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Pharmacology for nurses

Lecture notes
Text book:
Lippincott’s pharmacology, 6th Ed, 2015

References:
 Lilly, Rainforth Collins: Pharmacology and the nursing process, 6th Ed, 2017
 Amy M. Karch, Focus on nursing pharmacology, 5th Ed, 2017.

Contents:
PART 1: introduction to nursing pharmacology

I. Introduction to drugs.
II. Drugs and the body.

Part 2: Drugs affecting the central nervous system CNS.

I. Opioids.
II. Anesthetics.
III. Drugs for epilepsy.
IV. Anxiolytic and hypnotic drugs.
V. Antidepressants.
VI. Anti psychotics.

Part 3: Drugs affecting the autonomic nervous system ANS.

I. Cholinergic drugs.
II. Cholinergic-blocking drugs.
III. Adrenergic drugs.
IV. Adrenergic-blocking drugs.

Part 4: Drugs affecting the cardiovascular and renal systems.

I. Antihypertensive drugs.
II. Diuretic drugs.
III. Heart failure drugs.
IV. Antidysrhythmic drugs.
V. Antianginal drugs.
VI. Anticoagulants and antiplatelets
VII. Drugs for hyperlipidemia.

Part 5: Drugs affecting respiratory system.

Part 6: chemotherapeutic drugs

I. Principles of antimicrobial drugs.


II. Cell wall inhibitors.
III. Protein synthesis inhibitors.
IV. Quinolones, folic acid antagonists and UT antiseptics
V. Antimycobacterial drugs.
VI. Antifungal.
VII. Antiprotozoal drugs.
VIII. Anthelminitic drugs.
IX. Antiviral drugs.

Part 7: Antiinflammatory, antipyretic and analgesics.

Part 8: Drugs affecting the endocrine system.

I. Thyroid and anti thyroid drugs.


II. Drugs for diabetes.
III. Adrenal hormones.

Part 9: Drugs affecting the gastrointestinal system.

PART 1: introduction and the nursing


pharmacology
I: Introduction to drugs:
Any chemical that affects the physiologic processes of a living organism can broadly be defined
as a drug. The study or science of drugs is known as pharmacology. In clinical practice, health
care providers focus on how chemicals act on living organisms. Nurses deal with
pharmacotherapeutics, or clinical pharmacology, the branch of pharmacology that uses drugs to
treat, prevent, and diagnose disease.

For many reasons, understanding how drugs act on the body to cause changes and applying that
knowledge in the clinical setting are important aspects of nursing practice. A drug can have many
effects, and the nurse must know which ones may occur when a particular drug is administered.
Some drug effects are therapeutic, or helpful, but others are undesirable or potentially
dangerous. These negative effects are called adverse effects.

The nurse is in a unique position regarding drug therapy because nursing responsibilities
include the following:
• Administering drugs
• Assessing drug effects
• Intervening to make the drug regimen more tolerable
• Providing patient teaching about drugs and the drug regimen
• Monitoring the overall patient care plan to prevent medication errors

SOURCES OF DRUGS:
-Natural sources:
 Plant, animal, micro-organisms and minerals.
-Synthetic sources created using man-made chemicals rather than natural ingredients. A
number of synthetic drugs on the market, including Ecstasy, LSD
-Semisynthetic drugs.

Drug names:
Throughout the process of its development, a drug will acquire at least three different names.
1- The chemical name describes the drug’s chemical composition and
molecular structure.
2- The generic name, or nonproprietary name, is often much shorter and
simpler than the chemical name. The generic name is used in most
official drug compendiums to list drugs.
3- The trade name, or proprietary name, is the drug’s registered
trademark, which indicates that its commercial use and is restricted the
owner of the patent for the drug the patent owner is usually the
manufacturer of the drug.
II: Drugs and the body
To understand what happens when a drug is administered, the nurse must understand
pharmacodynamics—how the drug affects the body—and pharmacokinetics—how the body
acts on the drug. Knowing the basic principles of pharmacodynamics and pharmacokinetics
helps the nurse to anticipate therapeutic and adverse drug effects and to intervene in ways that
ensure the most effective drug regimen for the patient.

The amount of a drug that is needed to cause a therapeutic effect is called the critical
concentration.

A. Pharmacokinetics:
Pharmacokinetics involves the study of absorption, distribution, metabolism biotransformation),
and excretion of drugs.
- Absorption: First, absorption from the site of administration permits entry of the drug
(either directly or indirectly) into plasma
- Distribution: Second, the drug may then reversibly leave the bloodstream and distribute
into the interstitial and intracellular fluids.
- Metabolism: Third, the drug may be biotransformed by metabolism by the liver or other
tissues.
- Elimination: Finally, the drug and its metabolites are eliminated from the body in urine,
bile, or feces.

Using knowledge of pharmacokinetic parameters, clinicians can design optimal drug regimens,
including the route of administration, the dose, the frequency, and the duration of treatment.

In clinical practice, pharmacokinetic considerations include the:


- Onset of drug action.
- Drug half-life.
- Timing of the peak effect.
- Duration of drug effects.
- Metabolism or biotransformation of the drug.
- The site of excretion.
Routes of administration:

 A drug’s route of administration affects the rate and extent of absorption of that drug
 Enteral (GI tract)
 Parenteral
 Other.
 Enteral route:
- Administering the drug by mouth.
 Oral
 Sublingual/ Buccal

 Parenteral route:
- Introduces drugs directly to the systemic circulation

 Intravenous (fastest delivery into the blood circulation)


 Intramuscular
 Subcutaneous

 Other routes:
 Oral inhalation.
 Nasal inhalation.
 Transdermal.
 Topical.
 Rectal.
 Intrathecal.

1-Absorption:
Absorption is the transfer of a drug from the site of administration to thebloodstream. The rate
and extent of absorption depend on the environment where the drug is absorbed, chemical
characteristics of the drug, and the route of administration (which influences bioavailability).
Routes of administration other than intravenous may result in partial absorption and lower
bioavailability.

Factors influencing absorption:


1- PH of the abdorption site.
2- Blood flow to the absorption site.
3- Total surface area available for absorption.
4- Contact time at the absorption surface.

Bioavailability
Bioavailability is the rate and extent to which an administered drug reaches the systemic
circulation. For example, if 100 mg of a drug is administered orally and 70 mg is absorbed
unchanged, the bioavailability is 0.7 or 70%. Determining bioavailability is important for
calculating drug dosages for nonintravenous routes of administration. Many drugs administered
by mouth have a bioavailability of less than 100%, whereas drugs administered by the
intravenous route are 100% bioavailable.

2-Distribution:
Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the
interstitium (extracellular fluid) and the tissues. The distribution of a drug from the plasma to the
interstitium depends on cardiac output and local blood flow, capillary permeability, the degree of
binding of the drug to plasma and tissue proteins, and the relative lipophilicity of the drug.

A. Blood flow
The rate of blood flow to the tissue capillaries varies widely. For instance,
blood flow to the “vessel-rich organs” (brain, liver, and kidney) is greater than
that to the skeletal muscles. Adipose tissue, skin, and viscera have still lower
rates of blood flow. Once a drug enters the bloodstream (circulation), it is distributed
throughout the body.

B. Capillary permeability
Capillary permeability is determined by capillary structure and by the
chemical nature of the drug. Capillary structure varies in terms of the fraction
of the basement membrane exposed by slit junctions between endothelial
cells. In the liver and spleen, a significant portion of the basement membrane
is exposed due to large, discontinuous capillaries through which large plasma
proteins can pass (Figure 1.13A). In the brain, the capillary structure is
continuous, and there are no slit junctions (Figure 1.13B).

To enter the brain, drugs must pass through the endothelial cells of the CNS
capillaries or be actively transported. By contrast, lipid-soluble drugs readily
penetrate the CNS because they dissolve in the endothelial cell membrane.
Ionized or polar drugs generally fail to enter the CNS because they cannot
pass through the endothelial cells that have no slit junctions (Figure 1.13C).
These closely juxtaposed cells form tight junctions that constitute the blood–
brain barrier.
C.Binding of drugs to plasma proteins and tissues

1. Binding to plasma proteins: Reversible binding to plasma proteins


sequesters drugs in a nondiffusible form and slows their transfer out of the
vascular compartment. Albumin is the major drug-binding protein and may act
as a drug reservoir (as the concentration of free drug decreases due to
elimination, the bound drug dissociates from the protein). This maintains the
free drug concentration as a constant fraction of the total drug in the plasma.

2. Binding to tissue proteins: Many drugs accumulate in tissues, leading to


higher concentrations in tissues than in the extracellular fluid and blood.
Drugs may accumulate as a result of binding to lipids, proteins, or nucleic
acids. Drugs may also be actively transported into tissues. Tissue reservoirs
may serve as a major source of the drug and prolong its actions or cause local
drug toxicity.
D. Lipophilicity
The chemical nature of a drug strongly influences its ability to cross cell
membranes. Lipophilic drugs readily move across most biologic membranes.
The major factor influencing the distribution of lipophilic drugs is blood flow to
the area. In contrast, hydrophilic drugs do not readily penetrate cell
membranes and must pass through slit junctions.
At this point it is also beginning to be eliminated by the organs that metabolize and excrete
drugs primarily the liver and the kidneys. Only drug molecules that are not bound to plasma
proteins can freely distribute to extravascular tissue (outside the blood vessels) to reach their
site of action.

E.Distribution volme:
A theoretical volume, called the volume of distribution, is sometimes used to describe the
various areas in which drugs may be distributes. These areas, or compartments, may be the
blood, total body water, body fat, or other body tissues and organs. There are some sites in the
body into which it may be very difficult to distribute a drug. These sites typically either have a
poor blood supply (e.g., bone) or have physiologic barriers that it difficult for drugs to pass
through (e.g., the brain due to blood-brain barrier).

Placenta and Breast Milk


Many drugs readily pass through the placenta and affect the developing fetus in pregnant
women. As stated earlier, it is best not to administer any drugs to pregnant women because of
the possible risk to the fetus. Drugs should be given only when the benefit clearly outweighs any
risk. Many other drugs are secreted into breast milk and therefore have the potential to affect
the neonate.

3-Metabolism:

Once a drug enters the body, the process of elimination begins. The three
major routes of elimination are hepatic metabolism, biliary elimination, and
urinary elimination. Together, these elimination processes decrease the
plasma concentration exponentially. That is, a constant fraction of the drug
present is eliminated in a given unit of time. Metabolism leads to production of
products with increased polarity, which allows the drug to be eliminated.
B. Reactions of drug metabolism
The kidney cannot efficiently eliminate lipophilic drugs that readily cross cell
membranes and are reabsorbed in the distal convoluted tubules. Therefore,
lipid-soluble agents are first metabolized into more polar (hydrophilic)
substances in the liver via two general sets of reactions, called phase I and
phase II

Metabolism is the next step after absorption and distribution. The organ most responsible for
the metabolism of drugs is the liver. Other metabolic tissues include skeletal muscle, kidneys,
lungs, plasma, and intestinal mucosa.

Hepatic enzymes:

Hepatic metabolism involves the activity of a very large class of enzymes as cytochrome P-450
enzymes. These enzymes control a variety of reactions that aid in the metabolism of
medications. The P-450 system is one of the most important systems that influence drug-drug
interactions. The list of drugs that are metabolized by the P-450 enzyme system is constantly
changing as a new drugs introduced into the market.

The biotransformation capabilities of the liver can vary considerably from patient to patient.
Various factors that can alter the biotransformation of a drug, including genetics, diseases, and
the concurrent use of other medications many drugs can inhibit various drug-metabolizing
enzymes and are called enzyme inhibitors. Decreased or delayed drug metabolism results in the
accumulation of the drug and prolongation of the effects of the drug, which can lead to drug
toxicity. In contrast, stimulation of drug metabolism can cause diminishing pharmacologic
effects. This often occurs with the repeated administration of some drugs that can stimulate the
formation of new enzymes. Such drugs are said to be enzyme inducers.

First-pass effect:
A drug that is absorbed from the intestine must first pass through the liver before it reaches the
systemic circulation. If a large proportion of a drug is chemically processed into inactive
metabolites in the liver, then much smaller amount of drug will pass into the circulation. First-
pass effect reduces the bioavailability of the drug to less than 100%.

4-Excretion:
Drugs must be sufficiently polar to be eliminated from the body. Removal of
drugs from the body occurs via a number of routes, the most important being
elimination through the kidney into the urine. The actual act of renal excretion is
accomplished through glomerular filteration, active tubular reabsorption, and active tubular
secretion.

Drugs that have been made water soluble in the liver are often readily excreted from the kidney
by glomerular filtration. Other drugs are secreted or reabsorbed through the renal tubule by
active transport systems.

The active transport systems that move the drug into the tubule often do so by exchanging it for
acid or bicarbonate molecules. Therefore the acidity of urine can play an important role in drug
excretion.
This concept is important to remember when trying to clear a drug rapidly from the system or
trying to understand why a drug is being given at the usual dose but is reaching toxic levels in the
system.
One should always consider the patient’s kidney function and urine acidity before
administering a drug. Kidney dysfunction can lead to toxic levels of a drug in the body because
the drug cannot be excreted.

Half-life:
The time it takes for one half of the original amount of a drug to be removed from the body. It is
a measure of the rate at which a drug is removed from the body. After about five half-lives, most
drugs are considered to be effectively removed from the body. At that time approximately 97%
of the drug has been eliminated, and what little amount remains is usually too small to have
either therapeutic or toxic effects.

The concept of half-life is clinically useful for determining when steady state will be reached in a
patient taking a particular drug. With regard to blood levels, steady state of a drug refers to the
physiological state in which the amount of drug removed via elimination is equal to the
amount of drug absorbed with each drug dose. This physiological plateau phenomenon
typically occurs after 4-5 half-lives of administering drug. Therefore if a drug has an extremely
long half-life, it will take much longer for the drug to reach steady-state blood levels.
Once steady-state blood levels have been reached, there are consistent levels of drug in the
body that correlate with maximum therapeutic benefits. Nurses can use their knowledge of drug
half-life to explain the importance of following a schedule of drug administration in the hospital
or at home.
 Onset, Peak, and Duration.
The pharmacokinetic terms absorption, distribution, metabolism, and excretion are all used to
describe the movement of drugs through the body. The terms onset, peak, duration and trough
are used to describe drug effects. Peak and trough are used also to describe drug
concentrations, which are usually measured from blood samples.

Drug’s onset of action: is the time required for the drug to elicit a therapeutic response.
Drug’s Peak effect: is the time required for a drug to reach its maximum therapeutic response.
Duration of action of a drug: is the length of time that the drug concentration is sufficient to
elicit a therapeutic response. The length of time until the onset and peak of action and the
duration of action often play an important part in determining the peak level (highest blood
level) and trough level (lowest blood level) of a drug.

If the peak blood level is too high, then drug toxicity may occur. If the trough blood level is too
low, then the drug may not be at therapeutic levels. In therapeutic drug monitoring, peak and
trough values are measured to verify adequate drug exposure, maximize therapeutic effects, and
minimize drug toxicity.
B.Pharmacodynamics:
Pharmacodynamics is concerned with mechanisms of drug action in living tissues. Drug-induced
alterations in normal physiologic functions are explained by the principles of pharmacodynamics.
A positive change in a faulty physiologic system is called a therapeutic effect of a drug. Such as
effect is the goal of drug therapy.

Mechanism of action:
Drugs can produce therapeutic effects in several ways. The effects of a particular drug depend on
the characteristics of the cells or tissue targeted by the drug. Once the drug is at the site of
action, it can increase or decrease the rate at which that cell or tissue functions, or it can modify
the strength of function of that cell or tissue.
Drugs can exert their actions in three basic ways:
- Through receptors.
- Through enzymes.
- Nonselective interactions.

It should also be noted that not all mechanisms of action have been identified for all drugs.

Receptor interactions:
A receptor can be defined as a reactive site on the surface or inside of a cell. Once a drug binds
to and interacts with the receptor, a pharmacologic response is produced. The degree to which a
drug attaches to and binds with a receptor is called its affinity. The drug with the best “fit” and
strongest affinity for the receptor will elicit the greatest response from the cell or tissue. A
drug becomes bound to the receptor through the formation of chemical bonds between the
receptor on the cell and the drug molecule.

Drugs that bind to receptors interact with receptors in different ways either to elicit or to block a
physiologic response (agonist, partial agonist and antagonist).
Enzyme interactions:
Enzymes are the substances that catalyze nearly every biochemical interactions in a cell. Drugs
may either inhibit (most common) or enhances the action of specific enzyme.

Nonselective interactions:
Drugs with nonspecific mechanisms of action do not interact with receptors or enzymes. Instead,
their main targets are cell membranes and various cellular processes such as metabolic activities.
Some cancer drugs and antibiotics have this mechanism of action.

Therapeutic index:
It’s the ratio of a drug’s toxic level to the level that provides therapeutic benefits. The safety of a
particular drug therapy is determined by this index. A low therapeutic index means that the
difference between a therapeutically active dose and a toxic dose is small. A drug with a narrow
therapeutic index has a greater likelihood than other drugs causing an adverse reaction, and
therefore its use requires closer monitoring. Examples of such drugs are warfarine and digoxin.
In contrast, a drug with a high therapeutic index, such as amoxicillin, is rarely associated with
overdose.

Rights of Medication Administration


The 7 traditional rights of medication administration (right drug, right dose, right patient, right
route, right time, right reason, and right documentation) now include additional rights that
should also be considered (right education, right evaluation, and right to refuse the medication).
These rights are goals of the medication administration process, and discussion of the effort to
reduce medication errors and harm has expanded over the years. However, the focus on rights
has been on the nurse and not the system in which medication administration takes place.

Contraindications:
 Any condition of the patient, especially a disease state that makes the use of a given
medication dangerous for the patient. Careful attention to this assessment process
helps to ensure an optimal therapeutic plan for the patient.

Monitoring:
Once the appropriate therapy has been implemented, the effectiveness of the therapy must be
evaluated.
 One must be familiar with the drug’s:
 Intended therapeutic action (beneficial)
 Unintended but potential adverse effects (predictable, adverse reactions)

 Therapeutic index
 Drug concentration: Drug concentrations can be an important tool for evaluating the
clinical response to drug therapy. Certain drug levels are associated with therapeutic
responses, whereas other drug levels are associated with toxic effects. Toxic drug levels
are typically seen when the body’s normal mechanisms for metabolizing and excreting
drugs are comprised. This commonly occurs when the liver and kidney functions are
impaired or in neonates.

 Patient’s condition: a patient’s response to a drug may vary greatly depending on


physiologic and psychological demands. Disease of any kind, infection, CV function, and
GI function are just a few of the physiologic elements that can alter a patient’s
therapeutic response. Stress, depression and anxiety can also be important psychologic
factors affecting response.

 Interactions: drugs may interact with other drugs, with foods, or with agents
administered as part of laboratory tests. Knowledge of drug interactions is vital for the
appropriate monitoring of drug therapy. The more drugs a patient receives, the more
likely that a drug interaction will occur. Drug interaction is alteration of one drug by
another. A drug interaction can either increase or decrease the actions of one or both of
the involved drugs. The more drugs a patient is taking, the greater the risk of drug
interactions. Concurrently administered drugs may interact with each other and alter the
pharmacokinetics of one another during any of four phases of pharmacokinetics:
absorption, distribution, metabolism or excretion.

-Additive effects: When two drugs with similar actions are given together (1+1=2).
-Synergistic effects: Occur when two drugs administered together interact in such a way
that their combined effects are greater than the sum of the effects for each drug give
alone (1+1= more than 2). -Antagonistic effects: Occur when the combination of two
drugs results in drug effects that are less than the sum of effects of each drug given
separately (1+1= less than 2).
-Incompatibility is a term most commonly used to describe parenteral drugs. Drug
incompatibility occurs when two parenteral drugs or solutions are mixed together and
the result is a chemical deterioration of one or both of the drugs or formation of a
physical precipitate.

 Adverse drug events: is a broad term for any undesirable occurrence involving
medications.
The two common broad categories of adverse drug event are:
-Medication errors.
-Adverse drug reactions.

A medication error is a preventable situation. Medication errors occur during the


prescribing, dispensing, administering, or monitoring of drug therapy. These four phases
are collectively known as the medication use process.

An adverse drug reaction is any reaction to a drug that is unexpected and undesirable
and occurs at therapeutic drug dosages. They may or may not be preventable,
depending on the situation. Adverse drug reactions range from mild to more severe drug
reactions that can be life-threatening, or fatal.
There are four general categories of adverse drug events: pharmacologic reaction,
hypersensitivity (allergic) reaction, idiosyncratic reaction, and drug interaction.

A pharmacologic reaction is extension of the drug’s normal effects in the body; this type
is predictable, well-known adverse drug reactions resulting in minor or no changes in
patient management.

An allergic reaction involves the patient’s immune system. Immunoglobulin recognizes


the drug molecule, its metabolite, or another ingredient in a drug formulation as a
dangerous foreign substance. At this point, an immune response may occur. This
response can result in reactions ranging from mild reactions such as skin erythema or
mild rash to severe, even life-threatening reactions such as constriction of bronchial
airways and tachycardia.

An idiosyncratic reaction is not result of a known pharmacologic property of a drug or of


a patient allergy but instead occurs unexpectedly in a particular patient. Such a reaction
is a genetically determined abnormal response to normal dosages of a drug. An example
is that people who suffer from G6PD deficiency have idiosyncratic reactions to a wide
range of drugs.

 Other drug effects: other drug-related effects that must be considered during drug
therapy are teratogenic, mutagenic, and carcinogenic effects. Teratogenic effects of
drugs or other chemicals result in structural defects in the fetus. Compounds that
produce such effects are called teratogens. Mutagenic effects are permanent changes in
the genetic composition of living organisms and consist of alterations in chromosome
structure, the number of chromosomes, or the genetic code of DNA. Drugs capable of
inducing mutations are called mutagens. Carcinogenic effects are the cancer-causing
effects of drugs, other chemicals, radiation, and viruses. Agents that produce such
effects are called carcinogens.

III-Life-span considerations
 Pregnancy
 Breast-feeding
 Neonatal and pediatric
 Elderly

Drug therapy during pregnancy:


A fetus is exposed to many of the same substances as the mother, including any drugs that she
takes. Therefore, it is important to know and understand drug effects during gestational life. The
factors that contribute to the safety or potential harm of drug therapy during pregnancy can be
broadly broken down into three areas: drug properties, fetal gestational age, and maternal
factors.

Drug properties include the drug’s chemistry, dosage, and concurrently administered drugs.
Fetal gestational age: The fetus is at greatest risk for drug-induced first developmental defects
during the first trimester of pregnancy. And during the last trimester the greatest percentage of
maternally absorbed drug gets to the fetus.
Maternal factors: any change in mother’s physiology that impacts the pharmacokinetic
characteristics of drugs can affect the amount of drug to which the fetus may be exposed.
Maternal kidney and liver function play a critical role, especially if the drug crosses the placenta.

The FDA classifies drugs according to their safety for use during pregnancy. This system of drug
classification is based primarily on animal studies and limited human studies.

Drug therapy during breast-feeding:


The primary drug characteristics that increase the likelihood that a drug given to a breast-feeding
mother will end up in the breast milk include fat solubility, low molecular weight, nonionization,
and high concentration. Fortunately, breast milk is not the primary route for maternal excretion.
The actual amount of drug to which a breast-feeding infant is exposed is depends largely on the
volume of milk consumed. The ultimate decision as to whether a breast-feeding mother should
take a particular drug depends on the risk/benefit ratio.

Considerations for neonatal and pediatric patients:


The immaturity of organs is the physiologic factor most responsible for differences in the
pharmacokinetic and pharmacodynamic behavior of drugs in this age group. In young patients,
certain drugs may be toxic whereas others may be less toxic. The sensitivity of receptor sites may
also vary with age; thus higher or lower dosages may be required depending on the drug.

Factors Affecting Pediatric Drug Dosages:


 Skin is thin and permeable
 Stomach lacks acid to kill bacteria
 Lungs have weaker mucus barriers
 Body temperatures less well regulated, and dehydration occurs easily
 Liver and kidneys are immature, impairing drug metabolism and excretion

Considerations for elderly patients:


An elderly patient is defined as a person who is 65 years of age or older.
We care about this group due to:

 Increased incidence of chronic illnesses


 Sensory and motor deficits
 Polypharmacy (the simultaneous use of multiple medications).
 Have physiological changes affect the action of many drugs.

Physiological changes:
The collective physiologic changes associated with the aging process have amajor effect on the
disposition and action of drugs. CVS, GIT, renal system and liver are the most systems affected by
the aging process.

Pharmacokinetic changes:
 Absorption
 Gastric pH less acidic
 Gastric emptying slowed
 Movement through GI tract slowed
 Blood flow to GI tract reduced
 Use of laxatives may accelerate GI motility

 Distribution
 Lower total body water percentages
 Increased fat content
 Decreased production of proteins by the liver, resulting in decreased protein
binding of drugs (and increased circulation of free drugs)
 Metabolism
 Aging liver produces fewer microsomal enzymes, affecting drug metabolism
 Reduced blood flow to the liver
 Excretion
 Decreased glomerular filtration rate
 Decreased number of intact nephrons.

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