tardive dyskinesia, and contact dermatitis. Prochlorperazine is also a significant phenothiazine antipsychotic. 

Lin, G., Chu, K.-W., Damani, L. A., Hawes, E. M. Identification of lactams as in vitro metabolites of piperidine-type phenothiazine antipsychotic drugs. J. Pharmacol. Biomed. Anal. 1996,14, 727-738. 

T.A. Berger and W.H. Wilson, Separation of drugs by packed column supercritical fluid chromatography 1. Phenothiazine antipsychotics, J. Pharm. Sci., 83 281 (1994). 

Figure 11.12 Chemical structure of the prototypic phenothiazine antipsychotic.

Tramadol, phenothiazine antipsychotics and the majority of antidepressants, as well as a number of other drugs, can lower the seiznre threshold and are associated with an increased risk of convnlsions [6]. Again, these drugs may accumulate in patients with liver impairment such as cirrhosis or acute liver failure, and care must be taken if choosing to use them. This is especially important in alcoholics, who have an increased risk of seizures from acute alcohol withdrawal [7]. Examples of drugs that can lower the seizure threshold and should be used with caution/avoided are ... 

Acetylcholinesterase inhibitors Acetylcholinesterase inhibitors Phenothiazine antipsychotics Antagonize acetylcholine Avoid use of anticholinergics when... 

At about the same time, the drug imipramine was first produced. It was originally developed as a phenothiazine (antipsychotic), but was found to have antidepressant properties. Soon came amitriptyline, followed later by other "tricyclic" and "heterocyclic" antidepressants. 

A dtbenzoxazepinc derivative in use is loxapine succinate, 2-chloro-11-(4-methyl-1-pipcrazinyl)dibmzlb. / l. 4]oxazepine succinate (Daxoliit). The structural relationship to the phenothiazine antipsychotics is apparent. It is an effective antip.sychotic and has side effects similar to those ic-ported for the phenothiazines. 

Phenothiazine antipsychotic drugs Anticholinergic effects Ca " channel blockade ... 

A combination of an antipsychotic compound belonging to the phenothiazine series and a device allowing the rapid delivery of this phenothiazine antipsychotic was proposed for the acute treatment of headache [139]. 

In the case of vertebrates, phenothiazines have also been used as antipsychotic drugs for many years, before the beginning of the investigation of their action on a molecular level. Indeed, recently a number of works have appeared on the influence of phenothiazines on the nicotinic synaptic transmission, indicating that the contribution of cytochrome P-450 isoenzymes to N-demethylation and 5-sulphoxidation reactions was involved. The action of phenothiazine antipsychotics on the pre- and post-synaptic neurotransmission was experimentally examined on the tissues and enzymes extracted from the same neuronal tissues. Some phenothiazines were proposed to treat peripheral neuropathy. A new hope might also arise in the search for novel antipsychotic drugs based on phenothiazines to treat Alzheimer s disease and other taupathies, because these new compounds could inhibit tau filament formation. 

In general, other phenothiazine antipsychotic agents seem to undergo biotransforma-tions similar to those that occur with CPZ (370,394-404).Some differences exist, based on specific ring or side-chain substituents. Thioridazine (95) is oxidized on the 2-thio-... 

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