Ppt chapter 04

Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Chapter 4

Pharmacotherapeutics, Pharmacokinetics, and

Pharmacodynamics


Question

• One aspect of pharmacotherapeutics is the study of the clinical indications of drug therapy.

– A. True

– B. False


Answer

• A. True

• Rationale: Pharmacotherapeutics is the study of desired therapeutic goal from drug therapy, the clinical purpose—the indication—for giving a drug and the desired effect of the drug.


Pharmacotherapeutics

• Pharmacotherapeutics is the achievement of the desired therapeutic goal from drug therapy.

• Pharmacotherapeutics is the study of the clinical purpose—the indication—for giving a drug.

• The desired pharmacotherapeutics can be to induce a cure or prevent a problem.

• Nurses do need to question all orders if the intended pharmacotherapeutics of a drug does not correlate with the patient’s reason for receiving drug therapy.


Pharmacokinetics • Pharmacokinetics is the movement of the drug

particles inside the body.

• Absorption is the movement of the drug from the site of administration into the bloodstream.

• Distribution is the movement of the drug into the cells.

• Metabolism is the conversion of the drug into another substance or substances.

• Excretion is the removal of the drug.


Process by Which Drugs Move Through the Body• Drug molecules move during all phases of

pharmacokinetics.

• Drugs cross cell membranes in one of three ways:

– First, they can pass between the spaces or channels between the molecules in the membrane.

– Second, drugs can pass through the membrane with the help of a transport system.

– Third, drugs can penetrate the membrane directly.

• The chemistry of the drug particles also affects the movement of particles throughout the body.


Absorption

• Several variables affect the rate of drug absorption.

– Depends on the route of administration

– Affected by the speed at which the drug dissolves

• Drugs that are administered orally generally take the longest to be absorbed.

– Food or other drugs can interfere with absorption.


Absorption (cont.)

• Drugs given parenterally are absorbed more rapidly than drugs given orally.

– Intramuscular absorption is somewhat more rapid than subcutaneous absorption.

– Drugs that are administered intravenously are placed directly into the bloodstream.

• Large surface areas increase the rate of absorption.

• Blood flow also affects the rate of absorption—the greater the volume of blood flow, the faster the rate of absorption.

• Lipid solubility also alters absorption.

• pH also affects absorption.


Distribution

• The distribution of a drug throughout the body depends on three factors: blood flow to the tissues, the drug’s ability to leave the blood, and the drug’s ability to enter cells.

• The drug is transported to the tissues and cells through the circulatory system.

• Most drugs do not produce their effect while in the blood.


Protein-Bound Drugs

• Protein binding of drugs affects the distribution of a drug.

• When the drug is bound to protein, it is unable to pass through the capillary walls.

• The bonds will dissolve in time, and the drug molecules will become free and active.

• Drug dosages are calculated by the drug manufacturer based on the protein-binding characteristics of the drug.

• When the patient has a lower-than-expected protein level, the distribution of the drug is altered.


The Effects of Administering Protein-Bound Drugs


Question

• What will be the result of administering a highly protein-bound drug to a patient with liver failure?

– A. There will be no significant difference in the distribution of the drug.

– B. The drug will reach the target cells more quickly and therefore will not be as effective.

– C. The drug will reach the target cells more quickly, which could result in a toxic effect.

– D. The drug will take longer to reach the target cells, delaying the onset of action.


Answer

• C. The drug will reach the target cells more quickly, which could result in a toxic effect.

• Rationale: Patients with liver failure have lower levels of protein and albumin in their blood than patients without liver failure; therefore, the drug will reach the target cells more quickly, which could lead to a toxic effect. Remember that all recommended drug dosages are calculated based on a patient with normal protein levels.


Blood–Brain Barrier

• The capillary bed that services the brain is different from other capillary beds.

• Instead of wide spaces between the cells in the capillary walls, the cells are packed tightly together.

• This structure prevents drug molecules, and other foreign substances, from passing through and entering the brain.

• The purpose of the blood–brain barrier is to keep toxins and poisons from reaching the brain.

• At times, the mechanism will prevent treatment of a problem.


Placental Membrane

• The placental membrane separates the maternal circulation from the fetal circulation.

• It is not a barrier like the blood–brain barrier.

• Any drug that can pass through a membrane can pass through the placenta.

• In order to pass through the placenta, a drug must be lipophilic, not ionized, and not protein bound.


Metabolism

• Metabolism of drugs occurs primarily in the liver.

• Physiologic factors that impair the functioning of the liver decrease the ability of the liver to metabolize drugs.

• When drugs are metabolized, they are changed from their original form to a new form.

• Metabolism is sometimes referred to as biotransformation.

• Drugs are generally metabolized from substances that are lipophilic into substances that are hydrophilic.


Metabolites

• A product of metabolism is called a metabolite.

• Drugs that are metabolized are generally changed into an inactive form.

• Metabolism can convert a drug that has little or no therapeutic effect in its original form into the active form.

• Drugs that are inactive until metabolized into an active form are called prodrugs.

• An active metabolite may cause a different and potentially harmful effect.


First-Pass Effect

• Metabolism occurs at different rates for different drugs.

• The percentage of drug that is metabolized each time the drug circulates, or passes, through the liver is the same, but the total number of drug molecules that are metabolized will be different.

• Drugs that are highly metabolized lose much of their effectiveness during this first pass through the liver.

• This loss of effectiveness is called the first-pass effect.

• Drugs that experience a high first-pass effect may need higher oral doses to achieve a therapeutic level of circulating drug.


P-450 System • Liver metabolism is predominantly achieved by specific

liver enzymes.

• These microsomal enzymes are called the cytochrome P-450 system.

• The enzyme CYP3A4 is the most common and is responsible for the metabolism of most drugs.

• Some drugs either induce or inhibit the P-450 system, altering metabolism of other drugs.

• When a large quantity of one of these enzymes is present, more metabolism can occur through this pathway.

• This increase in metabolism rapidly decreases the amount of circulating drug.


Excretion

• Excretion is the process of removing a drug, or its metabolites, from the body.

• The most common route for drug excretion is through the urine.

• Diseases and pathophysiologic changes in the kidney decrease the effectiveness of the kidney in drug excretion.


Processes Involved in Renal Excretion • Three processes are involved in renal excretion of drugs.

• The first is glomerular filtration.

– Most drug particles pass easily through the spaces of the capillary walls into the urine in the proximal tubule.

• The second process is passive tubular reabsorption.

– The drug particles will try to move from the area of greater concentration to that of lesser concentration.

• The third process that affects excretion is active tubular secretion.

– Active transport systems in the renal tubule work to move some drugs from the blood and into the urine.


Factors That Affect Renal Excretion

• Drug excretion can be increased if the pH of the urine encourages the drug to become an ion.

• Overuse of the active transport system also affects excretion.

– As the transport system becomes overloaded, some of the drug particles will remain in the blood until they can be moved by the transport system.

• Two drugs can be given together to slow deliberately the rate of excretion of one or both of the drugs.


Question

• Which of the following drugs can be given with penicillin to slow the excretion of the drug?

– A. Birth control pill

– B. Rifampin

– C. Probenecid

– D. Warfarin


Answer

• C. Probenecid

• Rationale: Probenecid is a drug used to treat gout. In this situation, the probenecid is used not for its normal pharmacotherapeutic effect but solely to slow the rate of active transport and excretion of the antibiotic.


Factors that Affect Biliary Excretion

• A factor that affects excretion of drugs through bile is enterohepatic recirculation.

• Drug molecules that are in the bile are reabsorbed.

• This process lengthens the time the drug is present in the bloodstream and can produce an effect.


Half-Life

• The combined processes of metabolism and excretion are responsible for elimination of a drug from the body.

• The amount of time that is required to remove half (50%) of the blood concentration of a drug is called half-life.

• Drugs have various half-lives, based on their pharmacologic properties.

• In one half-life, a set percentage of the drug molecules present in the blood is eliminated.


Steady State• The point at which the amount of drug being

administered and the amount being eliminated balance off are equal

• At four to five half-lives, steady state is achieved.

• Increasing the dose has no effect on how quickly steady state can be achieved.

• Steady state is achieved based on the amount of time required for four to five half-lives to occur.

• The full pharmacotherapeutic response of a particular drug dose is measured when the drug has achieved steady state.


Clearance

• The rate at which drug molecules disappear from the circulatory system is effected by several factors.

• This rate is called clearance or clearance rate of a drug.

• Renal excretion and hepatic metabolism are the major modes of clearance.

• The gender of the patient can also alter the clearance of some drugs.

• Even though a drug’s clearance is shown to be statistically altered, this statistical difference does not necessarily create a clinical difference.


Pharmacodynamics

• Pharmacodynamics is the biologic, chemical, and physiologic actions of a particular drug within the body.

• The pharmacodynamics of a drug are responsible for its therapeutic effects and sometimes its adverse effects.

• Drugs cannot create new responses in the body; they can only turn on, turn off, promote, or block a response that the body is inherently capable of producing.


Drug–Receptor Interactions

• Most drugs create their effects in the body by attaching to special sites, called receptors.

• At the receptor site, the drug is able to stimulate the cell to act in a way that the cell is designed to act.

• Each type of receptor is responsible for producing a particular effect in the cell.

• An agonist causes the cell to act.

• An antagonist or blocker prevents something else from attaching to the cell blocking and action.

• If the drug is on the receptor, the other chemical cannot also be on the receptor.


Occupancy Theory • Single-occupancy theory

– The intensity of the body’s response to the drug is directly related to the number of receptors occupied by the drug.

– The maximum response occurs when all of the receptors have drug molecules attached.

• Modified occupancy theory

– Different drugs have different strengths of attractions, or affinity, for receptor sites.

– Once a drug is attached to a receptor, it has different abilities to stimulate the receptor.


Receptor Sensitivity

• Changes in receptor sensitivity

– Receptors are not static.

– Continual stimulation from an agonist usually makes the drug less effective.

– Continual blockage from an antagonist usually makes the drug more likely to react.

• Nonreceptor responses

– Drugs exert their effect by reacting physically or chemically with other molecules in the body.


Variables that Influence the Dose of a Drug • Potency and efficacy

– The level of the drug needed in the body to produce an effect

• Maintenance and loading doses

– Maintenance dose—daily dose

– Loading dose—larger than usual dose to reach a therapeutic effect quicker

• Therapeutic index

– The difference between an effective dose and a toxic dose


Potency and Efficacy • A certain level of drug must be present in the body to

produce an effect at all.

• This level is called the minimum effective concentration.

• The strength of the response to a drug increases proportionately as more drug is given.

• The amount of a drug that must be given in order to produce a particular response is called the potency of a drug.

• How well a drug produces its desired effect is called efficacy.

• The efficacy of a drug is related to its intrinsic activity.


Maintenance and Loading Doses

• Because people are unique, how individuals respond to a drug dose varies.

• The dose that is required to produce the therapeutic response in 50% of the population is called the effective dose 50% (ED50).

• The dose that is given consistently over time is called the maintenance dose.

• Patients who are started on drug therapy using the standard maintenance dose arrive at steady state after four to five half-lives.


Maintenance and Loading Doses (cont.)

• The patient’s medical condition may warrant immediate and full drug effect.

– If this is the case, a larger dose than usual is given initially.

– This initial large dose is called a loading dose.

– The loading dose is computed so that after some of the drug is eliminated, the drug concentration in the body is still in the therapeutic range.


Therapeutic Index

• The lethal dose is computed in a laboratory setting and analyzed statistically.

• The point at which the dose would be fatal in 50% of the population receiving that dose is called lethal dose 50% (LD50).

• To determine the safety of a drug, the ED50 is compared with the LD50.


Therapeutic Index (cont.)

• The relation of ED50 to LD50 is called the therapeutic index.

– TI = ED50 / LD50

• If the amount of a drug required to be the ED50 is similar to the amount that is the LD50, the mathematical ratio of the two values will equal a number close to one.

• When the ED50 and the LD50 do not differ by much, the drug is considered to have a narrow therapeutic index.


Drug Dosage and Blood Concentration

• As drug levels within the body increase, the patient is more likely to experience adverse effects from drug therapy.

• To help determine whether a drug’s dose is sufficient to be in the therapeutic range, but not so high as to cause adverse effects, blood levels of the drug are often measured.


Drug Dosage and Blood Concentration (cont.)

• Nurses need to monitor drug blood levels if samples are drawn and notify the physician or nurse practitioner if the level indicates that the blood levels are not in the therapeutic range.

• The therapeutic range can only be considered an average.

• Some patients experience the therapeutic effects from a drug when their blood levels show that the drug is at “subtherapeutic” levels.

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Ppt chapter 04