Depot administration

The intramuscular administration of antipsychotics acting for weeks prevents this independent action and improves compliance on the other hand, only highly potent antipsychotics such as fluphenazine, flupenthixol and haloperidol are suitable for depot administration and it is precisely these medicines that lead more frequently to EPS and dysphoric mood (van Putten et al, 1984). 

Another area of continuing use of conventional antipsychotics is for the noncom-pliant patient who may require monthly injections of a depot antipsychotic. No atypical antipsychotic is yet available for depot administration, although such formulations are under development. Otherwise, most clinicians generally try several different atypical antipsychotics before resorting to a trial of clozapine (with its encumbrance of weekly or biweekly blood counts), conventional antipsychotics, or various combination therapies of atypical antipsychotics with other agents (Fig. 11 — 52 second- and third-line treatments). 

Conversely, certain forms of intramuscular antipsychotics that enter the bloodstream slowly have been developed. This method of depot administration may prove helpful if the patient has poor selfadherence to drug therapy and neglects to take his or... 

Augustin AJ, D Amico DJ, Mieler WF, et al. Safety of posterior juxtascleral depot administration of the angiostatic cortisone anecortave acetate for treatment of subfoveal choroidal neovascularization in patients with age-related macular degeneration. Graefes Arch CUn Exp Ophthalmol 2005 243 9-12. 

Sociocultural, illness, and biological factors affect individual attitudes towards psychotropic medications. Health beliefs or explanatory models, particularly causal attributions regarding the illness and the treatment options afforded within such models, exert a profound influence on patients attitudes and behavior regarding medications (Smith, Lin Mendoza, 1993). Such effects can be subtle and can occur during the course of treatment even if there has been initial successful negotiation about the nature of the illness and treatment. In psychiatric illness little research has been leveled at the personal meaning that patients bring to treatment practices such as electro-convulsive therapy (ECT), oral medications, and depot injections, or to the transition between different administrative routes and types of medications. 

Factors known to influence the clearance of drugs from interstitial sites, following extravasation or parenteral interstitial or transepithelial administration, include size and surface characteristics of particles, formulation medium, the composition and pH of the interstitial fluid, and disease within the interstitium. Studies indicate that soluble macromolecules smaller than 30 nm can enter the lymphatic system, whereas particulate materials larger than 50 nm are retained in the interstitial sites and serve as a sustained-release depot. The use of lipids or an oil in a formulation and the presence of a negative surface charge all appear to... 

Naltrexone, 50 to 100 mg/day, has been associated with reduced craving and fewer drinking days. It should not be given to patients currently dependent on opiates as it can precipitate a severe withdrawal syndrome. A new depot formulation allows monthly administration in a usual dose of 380 mg intramuscularly. 

Many drugs are administered as parenterals for speed of action because the patient is unable to take oral medication or because the drug is a macromolecule such as a protein that is unable to be orally absorbed intact due to stability and permeability issues. The U.S. Pharmacopoeia defines parenteral articles as preparations intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal. They include intravenous, intramuscular, or subcutaneous injections. Intravenous injections are classified as small volume (<100 mL per container) or large volume (>100 mL per container) injections. The majority of parenteral dosage forms are supplied as ready-to-use solutions or reconstituted into solutions prior to administration. Suspension formulations may also be used,101 although their use is more limited to a subcutaneous (i.e., Novolin Penfill NOVO Nordisk) or intramuscular (i.e., Sandostatin LAR Depot Novartis) injection. Intravenous use of disperse systems is possible but limited (i.e., Doxil Injection Ortho Biotec). 

Like fluphenazine, haloperidol is available in oral, injectable, and depot forms. In schizophrenia, haloperidol is begun at doses of 5 mg daily and increased as needed. Lower doses are used for most other indications. The depot form of haloperidol is initiated by administration of a 50mg test dose. Depot haloperidol is given monthly at about 20 times the daily dose of the oral form. The maximum depot dose is 200 mg per month. Dose dumping does not seem to be a problem with depot haloperidol. 

One of the main disadvantages of depot parenteral preparations is that administration of these preparations may not be acceptable to the patient. The depot preparation requires a lower dosing frequency when compared with other dosage forms. 

Restricted diffusion also limits tissue distribution after intraparenchymal drug administration, as shown in Figure 2.7c and d. Distribution has been measured in the rat brain after implantation of polymer discs containing NGF [66]. Drug concentrations decreased to less than 10% of the values measured on the disc surface within a distance of 2-3 mm, even after prolonged periods of several days. Therefore, applying this approach in the larger human brain would require the stereotaxic placement of multiple intraparenchymal depots, as has been evaluated in rat brain [67], on a repetitive schedule. 

Intramuscular administration in depot form. In its anionic form (-COO ) penicillin G forms poorly water-soluble salts with substances containing a positively charged amino group (procaine, p. 208 clemizole, an antihistamine benzathine, dicationic). Depending on the substance, release of penicillin from the depot occurs over a variable interval. 

Switching from other antipsychotics - The period of overlapping antipsychotic administration should be minimized. When switching patients with schizophrenia from depot antipsychotics, if medically appropriate, initiate quetiapine therapy in place of the next scheduled injection. Periodically reevaluate the need for continuing existing EPS medication. 

Insulin, whatever its source, may be formulated in a number of ways. This directly affects its activity profile upon administration to diabetic patients. Fast (short)-acting insulins are those preparations that yield an elevated blood insulin concentration relatively quickly after their administration, which is usually by s.c. or, less commonly, by i.m. injection. Slow-acting insulins, on the other hand, enter the circulation much more slowly from the depot (injection) site. This is characterized by a slower onset of action, but one of longer duration (Table 8.4). 

Huphenazine is a short acting agent. Eor the management of agitated and potentially violent patients its hydrochloride formulation is frequently used for parenteral administration. Fluphenazine decanoate is a widely used depot preparation. Although its principal pharmacological activities are similar to those of the other phenothiazines fluphenazine displays only weak sedative action and it shows little anticholinergic and hypotensive effect. 

Ethambutol is a synthetic agent and not related to any of the other tuberculostatics. Its mechanism of action is not well understood but in actively dividing mycobacteria it appears to be an inhibitor of mycobacterial RNA synthesis. It also has effects on bacterial phosphate metabolism and on polyamine synthesis. It is an bacteriostatic agent and its main function in combination therapy is to delay the occurrence of resistance, mainly against isoniazid and rifampicin. It is well absorbed after oral administration. It is widely distributed, except to the CNS. Protein binding is about 20-30%. It is mainly excreted unchanged in the bile and urine with an elimination half-life of 3 h. Ethambutol is concentrated in erythrocytes and thus provides a depot for continuous release. 

Route of administration Humatrope and Saizen are intended for subcutaneous or intramuscular administration. Genotropin, Nutropin, and Serostim are intended for subcutaneous use. Norditropin is intended for subcutaneous injection in the thighs after reconstitution. Nutropin Depot in administered by subcutaneous injection once or twice a month. 

B. Indications and use Lupron Injection, Lupron Depot, Lupron Depot-3 Month, and Lupron Depot-4 Month are indicated in the palliative treatment of advanced prostate cancer. These products offer an alternative treatment when orchiectomy or estrogen administration is either not indicated or unacceptable to the patient. Lupron Injection Pediatric and Lupron Depot-PED are indicated in the treatment of children with central precocious puberty. Lupron Depot and Lupron Depot-3 Month are indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions. 

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