Patient AO has a history of ob

Patient AO has a history of obesity and has recently gained 9pounds. The patient has been diagnosed with hypertension andhyperlipidemia. Drugs currently prescribed include thefollowing:

Atenolol 12.5 mg daily

Doxazosin 8 mg daily

Hydralazine 10 mg qid

Sertraline 25 mg daily

Simvastatin 80 mg daily

Post an explanation of how the factor youselected might influence the pharmacokinetic and pharmacodynamicprocesses in the patient from the case study you selected. Then,describe how changes in the processes might impact the patient’srecommended drug therapy. Finally, explain how you might improvethe patient’s drug therapy plan.


an explanation of how the factor you selected mightinfluence the pharmacokinetic and pharmacodynamic processes in thepatient from the case study you selected. Then, describe howchanges in the processes might impact the patient’s recommendeddrug therapy. Finally, explain how you might improve the patient’sdrug therapy plan.

Influnce of the Atenolol in PharmokineticNature:

The goal of therapeutics is to achieve a desired beneficialeffect with minimal adverse effects. When a medicine has beenselected for a patient, the clinician must determine the dose thatmost closely achieves this goal. A rational approach to thisobjective combines the principles of pharmacokinetics withpharmacodynamics to clarify the dose-effect relationship

The “standard” dose of a drug is based on trials inhealthy volunteers and patients with average ability to absorb,distribute, and eliminate

Dose of Drug Adiministered


Volume of Distribution:

Volume of distribution (V) relates the amount of drug in thebody to the concentration of drug (C) in blood or plasma: Thevolume of distribution may be defined with respect to blood,plasma, or water (unbound drug), depending on the concentrationused in equation (1) (C = C b , C p , or C u ). That the Vcalculated from equation (1) is an apparent volume may beappreciated by comparing the volumes of distribution of drugs suchas digoxin or chloroquine with some of the physical volumes of thebody. Volume of distribution can vastly exceed any physical volumein the body because it is the volume apparently necessary tocontain the amount of drug homogeneously at the concentration foundin the blood, plasma, or water. Drugs with very high volumes ofdistribution have much higher concentrations in extravasculartissue than in the vascular compartment, ie, they are nothomogeneously distributed. Drugs that are completely retainedwithin the vascular compartment, on the other hand, have a minimumpossible volume of distribution equal to the blood component inwhich they are distributed, eg, 0.04 L/kg body weight or 2.8 L/70kg for a drug that is restricted to the plasma compartment.Clearance Drug clearance principles are similar to the clearanceconcepts of renal physiology. Clearance of a drug is the factorthat predicts the rate of elimination in relation to the drugconcentration: Clearance, like volume of distribution, may bedefined with respect to blood (CL b ), plasma (CL p ), or unboundin water (CL u ), depending on the concentration measured. It isimportant to note the additive

Volume Distribution Formula:

V=  Amount of drug in thebody


Clearance Formula:

CL= Rate ofelimanation


character of clearance: Elimination of drugfrom the body may involve processes occurring in the kidney, thelung, the liver, and other organs. Dividing the rate of eliminationat each organ by the concentration of drug presented to it yieldsthe respective clearance at that organ.


2.Oral Availability (F) (%)-56

3.Urinary Excretion (%)1-94

4.Bound in Plasma (%) -5

5.Clearance (L/h/70 kg)2-10.2

6.Volume of Distribution (L/70 kg) -67

7.Half-Life (h)-6.1

8.Target Concentration

9.Toxic Concentration 1mg/dl


2.Oral Availability (F) (%)-40

3.Urinary Excretion (%)1-10

4.Bound in Plasma (%) -87

5.Clearance (L/h/70 kg)2-234

6.Volume of Distribution (L/70 kg) -105

7.Half-Life (h)-1

8.Target Concentration-01mg/ml

9.Toxic Concentration- ….

the pharmacodynamics of doxazosin and atenolol werecompared on single study days in 39 patients with mild to moderatehypertension receiving long-term double-blind treatment. Thepharmacokinetics of doxazosin were investigated in the 20 patientsreceiving doxazosin. Individually titrated once daily doses ofdoxazosin were 1, 2, 4, 8 or 16 mg and of atenolol 50 or 100 mg.Patients were first investigated after at least one month onconstant dose and then again after at least a further threemonths. Mean plasma concentrations of doxazosin wereproportional to dose and the plasma half-life was 11.5 h andindependent of dose. There was low variability of doxazosin plasmaconcentrations between patients receiving the same dose.Concentrations and half-life were unchanged during the periodbetween investigations. Mean reductions of AUC (0–12 h) bloodpressure during the 12-h period post-dose and of blood pressure at24 h post-dose were not statistically different between doxazosinand atenolol. There was effective control of blood pressure by bothdrugs at all time points of the day. The pharmacokinetic andpharmacodynamic results obtained in this study are compatible withthe use of doxazosin in a once daily dose regimen for the treatmentof essential hypertension.

Drug recommendations:

Combination treatments of anti-obesity drugs showeddisappointing results. The first important clinical study forweight reduction combining drugs used phentermine and fenfluramineas previously mentioned. The trial showed a highly significantweight reduction. However, fenfluramine was withdrawn from themarket worldwide on September 15, 1997, because of heart valvedamage . Combination treatment of orlistat and sibutramine, whichhad been approved only for long-term use, did not induce anyfurther weight loss [53]. Because none of the single-agent drugsthat have been approved or appear close to approval haveconsistently been able to achieve a weight loss of more thanapproximately 10% of body weight , several other combinations ofexisting drugs are now under development and may be the nexttherapeutic option for treatment of obesity.

Serotonin receptor activation:

Lorcaserin is a selective serotonin 2C (5HT2c)receptor agonist that was anticipated to recapitulate the weightloss effects of fenfluramine without its adverse cardiac effects.51Lorcaserin 10mg BID was FDA-approved in 2012 on the basis of twolarge randomized, placebo-controlled trials in nondiabetic patients(BLOOM,31 n=3182, 50% attrition; BLOSSOM,32 n=4004, 45% attrition)along with a third, smaller trial in adults with type 2 diabetes(BLOOM-DM,30 n=603, 34% attrition). In these trials, participantsreceived low-intensity nutritional and exercise counseling.Lorcaserin decreased body weight modestly, by about 3.2 kg (~3.2%of initial body weight) more than placebo.29 However, significantlymore patients treated with lorcaserin 10mg bid than placebo lost≥5% (BLOOM: 47 vs. 20%, BLOSSOM: 47 vs. 25%, BLOOM-DM: 37 vs. 16%)or ≥10% (BLOOM: 23 vs. 8%, BLOSSOM: 23 vs. 10%, BLOOM-DM: 16 vs.4%) of their initial weight. Reduction in body weight belowbaseline in the one study31 with data from participants who tooklorcaserin for 2 years had average weight loss of 5.6 kg, versus2.4 kg among placebo-treated participants. Blood pressure, totalcholesterol, LDL-cholesterol, and triglycerides also decreasedsignificantly more in lorcaserin-treated participants.52 Amongpatients with diabetes, lorcaserin treatment led to lower bodyweight and improved glycated hemoglobin concentrations.30 Adverseeffects include headache, nausea, fatigue, and dizziness.52Although neither incidence of valvulopathy nor hypertension wasstatistically greater during lorcaserin than placebo treatment,both were numerically somewhat more prevalent and the FDA hasrequested that a post-approval trial to assess the long-termcardiovascular effects of lorcaserin be conducted.5

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