Drug action elimination

The terminator of drug action is, of course, elimination. Elimination is a composite of excretion (kidney, etc.) and biotransformation (metabolism). The primary measure of drug elimination from the whole body is clearance, CLt, defined as the volume of plasma fluid removed of drug per unit time. It is a direct measure of the loss of the drug from the system and can be calculated from Eq. (3.5) after IV administration of a dose of the drug. 

An alternative coupling strategy that avoids potential steric hindrance of drug action and eliminates the need for cleavability utilizes long, flexible spacer arms, e.g. biotin-derivatized polyethylene glycol (PEG) linkers with molecular weights of 2000 or 5000 Da [93,94]. 

TIVA has become feasible thanks to the introduction of agents with a suitably short duration of action, including the injectable anesthetics propofol and etomidate, the analgesics alfentanil und remifentanil, and the muscle relaxant mivacurium. These drugs are eliminated within minutes after being adminster-ed, irrespective of the duration of anesthesia. 

Define objectives of treatment before initiation of a drug Note frequency and severity for a drug Dependant on age, disease, and individual patient factors Include drug action, absorption, elimination, and protein binding Are they clinically significant ... 

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. 

Refined Focus In this edition, we chose to focus more on drug classes rather than on individual drugs, eliminate unnecessary detail such as chemical structures, and maintain emphasis on structure-activity relationships in drug action and development. 

Mechanism of Action Aketolide that blocks protein synthesis by binding to ribosomal receptor sites on the bacterial cell wall. Therapeutic Effect Bactericidal. Pharmacokinetics Protein binding 60%-70%. More of drug is concentrated in WBCs than in plasma, and drug is eliminated more slowly fromWBCs than from plasma. Partially metabolized by the liver. Minimally excreted in feces and urine. Half-life 10 hr. 

An often-misunderstood principle is that concentration in the blood rises until the rate of absorption equals the rate at which drug is being removed from the body (the so-called peak). This peak does not occur when absorption is complete but rather when the rate of absorption equals the rate of elimination. The time to peak is therefore determined by both absorption and elimination rates in the individual patient. Patients with faster elimination will have earlier peaks than will patients with slower elimination, even when the rate of drug absorption is the same (Fig. 4.2). The extent of absorption is usually expressed as the fraction absorbed or bioavailability. This is an important determinant of drug action. While rate and extent of absorption are related, they are different. In general, the onset and magnitude of effects are related to the rate of absorption, while the average steady state concentrations are related to the extent of absorption. 

Goldstein A, Aronow L, Kalman SM (1968) The absorption, distribution and elimination of drugs — passage of drugs across the placenta. In Goldstein A, Aronow L, Kalman SM ed. Principles of drug action the basis of pharmacology. New York, Harper and Row, p 179. 

Pratt WB. The entry, distribution and elimination of drugs. In Pratt WB, Taylor P, eds. Principles of Drug Action. 3rd ed. New York Churchill Livingstone, 1990. 

Pharmacokinetic properties Pethidine (Mather and Meffin, 1978) has a faster onset and a shorter duration of action than morphine. After oral administration about 50% of the drug is eliminated by first-pass metabolism. N-demethylation yields the active metabolite nor-pethidine, and hydrolytic cleavage the inactive metabolites pethidinic and nor-pethidinic acid. The half-life of pethidine is about 3- 6 h. Nor-pethidine has a much slower elimination with a half life of up to 20 h. 

The pharmacokinetic phase of drug action includes the Absorption, Distribution, Metabolism and Elimination (ADME) of the drug. Many of the factors that influence drug action apply to all aspects of the pharmacokinetic phase. Solubility (see Section 3.3), for example, is an important factor in the absorption, distribution and elimination of a drug. Furthermore, the rate of drug dissolution, that is, the rate at which a solid drug dissolves in the aqueous medium, controls its activity when a solid drug is administered by enteral routes (see Section 2.6) as a solid or suspension. 

However, after a short time, the drug leaves the brain again and accumulates in the lean tissues (such as muscle), from where it finally redistributes to the body fat. This reflects that the fat provides the most favourable (lipophilic) environment however, since it is only weakly perfused, substance exchange works more slowly than with the other tissues. Note that, in this particular case, drug action is not terminated by elimination of the drug (as is usually the case), but solely by its redistribution from the site of action (the brain) to inert reservoirs (muscle / fat). Ultimate elimination is very slow - it takes days to complete - and involves hepatic metabolism of the drug, followed by urinary excretion. 

The relationship between drug action and the processes of absorption, distribution, and elimination has been successfully applied in clinical pharmacology for the optimisation and individualisation of therapy. In clinical and forensic toxicology, similar relationships are applied in the interpretation of analytical results. 

Pharmacokinetics is defined as the quantitative analysis of the processes of drug absorption, distribution, and elimination that determine the time course of drug action. Pharmacodynamics deals with the mechanism... 

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