chapter 5: nonopioid (nonnarcotic) analgesics copyright © 2011, 2007 mosby, inc., an affiliate of...

Chapter 5:Chapter 5:

Nonopioid (Nonnarcotic) AnalgesicsNonopioid (Nonnarcotic) Analgesics

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

22Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Chapter 5 OutlineChapter 5 Outline

Nonopioid (Nonnarcotic) AnalgesicsNonopioid (Nonnarcotic) Analgesics PainPain ClassificationClassification SalicylatesSalicylates Nonsteroidal antiinflammatory drugsNonsteroidal antiinflammatory drugs AcetaminophenAcetaminophen Drugs used to treat goutDrugs used to treat gout


Nonopioid (Nonnarcotic) Nonopioid (Nonnarcotic) AnalgesicsAnalgesics

Haveles (p. 49)Haveles (p. 49) Pain control is of great importance in dental Pain control is of great importance in dental

practicepractice Pain is often the issue that brings a patient to the Pain is often the issue that brings a patient to the

dental officedental office Conversely, pain may keep the patient from Conversely, pain may keep the patient from

seeking dental careseeking dental care The dental health care provider must be able The dental health care provider must be able

to recognize and evaluate a patient’s need for to recognize and evaluate a patient’s need for medicationmedication


PainPain

Haveles (p. 49)Haveles (p. 49) Pain is the means by which the body is made Pain is the means by which the body is made

urgently aware of tissue damageurgently aware of tissue damage Pain is a diagnostic symptom of an underlying Pain is a diagnostic symptom of an underlying

pathologic conditionpathologic condition The two components of pain are perception The two components of pain are perception

and reactionand reaction Perception: the physical componentPerception: the physical component Reaction: psychologic componentReaction: psychologic component

cont’d…cont’d…


PainPain

Haveles (pp. 49-50) (Figs. 5-1, 5-2) Haveles (pp. 49-50) (Figs. 5-1, 5-2) Individuals are very uniform in the perception Individuals are very uniform in the perception

of pain and variable in reaction to itof pain and variable in reaction to it The pain threshold is raised by sleep, sympathy, The pain threshold is raised by sleep, sympathy,

activities and analgesicsactivities and analgesics Analgesic therapy must be selected for the Analgesic therapy must be selected for the

individualindividual A level of discomfort that may not require drug A level of discomfort that may not require drug

treatment in one person may demand extreme treatment in one person may demand extreme therapy in anothertherapy in another


ClassificationClassification

Haveles (pp. 50) (Fig. 5-2)Haveles (pp. 50) (Fig. 5-2) Analgesic agents can de divided into two Analgesic agents can de divided into two

groups groups Nonopioid, nonnarcotic, peripheral, mild, and Nonopioid, nonnarcotic, peripheral, mild, and

antipyretic analgesicsantipyretic analgesics Opioid, narcotic, central, and strong analgesicsOpioid, narcotic, central, and strong analgesics



ClassificationClassification Haveles (pp. 50-51) (Fig. 5-3)Haveles (pp. 50-51) (Fig. 5-3)

An important difference between nonopioid and An important difference between nonopioid and opioid analgesics is the site of actionopioid analgesics is the site of action Nonopioid analgesics act primarily at peripheral nerve Nonopioid analgesics act primarily at peripheral nerve

endings, although their antipyretic effect is mediated endings, although their antipyretic effect is mediated centrallycentrally

Opioids act primarily in the central nervous system Opioids act primarily in the central nervous system (CNS)(CNS)

Another difference is the mechanism of actionAnother difference is the mechanism of action Nonopioid analgesics inhibit prostaglandin synthesisNonopioid analgesics inhibit prostaglandin synthesis Opioids affect the response to pain by depressing the Opioids affect the response to pain by depressing the

CNSCNScont’d…cont’d…


ClassificationClassification

Haveles (p. 50) (Box 5-1)Haveles (p. 50) (Box 5-1) Nonopioids can be divided into salicylates Nonopioids can be divided into salicylates

(aspirin-like), acetaminophen, and the (aspirin-like), acetaminophen, and the nonsteroidal antiinflammatory drugs (NSAIDs) nonsteroidal antiinflammatory drugs (NSAIDs)


SalicylatesSalicylates Haveles (pp. 50-51) (Box 5-2)Haveles (pp. 50-51) (Box 5-2)

Acetylsalicylic acidAcetylsalicylic acid ChemistryChemistry Mechanism of actionMechanism of action PharmacokineticsPharmacokinetics Pharmacologic effectsPharmacologic effects Adverse reactionsAdverse reactions ToxicityToxicity Drug interactionsDrug interactions UsesUses Dose and preparationsDose and preparations

Other salicylatesOther salicylates DiflunisalDiflunisal



SalicylatesSalicylates

Haveles (pp. 50-51) (Box 5-2)Haveles (pp. 50-51) (Box 5-2) Since antiquity, extracts of willow bark Since antiquity, extracts of willow bark

containing salicin have been used to reduce containing salicin have been used to reduce feverfever Many other salicylates have been synthesized, but Many other salicylates have been synthesized, but

aspirin is the most useful salicylate for analgesiaaspirin is the most useful salicylate for analgesia Aspirin is the prototype salicylateAspirin is the prototype salicylate


ChemistryChemistry

Haveles (pp. 50-51) (Fig. 5-4)Haveles (pp. 50-51) (Fig. 5-4) Acetylsalicylic acid (ASA, aspirin) is broken Acetylsalicylic acid (ASA, aspirin) is broken

down into acetic acid and salicylic aciddown into acetic acid and salicylic acid Acetic acid imparts the vinegar odor to a bottle of Acetic acid imparts the vinegar odor to a bottle of

aspirinaspirin


Mechanism of ActionMechanism of Action

Haveles (pp. 51-52) (Fig. 5-5)Haveles (pp. 51-52) (Fig. 5-5) Aspirin’s analgesic, antipyretic, Aspirin’s analgesic, antipyretic,

antiinflammatory, and antiplatelet effects are antiinflammatory, and antiplatelet effects are related to the ability to inhibit prostaglandin related to the ability to inhibit prostaglandin synthesissynthesis Aspirin inhibits cyclooxygenase (COX) to block Aspirin inhibits cyclooxygenase (COX) to block

production of prostaglandinsproduction of prostaglandins Prostaglandins can sensitize pain receptors to Prostaglandins can sensitize pain receptors to

substances such as bradykininsubstances such as bradykinin A reduction in prostaglandins results in a reduction A reduction in prostaglandins results in a reduction

in painin pain


PharmacokineticsPharmacokinetics

Haveles (pp. 51-52)Haveles (pp. 51-52) Aspirin is rapidly and almost completely Aspirin is rapidly and almost completely

absorbed from the stomach and small intestineabsorbed from the stomach and small intestine Widely distributed into most body tissues and fluidsWidely distributed into most body tissues and fluids

The half-life varies with the dose because a The half-life varies with the dose because a constant constant amountamount rather than constant rather than constant percentage percentage is metabolized per hour is metabolized per hour This type of metabolism is called This type of metabolism is called zero-order kinetics zero-order kinetics


Pharmacologic Effects Pharmacologic Effects Haveles (pp. 52-53) (Figs. 5-6, 5-7, 5-8, 5-9)Haveles (pp. 52-53) (Figs. 5-6, 5-7, 5-8, 5-9)

Analgesic: relieves mild to moderate painAnalgesic: relieves mild to moderate pain Antipyretic: reduces fever by inhibition of Antipyretic: reduces fever by inhibition of

prostaglandin synthesis in hypothalamus; no effect on prostaglandin synthesis in hypothalamus; no effect on normal body temperaturenormal body temperature

Antiinflammatory: causes decreased Antiinflammatory: causes decreased erythemaerythema and and swellingswelling

Uricosuric: large doses produce uricosuric effect, Uricosuric: large doses produce uricosuric effect, small doses produce uric acid retentionsmall doses produce uric acid retention

Antiplatelet: irreversibly binds to platelets, depending Antiplatelet: irreversibly binds to platelets, depending on dose, can inhibit either prostacyclin (inhibit on dose, can inhibit either prostacyclin (inhibit aggregation) or thromboxane Aaggregation) or thromboxane A22 (stimulates (stimulates aggregation)aggregation)


Adverse Reactions Adverse Reactions

Haveles (pp. 53-54) (Table 5-1)Haveles (pp. 53-54) (Table 5-1) Gastrointestinal effects: may be simple Gastrointestinal effects: may be simple

dyspepsia, nausea, vomiting, or gastric dyspepsia, nausea, vomiting, or gastric bleedingbleeding

Bleeding: interferes with clotting mechanism Bleeding: interferes with clotting mechanism by reducing platelet adhesivenessby reducing platelet adhesiveness

Reye syndrome: in children and adolescents Reye syndrome: in children and adolescents with either chickenpox or influenza, aspirin with either chickenpox or influenza, aspirin has been associated with Reye syndromehas been associated with Reye syndrome




Hepatic and renal effects: rarely, aspirin can Hepatic and renal effects: rarely, aspirin can produce hepatotoxicity produce hepatotoxicity Renal papillary necrosis and interstitial nephritis is Renal papillary necrosis and interstitial nephritis is

associated with use of certain analgesicsassociated with use of certain analgesics Pregnancy and nursing: human studies have found Pregnancy and nursing: human studies have found

only a slight positive correlation between chronic only a slight positive correlation between chronic aspirin ingestion and congenital abnormalitiesaspirin ingestion and congenital abnormalities With abuse, increased risk of stillbirth, neonatal death, With abuse, increased risk of stillbirth, neonatal death,

and decreased birth weightand decreased birth weight Hypersensitivity: incidence of true allergy less than Hypersensitivity: incidence of true allergy less than

1%, asthmatics are more likely hypersensitive1%, asthmatics are more likely hypersensitive Aspirin hypersensitivity triad—Aspirin hypersensitivity triad—aspirin hypersensitivity, aspirin hypersensitivity,

asthma, asthma, andand nasal polyps nasal polyps—often occur together—often occur together


ToxicityToxicity

Haveles (p. 54)Haveles (p. 54) An overdose can produce harmful effects and An overdose can produce harmful effects and

even deatheven death SymptomsSymptoms

At a certain level, salicylism occurs, characterized At a certain level, salicylism occurs, characterized by tinnitus, headache, nausea, vomiting, by tinnitus, headache, nausea, vomiting, dizziness, and dimness of visiondizziness, and dimness of vision

At higher levels, stimulation of respiration leads to At higher levels, stimulation of respiration leads to hyperventilation, producing respiratory alkalosishyperventilation, producing respiratory alkalosis

The cause of death is usually acidosis and The cause of death is usually acidosis and electrolyte imbalanceelectrolyte imbalance

cont’d...cont’d...


Toxicity Toxicity

PreventionPrevention Children are the primary victims of accidental Children are the primary victims of accidental

poisoningpoisoning Education of parents regarding potential for Education of parents regarding potential for

poisoning and proper storage and childproof poisoning and proper storage and childproof containers have reduced accidental poisonings in containers have reduced accidental poisonings in childrenchildren



Toxicity Toxicity

Haveles (pp. 54-55) (Box 5-3) Haveles (pp. 54-55) (Box 5-3) TreatmentTreatment

Involves removing excess drug in the stomach by Involves removing excess drug in the stomach by inducing emesis or administering activated inducing emesis or administering activated charcoalcharcoal

Other symptoms are treated symptomaticallyOther symptoms are treated symptomatically


Drug Interactions Drug Interactions

Haveles (pp. 54-55) (Table 5-1)Haveles (pp. 54-55) (Table 5-1) Warfarin: an oral anticoagulant highly protein Warfarin: an oral anticoagulant highly protein

bound to plasma protein binding sites; aspirin bound to plasma protein binding sites; aspirin can displace warfarin from binding sites can displace warfarin from binding sites increasing its anticoagulant effectincreasing its anticoagulant effect

Probenecid: aspirin interferes with Probenecid: aspirin interferes with probenecid’s uricosuric effect, can cause an probenecid’s uricosuric effect, can cause an acute attack of goutacute attack of gout



Drug InteractionsDrug Interactions

Methotrexate (MTX): an antineoplastic drug Methotrexate (MTX): an antineoplastic drug used to treat certain cancers and autoimmune used to treat certain cancers and autoimmune diseases; aspirin can displace it from protein-diseases; aspirin can displace it from protein-binding sites and interfere with clearance binding sites and interfere with clearance causing increased serum concentration and causing increased serum concentration and MTX toxicityMTX toxicity

Sulfonylureas: higher doses of salicylates may Sulfonylureas: higher doses of salicylates may produce an hypoglycemic effectproduce an hypoglycemic effect

Antihypertensives: aspirin reduces the effect of Antihypertensives: aspirin reduces the effect of many antihypertensives including angiotensin-many antihypertensives including angiotensin-converting enzyme (ACE) inhibitors, converting enzyme (ACE) inhibitors, ββ-blockers, -blockers, and thiazide and loop diureticsand thiazide and loop diuretics


UsesUses

Haveles (p. 55)Haveles (p. 55) Analgesia for mild to moderate painAnalgesia for mild to moderate pain Antipyretic effect useful to control fever but Antipyretic effect useful to control fever but

should be avoided in children (Reye should be avoided in children (Reye syndrome)syndrome)

Antiinflammatory action used to treat Antiinflammatory action used to treat inflammatory conditions such as rheumatic inflammatory conditions such as rheumatic fever and arthritis fever and arthritis

Because of effect on platelet aggregation, Because of effect on platelet aggregation, used to prevent unwanted clottingused to prevent unwanted clotting


Dose and Preparations Dose and Preparations

Haveles (pp. 55-56, 62) (Tables 5-9, 5-2)Haveles (pp. 55-56, 62) (Tables 5-9, 5-2) Usual adult dose for treatment of pain or fever Usual adult dose for treatment of pain or fever

is 325-650 mg every 4 hoursis 325-650 mg every 4 hours For prevention of myocardial infarction, the For prevention of myocardial infarction, the

dose is 75-325 mg/daydose is 75-325 mg/day Children’s dose is 10-15 mg/kg every 4-6 Children’s dose is 10-15 mg/kg every 4-6

hourshours



Dose and PreparationsDose and Preparations

Haveles (pp. 55)Haveles (pp. 55) Regular aspirin: 325-mg tablet and 81-mg Regular aspirin: 325-mg tablet and 81-mg

children’s tablet children’s tablet (Bayer, Empirin, St. Joseph, Bayer; low dose)(Bayer, Empirin, St. Joseph, Bayer; low dose)

Enteric coated aspirin: a coating that dissolves Enteric coated aspirin: a coating that dissolves in the intestine rather than the stomachin the intestine rather than the stomach (Ecotrin, Ecotrin; low dose)(Ecotrin, Ecotrin; low dose)




CombinationsCombinations With buffer: claimed to produce fewer With buffer: claimed to produce fewer

gastrointestinal (GI) effects (Bufferin, Ascriptin)gastrointestinal (GI) effects (Bufferin, Ascriptin) With another analgesic: combined with an opioid With another analgesic: combined with an opioid

analgesic or acetaminophenanalgesic or acetaminophen With sedatives: if anxiety is a substantial With sedatives: if anxiety is a substantial

component of paincomponent of pain With caffeine: caffeine potentiates the analgesic With caffeine: caffeine potentiates the analgesic

effect of aspirin and other analgesics (Excedrin, effect of aspirin and other analgesics (Excedrin, Anacin, Fiorinal)Anacin, Fiorinal)


Other SalicylatesOther Salicylates

Haveles (pp. 55-56)Haveles (pp. 55-56) Sodium, choline, magnesium salicylate and Sodium, choline, magnesium salicylate and

salicylamide, and salsalatesalicylamide, and salsalate Claim to have fewer GI side effectsClaim to have fewer GI side effects Two advantages of these agents are they are Two advantages of these agents are they are

thought to have no effect on platelets and no thought to have no effect on platelets and no cross-hypersensitivity with aspirincross-hypersensitivity with aspirin

Magnesium is contraindicated in renal disease, Magnesium is contraindicated in renal disease, sodium is contraindicated in cardiovascular sodium is contraindicated in cardiovascular diseasedisease


diflunisal (Dolobid)diflunisal (Dolobid)

Haveles (p. 56)Haveles (p. 56) A salicylate classified as a NSAIDA salicylate classified as a NSAID

Can be administered before a dental procedure to Can be administered before a dental procedure to delay the onset of postsurgical paindelay the onset of postsurgical pain

Antipyretic effect is not clinically usefulAntipyretic effect is not clinically useful


Nonsteroidal Antiinflammatory Nonsteroidal Antiinflammatory DrugsDrugs

Haveles (pp. 56-61)Haveles (pp. 56-61) Chemical classificationChemical classification Mechanism of actionMechanism of action PharmacokineticsPharmacokinetics Pharmacologic effectsPharmacologic effects Adverse reactionsAdverse reactions Drug interactionsDrug interactions Contraindications and cautionsContraindications and cautions Therapeutic usesTherapeutic uses Specific nonsteroidal antiinflammatory agentSpecific nonsteroidal antiinflammatory agent



Nonsteroidal Antiinflammatory Nonsteroidal Antiinflammatory DrugsDrugs

Haveles (p. 56)Haveles (p. 56) A rapidly growing group with important A rapidly growing group with important

application in dentistryapplication in dentistry Mechanism of action and many of their Mechanism of action and many of their

pharmacologic effects and adverse reactions pharmacologic effects and adverse reactions resemble aspirinresemble aspirin

Many authors agree they are the most useful Many authors agree they are the most useful drug group for treatment of dental paindrug group for treatment of dental pain Currently make up only a small percentage of Currently make up only a small percentage of

analgesic prescriptionsanalgesic prescriptions


Chemical ClassificationChemical Classification

Haveles (p. 56)Haveles (p. 56) Divided into several chemical derivatives: Divided into several chemical derivatives:

propionic acids, acetic acids, fenamates, propionic acids, acetic acids, fenamates, pyrazolones, oxicams, and otherspyrazolones, oxicams, and others


Examples of Nonselective Examples of Nonselective Nonsteroidal Antiinflammatory DrugsNonsteroidal Antiinflammatory Drugs

Haveles (pp. 56-57) (Table 5-3)Haveles (pp. 56-57) (Table 5-3) Propionic acid derivativesPropionic acid derivatives

ibuprofen (Motrin, Advil)ibuprofen (Motrin, Advil) flurbiprofen (Ansaid-PO, Ocufen-ophth)flurbiprofen (Ansaid-PO, Ocufen-ophth) fenoprofen (Nalfon)fenoprofen (Nalfon) naproxen (Naprosyn)naproxen (Naprosyn) naproxen sodium (Anaprox)naproxen sodium (Anaprox) ketoprofen (Orudis)ketoprofen (Orudis) ketoprofen (Oruvail)ketoprofen (Oruvail) oxaprozin (Daypro)oxaprozin (Daypro)



Examples of Nonselective Nonsteroidal Examples of Nonselective Nonsteroidal Antiinflammatory DrugsAntiinflammatory Drugs

Acetic acid derivativesAcetic acid derivatives indomethacin (Indocin)indomethacin (Indocin) indomethacin SR (Indocin SR)indomethacin SR (Indocin SR) sulindac (Clinoril)sulindac (Clinoril) tolmetin (Tolectin)tolmetin (Tolectin) diclofenac (Cataflam)diclofenac (Cataflam) diclofenac (Voltaren)diclofenac (Voltaren) etodolac (Lodine)etodolac (Lodine) etodolac (Lodine-XL)etodolac (Lodine-XL) ketorolac (Toradol)ketorolac (Toradol)



Examples of Nonselective Nonsteroidal Examples of Nonselective Nonsteroidal Antiinflammatory DrugsAntiinflammatory Drugs

Nonacidic agentNonacidic agent nabumetone (Relafen)nabumetone (Relafen)

Fenamic acid derivativesFenamic acid derivatives meclofenamate (Meclomen)meclofenamate (Meclomen) mefenamic acid (Ponstel)mefenamic acid (Ponstel)

SalicylatesSalicylates diflunisal (Dolobid)diflunisal (Dolobid)

OxicamsOxicams piroxicam (Feldene)piroxicam (Feldene) meloxicam (MOBIC)meloxicam (MOBIC)


Mechanism of Action Mechanism of Action

Haveles (p. 56)Haveles (p. 56) Similar to aspirin, NSAIDs inhibit the enzyme Similar to aspirin, NSAIDs inhibit the enzyme

COX (prostaglandin synthase)COX (prostaglandin synthase) Results in a reduction in the formation of Results in a reduction in the formation of

prostaglandin precursors and thromboxanes from prostaglandin precursors and thromboxanes from arachidonic acid arachidonic acid


PharmacokineticsPharmacokinetics

Haveles (pp. 56-57) (Table 5-3)Haveles (pp. 56-57) (Table 5-3) Most NSAIDs peak in about 1-2 hoursMost NSAIDs peak in about 1-2 hours

Food reduces the rate but not the extent of Food reduces the rate but not the extent of absorptionabsorption

No effect on absorption of NSAIDs with oral No effect on absorption of NSAIDs with oral antacids, except for diflunisalantacids, except for diflunisal

Metabolized in liver, excreted in kidneysMetabolized in liver, excreted in kidneys


Pharmacologic EffectsPharmacologic Effects

Haveles (pp. 56, 58)Haveles (pp. 56, 58) Analgesic, antipyretic, and antiinflammatory Analgesic, antipyretic, and antiinflammatory

actions of NSAIDs result from same actions of NSAIDs result from same mechanism as aspirin inhibition of mechanism as aspirin inhibition of prostaglandin synthesis by inhibiting COXprostaglandin synthesis by inhibiting COX Useful for treating dysmenorrhea because an Useful for treating dysmenorrhea because an

excess of prostaglandins in the uterine wall excess of prostaglandins in the uterine wall produces painful contractionsproduces painful contractions



Haveles (p. 58)Haveles (p. 58) GI effects: gastric irritation, pain, and bleeding GI effects: gastric irritation, pain, and bleeding

problems leading to tarry stools can occur with problems leading to tarry stools can occur with all NSAIDsall NSAIDs NSAIDs can interfere with normal protective NSAIDs can interfere with normal protective

mechanisms in the stomachmechanisms in the stomach CNS effects: dose-dependent side effects CNS effects: dose-dependent side effects

include sedation, dizziness, confusion, mental include sedation, dizziness, confusion, mental depression, headache, vertigo, and convulsionsdepression, headache, vertigo, and convulsions



Adverse ReactionsAdverse Reactions

Blood clotting: Blood clotting: reversiblyreversibly inhibit platelet inhibit platelet aggregationaggregation In contrast to aspirin, the effect remains only as In contrast to aspirin, the effect remains only as

long as the drug is present in the bloodlong as the drug is present in the blood Renal effects: renal failure, cystitis, and Renal effects: renal failure, cystitis, and

increased incidence of urinary tract infectionsincreased incidence of urinary tract infections Other effects: muscle weakness, ringing ears, Other effects: muscle weakness, ringing ears,

hepatitis, hematologic problems, and blurred hepatitis, hematologic problems, and blurred visionvision



Adverse Reactions Adverse Reactions Oral effects: ulcerative stomatitis, gingival Oral effects: ulcerative stomatitis, gingival

ulcerations, dry mouthulcerations, dry mouth Hypersensitivity reactions: can induce a wide Hypersensitivity reactions: can induce a wide

range, including hives or itching, angioneurotic range, including hives or itching, angioneurotic edema, chills and fever, Stevens-Johnson edema, chills and fever, Stevens-Johnson syndrome, exfoliative dermatitis, and epidermal syndrome, exfoliative dermatitis, and epidermal necrolysisnecrolysis

Pregnancy and nursing considerations: given Pregnancy and nursing considerations: given late in pregnancy can prolong gestation, delay late in pregnancy can prolong gestation, delay parturition, and produce parturition, and produce dystociadystocia—premature —premature closing of ductus arteriosusclosing of ductus arteriosus



Haveles (p. 58) (Table 5-4)Haveles (p. 58) (Table 5-4) Drug InteractionsDrug Interactions

Lithium: may increase lithium toxicity in patients Lithium: may increase lithium toxicity in patients taking lithium for bipolar affective disorderstaking lithium for bipolar affective disorders

Digoxin: may increase effect of digoxin used for Digoxin: may increase effect of digoxin used for congestive heart failurecongestive heart failure

May decrease effect of antihypertensives, such as May decrease effect of antihypertensives, such as diuretics, ACE inhibitors, and diuretics, ACE inhibitors, and ββ-blockers-blockers

Can increase toxicity of cyclosporin and MTXCan increase toxicity of cyclosporin and MTX


Contraindications and CautionsContraindications and Cautions

Haveles (pp. 58-59) (Box 5-4) (Table 5-5)Haveles (pp. 58-59) (Box 5-4) (Table 5-5) Related to their adverse reactionsRelated to their adverse reactions

Caution for patients with asthma, cardiovascular or Caution for patients with asthma, cardiovascular or renal diseases with fluid retention, coagulopathies, renal diseases with fluid retention, coagulopathies, peptic ulcer, and ulcerative colitispeptic ulcer, and ulcerative colitis

Higher risk for adverse reactions for those with Higher risk for adverse reactions for those with renal function impairment or history of previous renal function impairment or history of previous hypersensitivity to aspirin or other NSAIDs and hypersensitivity to aspirin or other NSAIDs and geriatric patientsgeriatric patients


Therapeutic UsesTherapeutic Uses

Haveles (pp. 58-59) (Fig. 5-9)Haveles (pp. 58-59) (Fig. 5-9) Medical: uses include osteoarthritis, Medical: uses include osteoarthritis,

rheumatoid arthritis, gouty arthritis, fever, rheumatoid arthritis, gouty arthritis, fever, dysmenorrhea, and paindysmenorrhea, and pain Accepted unlabeled indications include bursitis Accepted unlabeled indications include bursitis

and tendonitisand tendonitis Dental: many studies find NSAIDs are Dental: many studies find NSAIDs are

equivalent in analgesic efficacy to opioid equivalent in analgesic efficacy to opioid analgesics in many clinical situationsanalgesics in many clinical situations


Specific Nonsteroidal Specific Nonsteroidal Antiinflammatory DrugsAntiinflammatory Drugs

Haveles (pp. 60-61)Haveles (pp. 60-61) IbuprofenIbuprofen Naproxen and naproxen sodiumNaproxen and naproxen sodium Other NSAIDsOther NSAIDs COX II-specific agentsCOX II-specific agents


IbuprofenIbuprofen(Advil, Motrin)(Advil, Motrin)

Haveles (pp. 59-60) (Fig. 5-9)Haveles (pp. 59-60) (Fig. 5-9) The oldest member of the NSAIDsThe oldest member of the NSAIDs

Rapidly absorbed orally, food decreases rate but Rapidly absorbed orally, food decreases rate but not extent of absorptionnot extent of absorption

The drug of choice for dental pain when an NSAID The drug of choice for dental pain when an NSAID is indicatedis indicated

Usual dose is 400-800 mg every 4-6 hoursUsual dose is 400-800 mg every 4-6 hours


naproxen and naproxen sodium naproxen and naproxen sodium (Naprosyn, Anaprox)(Naprosyn, Anaprox)

Haveles (pp. 57, 60) (Fig. 5-10; Table 5-3)Haveles (pp. 57, 60) (Fig. 5-10; Table 5-3) Propionic acid NSAIDs with longer half-lives Propionic acid NSAIDs with longer half-lives

than ibuprofenthan ibuprofen Can be administered on an 8- to 12-hour scheduleCan be administered on an 8- to 12-hour schedule Given with a loading doseGiven with a loading dose


Other Nonsteroidal Other Nonsteroidal Antiinflammatory DrugsAntiinflammatory Drugs

Haveles (pp. 57, 60) (Table 5-3)Haveles (pp. 57, 60) (Table 5-3) Fenoprofen, ketorolac, or diflunisal may be Fenoprofen, ketorolac, or diflunisal may be

used for patients who do not respond to used for patients who do not respond to ibuprofen or naproxenibuprofen or naproxen

ketorolac (Toradol) is a newer NSAIDketorolac (Toradol) is a newer NSAID Oral ketorolac is indicated only as continuation Oral ketorolac is indicated only as continuation

therapy to intravenous or intramuscular ketorolactherapy to intravenous or intramuscular ketorolac


Cyclooxygenase II-Specific Cyclooxygenase II-Specific AgentsAgents

Haveles (pp. 60-61) (Table 5-6)Haveles (pp. 60-61) (Table 5-6) Current NSAIDs inhibit both COX I and COX IICurrent NSAIDs inhibit both COX I and COX II

COX I is an enzyme responsible for adverse reactions COX I is an enzyme responsible for adverse reactions of NSAIDsof NSAIDs

COX II is synthesized only when inflammation occursCOX II is synthesized only when inflammation occurs COX II-specific inhibitors, because they inhibit COX II-specific inhibitors, because they inhibit

COX II (good) more than COX I (bad), should COX II (good) more than COX I (bad), should have fewer adverse reactions than the former have fewer adverse reactions than the former NSAIDsNSAIDs Clinically they are equivalent to nonselective NSAIDsClinically they are equivalent to nonselective NSAIDs



Cyclooxygenase II-Specific Cyclooxygenase II-Specific AgentsAgents

rofecoxib (Vioxx) and valdecoxib (Bextra) rofecoxib (Vioxx) and valdecoxib (Bextra) were removed from the market as a result of were removed from the market as a result of a high incidence of cardiovascular events a high incidence of cardiovascular events (heart attack) associated with these drugs(heart attack) associated with these drugs The theory is they may suppress prostacyclin The theory is they may suppress prostacyclin

(PGI2), which is synthesized by vascular (PGI2), which is synthesized by vascular endothelium and smooth muscleendothelium and smooth muscle

Inhibition of the COX II enzyme may also inhibit Inhibition of the COX II enzyme may also inhibit the function of endothelial cellsthe function of endothelial cells


AcetaminophenAcetaminophen

Haveles (pp. 61-62)Haveles (pp. 61-62) PharmacokineticsPharmacokinetics Pharmacologic effectsPharmacologic effects Adverse reactionsAdverse reactions Drug interactionsDrug interactions UsesUses Dose and preparationsDose and preparations


acetaminophen (Tylenol)acetaminophen (Tylenol)

Haveles (p. 61)Haveles (p. 61) Acetaminophen is the only member of the Acetaminophen is the only member of the pp--

aminophenols currently available for clinical aminophenols currently available for clinical useuse Used as an analgesic and antipyretic in children Used as an analgesic and antipyretic in children

and in adults when aspirin is contraindicatedand in adults when aspirin is contraindicated


Pharmacokinetics Pharmacokinetics

Haveles (p. 61)Haveles (p. 61) Rapidly and completely absorbed from the GI Rapidly and completely absorbed from the GI

tract; peak plasma level in 1-3 hourstract; peak plasma level in 1-3 hours Metabolized by liver microsomal enzymesMetabolized by liver microsomal enzymes

With large doses, an intermediate metabolite With large doses, an intermediate metabolite is produced that is thought to be hepatotoxic is produced that is thought to be hepatotoxic and possibly nephrotoxicand possibly nephrotoxic


Pharmacologic EffectsPharmacologic Effects

Haveles (p. 61)Haveles (p. 61) Analgesic and antipyretic effects are about Analgesic and antipyretic effects are about

the same potency as aspirinthe same potency as aspirin Acetaminophen does not possess any Acetaminophen does not possess any

clinically significant antiinflammatory effectclinically significant antiinflammatory effect Unlike aspirin, acetaminophen does not Unlike aspirin, acetaminophen does not

produce gastric bleeding or affect platelet produce gastric bleeding or affect platelet adhesiveness or uric acid excretionadhesiveness or uric acid excretion


Adverse ReactionsAdverse Reactions

Haveles (pp. 61-62) (Table 5-7)Haveles (pp. 61-62) (Table 5-7) Hepatic effects: the toxic metabolite that Hepatic effects: the toxic metabolite that

contributes to hepatic necrosis is N-acetyl-p-contributes to hepatic necrosis is N-acetyl-p-benzoquinone iminebenzoquinone imine Hepatic necrosis may occur after ingestion of a Hepatic necrosis may occur after ingestion of a

single dose of 20-25 gramssingle dose of 20-25 grams Patients with hepatic disease should avoid Patients with hepatic disease should avoid

acetaminophenacetaminophen Alcoholics or patients who ingest three or more Alcoholics or patients who ingest three or more

alcoholic beverages a day should avoid alcoholic beverages a day should avoid acetaminophenacetaminophen


Treatment of ToxicityTreatment of Toxicity

Haveles (p. 62)Haveles (p. 62) Should begin with gastric lavage if a drug has Should begin with gastric lavage if a drug has

recently been ingestedrecently been ingested Administration of activated charcoal and Administration of activated charcoal and

magnesium or sodium sulfate solution should magnesium or sodium sulfate solution should followfollow


Nephrotoxicity Nephrotoxicity

Nephrotoxicity has been associated with Nephrotoxicity has been associated with long-term consumption of acetaminophenlong-term consumption of acetaminophen Primary lesion appears to be a papillary necrosis Primary lesion appears to be a papillary necrosis

with secondary interstitial nephritiswith secondary interstitial nephritis Concurrent chronic use of the combination of Concurrent chronic use of the combination of

acetaminophen and aspirin or NSAIDs increases acetaminophen and aspirin or NSAIDs increases risk of analgesic nephropathy, renal papillary risk of analgesic nephropathy, renal papillary necrosis, end-stage renal disease, and cancer of necrosis, end-stage renal disease, and cancer of the kidney or urinary bladderthe kidney or urinary bladder



Haveles (p. 62)Haveles (p. 62) Acetaminophen is remarkably free of drug Acetaminophen is remarkably free of drug

interactions at its usual therapeutic dosesinteractions at its usual therapeutic doses Hepatotoxicity can be potentiated by Hepatotoxicity can be potentiated by

administration of agents that induce hepatic administration of agents that induce hepatic microsomal enzymesmicrosomal enzymes


UsesUses

Haveles (p. 62)Haveles (p. 62) Acetaminophen is used as an analgesic and Acetaminophen is used as an analgesic and

antipyreticantipyretic Especially useful in patients who have aspirin Especially useful in patients who have aspirin

hypersensitivity or in whom aspirin-induced gastric hypersensitivity or in whom aspirin-induced gastric irritation would be a problemirritation would be a problem

Used as an antipyretic instead of aspirin for young Used as an antipyretic instead of aspirin for young childrenchildren



Haveles (p. 62) (Tables 5-8, 5-9) Haveles (p. 62) (Tables 5-8, 5-9) Available in many combinations and elixirsAvailable in many combinations and elixirs

Usual adult dose is 325-650 mg every 4-6 hours or Usual adult dose is 325-650 mg every 4-6 hours or 1000 mg three to four times a day1000 mg three to four times a day• Not more than 4 grams in 24 hours should be ingested Not more than 4 grams in 24 hours should be ingested

by adultsby adults

Various elixirs, drops, and chewable tablets are Various elixirs, drops, and chewable tablets are available for childrenavailable for children• The elixir is 120 mg/5 ml or 160 mg/5 mlThe elixir is 120 mg/5 ml or 160 mg/5 ml

• Drops contain 60 mg/0.6 mlDrops contain 60 mg/0.6 ml


Drugs Used to Treat GoutDrugs Used to Treat Gout

Haveles (pp. 62-63)Haveles (pp. 62-63) Gout is an inherited disease occurring primarily Gout is an inherited disease occurring primarily

in men, with an onset that usually involves one in men, with an onset that usually involves one joint, often the big toe or kneejoint, often the big toe or knee Both hyperuricemia and urate crystals, or tophi, may Both hyperuricemia and urate crystals, or tophi, may

be found in joints or other tissuebe found in joints or other tissue Excess uric acid may be the result of excessive Excess uric acid may be the result of excessive

production or reduced excretion of uric acidproduction or reduced excretion of uric acid The disease responds to colchicineThe disease responds to colchicine



Drugs Used to Treat GoutDrugs Used to Treat Gout

Both NSAIDs and colchicine are used to treat Both NSAIDs and colchicine are used to treat acute attacks of goutacute attacks of gout

Probenecid and allopurinol are available to Probenecid and allopurinol are available to prevent goutprevent gout


colchicine colchicine

Haveles (p. 63)Haveles (p. 63) For treatment of an acute attack of goutFor treatment of an acute attack of gout

Appears to inhibit the chemotactic property of Appears to inhibit the chemotactic property of leukocytosis and interfere with the inflammatory leukocytosis and interfere with the inflammatory response to urate crystalsresponse to urate crystals


allopurinol allopurinol

Haveles (p. 63)Haveles (p. 63) Inhibits the synthesis or uric acidInhibits the synthesis or uric acid

Used to prevent excess uric acid from formingUsed to prevent excess uric acid from forming Used in patients receiving either Used in patients receiving either

chemotherapy or irradiation for malignancy chemotherapy or irradiation for malignancy The death of many cells causes release of large The death of many cells causes release of large

amounts of uric acid precursorsamounts of uric acid precursors Side effects include hepatotoxicity of aSide effects include hepatotoxicity of a

hypersensitivity typehypersensitivity type


probenecid (Benemid)probenecid (Benemid)

Haveles (pp. 53, 63) (Fig. 5-7) Haveles (pp. 53, 63) (Fig. 5-7) A uricosuric agent A uricosuric agent

Causes increased excretion of uric acidCauses increased excretion of uric acid Blocks the tubular reabsorption of filtered urate, Blocks the tubular reabsorption of filtered urate,

prevents new tophi and mobilizes those presentprevents new tophi and mobilizes those present GI side effects and hypersensitivity may occurGI side effects and hypersensitivity may occur

Headaches and sore gingiva have also been Headaches and sore gingiva have also been reportedreported

Increases the level of the NSAIDs and Increases the level of the NSAIDs and penicillinpenicillin

chapter 5: nonopioid (nonnarcotic) analgesics copyright © 2011, 2007 mosby, inc., an affiliate of...

Documents