chapter 11: antianxiety agents copyright © 2011, 2007 mosby, inc., an affiliate of elsevier. all...

Chapter 11:Chapter 11:

Antianxiety AgentsAntianxiety Agents

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

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

DHY 1330 - TherapeuticsDHY 1330 - Therapeutics Chapter 11 OutlineChapter 11 Outline Antianxiety AgentsAntianxiety Agents

DefinitionsDefinitions BenzodiazepinesBenzodiazepines BarbituratesBarbiturates Nonbenzodiazepine-nonbarbiturate sedative-Nonbenzodiazepine-nonbarbiturate sedative-

hypnoticshypnotics Nonbenzodiazepine benzodiazepine receptor Nonbenzodiazepine benzodiazepine receptor

agonistsagonists Melatonin receptor agonistMelatonin receptor agonist Centrally acting muscle relaxantsCentrally acting muscle relaxants Miscellaneous agentsMiscellaneous agents General comments about antianxiety agentsGeneral comments about antianxiety agents


Antianxiety AgentsAntianxiety Agents Haveles (pp. 136-137) (Fig. 11-1)Haveles (pp. 136-137) (Fig. 11-1)

Objectively assessing the patient’s anxiety is Objectively assessing the patient’s anxiety is necessary on both the first and subsequent necessary on both the first and subsequent visitsvisits The dental team will most commonly use orally The dental team will most commonly use orally

administered drugs to provide relaxation for an administered drugs to provide relaxation for an anxious patientanxious patient

Intravenous (IV) administration is used Intravenous (IV) administration is used infrequently; most states require a separate infrequently; most states require a separate certificate to administer IV agents or provide certificate to administer IV agents or provide conscious sedationconscious sedation

The dosing of a particular antianxiety agent is The dosing of a particular antianxiety agent is vastly variable, involving intrapatient and vastly variable, involving intrapatient and interpatient variationinterpatient variation


DefinitionsDefinitions

Haveles (p. 137) (Fig. 11-2)Haveles (p. 137) (Fig. 11-2) Sedative-hypnotic agents can produce Sedative-hypnotic agents can produce

varying degrees of central nervous system varying degrees of central nervous system (CNS) depression, depending on the dose (CNS) depression, depending on the dose administeredadministered A small dose will produce mild CNS depression A small dose will produce mild CNS depression

described as described as sedationsedation—reduction of activity and —reduction of activity and simple anxietysimple anxiety• This level has some anxiolytic effectsThis level has some anxiolytic effects

A larger dose of the same drug, the A larger dose of the same drug, the hypnotic hypnotic dose, dose, will produce greater CNS depressionwill produce greater CNS depression

In even larger doses, sedative-hypnotics may In even larger doses, sedative-hypnotics may produce anesthesia and finally deathproduce anesthesia and finally death


BenzodiazepinesBenzodiazepines

Haveles (pp. 137-142)Haveles (pp. 137-142) ChemistryChemistry PharmacokineticsPharmacokinetics Mechanism of actionMechanism of action Pharmacologic effectsPharmacologic effects Adverse reactionsAdverse reactions Abuse and toleranceAbuse and tolerance Drug interactionsDrug interactions Medical usesMedical uses Management of the dental patient taking Management of the dental patient taking

benzodiazepinesbenzodiazepines


ChemistryChemistry

Haveles (pp. 137-138) (Table 11-1)Haveles (pp. 137-138) (Table 11-1) Named according to their structure—a 1, 4—Named according to their structure—a 1, 4—

benzodiazepine nucleusbenzodiazepine nucleus chlordiazepoxide (Librium) was synthesized in 1955chlordiazepoxide (Librium) was synthesized in 1955 diazepam (Valium) was synthesized in 1959 and diazepam (Valium) was synthesized in 1959 and

marketed in 1963marketed in 1963 When an additional ring was added, triazolam When an additional ring was added, triazolam

was synthesizedwas synthesized Next, midazolam and flumazenil were synthesizedNext, midazolam and flumazenil were synthesized


PharmacokineticsPharmacokinetics Haveles (pp. 138-139)Haveles (pp. 138-139)

Benzodiazepines are well absorbed when Benzodiazepines are well absorbed when administered by the oral routeadministered by the oral route The onset of action is related to their lipid solubilityThe onset of action is related to their lipid solubility

Benzodiazepines are available as tablets, capsules, Benzodiazepines are available as tablets, capsules, oral solution, rectal gel, and injectable formoral solution, rectal gel, and injectable form For benzodiazepines available in parenteral form the IV For benzodiazepines available in parenteral form the IV

route produces a rapid, predictable response; ideal for route produces a rapid, predictable response; ideal for conscious sedationconscious sedation

Benzodiazepines cross the blood-brain and Benzodiazepines cross the blood-brain and placental barriers to produce an effect on the CNS placental barriers to produce an effect on the CNS and the fetusand the fetus

cont’d…cont’d…


PharmacokineticsPharmacokinetics

Haveles (pp. 138-139)Haveles (pp. 138-139) Benzodiazepines are metabolized by phase II Benzodiazepines are metabolized by phase II

metabolism alone or by phase I metabolism metabolism alone or by phase I metabolism followed by phase II metabolismfollowed by phase II metabolism Phase I metabolism involves oxidation, reduction, Phase I metabolism involves oxidation, reduction,

hydrolysis, dealkylation, and hydroxylationhydrolysis, dealkylation, and hydroxylation• It is It is hard hard metabolism; it is affected by external factors metabolism; it is affected by external factors

such as other drugs and hepatic diseasesuch as other drugs and hepatic disease

Phase II involves glucuronidationPhase II involves glucuronidation• It is It is easy easy metabolism; unaffected by external factorsmetabolism; unaffected by external factors


Mechanism of ActionMechanism of Action

Haveles (p. 139)Haveles (p. 139) Benzodiazepines enhance or facilitate the Benzodiazepines enhance or facilitate the

action of the neurotransmitter by exerting action of the neurotransmitter by exerting their effects in the CNS mediated by their effects in the CNS mediated by γγ--aminobutyric acid (GABA), a major inhibitory aminobutyric acid (GABA), a major inhibitory neurotransmitterneurotransmitter The inhibitor effect of GABA is enhancedThe inhibitor effect of GABA is enhanced


Pharmacologic EffectsPharmacologic Effects

Haveles (p. 139)Haveles (p. 139) Behavioral effectsBehavioral effects

Clinical effects in humans are anxiety and panic Clinical effects in humans are anxiety and panic reduction at low doses and drowsiness and even reduction at low doses and drowsiness and even sleep at higher dosessleep at higher doses

Antiseizure effectsAntiseizure effects Increase the seizure thresholdIncrease the seizure threshold

Muscle relaxationMuscle relaxation Can produce relaxation of skeletal musclesCan produce relaxation of skeletal muscles


Adverse Reactions of Adverse Reactions of BenzodiazepinesBenzodiazepines

Haveles (p. 139)Haveles (p. 139) In general, benzodiazepines, used alone, In general, benzodiazepines, used alone,

have a wide margin of safetyhave a wide margin of safety They all have similar adverse effects but differ in They all have similar adverse effects but differ in

their frequencytheir frequency




CNS effectsCNS effects The most common side effect is depression The most common side effect is depression

manifested as fatigue, drowsiness, muscle manifested as fatigue, drowsiness, muscle weakness, and ataxiaweakness, and ataxia• The use of parenteral benzodiazepines during a dental The use of parenteral benzodiazepines during a dental

appointment reduces anxiety and alters perception of appointment reduces anxiety and alters perception of timetime

Diazepam’s long half-life and metabolism to an active Diazepam’s long half-life and metabolism to an active metabolite prolongs its duration of actionmetabolite prolongs its duration of action

Midazolam is metabolized primarily to inactive metabolitesMidazolam is metabolized primarily to inactive metabolites

• flunitrazepam (Rohypnol) is available in Europeflunitrazepam (Rohypnol) is available in Europecont’d…cont’d…



Anterograde amnesiaAnterograde amnesia Produced beginning when the drug is takenProduced beginning when the drug is taken

Respiratory effectsRespiratory effects Doses of diazepam have occasionally been reported Doses of diazepam have occasionally been reported

to produce respiratory depressionto produce respiratory depression Cardiovascular effectsCardiovascular effects

Relief of anxiety may result in a fall in blood pressure Relief of anxiety may result in a fall in blood pressure and pulse rateand pulse rate




Visual effectsVisual effects Contraindicated in angle-closure (narrow-angle) Contraindicated in angle-closure (narrow-angle)

glaucoma and can produce diplopia (single object glaucoma and can produce diplopia (single object viewed as two), nystagmus (rhythmic oscillation of the viewed as two), nystagmus (rhythmic oscillation of the eyeballs), and blurred visioneyeballs), and blurred vision

Dental effectsDental effects Have been reported to produce xerostomia, increased Have been reported to produce xerostomia, increased

salivation, swollen tongue, and a bitter or metallic tastesalivation, swollen tongue, and a bitter or metallic taste ThrombophlebitisThrombophlebitis

Parenteral diazepam may cause thrombophlebitis Parenteral diazepam may cause thrombophlebitis because propylene glycol is used to solubilize itbecause propylene glycol is used to solubilize it




Other effectsOther effects Can produce cramps or pain, difficulty in urination, Can produce cramps or pain, difficulty in urination,

allergic reactionsallergic reactions Pregnancy and lactation considerationsPregnancy and lactation considerations

Increased risk of congenital malformations if taken Increased risk of congenital malformations if taken in the first trimester of pregnancy has been in the first trimester of pregnancy has been reportedreported


Abuse and ToleranceAbuse and Tolerance

Haveles (p. 140)Haveles (p. 140) OverviewOverview

Benzodiazepines can be abused; physical Benzodiazepines can be abused; physical dependence and tolerance have been documenteddependence and tolerance have been documented• Their abuse and addiction potential is less than that of the Their abuse and addiction potential is less than that of the

other sedative-hypnotic agents such as barbituratesother sedative-hypnotic agents such as barbiturates

• Benzodiazepines have a wider TI than barbituratesBenzodiazepines have a wider TI than barbiturates

• Combining with other CNS depressants can reduce the Combining with other CNS depressants can reduce the safetysafety



Abuse and ToleranceAbuse and Tolerance

Haveles (p. 140)Haveles (p. 140) Treatment of overdoseTreatment of overdose

With recent ingestion, emesis may be inducedWith recent ingestion, emesis may be induced• Activated charcoal and a saline catharticActivated charcoal and a saline cathartic

To reduce some of the effects of a To reduce some of the effects of a benzodiazepine, flumazenil (Romazicon), a benzodiazepine, flumazenil (Romazicon), a benzodiazepine antagonist for IV administration benzodiazepine antagonist for IV administration may be usedmay be used


Drug InteractionsDrug Interactions

Haveles (pp. 140-141)Haveles (pp. 140-141) Benzodiazepines will interact in an additive Benzodiazepines will interact in an additive

fashion with other CNS depressantsfashion with other CNS depressants Drugs that inhibit oxidative metabolism (phase I Drugs that inhibit oxidative metabolism (phase I

metabolism) may increase the effect of metabolism) may increase the effect of benzodiazepines that undergo phase I metabolismbenzodiazepines that undergo phase I metabolism

Selective serotonin uptake inhibitors alter Selective serotonin uptake inhibitors alter clearance of diazepamclearance of diazepam

May reduce the effectiveness of levodopaMay reduce the effectiveness of levodopa May increase the effect of digoxin, phenytoin, May increase the effect of digoxin, phenytoin,

and probenecidand probenecid


Medical Uses Medical Uses

Haveles (p. 141)Haveles (p. 141) Useful in short-term treatment of anxiety, Useful in short-term treatment of anxiety,

panic attacks, insomnia, and alcohol panic attacks, insomnia, and alcohol withdrawalwithdrawal Used for acute treatment of seizuresUsed for acute treatment of seizures Used for conscious sedation, general anesthesia, Used for conscious sedation, general anesthesia,

or during surgeryor during surgery



Medical UsesMedical Uses

Anxiety controlAnxiety control Generalized anxiety disorders and panic disorder;Generalized anxiety disorders and panic disorder;

manifestations of anxiety include restlessness, manifestations of anxiety include restlessness, tension, tachycardia, and dyspneatension, tachycardia, and dyspnea

Insomnia managementInsomnia management If a manifestation of anxietyIf a manifestation of anxiety

Treatment of epilepsy (seizures)Treatment of epilepsy (seizures) Diazepam or lorazepam is the drug of choice Diazepam or lorazepam is the drug of choice



Medical UsesMedical Uses

Treatment of alcoholismTreatment of alcoholism Used in treatment of alcohol withdrawal syndromeUsed in treatment of alcohol withdrawal syndrome

Control of muscle spasmsControl of muscle spasms Used to control muscle spasticity that Used to control muscle spasticity that

accompanies diseases such as multiple sclerosis accompanies diseases such as multiple sclerosis and cerebral palsyand cerebral palsy


Management of the Dental Management of the Dental Patient Taking BenzodiazepinesPatient Taking Benzodiazepines

Haveles (pp. 141-142) (Box 11-2)Haveles (pp. 141-142) (Box 11-2) Dental proceduresDental procedures

Orally administered diazepam to allay apprehensionOrally administered diazepam to allay apprehension PremedicationPremedication

Used before surgical procedures to allay anxietyUsed before surgical procedures to allay anxiety Conscious sedationConscious sedation

Usually accompanied by IV administrationUsually accompanied by IV administration• Muscle relaxation and anterograde amnesia (events after Muscle relaxation and anterograde amnesia (events after

the injection)the injection)



Management of the Dental Management of the Dental Patient Taking BenzodiazepinesPatient Taking Benzodiazepines

Conscious sedationConscious sedation Parenteral benzodiazepines have been associated Parenteral benzodiazepines have been associated

with respiratory depression and arrest when used with respiratory depression and arrest when used for conscious sedationfor conscious sedation• Require continuous monitoring of respiratory and cardiac Require continuous monitoring of respiratory and cardiac

functionfunction

• Dentists without additional training cannot use conscious Dentists without additional training cannot use conscious sedationsedation


Benzodiazepines Benzodiazepines

Haveles (p. 138) (Table 11-1)Haveles (p. 138) (Table 11-1) alprazolam alprazolam chlordiazepoxide (Librium) chlordiazepoxide (Librium) clonazepam (Klonopin)clonazepam (Klonopin) chlorazepate (Tranxene)chlorazepate (Tranxene) diazepam (Valium) diazepam (Valium) estazolam (ProSom)estazolam (ProSom) flurazepam (Dalmane)flurazepam (Dalmane)



Benzodiazepines Benzodiazepines

Haveles (p. 138) (Table 11-1)Haveles (p. 138) (Table 11-1) halazepam (Paxipam)halazepam (Paxipam) lorazepam (Ativan)lorazepam (Ativan) midazolam (Versed) midazolam (Versed) oxazepam (Serax) oxazepam (Serax) quazepam (Doral)quazepam (Doral) temazepam (Restoril)temazepam (Restoril) triazolam (Halcion)triazolam (Halcion)


Barbiturates Barbiturates

Haveles (pp. 142-144)Haveles (pp. 142-144) ChemistryChemistry PharmacokineticsPharmacokinetics Mechanism of actionMechanism of action Pharmacologic effectsPharmacologic effects Adverse reactionsAdverse reactions Chronic long-term useChronic long-term use ContraindicationsContraindications Drug interactionsDrug interactions UsesUses



BarbituratesBarbiturates Haveles (p. 142)Haveles (p. 142)

The original sedative-hypnotic agentsThe original sedative-hypnotic agents Problems with their use are well documentedProblems with their use are well documented Associated with a high rate of abuse and complete Associated with a high rate of abuse and complete

cardiovascular and respiratory depression with overdosecardiovascular and respiratory depression with overdose Benzodiazepines have almost completely replaced Benzodiazepines have almost completely replaced

barbiturates for treating anxiety and insomniabarbiturates for treating anxiety and insomnia Barbiturates are still used as anticonvulsants and Barbiturates are still used as anticonvulsants and

to induce general anesthesiato induce general anesthesia


Chemistry of BarbituratesChemistry of Barbiturates

Haveles (p. 142)Haveles (p. 142) Formed by substitution of R groups on the Formed by substitution of R groups on the

barbiturate nucleus sites A and Bbarbiturate nucleus sites A and B The oxygen atom may be replaced with a sulfur The oxygen atom may be replaced with a sulfur

atom site Catom site C Compounds with S substitution are effective as IV Compounds with S substitution are effective as IV

agents such as thiopentalagents such as thiopental


Pharmacokinetics of BarbituratesPharmacokinetics of Barbiturates

Haveles (p. 142)Haveles (p. 142) Absorption: barbiturates are well absorbed Absorption: barbiturates are well absorbed

orally and rectally; used intravenously but not orally and rectally; used intravenously but not intramuscularlyintramuscularly

Distribution: IV agents are inactivated by Distribution: IV agents are inactivated by redistribution from site of action in the CNS, redistribution from site of action in the CNS, to muscles, and adipose tissueto muscles, and adipose tissue

Metabolism: short- and intermediate-acting Metabolism: short- and intermediate-acting barbiturates are rapidly and almost barbiturates are rapidly and almost completely metabolized by the livercompletely metabolized by the liver

Excretion: long-acting barbiturates are largely Excretion: long-acting barbiturates are largely excreted through the kidneys as a free drugexcreted through the kidneys as a free drug


Mechanism of Action Mechanism of Action

Haveles (p. 142)Haveles (p. 142) Barbiturates produce their effect by Barbiturates produce their effect by

enhancing GABA receptor binding and enhancing GABA receptor binding and prolong the opening of chloride channelsprolong the opening of chloride channels In higher dose may also act directly on chloride In higher dose may also act directly on chloride

channelschannels Mechanism is less specific than Mechanism is less specific than

benzodiazepines; may account for ability to benzodiazepines; may account for ability to induce surgical anesthesia and pronounced induce surgical anesthesia and pronounced generalized CNS depression effectsgeneralized CNS depression effects



Haveles (pp. 142-143)Haveles (pp. 142-143) CNS depressionCNS depression

With normal doses, relaxation occursWith normal doses, relaxation occurs• With larger doses, inhibitory fibers of the CNS are With larger doses, inhibitory fibers of the CNS are

depressed, resulting in disinhibition and euphoriadepressed, resulting in disinhibition and euphoria

• When higher doses are administered, hypnosis can be When higher doses are administered, hypnosis can be producedproduced

• Even higher doses, can result in anesthesia, with Even higher doses, can result in anesthesia, with respiratory and cardiovascular depression and finally arrestrespiratory and cardiovascular depression and finally arrest




Haveles (p. 143)Haveles (p. 143) AnalgesiaAnalgesia

Barbiturates have no significant analgesic effectBarbiturates have no significant analgesic effect Anticonvulsant effectAnticonvulsant effect

Barbiturates have anticonvulsant actionBarbiturates have anticonvulsant action• Long-acting agents are used to treat epilepsyLong-acting agents are used to treat epilepsy


Adverse ReactionsAdverse Reactions Haveles (p. 143)Haveles (p. 143)

Sedative or hypnotic dosesSedative or hypnotic doses In usual doses, barbiturates are relatively safeIn usual doses, barbiturates are relatively safe

• CNS depression may be exaggerated in elderly and CNS depression may be exaggerated in elderly and debilitated patients or those with liver or kidney impairmentdebilitated patients or those with liver or kidney impairment

Anesthetic dosesAnesthetic doses With higher doses, concentrations in the blood can With higher doses, concentrations in the blood can

be lethalbe lethal Acute poisoningAcute poisoning

Although a lethal dose can only be approximated, Although a lethal dose can only be approximated, severe poisoning will follow ingestion of 10 times the severe poisoning will follow ingestion of 10 times the hypnotic dose; life may be threatened when more hypnotic dose; life may be threatened when more than 15 times the hypnotic dose is consumedthan 15 times the hypnotic dose is consumed


Chronic Long-Term UseChronic Long-Term Use

Haveles (p. 143)Haveles (p. 143) Chronic use of barbiturates can lead to Chronic use of barbiturates can lead to

physical and psychologic dependencephysical and psychologic dependence The addict becomes progressively depressed and The addict becomes progressively depressed and

is unable to functionis unable to function Tolerance develops to most effects but not to Tolerance develops to most effects but not to

the lethal dosethe lethal dose A larger and larger dose must be used to produce A larger and larger dose must be used to produce

an effect, and this dose can approximate the lethal an effect, and this dose can approximate the lethal dosedose


ContraindicationsContraindications

Haveles (p. 143)Haveles (p. 143) Barbiturates are absolutely contraindicated in Barbiturates are absolutely contraindicated in

patients with intermittent porphyria or a patients with intermittent porphyria or a positive family history of porphyriapositive family history of porphyria Porphyria: a group of disorders involving heme Porphyria: a group of disorders involving heme

biosynthesisbiosynthesis Barbiturates can stimulate and increase the Barbiturates can stimulate and increase the

synthesis of porphyrins which are already at synthesis of porphyrins which are already at an excessive level in this diseasean excessive level in this disease


Drug InteractionsDrug Interactions

Haveles (pp. 143-144) (Box 11-3)Haveles (pp. 143-144) (Box 11-3) Barbiturates are stimulators of liver Barbiturates are stimulators of liver

microsomal enzyme productionmicrosomal enzyme production These enzymes are responsible for the metabolism These enzymes are responsible for the metabolism

of many drugsof many drugs An increase in these enzymes could increase the An increase in these enzymes could increase the

rate of drug destruction and decrease the duration rate of drug destruction and decrease the duration of actionof action


Uses of BarbituratesUses of Barbiturates

Haveles (pp. 143-144) (Table 11-2)Haveles (pp. 143-144) (Table 11-2) Therapeutic uses are determined by duration Therapeutic uses are determined by duration

of actionof action Ultrashort-acting barbiturates are used Ultrashort-acting barbiturates are used

intravenously for induction of general anesthesiaintravenously for induction of general anesthesia Short- and intermediate-acting barbiturates: little Short- and intermediate-acting barbiturates: little

medical use; replaced by benzodiazepinesmedical use; replaced by benzodiazepines Long-acting barbiturates: used for treatment of Long-acting barbiturates: used for treatment of

epilepsyepilepsy


Nonbenzodiazepine-Nonbarbiturate Nonbenzodiazepine-Nonbarbiturate Sedative-HypnoticsSedative-Hypnotics

Haveles (p. 144)Haveles (p. 144) chloral hydrate (Noctec)chloral hydrate (Noctec) buspirone (BuSpar)buspirone (BuSpar)


chloral hydratechloral hydrate(Noctec)(Noctec)

Haveles (p. 144)Haveles (p. 144) An inexpensive, orally effective sedative-An inexpensive, orally effective sedative-

hypnotic drug with a rapid onset and short hypnotic drug with a rapid onset and short duration of actionduration of action Therapeutic doses do not produce pronounced Therapeutic doses do not produce pronounced

respiratory or cardiovascular depressionrespiratory or cardiovascular depression Gastric irritation can be minimized by taking Gastric irritation can be minimized by taking

with milk or foodwith milk or food Used in dentistry for preoperative sedation of Used in dentistry for preoperative sedation of

childrenchildren The dose is 50 mg/kg, up to a maximum of 1 gThe dose is 50 mg/kg, up to a maximum of 1 g


buspironebuspirone(BuSpar)(BuSpar)

Haveles (p. 144)Haveles (p. 144) Unique in structure and actionUnique in structure and action

Mechanism of action is unknown; believed to be Mechanism of action is unknown; believed to be related to interactions with neurotransmitters in the related to interactions with neurotransmitters in the CNSCNS

Anxioselective Anxioselective because of its selective because of its selective anxiolytic action without hypnotic, anxiolytic action without hypnotic, anticonvulsant, or muscle-relaxant propertiesanticonvulsant, or muscle-relaxant properties Most patients prefer the benzodiazepinesMost patients prefer the benzodiazepines


Nonbenzodiazepine-Benzodiazepine Nonbenzodiazepine-Benzodiazepine Receptor AgonistsReceptor Agonists

Haveles (p. 144)Haveles (p. 144) Zolpidem, zaleplon, and eszopiclone Zolpidem, zaleplon, and eszopiclone

comprise a new class of drugs that are not comprise a new class of drugs that are not benzodiazepines but appear to bind to benzodiazepines but appear to bind to benzodiazepine receptors and decrease benzodiazepine receptors and decrease sleep latency with little effect on sleep stages sleep latency with little effect on sleep stages All are thought to have agonist effects on GABAAll are thought to have agonist effects on GABA These drugs are used to treat insomnia onlyThese drugs are used to treat insomnia only


zolpidemzolpidem(Ambien)(Ambien)

Haveles (pp. 144-145)Haveles (pp. 144-145) Recently developed hypnotic indicated for Recently developed hypnotic indicated for

short-term management of insomniashort-term management of insomnia Has hypnotic and anxiolytic effects, but receptor Has hypnotic and anxiolytic effects, but receptor

specificity produces less muscle-relaxant and specificity produces less muscle-relaxant and anticonvulsant effectsanticonvulsant effects

Likely to be useful in dentistry when an oral Likely to be useful in dentistry when an oral anxiolytic agent is desired for relaxing an anxiolytic agent is desired for relaxing an anxious dental patientanxious dental patient


zaleplonzaleplon(Sonata)(Sonata)

Haveles (p. 145)Haveles (p. 145) A rapid-acting hypnotic that is less potent and A rapid-acting hypnotic that is less potent and

has a shorter duration of action than zolpidemhas a shorter duration of action than zolpidem Appears to have a lower risk of next-day residual Appears to have a lower risk of next-day residual

effects, even with use in the middle of the nighteffects, even with use in the middle of the night


eszopicloneeszopiclone(Lunesta)(Lunesta)

Haveles (p. 145)Haveles (p. 145) The newest agent of this class available in The newest agent of this class available in

the United Statesthe United States Anterograde amnesia has been reportedAnterograde amnesia has been reported Some patients report an unpleasant tasteSome patients report an unpleasant taste Eszopiclone could impair driving the morning after Eszopiclone could impair driving the morning after

nighttime administrationnighttime administration


Melatonin Receptor AgonistMelatonin Receptor Agonist

Haveles (p. 145)Haveles (p. 145) ramelteon (Rozeram) has been approved for ramelteon (Rozeram) has been approved for

treatment of insomnia characterized by treatment of insomnia characterized by difficulty falling asleepdifficulty falling asleep An indenofuran derivative highly selective for An indenofuran derivative highly selective for

melatonin type 1 (MTmelatonin type 1 (MT11) and melatonin type 2 (MT) and melatonin type 2 (MT22) )

receptorsreceptors Animal studies indicate that the MTAnimal studies indicate that the MT1 1 receptor receptor

regulates sleep, and the MTregulates sleep, and the MT22 receptor may mediate receptor may mediate

the phase-shifting effects of melatonin on a 24-hour the phase-shifting effects of melatonin on a 24-hour biologic clockbiologic clock


Centrally Acting Muscle Centrally Acting Muscle RelaxantsRelaxants

Haveles (p. 145)Haveles (p. 145) Exert their effects on the CNS to produce Exert their effects on the CNS to produce

skeletal muscle relaxationskeletal muscle relaxation



Centrally Acting Muscle Centrally Acting Muscle RelaxantsRelaxants

Haveles (p. 145)Haveles (p. 145) Pharmacologic effectsPharmacologic effects

All CNS muscle relaxants produce some degree of All CNS muscle relaxants produce some degree of sedative effect because their action is on the CNSsedative effect because their action is on the CNS• The sedative effects dominate over the “selective” The sedative effects dominate over the “selective”

muscle-relaxant activitymuscle-relaxant activity

• Useful in treating muscle spasms and back and neck Useful in treating muscle spasms and back and neck painpain



Centrally Acting Muscle RelaxantsCentrally Acting Muscle Relaxants

Haveles (pp. 145-146)Haveles (pp. 145-146) Individual centrally acting muscle relaxantsIndividual centrally acting muscle relaxants

OverviewOverview• Exert their muscle-relaxing properties indirectly by producing Exert their muscle-relaxing properties indirectly by producing

CNS depressionCNS depression Have no direct effect on striated muscle; do not directly relax Have no direct effect on striated muscle; do not directly relax

tense skeletal musclestense skeletal muscles

UseUse• An adjunct to rest and physical therapy for relief of muscle An adjunct to rest and physical therapy for relief of muscle

spasm associated with acute painful musculoskeletal spasm associated with acute painful musculoskeletal conditionsconditions

May be used for symptomatic relief of temporomandibular joint May be used for symptomatic relief of temporomandibular joint disorderdisorder


Examples of Centrally Acting Examples of Centrally Acting Skeletal Muscle RelaxantsSkeletal Muscle Relaxants

Haveles (p. 145) (Table 11-3)Haveles (p. 145) (Table 11-3) carisoprodol (Soma)carisoprodol (Soma) chlorzoxazone (Parafon Forte DSC)chlorzoxazone (Parafon Forte DSC) methocarbanol (Robaxin)methocarbanol (Robaxin) orphenadrine (Norflex)orphenadrine (Norflex) cyclobenzapine (Flexeril)cyclobenzapine (Flexeril) diazepam (Valium)diazepam (Valium)


Miscellaneous AgentsMiscellaneous Agents Haveles (p. 146)Haveles (p. 146)

baclofen (Lioresal)baclofen (Lioresal) Inhibits both monosynaptic and polysynaptic reflexes at the Inhibits both monosynaptic and polysynaptic reflexes at the

spinal levelspinal level• Indicated for spasticity from multiple sclerosis or spinal cord injuries or Indicated for spasticity from multiple sclerosis or spinal cord injuries or

diseases diseases

tizanidine (Zanaflex)tizanidine (Zanaflex) A short-acting muscle relaxantA short-acting muscle relaxant

• Centrally acting Centrally acting αα-adrenergic receptor agonist-adrenergic receptor agonist

dantrolene (Dantrium)dantrolene (Dantrium) Affects contractile response of skeletal muscle by acting on Affects contractile response of skeletal muscle by acting on

the muscle itselfthe muscle itself• Indicated for treatment of spasticity from upper motor neuron disordersIndicated for treatment of spasticity from upper motor neuron disorders


General Comments About General Comments About Antianxiety AgentsAntianxiety Agents

Haveles (pp. 146-147)Haveles (pp. 146-147) Analgesic-sedative combinationsAnalgesic-sedative combinations Special considerationsSpecial considerations PrecautionsPrecautions


Analgesic-Sedative CombinationsAnalgesic-Sedative Combinations

Haveles (p. 146) (Box 11-4)Haveles (p. 146) (Box 11-4) Both sedation and analgesia can be obtained Both sedation and analgesia can be obtained

from opioid analgesics alonefrom opioid analgesics alone Prescribing an opioid to add sedation to analgesia Prescribing an opioid to add sedation to analgesia

is undesirable unless the analgesic potency is is undesirable unless the analgesic potency is requiredrequired

In cases in which anxiety is an important In cases in which anxiety is an important component in pain relief, either a nonopioid or an component in pain relief, either a nonopioid or an opioid can be used concomitantly with a sedativeopioid can be used concomitantly with a sedative


Special ConsiderationsSpecial Considerations

Haveles (p. 146)Haveles (p. 146) Patients who are to use antianxiety agents Patients who are to use antianxiety agents

should be driven to and from the dental should be driven to and from the dental appointmentappointment

Drugs are not a substitute for patient Drugs are not a substitute for patient management management

Drugs should not be substituted for patient Drugs should not be substituted for patient education or for the proper psychologic education or for the proper psychologic approach to patient careapproach to patient care


PrecautionsPrecautions Haveles (p. 147)Haveles (p. 147)

Patients with impaired elimination may experience Patients with impaired elimination may experience exaggerated effects of these medications exaggerated effects of these medications

Depression caused by all sedative-hypnotics will add to Depression caused by all sedative-hypnotics will add to depression caused by other CNS depressantsdepression caused by other CNS depressants

The patient should be accompanied by a responsible The patient should be accompanied by a responsible adult who can drive the patient homeadult who can drive the patient home

Psychic and physical dependence has been observed Psychic and physical dependence has been observed with almost all drugs used to allay anxietywith almost all drugs used to allay anxiety

Suicide may be attempted by taking sedative-hypnotic Suicide may be attempted by taking sedative-hypnotic drugsdrugs

These drugs should never be administered to pregnant These drugs should never be administered to pregnant women or to those who may be pregnant unless the women or to those who may be pregnant unless the potential benefit to the mother outweighs the risk to the potential benefit to the mother outweighs the risk to the fetusfetus

Sedatives do Sedatives do not not provide analgesiaprovide analgesia

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