Chapter 2: Drug Action and Handling

Chapter 2: Drug Action and Handling
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Chapter 2 Outline Drug Action and Handling
Characterization of drug action Mechanism of action of drugs Pharmacokinetics Routes of administration and dose forms Factors that alter drug effects

Drug Action and Handling
The dental health care worker must be familiar with some basic principles of pharmacology to discuss drugs used in dentistry and those that patients may be taking Understanding how drugs work, what effects they can have, and what problems they can cause can aid communication cont’d…

Haveles (p. 12) Historically, drugs were discovered by randomly searching for active components among plants, animals, minerals, and soil Today, organic synthetic chemistry researchers are responsible primarily for developing new drugs cont’d…

Parent compounds that exhibit known pharmacologic activity are chemically modified to produce congeners or analogs: agents of similar chemical structure with similar pharmacologic effect This technique of modifying a chemical molecule to provide more useful therapeutic agents evolved from studies of the relationship between chemical structure and the biologic activity, called the structure-activity relationship (SAR)

Characterization of Drug Action
Haveles (pp ) Log dose effect curve Potency Efficacy Chemical signaling between cells

Log Dose Effect Curve Haveles (pp ) (Fig. 2-1) The effect a drug exerts on biologic systems can be related quantitatively to the dose of the drug given A curve will result if the dose of the drug is plotted against the intensity of the effect cont’d…

Log Dose Effect Curve Haveles (pp ) (Fig. 2-2) If this curve is replotted using the log of the dose (log dose) versus the response, another curve is produced The potency and efficacy of the drug’s action may be determined from this curve

Potency Haveles (p. 13) (Fig. 2-3) Potency of a drug is a function of the amount of the drug required to produce an effect Potency is shown by the location of that drug’s curve along the log-dose axis (x-axis) More of a less-potent drug is required to produce a desired effect equivalent to that of a more potent drug

Efficacy Haveles (pp ) (Fig. 2-5) Efficacy is the maximal intensity of effect or response that can be produced by a drug Administering more drug will not increase the efficacy but can often increase the probability of an adverse reaction The efficacy of a drug increases as the height of the curve increases cont’d…

Efficacy “The efficacy and the potency of a drug are unrelated”
Drugs may be equally efficacious, but differ in potency Death is the endpoint when measuring the lethal dose The median lethal dose (LD50) is the dose when one half of the subjects die Are quotation marks needed?

Chemical Signaling Among Cells
Haveles (p. 14) The brain regulates the body through the autonomic nervous system Messages from the brain must be transmitted to many part of the body commanding the parts to “do something” Complex mechanisms for transmitting these messages allow for amplification or damping of the effect cont’d…

Chemical Signaling Among Cells
Haveles (p. 14) Neurotransmitters are chemicals responsible for transporting a wide variety of messages across the synapse Chemical signaling involves release of neurotransmitters and local substances and hormone secretion

Neurotransmitters Haveles (p. 14) (Fig. 2-6) Messengers that move the electrical impulses from a nerve are transmitted across the synapse via neurotransmitters The neurotransmitters are released and quickly travel across the synapse to the receptor At least fifty different agents can transmit messages

Local Substances Some organs secrete chemicals that work near them
These chemicals are not released into systemic circulation cont’d…

Local Substances Prostaglandins and histamine are examples of local substances Histamines can produce a localized allergic reaction Prostaglandins contract uterine muscles and become important when a baby is born When released in the stomach, they protect its lining

Hormones Secreted to produce effects throughout the body
Examples include insulin, thyroid hormone, and adrenocorticosteroids Reactions are usually slower than the ones associated with neurotransmitters

Mechanism of Action of Drugs
Haveles (pp ) Nerve transmission Receptors Agonists and antagonists cont’d…

Mechanism of Action of Drugs
Haveles (p. 14) Drugs elicit pharmacologic effects after they have been distributed to their sites of action The effect occurs because of a modulation in the function of an organism Drugs do not impart a new function to an organism They either produce the same action as an endogenous agent or block the action of an endogenous agent

Nerve Transmission Haveles (pp ) Transmission of impulses travels along the nerve producing a nerve action potential The action potential is triggered by the neurotransmitter released at the previous synapse cont’d…

Nerve Transmission The processes involved in the drug’s effect begin with the drug-receptor interaction The receptors interact with both endogenous substances and drugs This drug-receptor interaction results in a conformational (shape) change, which may allow the drug inside the cell to produce its effect, or it may cause release of a second messenger, which then produces the effect cont’d…

Nerve Transmission Many of the effects involve altering enzyme-regulated reactions or regulatory processes for protein synthesis after a series of reactions Similar to a chain reaction

Receptors Haveles (p. 15) Once a drug passes through a biologic membrane, it is carried to many different areas of the body, or site of action, to exert its therapeutic effect or adverse effect To do this, the drug must bind with the receptor site on the cell membrane cont’d…

Receptors Haveles (p. 15) (Fig. 2-7) Drug receptors appear to consist of many large molecules that exist either on the cell membrane or within the cell itself More than one receptor type or identical receptors can be found at the site of action Usually, a specific drug will bind with a specific receptor in a lock-and-key fashion cont’d…

Receptors Different drugs often compete for the same receptor sites
Haveles (p. 15) (Fig. 2-8) Different drugs often compete for the same receptor sites The drug with stronger affinity for the receptor will bind to more receptors than the drug with weaker affinity Drugs with stronger affinity for receptor sites are more potent than drugs with weaker affinity for receptor sites

Agonists and Antagonists
Haveles (pp ) (Fig. 2-9) When a drug combines with a receptor, it may produce enhancement or inhibition of the function These drugs are classified as either agonists or antagonists

Agonist An agonist is a drug that Haveles (p. 15)
Has affinity for the receptor Combines with the receptor Produces an effect

Antagonists An antagonist counteracts the action of the agonist
Haveles (pp ) (Fig. 2-9) An antagonist counteracts the action of the agonist Three different types of antagonists Competitive antagonist Noncompetitive antagonist Physiologic antagonist

Competitive Antagonist
A drug that Has affinity for a receptor Combines with the receptor Produces no effect This causes a shift to the right in the dose-response curve The antagonist competes with the agonist for the receptor The outcome depends on the relative affinity and concentrations of each agent

Noncompetitive Antagonist
Binds to a different receptor site than the agonist This reduces the maximal response of the agonist

Physiologic Antagonist
Has affinity for a different receptor site than the agonist Decreases the maximal effect of the agonist by producing an opposite effect via different receptors

Haveles (p. 16) Transport carriers are systems available for moving neurotransmitters or drugs into the cell Neurotransmitter precursors must be taken into the cell by an active transport pump The precursor for norepinephrine is tyramine, therefore it must be pumped into the cell After the neurotransmitter is synthesized, it is placed in granules that await a signal to dump their contents into the synapse cont’d…

The neurotransmitter can take three paths after it is released It can be broken down by enzymes It can migrate to the receptor and interact to produce an effect It can be taken up by the presynaptic nerve ending Reuptake is an easy way to recover the neurotransmitter for future use

Pharmacokinetics Passage across body membranes Absorption Distribution
Haveles (pp ) Passage across body membranes Absorption Distribution Half-life Blood-brain barrier Redistribution Metabolism (biotransformation) cont’d…

Pharmacokinetics Haveles (p. 16) The study of how a drug enters the body, circulates within the body, is changed by the body, and leaves the body Factors influencing movement are described in four major steps (ADME) Absorption Distribution Metabolism Excretion

Passage Across Body Membranes
Haveles (pp ) Passive transfer Specialized transport cont’d…

Haveles (pp ) The amount of drug passing through a cell membrane and the rate at which a drug moves are important in describing the time course of action and the variation in individual response to a drug Before a drug is absorbed, distributed, metabolized, and eliminated, it must pass through various membranes such as cellular membranes, blood capillary membranes, and intracellular membranes These membranes share physicochemical characteristics that influence the passage of drugs across their borders cont’d…

Haveles (p. 16) Membranes are composed of lipids, proteins, and carbohydrates Membrane lipids make the membrane relatively impermeable to ions and polar molecules Membrane proteins make up the structural components of the membrane and help move the molecules across the membrane during the transport process Membrane carbohydrates are combined with either proteins or lipids cont’d…

The lipid molecules orient themselves to form a fluid bimolecular leaflet with hydrophobic (lipophilic) ends in and hydrophilic charged ends out Throughout the membrane is a system of pores through which low–molecular-weight and small-size chemicals can pass cont’d…

The physicochemical properties of drugs that influence their passage across biologic membranes are lipid solubility, degree of ionization, and molecular size and shape Mechanisms of transfer are passive transfer and specialized transport

Passive Transfer Haveles (pp. 16-17) (Fig. 2-10)
Lipid-soluble substances move across the lipoprotein membrane by a passive transfer process called simple diffusion Directly proportional to concentration gradient of the drug across the membrane and the degree of lipid solubility cont’d…

Passive Transfer Water-soluble molecules small enough to pass through membrane pores may be carried through pores by bulk flow of water This process of filtration through single-cell membrane may occur with drugs having a molecular weight of 200 or less Drugs with molecular weights of 60,000 can “filter” through capillary membranes

Specialized Transport
Haveles (pp ) (Fig. 2-14) Certain substances are transported across cell membranes by processes more complex than simple diffusion or filtration Active transport is a process by which a substance is transported against a concentration or electrochemical gradient Facilitated diffusion does not move against a concentration gradient Pinocytosis may explain the passage of macromolecular substances into cells

Absorption Effect of ionization Oral absorption
Haveles (p. 17) Effect of ionization Weak acids Weak bases Oral absorption Absorption from injection site cont’d…

Absorption Haveles (p. 17) The process by which drug molecules are transferred from the site of administration to the circulating blood Requires the drug to pass through biologic membranes cont’d…

Absorption The rate of absorption of a drug involves these factors
Physicochemical factors The site of absorption, which is determined by the route of administration The drug’s solubility

Effect of Ionization Haveles (p. 17) (Fig. 2-10) Drugs that are weak electrolytes dissociate in solution and equilibrate into a nonionized form and an ionized form The nonionized, or uncharged, portion acts similar to a nonpolar, lipid-soluble compound that readily crosses body membranes The ionized portion will traverse these membranes with greater difficulty because it is less lipid soluble cont’d…

Effect of Ionization Haveles (p. 17) The pH of tissues at the site of administration and dissociation characteristics (acid dissociation constant, or pKa) of the drug will determine the amount of drug in the ionized and nonionized state The proportion in each state will determine the ease with which the drug will penetrate tissue Definition of pKa okay?

Weak Acids When the pH at the site of absorption increases, the hydrogen ion concentration falls This results in an increase in the ionized form (A–), which cannot easily penetrate tissues If the pH of the site falls, the hydrogen ion concentration will rise This results in an increase in the un-ionized form (HA), which can more easily penetrate tissues

Weak Bases If the pH of the site rises, the hydrogen ion concentration will fall This results in an increase in the un-ionized form (B), which can more easily penetrate tissues If the pH of the site falls, the hydrogen ion concentration will rise This results in an increase in the ionized form (BH+), which cannot easily penetrate tissues

Effect of Ionization In summary cont’d…
Weak acids are better absorbed when the pH is less than the pKa Weak bases are better absorbed with the pH is greater than the pKa cont’d…

Effect of Ionization Haveles (p. 17) In the presence of infection, the acidity of the tissue increases (and the pH decreases), and the effect of local anesthetics decreases In the presence of infection, the (H+) increases because of accumulating waste products in the infected area The increase in (H+) leads to an increase in ionization and a decrease in penetration of the membrane by local anesthetic

Oral Absorption Haveles (p. 17) Unless the drug is administered as a solution, the absorption of the drug in the gastrointestinal (GI) tract involves release from a dose form such as a tablet or capsule This release requires the following steps before absorption can take place Disruption: initial disruption of coating or shell Disintegration: contents must break apart Dispersion: particles must spread Dissolution: drug must be dissolved in GI fluid

Absorption from Injection Site
Haveles (p. 17) Depends on solubility of the drug and the blood flow at that site Drugs with low water solubility are absorbed very slowly after intramuscular injection Drugs in suspension are absorbed much more slowly than those in solution Drugs that are the least soluble will have the longest duration of action

Distribution Basic principles
Haveles (pp ) Basic principles All drugs occur in two forms in blood: bound to plasma proteins and the free drug The free drug is the form that exerts the pharmacologic effect The bound drug is a reservoir for the drug cont’d…

Distribution The proportion in each form is dependent on the properties of that specific drug (percent protein bound) Within each body compartment, the drug is split between the bound drug and the free drug Only the free drug can pass across cell membranes cont’d…

Distribution For a drug to exert its activity, it must be made available at its site of action in the body The mechanism by which this is accomplished is distribution—the passage of the drug into various body fluid compartments such as plasma, interstitial fluids, and intracellular fluids The manner in which a drug is distributed in the body will determine how rapidly it produces the desired response, the duration of that response, and, in some cases, whether a response will occur at all cont’d…

Distribution Drug distribution occurs when a drug moves to various sites in the body, including its site of action in specific tissues Drugs are also distributed to areas where no action is desired (nonspecific tissues) Some drugs are poorly distributed to certain regions Some drugs are distributed to their site of action and then redistributed to another tissue site cont’d…

Distribution The distribution is determined by several factors
Size of the organ Blood flow to the organ Solubility of the drug Plasma protein–binding capacity Presence of barriers (blood-brain barrier, placenta)

Distribution by Plasma
Haveles (p. 18) After absorption from the site of administration, a drug is distributed to its site of action by blood plasma Biologic activity is related to the concentration of free, unbound drug in plasma Drugs are bound reversibly to plasma proteins such as albumin and globulin The bound drug is considered a storage site Only the unbound form is biologically active

Half-Life Haveles (p. 18) (Fig. 2-11) The amount of time that passes for the concentration of a drug to fall to one half of its blood level (t1/2) When the half-life is short, the duration of action is short When the half-life is long, the duration of action is long cont’d…

Half-Life Only 3% to 6% of the drug remains after four or five half-lives; we can say the drug is essentially gone Conversely, about four or five half-lives of repeated dosing are needed for a drug’s level to build up to a steady state in the body

Blood-Brain Barrier Haveles (pp ) The tissue sites of distribution should be considered before administration of a drug To penetrate the central nervous system, a drug must cross the blood-brain barrier Passage of a drug across this barrier is related to the drug’s lipid solubility and degree of ionization To diffuse transcellularly, the drug must penetrate the epithelial and basement membrane cells

Placenta Haveles (p. 19) Involves simple diffusion according to the degree of lipid solubility The placenta may act as a selective barrier against a few drugs; most drugs pass easily across the placental barrier When agents are administered to the mother, they are concomitantly administered to the fetus

Enterohepatic Circulation
Haveles (p. 19) Most drugs are absorbed in the intestines, distributed through serum, pass to specific and nonspecific sites of action, and then go to the liver, where they are metabolized before being excreted via the kidneys For enterohepatic circulation, the steps are the same until the drug is metabolized cont’d…

Enterohepatic Circulation
With enterohepatic circulation, after the drug is metabolized, the metabolite is secreted via bile into the intestine The metabolite is broken down by enzymes and releases the drug The drug is then absorbed again and the process continues After being taken up by the liver a second time, these drugs are again secreted into the bile This circular pattern continues, with some drug escaping with each passing This process prolongs the effect of a drug

Redistribution Haveles (p. 19) The movement of a drug from the site of action to nonspecific sites of action The drug’s duration of action can be affected by redistribution of the drug from one organ to another If redistribution occurs between specific sites and nonspecific sites, a drug’s action will be terminated

Metabolism (Biotransformation)
Haveles (pp ) First-pass effect Phase I Phase II Excretion Kinetics Renal route Extrarenal routes Biliary excretion Other Saliva Gingival crevicular fluid

Metabolism Haveles (p. 19) The body’s way of changing a drug so that it can be more easily excreted by the kidneys Many drugs undergo metabolic transformation or change, most commonly in the liver The metabolite formed is usually more polar and less lipid soluble than the parent compound This means renal tubular absorption of the metabolite will be reduced because renal tubular absorption favors lipid-soluble compounds cont’d…

Metabolism Drugs can be metabolized by three different means
Haveles (p. 19) (Fig. 2-12) Drugs can be metabolized by three different means Active to inactive An inactive metabolite is formed from an active parent drug (most common process) Inactive to active An inactive parent drug (prodrug) may be transformed to an active compound Active to active An active parent drug may be converted to a second active compound, which is then converted to an inactive product

First-Pass Effect Haveles (pp ) Metabolism of drugs may be divided into two general types: phase I and phase II If the drug has no functional groups with which to combine, then it must undergo a phase I reaction

Phase I Reaction Haveles (pp. 19-20)
In phase I reactions, lipid molecules are metabolized by the three processes of Oxidation Reduction Hydrolysis

Oxidation When a drug that is administered does not possess an appropriate functional group that is suitable for combining with body acids (conjugation), the body has more difficulty detoxifying the drug An enzyme system responsible for the oxidative metabolism of many drugs is located in the liver The enzymes are located in the endoplasmic reticulum and are called microsomal enzymes

Hydrolysis Some ester compounds are metabolized by hydrolysis
Hydrolytic enzymes found in plasma and in a variety of tissues break up esters and add water Ester local anesthetics are inactivated by plasma cholinesterases

Reduction Many reduction reactions are mediated by enzymes found in hepatic microsomes

Microsomal Enzymes Haveles (pp ) (Fig. 2-13; Table 2-1) Phase I reactions are carried out by microsomal or cytochrome P-450 enzymes, known as mixed function oxidases in the liver Phase I metabolism may be affected by other drugs that alter microsomal enzyme inhibition or induction cont’d…

Microsomal Enzymes Induction: the P-450 hepatic microsomal enzymes can be induced (the amount of enzyme increased) by some drugs and by smoking tobacco Hepatic enzymes can be divided into many categories called isoenzymes Inhibition: inhibition of the metabolism of certain drugs may occur through several mechanisms With inhibition, the blood levels and action of the drugs metabolized by these enzymes will be increased

Phase II Reactions Haveles (p. 20) Phase II reactions involve conjugation with the following agents: glucuronic acid, acetic acid, or an amino acid The most common conjugation, called glucuronidation, occurs with glucuronic acid The enzymes that mediate the conjugation are called transferases

Excretion Haveles (pp ) Drugs may be excreted by any of several routes, but renal excretion is most important Extrarenal routes include the lungs, bile, GI tract, sweat, saliva, and breast milk Drugs may be excreted unchanged or as metabolites Okay to add “breast” to milk?

Kinetics Haveles (pp. 18, 20) (Fig. 2-11) The mathematical representation of the way in which drugs are removed from the body The most common mechanism is first-order kinetics cont’d…

Kinetics Haveles (pp. 20, 22) (Fig. 2-14) A few drugs, such as aspirin and alcohol, exhibit zero-order kinetics With zero-order kinetics, the rate of metabolism remains constant over time, and the same amount of the drug is metabolized per unit of time, regardless of dose With high doses, the metabolism of the drug cannot increase, and the duration of action of the drug can be greatly prolonged

Renal Route Haveles (pp ) Elimination of substances in the kidney can occur through three routes Glomerular filtration (most common) The unchanged drug or its metabolites are filtered through the glomeruli and concentrated in renal tubular fluid Active tubular secretion The drug is transported from the bloodstream, across renal tubular epithelial cells, and into renal tubular fluid Passive tubular diffusion Favors resorption of nonionized, lipid-soluble compounds More ionized metabolites have more difficulty penetrating the cell membranes of the renal tubules and are likely to be retained in tubular fluid and eliminated in urine

Extrarenal Routes Haveles (p. 21) Gases used in general anesthesia are excreted across lung tissue by simple diffusion Alcohol is partially excreted by the lungs

Biliary Excretion Haveles (p. 21) The major route by which systemically absorbed drugs enter the GI tract and are eliminated in feces Drugs excreted in bile may be reabsorbed from the intestines (enterohepatic circulation) This enterohepatic circulation prolongs a drug’s action

Other Breast milk and sweat Haveles (p. 21)
Minor routes of elimination Distribution of drugs in breast milk may be a potential source of undesirable effects for the nursing infant Okay to add “breast” to milk?

Saliva Drugs can be excreted in saliva
Haveles (p. 21) Drugs can be excreted in saliva They are usually swallowed and their fate is the same as drugs ingested orally Most drugs secreted in the salivary glands enter saliva by simple diffusion Drug levels in saliva have been studied to see if they can be used to monitor therapy with certain agents

Gingival Crevicular Fluid (GCF)
Haveles (p. 22) Drugs excreted in the GCF produce a higher level of drug in the gingival crevices, which can increase their usefulness in the treatment of periodontal disease Tetracycline is concentrated in GCF This means that the drug level in GCF will be several times higher than the blood level

Routes of Administration and Dose Forms
Haveles (pp ) Routes of administration Oral route Rectal route Intravenous route Intramuscular route Subcutaneous route Intradermal route Intrathecal route Intraperitoneal route Inhalation route Topical route Other routes Dose forms

Routes of Administration
Haveles (pp ) (Fig. 2-15) Route of administration affects both the onset and duration of response Onset: the time required for the drug to begin to have its effect Duration: the length of a drug’s effect cont’d…

The routes can be classified as enteral or parenteral Drugs given by the enteral route are placed directly into the GI tract by oral or rectal administration The parenteral route bypasses the GI tract and includes injection routes, inhalation, and topical administration In practice, parenteral usually means injection cont’d…

Haveles (p. 22) Oral administration is considered safest, least expensive, and most convenient, but the parenteral route has certain advantages cont’d…

Haveles (p. 22) Advantages of the parenteral route Injection results in fast absorption, which produces a rapid onset and more predictable response than oral administration Useful for emergencies, unconsciousness, lack of cooperation, or nausea Some drugs must be administered by injection to remain active cont’d…

Haveles (pp ) (Fig. 2-15) Disadvantages of the parenteral route Asepsis must be maintained to prevent infection An intravascular injection may occur by accident Administration by injection is more painful Removing the drug is difficult Adverse effects may be more pronounced Self-medication is difficult More dangerous and expensive than oral medication

Oral Route The simplest way to introduce a drug into the body
Haveles (pp ) The simplest way to introduce a drug into the body Allows for many different dose forms: tablets, capsules, and liquids are conveniently given cont’d…

Oral Route Advantages of the oral route
A large absorbing area present in the small intestine Slower onset of action than parenterally administered agents cont’d…

Oral Route Disadvantages of the oral route
Stomach and intestinal irritation may result in nausea and vomiting Certain drugs, such as insulin, are inactivated by GI tract acidity or enzymes Some orally administered drugs may be inactivated by the hepatic (liver) portal circulation (first-pass effect) Blood levels after oral administration are less predictable than for parenteral administration Drug interactions can occur when two drugs are in the stomach The oral route necessitates greater patient cooperation

Rectal Route Drugs may be given as suppositories, creams, or enemas
Haveles (p. 23) Drugs may be given as suppositories, creams, or enemas May be used if the patient is vomiting or unconscious May be used for either a local or systemic effect, but because most drugs are poorly and irregularly absorbed rectally, this route is not often used to achieve a systemic drug effect

Intravenous Route Produces the most rapid drug response
Haveles (p. 23) Produces the most rapid drug response The absorption phase is bypassed More predictable drug response than oral administration The route of choice for an emergency situation Disadvantages include phlebitis caused by local irritation, drug irretrievability, allergy, and side effects related to high plasma concentration of the drug

Intramuscular Route Haveles (p. 24) Absorption of drugs injected into the muscle occurs as a result of high blood flow through skeletal muscle Somewhat irritating drugs may be tolerated if given by the intramuscular route May be used for injection of suspensions for a sustained effect Injections are usually into the deltoid or gluteal mass

Subcutaneous Route Haveles (p. 24) Injection of solutions or suspensions of drugs into subcutaneous tissue to gain access to systemic circulation If irritating solutions are injected, sterile abscesses may result Commonly used for administration of insulin

Intradermal Route Haveles (p. 24) Small amounts of drugs, such as local anesthetics, may be injected into the epidermis Produces a small bump (bleb) as the liquid is injected just under the skin Used for tuberculin skin test

Intrathecal Route Haveles (p. 24) Injection of solutions into the spinal subarachnoid space May be used for spinal anesthesia or for the treatment of certain forms of meningitis

Intraperitoneal Route
Haveles (p. 24) Placing fluid into the peritoneal cavity, where exchange of substances can occur A drug may be absorbed through mesenteric veins May be used for peritoneal dialysis Used as a substitute for the failing kidney to manage patients with renal failure

Inhalation Route Haveles (pp ) May be used in the administration of gaseous, microcrystalline, liquid, or powdered form of drugs An example of inhalers being used for their local effects are those used to treat asthma General anesthetic in the form of volatile liquids or gases are examples of the use of the inhalation route for systemic effects

Topical Route Application to body surfaces Haveles (p. 25)
May administered to skin, oral mucosa, and even sublingually May be intended to produce either local or systemic effects Generally used on skin for local effect cont’d…

Topical Route Rarely, systemic side effects can occur from topical administration of drugs for their local effect An example is administration of topical corticosteroids over a large portion of the body, resulting in symptoms of systemic toxicity Interruptions in the mucous membranes or mucosal inflammation increase the likelihood of a systemic effect Examples of drugs applied topically for a systemic effect include transdermal patches and sublingual spray or tablet administration

Subgingival Strips and Gels
Haveles (p. 25) Dental-specific topical application involves the placement of drug-impregnated strips or gels subgingivally Doxycycline gel (Atridox), and the chlorhexidine-containing chip (PerioChip) are examples of agents administered into the gingival crevice

Transdermal Patch Haveles (p. 25) (Fig. 2-16) Designed to provide continuous controlled release through a semipermeable membrane over a given period after application of drug to the intact skin Eliminates the need for repeated oral dosing The most common problems with transdermal patches are local irritation, erythema, and edema

Topical Anesthesia Haveles (p. 25) Applied directly to mucous membranes and rapidly absorbed into systemic circulation An example is the combination of lidocaine and prilocaine (Oraqix)

Sublingual and Buccal Routes
Haveles (p. 25) Two ways in which drugs can be applied topically The mucous membranes of the oral cavity provide a convenient absorbing surface for the systemic administration of many drugs Absorption of many drugs into systemic circulation occurs rapidly Avoids both first-pass effect and GI acid and enzymes

Other Routes Haveles (p. 25) Drugs such as progestins (Norplant), can be implanted under the skin to release a drug over a long duration (5 years) Pumps that deliver intravenous drugs can be implanted in the body When insulin pumps are used, they can be programmed externally

Dose Forms Haveles (pp ) (Table 2-2) The most commonly used dose forms in dentistry are the tablet and capsule given orally Liquid solutions or suspensions are often prescribed for children For injection, the drug may be in solution, such as local anesthetic, or it may be in suspension, such as procaine penicillin G

Factors that Alter Drug Effects
Haveles (pp ) Patient compliance Psychologic factors Tolerance Pathologic state Time of administration Route of administration Sex Genetic variation Drug interactions Age and weight Environment Other

Patient Compliance Haveles (p. 25) Through either lack of understanding or motivation, patients often do not take their medication as prescribed or not at all May result from faulty communication, inadequate patient education, or the patient’s health belief system

Psychologic Factors The attitude of the prescriber and the dental staff can affect the efficacy of the drug prescribed A placebo is a dose form that looks similar to the active agent but contains no active ingredients The magnitude of the placebo effect depends on the patient’s perception; individual variation is large

Tolerance Defined as the need for an increasingly larger dose to get the same effect as with the original dose, or a decreased effect after repeated administration of a given dose of a drug Cross-tolerance may occur with related compounds People under stress may need a larger dose for an effect Tachyphylaxis is the very rapid development of tolerance

Pathologic State Diseased patients may respond to medication differently than other patients Patients with hyperthyroidism are extremely sensitive to the toxic effects of epinephrine Patients with liver or kidney disease may metabolize or excrete drugs differently, potentially leading to increased duration of drug action

Time of Administration
The time of administration, especially in relation to meals, may alter the response to the drug Certain drugs with a sedative action are best administered at bedtime

Route of Administration
Enteral routes are slower, less predictable, and safer than parenteral routes

Sex Women may be more sensitive than men to certain drugs, perhaps because of their smaller size or their hormones Pregnancy alters the effects of certain drugs Women of child-bearing age should avoid teratogenic drugs The health care provider should determine whether the patient is pregnant before administering any agent

Genetic Variation Differences in patient responses to drugs have been associated with variations in ability to metabolize certain drugs Certain populations have a higher incidence of adverse effects to some drugs—a genetic predisposition

Drug Interactions A drug’s effect may be modified by previous or concomitant administration of another drug Many mechanisms exist by which drug interactions may modify a patient’s treatment

Age and Weight The child’s weight should be used to determine the child’s dose The manufacturer’s recommendations for children’s dosing would be best Older patients may respond differently to drugs than younger patients Whether it is caused by changes in renal or liver function or whether being elderly predisposes this sensitivity is controversial

Environment The environment contains many substances that may affect the action of drugs Smoking induces enzymes; therefore higher doses of benzodiazepines are needed to produce the same effect as compared with nonsmokers Chemical contaminants such as pesticides or solvents can have an effect on a drug’s action

Other The action of drugs can be altered by the patient-provider interaction If the patient “believes” in the substance or process, then the patient’s opinion will enhance the drug’s effect The attitude of both the patient and the provider can alter the physiology of the body

Chapter 2: Drug Action and Handling

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