Duration of drug action

Fhtients with kidney disease may exhibit drug toxicity and a longer duration of drug action. The dosage of drugp may be reduced to prevent the accumulation of toxic levels in the blood or further injury to the kidney. 

Despite the fact that the present classifications are extremely convenient for practical medical personnel, it should be kept in mind that the duration of drug action—especially of the first three groups of compounds—depends on various factors besides the structure of the compounds, such as drug form, method of administration, pathology for which the drug is being used, general treatment time, etc. 

Excretion, along with metabolism and tissue redistribution, is important in determining both the duration of drug action and the rate of drug elimination. Excretion is a process whereby drugs are transferred from the internal to the external environment, and the principal organs involved in this activity are the kidneys, lungs, biliary system, and intestines. 

Benzodiazepines are ciassified as short, medium, and iong acting. This reiates to the duration of drug action in the body. Length of action can aiso be infiuenced by the heaith of the patient s iiver and the patient s age and weight. ... 

For a patient in severe pain, the administration of an opioid analgesic is usually considered a primary part of the overall management plan. Determining the route of administration (oral, parenteral, neuraxial), duration of drug action, ceiling effect (maximal intrinsic activity), duration of therapy, potential for adverse effects, and the patient s past experience with opioids all should be addressed. One of the principal errors made by physicians in this setting is failure to adequately assess a patient s pain and to match its severity with an appropriate level of therapy. Just as important is the principle that following delivery of the therapeutic plan, its effectiveness must be reevaluated and the plan modified, if necessary, if the response was excessive or inadequate. 

Remmer H. In Brodie BB, Erdos EG, eds. Metabolic Factors Controlling Duration of Drug Action, Proceedings of First International Pharmacological Meeting, Vol. 6. New York Macmillan, 1962. 

Experimental demonstration of inhibition can be carried out by observing in vivo symptoms. The measurement of the effect of an inhibitor on the duration of drug action in vivo is the most common method of demonstrating inhibitory action. The most useful and reliable in vivo tests involve the measurement of effects on the hexobarbital sleeping time or the zoxazolamine paralysis time. Both of these drugs are fairly rapidly deactivated by hepatic microsomal CYP isoforms, and thus CYP inhibitors prolong their action. 

Gels and creams are generally easier to apply to animals but are less occlusive than ointments. Ointments provide a longer duration of drug action, and the occlusive effect may enhance preparation of the active ingredi-ent(s) to the site of infection. 

Age can influence drug effects if the user is very young or old. Children are more sensitive to drugs because enzyme systems that metabolize drugs may not be fully developed. As a result, the drug stays active longer. In the elderly these same enzyme systems may be impaired, with the same result of increased duration of drug action. 

Controlled dissolution from a formulation may be critical for the control of duration of drug action. Extended release formulations are useful for most drug delivery routes. 

K4. Kalow, W., Esterase Action. In Metabolic Factors Controlling Duration of Drug Action (B. B. Brodie and E. G. Erdos, eds.), Vol. 6 of Proc. 1st Int. Pharmacol. Meeting, pp. 137-146. Pergamon, Oxford, 1962. 

In many cases, metabolism of a drug results in its conversion to compounds that have little or no pharmacologic activity. In such cases, biotransformation rate can be a primary factor determining the duration of drug action. 

Flurazepam is rapidly metabolized into hydroxyethylflurazepam (the major metabolite) and A -desalkyl flurazepam. These metabolites are pharmacologically active, resulting in a relatively long duration of drug action. 

Overactive urinary bkuMer disease can be successfully treated with muscarinic antagonists, primarily tolterodine and trospium chloride, which lower intravesicular pressure, increase capacity, and reduce the frequency of contractions by antagonizing parasympathetic control of the bladder. Oxybu-tynin is used as a transdermal system (oxytrol) that delivers 3.9 mg/day and is associated with a lower incidence of side effects than the oral immediate- or extended-release formulations. Tolterodine is metabolized by CYP2D6 to a 5-hydroxymethyl metabolite since this metabolite possesses similar activity to the parent drug, variations in CYP2D6 levels do not affect the duration of drug action. Trospium is as effective as oxybutynin, with better tolerability. Solifenacin is newly approved for overactive bladder with a favorable efficacy side effect ratio. Stress urinary incontinence has been treated with some success with duloxetine (YENTREVE), which acts centrally to influence 5-HT and NE levels. 

Phenobarbital can induce drug-metabolizing enzymes and thereby may reduce the duration of drug action. Displacement of drug from tissue may transiently increase the intensity of the effect but will decrease the volume of distribution and thereby reduce the half-life. Cimetidine is recognized as an inhibitor of P450 and may also decrease hepatic blood flow under some circumstances. The answer is (B). 

Which three routes of administration require drug injection How do these three routes compare with regard to onset and duration of drug action and risk of adverse effects ... 

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