Drug action termination

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. 

Meets minimum acceptable profile (MAP) Does not have the desired effect and does not meet MAP Has desired effect but does not meet MAP Progress the drug into full development Terminate the project Bring forward back-up compounds. May be suitable to use as probe in man to evaluate basis for drug action or to develop methodology to be apphed to back-up compounds... 

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. 

In patients with significantly impaired liver or kidney function, for these are the principal organs that terminate drug action... 

If bioactivation is involved in therapeutic action, the active metabolite or a derivative thereof may be used as a drag, possibly with even more success. Termination of drug action and consequent elimination does not necessarily depend on pharmacon metabolism. Drugs are known that are practically not... 

NA has its action terminated by uptake. The tricyclic drug desipramine is an example of a potent inhibitor of this uptake mechanism as well as the newer SNRIs (venlafaxine) and cocaine (5). NA or DA present in a free state within the presynaptic terminal can be degraded by the enzyme MAO, which appears to be located in the outer membrane of mitochondria. Pargyline is an effective inhibitor of MAO (6). NA can be inactivated by the membrane-bound enzyme catechol-O-methyltransferase (COMT). Tropolone is an inhibitor of COMT. The normetanephrine (NM) formed by the action of COMT on NE can be further metabolised by MAO to... 

Zidovudine is a thymidine (a nucleoside) analogue and was the first drug introduced that inhibits reverse transcriptase. This action terminates the growing viral DNA strand. Because of HIV resistance, several similar drugs have been developed, including abacavir and lamivudine. 

Describe the termination of drug action, after demeclocycline withdrawal. 

Principles of drug action - presynaptic nerve terminal... 

Drug metabolism as a mechanism of termination of drug action The action of many drugs (eg, phenothiazines) is terminated before they are excreted because they are metabolized to biologically inactive derivatives. 

The use of a silastic vaginal ring impregnated with medroxyprogesterone acetate and inserted on day one of the cycle for 28 days represents yet another variation of the depot concept [167]. LH release and ovulation were inhibited as expected. Removal of the ring was followed by withdrawal bleeding in about 48 hours. In contrast to the depot injection, this technique provides rapid termination of drug action. 

The role of esters in terminating drug action 105 Participation of the ester group in drug action 105 The ester linkage in polymeric drugs 107... 

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