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Monitoring Drug Therapy

Monitoring Drug Therapy. Phase III May 2009. The goal of therapeutics. The goal of therapeutics is to achieve a desired beneficial effect with minimal adverse effects. The physician must determine the dose that most closedly achieve this goal. PK-PD. Pharmacodynamics

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Monitoring Drug Therapy

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  1. Monitoring Drug Therapy Phase III May 2009

  2. The goal of therapeutics • The goal of therapeutics is to achieve a desired beneficial effect with minimal adverse effects. • The physician must determine the dose that most closedly achieve this goal.

  3. PK-PD • Pharmacodynamics • governs the concentration-effect part of the interaction • The maximum response and sensitivity determine the magnitude of the effect at a particular concentration (Emax and EC50). • Pharmacokinetics • deals with the dose-concentration part. • The absorption, distribution, metabolism and elimination determine how rapidly and for how long the drug will appear at the target organ.

  4. Fundamental hypothesis of pharmacology Fundamental hypothesis of pharmacology states that a relationship exists between a beneficial (or toxic) effect of a drug and the concentration of the drug.

  5. DOSE-EFFECT RELATIONSHIP

  6. DOSE-EFFECT RELATIONSHIP

  7. THERAPEUTIC WINDOW

  8. Quantal Dose-Response Plots

  9. Volume of Distribution • Volume of distribution (Vd) relates the amount of drug in the body to the concentration of drug (C) in blood or plasma: Volume of distribution (Vd)= amount of drug in the body C The volume of distribution may be defined with respect to blood, plasma, or water (unbound drug), depending on the concentration used in equation (1) (C = Cb, Cp, or Cu). Drugs that are completely retained within the vascular compartment, on the other hand, have a minimum possible volume of distribution equal to the blood component in which they are distributed, eg, 0.04 L/kg body weight or 2.8 L/70 kg for a drug that is restricted to the plasma compartment.

  10. Volume of distribution (Vd) • Clearence (Cl) • Half life (t1/2) • Bioavailability • Bioequivalence

  11. Loading dose • Maintenece dose • Therapeutic window

  12. A rational dosage regimen is based on the assumption that there is a target concentration that will produce the desired therapeutic effect.

  13. Maintenance Dose • In most clinical situations, drugs are administered in such a way as to maintain a steady state of drug in the body, ie, just enough drug is given in each dose to replace the drug eliminated since the preceding dose. • Calculation of the appropriate maintenance dose is a primary goal. • dosing rate = rate of elimination • maintenance dose = dosing rate X dosing interval

  14. Plasma conc. are measured: • Lithium • Digoxin • Phenitoin • Cyclosporin • Theophyline

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