adverse effects of drugs
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent (Ia ) in the heart. It is a stereoisomer of quinine, originally derived from the bark of. and customer support structure to aid them in selecting the best toxi- opioids, and aspirin are commonly used agents that are available as single .. not limited to hydration, kidney and liver function, time and dose of drug ingestion as the detection of drugs and metabolites in relation to clinical toxicology testing. It is re-. Other salicylates discussed on this web site are salsalate and choline and caused or worsened by other drugs known to impair sexual function. The paper and its subsequent publicity appear to be little more than a public relations ploy. .. Find out why mirabegron is the wrong choice for treating this condition.
In certain embodiments, the levels of D2O shown to cause toxicity in animals is much greater than even the maximum limit of exposure caused by administration of the deuterium enriched compound as disclosed herein. Thus, in certain embodiments, the deuterium-enriched compound disclosed herein should not cause any additional toxicity due to the formation of D2O or DHO upon drug metabolism.
In certain embodiments, if RR24 are deuterium, then at least one of R1-R19 are deuterium. All publications and references cited herein are expressly incorporated herein by reference in their entirety. However, with respect to any similar or identical terms found in both the incorporated publications or references and those explicitly put forth or defined in this document, then those terms definitions or meanings explicitly put forth in this document shall control in all respects.
As used herein, the terms below have the meanings indicated. This range may be integral or continuous between and including the end values. Because the naturally occurring distribution of deuterium is about 0. The deuterium enrichment can be determined using conventional analytical methods known to one of ordinary skill in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy. Asymmetric centers exist in the compounds disclosed herein.
It should be understood that the invention encompasses all stereochemical isomeric forms, including diastereomeric, enantiomeric, and epimeric forms, as well as D-isomers and L-isomers, and mixtures thereof. Individual stereoisomers of compounds can be prepared synthetically from commercially available starting materials which contain chiral centers or by preparation of mixtures of enantiomeric products followed by separation such as conversion to a mixture of diastereomers followed by separation or recrystallization, chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method known in the art.
Starting compounds of particular stereochemistry are either commercially available or can be made and resolved by techniques known in the art. Additionally, the compounds disclosed herein may exist as geometric isomers. The present invention includes all cis, trans, syn, anti, entgegen Eand zusammen Z isomers as well as the appropriate mixtures thereof. Additionally, compounds may exist as tautomers; all tautomeric isomers are provided by this invention.
Additionally, the compounds disclosed herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms.
A bond may be single, double, or triple unless otherwise specified. A dashed line between two atoms in a drawing of a molecule indicates that an additional bond may be present or absent at that position.
Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner.
In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the disorders described herein. Sub-types of the adrenoreceptors, alpha-1, alpha-2, beta-1, beta-2, and beta-3, can be identified on the basis of their pharmacological properties and physiological effects. Betaadrenoceptors are known to occur in adipose tissue and the gastrointestinal tract. Betaadrenoceptor agonists are thought to be useful as thermogenic anti-obesity agents and as anti-diabetic agents.
Additionally, betaadrenoreceptor signaling is known to induce relaxant effects on the human detrusor muscle. Thus, selective stimulation of betaadrenoceptors in the human bladder would be expected to cause bladder relaxation, and as such it may represent a novel strategy in the treatment of overactive bladder. A betaadrenoreceptor-mediated disorder may be completely or partially mediated by modulating betaadrenoreceptor activity. In particular, a betaadrenoreceptor-mediated disorder is one in which modulation of betaadrenoreceptor activity results in some effect on the underlying disorder e.
A betaadrenoreceptor modulator may activate the activity of a betaadrenoreceptor, may activate or inhibit the activity of a betaadrenoreceptor depending on the concentration of the compound exposed to the betaadrenoreceptor, or may inhibit the activity of a betaadrenoreceptor. A betaadrenoreceptor modulator may increase the probability that such a complex forms between the betaadrenoreceptor and the natural binding partner, may increase or decrease the probability that a complex forms between the betaadrenoreceptor and the natural binding partner depending on the concentration of the compound exposed to the betaadrenoreceptor, and or may decrease the probability that a complex forms between the betaadrenoreceptor and the natural binding partner.
In some embodiments, modulation of betaadrenoreceptors may be assessed using the method described in US ; US ; and Takasu et al. Prodrugs are often useful because, in some situations, they may be easier to administer than the parent compound.
They may, for instance, be bioavailable by oral administration whereas the parent compound is not. The prodrug may also have enhanced solubility in pharmaceutical compositions over the parent compound. A prodrug may be converted into the parent drug by various mechanisms, including enzymatic processes and metabolic hydrolysis.
Design5, ; Pauletti et al. The compounds disclosed herein can exist as therapeutically acceptable salts. The salts can be prepared during the final isolation and purification of the compounds or separately by reacting the appropriate compound with a suitable acid or base.
Therapeutically acceptable salts include acid and basic addition salts.
Suitable bases for use in the preparation of pharmaceutically acceptable salts, including, but not limited to, inorganic bases, such as magnesium hydroxide, calcium hydroxide, potassium hydroxide, zinc hydroxide, or sodium hydroxide; and organic bases, such as primary, secondary, tertiary, and quaternary, aliphatic and aromatic amines, including L-arginine, benethamine, benzathine, choline, deanol, diethanolamine, diethylamine, dimethylamine, dipropylamine, diisopropylamine, 2- diethylamino -ethanol, ethanolamine, ethylamine, ethylenediamine, isopropylamine, N-methyl-glucamine, hydrabamine, 1H-imidazole, L-lysine, morpholine, 4- 2-hydroxyethyl -morpholine, methylamine, piperidine, piperazine, propylamine, pyrrolidine, 1- 2-hydroxyethyl -pyrrolidine, pyridine, quinuclidine, quinoline, isoquinoline, secondary amines, triethanolamine, trimethylamine, triethylamine, N-methyl-D-glucamine, 2-amino hydroxymethyl -1,3-propanediol, and tromethamine.
While it may be possible for the compounds of the subject invention to be administered as the raw chemical, it is also possible to present them as a pharmaceutical composition. Accordingly, provided herein are pharmaceutical compositions which comprise one or more of certain compounds disclosed herein, or one or more pharmaceutically acceptable salts, prodrugs, or solvates thereof, together with one or more pharmaceutically acceptable carriers thereof and optionally one or more other therapeutic ingredients.
Proper formulation is dependent upon the route of administration chosen.
Any of the well-known techniques, carriers, and excipients may be used as suitable and as understood in the art; e. The pharmaceutical compositions disclosed herein may be manufactured in any manner known in the art, e. The pharmaceutical compositions may also be formulated as a modified release dosage form, including delayed- extended- prolonged- sustained- pulsatile- controlled- accelerated- and fast- targeted- programmed-release, and gastric retention dosage forms.
These dosage forms can be prepared according to conventional methods and techniques known to those skilled in the art see, Remington: The compositions include those suitable for oral, parenteral including subcutaneous, intradermal, intramuscular, intravenous, intraarticular, and intramedullaryintraperitoneal, transmucosal, transdermal, rectal and topical including dermal, buccal, sublingual and intraocular administration although the most suitable route may depend upon for example the condition and disorder of the recipient.
The compositions may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. In general, the compositions are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation. Formulations of the compounds disclosed herein suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion.
The active ingredient may also be presented as a bolus, electuary or paste. Pharmaceutical preparations which can be used orally include tablets, push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol.
Tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with binders, inert diluents, or lubricating, surface active or dispersing agents.
Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein.
All formulations for oral administration should be in dosages suitable for such administration. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols.
In addition, stabilizers may be added.
Dragee cores are provided with suitable coatings. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses. Cephalosporins are relatives of the penicillins and have a similar, if slightly expanded, range of action. They have a good safety record but certain problems can occur with their use. Diarrhea is the most common adverse effect, and it may become so bad that treatment must be stopped.
Aspirin, a nonsteroidal anti-inflammatory drug NSAIDis the most well-known and frequently used salicylate. Other salicylates discussed on this web site are salsalate and choline and magnesium salicylates.
Sleeping Pills and Tranquilizers [ hide all summaries ] Older adults have a much more difficult time eliminating benzodiazepines and similar drugs from their bloodstreams and these drugs can thus accumulate in their bodies. Also, older adults are more sensitive to the effects of many of these drugs than are younger adults. For older adults the risk of serious adverse drug effects is significantly increased. Serious adverse effects may include: Tetracyclines [ hide all summaries ] Tetracyclines are rarely the antibiotics of choice to treat bacterial infections that are common in older adults.
In general, tetracyclines are used to treat such infections as urethritis inflammation of the urinary tractprostate infections, pelvic inflammatory disease, acne, Rocky Mountain spotted fever, recurrent bronchitis in people with chronic lung disease, walking pneumonia, and other miscellaneous infections. Ulcers and Gastroesophageal Reflux Disease GERD [ hide all summaries ] There are nondrug treatments, with no safety concerns, and less expensive drugs that may be effective for GERD; these should be tried before you use any drugs for heartburn.
First, try to avoid foods that trigger your condition e. Second, avoid food, and particularly alcohol, within two or three hours of bedtime. Third, elevate the head of the bed about six inches or sleep with extra pillows.
The conversion of piperazine to aminopropyl colored red increases the selectivity for Alpha-1a receptors. Doxazosin 2,4-diamino-6,7-dimethoxyquinazoline variations for in vitro and in vivo performance. A key factor in these structures was the derivations from 2,4-diamino-6,7-dimethoxyquinazoline nucleus that was replaced for norepinephrine.
And N-1 which protonated quinazoline was also a key factor. Tamsulosin is most potent alpha 1 blocker and has the most selectivity for alpha 1a blockers.
It doesn't do anything for beta-adrenoceptors because it lacks beta-hydroxyl group and therefor can not block beta-receptors. Dibenzyline was the first brand name marketed. Today phenoxybenzamine is not the first choice due to many side effects like lowering blood pressure. Prazosin was synthesized in when Constantin and Hess were trying to discover a vasodilator which had a minimal effect on cardiac activity.
Doxazosin and Tamsulosin was approved after. The first line treatment choice today to treat BPH is tamsulosin. It is not because it is better tolerated or had greater efficacy than the previous drugs.