Effect therapeutic

Layered tablets are also used for a prolonged or sustained therapeutic effect. In this case, one layer disintegrates and dissolves rapidly to provide the initial dosing, whereas the other is designed for controlled release. 

Since the development of the Spansule brand (Smith Kline Beech am) of coated beads and granules in the late 1960s, various dmg product technologies have been developed and patented to achieve extended durations of therapeutic effects. Each of these does so by various mechanisms of control of dmg release from adrninistered dosage forms. Each method has its advantages and disadvantages, a discussion of which is available in the pharmaceutical hterature (see Drug delivery systems) (21). 

Prolonged Action Parenterals Injections. Intramuscular injections have been developed to achieve prolonged therapeutic effects. This can be accompHshed by suspension of dmg particles in oils or flowable gels, from which the dmg slowly diffuses. Aqueous suspensions can also provide such therapeutic response. In these cases, the soHd dmg crystals generally are quite water insoluble and of a controlled particle size and crystallized form. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

The second-generation antidepressants, particularly RIMAs and SSRJs, are much less toxic ia overdose than the older TCAs and irreversible MAO inhibitors. However, similar to first-generation antidepressants, the therapeutic effect only becomes manifest after several weeks. Up to one-third of depressed patients are nonresponders. Ideally, an antidepressant would combine a more rapid onset of action with greater clinical efficacy and a higher responder rate, as well as even better tolerability. 

Nutrients and diet supplements without claims of therapeutic effects are considered foods, and are thus regulated by the U.S. Food and Dmg Administration. These are further subject to specific food regulations. Specifications for pyridoxine hydrochloride (7) for foods are given in the Food Chemicals Codex (80) and for pharmaceuticals in the US. Pharmacopeia (81). General test methods have been summarized (82). 

Potassium Iodide. When potassium iodide [7681-11-0] is adrninistered orally for several (6—8) weeks, a therapeutic effect may be obtained ia the subcutaneous form of sporotrichosis. Amphotericin B is used iatravenously to treat systemic sporotrichosis. The KI dosage is usually a saturated solution ia water (1 g/mL). The usual oral dose is 30 mg/kg/d. Children should receive five droplets, three times a day (after meals) the dose may be iacreased to 15—20 droplets. Side effects iaclude digestive disorders, swelling of the saUvary glands, and lacrimation. Thyroid function tests may be disturbed. 

Miconazole. Miconazole (Fig. 2, 7a) is also available as a sterile solution for intravenous infusion. Miconazole has a therapeutic effect on systemic mycoses due to C albicans A.spergillusfumigatus Cyptococcus neoformans Blastomyces dermatitidis Histoplasma capsulatum Coccidioides immitis Paracoccidioides brasiliensis and Petriellidum boydii. 

P-D-Arabinofuranosylcytosine [147-94-4] (ara-C, 16), C H N O, reportedly has had significant therapeutic effects in patients with localized herpes zoster, herpes eye infections, and herpes encephaUtis (33), although several negative results have also been reported (34) (Fig. 2). Ara-C, also known as cytarabine, is quite toxic and is only recommended for very severe viral infections. It is rapidly deaminated in humans to the relatively inactive ara-U Ara-C is converted in the cell to the 5 -monophosphate by deoxycytidine kinase, followed by formation of the corresponding di- and triphosphate. The triphosphate has been shown to inhibit DNA polymerase. 

Procainamide. Procainamide hydrochloride is a ben2amide, synthesized to prolong the therapeutic effects of the local anesthetic procaine [59-46-1] (13) (see Anesthetics). The dmg is effective in a wide range of supraventricular and ventricular arrhythmias (14). 

Propranolol. Propranolol hydrochloride, considered the prototype of the P-adrenoceptor blocking agents, has been in use since 1964. It is a nonselective, highly Hpid-soluble P-adrenoceptor blocker having no ISA. It is a mixture of (+) and (—) enantiomers, and the (—) enantiomer is the active moiety. The local anesthetic effects of propranolol are equipotent to those of Hdocaine [137-58-6] C 4H22N20, (see Anesthetics). Therapeutic effects include termination of catecholamine-induced arrhythmias, conversion of SA nodal tachycardias (including flutter and fibrillation) and AV nodal tachyarrhythmias to normal sinus rhythm, digitahs-induced arrhythmias, and ventricular arrhythmias (1,2). The dmg also has cardioprotective properties (37,39). 

A dmg deHvery system is a vehicle that provides a stable environment to store an active ingredient prior to usage, and controls the release of the dmg duting usage. Typically, it is desirable for the system to be stable for a period of at least two years from the date of manufactuting. The type of release profile depends on the strategy to optimize the therapeutic effect, eg, sustained, constant, or specific temporal patterns. 

DOPA in the bloodstream can be taken up into neural tissue and into tissue devoid of tyrosine hydroxylase, thus bypassing the rate-limiting enzymatic synthetic step (35). Uptake of DOPA by the brain is the basis of the therapeutic effect of DOPA in the treatment of Parkinson s disease (a... 

When in the late 1940 s the remarkable therapeutic effects of the glucocorticoids cortisone and hydrocortisone were discovered, new raw materials had to be developed to produce these complicated molecules, and new synthetic methods devised to convert either a 20-ketopregnane or 21-acetoxy-20-ketopregnane to the dihydroxyacetone side-chain characteristic of these corticoids. This latter challenge produced some extremely useful new organic chemical reactions, many of which have wider application outside of steroids. 

FIGURE 8.23 Kinetic profiles of the plasma concentrations of three different drags taken by the oral route. If absorption is rapid, toxic effects may ensue (red line). If too slow, a therapeutically effective level may not be attained (blue line). 

FIGURE 8.25 Repeated oral administration of drags leads to steady-state plasma concentrations. If elimination is rapid and administration not often enough, then an elevated and therapeutically effective steady-state concentration may not be achieved (green lines). In contrast, if elimination is very slow (or administration too often), then an accumulation of the drag may be observed with no constant steady state (red line). Bine line shows a correct balance between frequency of administration and elimination. 

All drugs, in addition to their therapeutic effects, have the potential to do harm, i.e. to cause adverse/unwanted reactions (side effects). These may or may not be related to the principal pharmacological action of the drug. Examples of the second category are toxic effects of metabolites of a drug or immunological reactions. 

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