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A 80 y old with insomnis is changed from TEMAZEPAM to FLURazepam by her MD,becouse the former no longer seemed effective.Althou initialy it seemed to work well in several weeks she began to notice that she was tired most of the day.The most likely reason is:
\1. A rare recognised allergy to flurazepam
2.Withdrawal from Temazepam
3.The diferent method of methabolism for the two drugs
4.An overdose of Flurzepame
5.An elimination effect becouse flurazepam is renaly excreted
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4 : the drug´s metabolites are active too. Guess her Doc should know that
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3/
In the elderly metabolites has longer halflife-longer than other age.
this patient was switch from short to very long acting drug
so it is not overdose- it is longer metabolic proces
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yeah mamamia, you´re right, their metabolic capacity is reduced, but that´s not the point. The point is, the physician failured to realize that due to the age-associated decrease in rate of metabolism, there´s gonna be an accumulation of drug, plus metabolites. The pharmacological impact is that, the active metabolites predispose, and eventually cause an overdose.
by the way 3 states: different methods of metabolism, which is wrong, cos benzodiazepines are basically metabolized in the same way(i.e. hydrolysis and glucuronization), but for some exceptions, and i can´t remember those 2 belonging to the exception
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that is the answer for the book
step 2 exam ceneral clinical sciences
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guess you´re right mamaria
ok guys this is what i found.
Pharmacokinetics
In a single and multiple dose absorption, distribution, metabolism, and excretion (ADME) study, using 3H labeled drug. Temazepam was well absorbed and found to have minimal (8%) first pass metabolism. There were no active metabolites formed and the only significant metabolite present in blood was the O-conjugate. The unchanged drug was 96% bound to plasma proteins. The blood level decline of the parent drug was biphasic and the short half-life ranging from 0.4-0.6 hours and the terminal half life ranging from 3.5-18.4 hours (mean 8.8 hours), depending on the study population and the method of determination. Metabolites were formed with a half-life of 10 hours and excreted with a half-life of approximately 2 hours. Thus, formation of the major metabolite is the rate limiting step in the biodisposition of temazepam. There is no accumulation of metabolites. A dose-proportional relationship has been established for the area under the plasma concentration/time curve over the 15-30 mg dose range.
Temazepam was completely metabolized through conjugation prior to excretion: 80%-90% of the dose appeared in the urine. The major metabolite was th O-conjugate of temazepam (90%): the O-conjugate of N- desmethyl temazepam was a minor metabolite (7%).
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CLINICAL PHARMACOLOGY
Flurazepam hydrochloride is rapidly absorbed from the G.I. tract. Flurazepam is rapidly metabolized and is excreted primarily in the urine. Following a single oral dose, peak flurazepam plasma concentrations occur at 30 to 60 minutes post-dosing. The mean apparent half-life of flurazepam is 2.3 hours. The blood level profile of flurazepam and its major metabolites was determined in man following the oral administration of 30 mg daily for 2 weeks. The N1-hy-droxyethyl- flurazepam was measurable only during the early hours after a 30 mg dose and was not detectable after 24 hours. The major metabolite in blood was N1-desalkyl-flurazepam, which reached steady-state (plateau) levels after 7 to 10 days of dosing, at levels approximately five to sixfold greater than the 24-hour levels observed on Day 1. The half life of elimination of N1-des-alkyl- flurazepam ranged from 47 to 100 hours. The major urinary metabolite is conjugated N1-hydroxyethyl- flurazepam which accounts for 22 to 55 percent of the dose. Less than 1% of the dose is excreted in the urine as N1-desalkyl-flurazepam.
The pharmacokinetic profile may be responsible for the clinical observation that flurazepam is increasingly effective on the second or third night of consecutive use and that for one or two nights after the drug is discontinued both sleep latency and total wake time may still be decreased.
