Central Nervous System Depressants

CNS Depressants SedativesDrugs that have an inhibitory effect on the CNS to the degree that they reduce:NervousnessExcitabilityIrritabilitywithout causing sleep

CNS Depressants HypnoticsCalm or soothe the CNS to the point that they cause sleep

CNS DepressantsSedative-Hypnoticsdose dependent:At low doses, calm or soothe the CNS without inducing sleepAt high doses, calm or soothe the CNSto the point of causing sleep

Sedative-Hypnotics: BarbituratesFirst introduced in 1903, standard agents for insomnia and sedationHabit-formingOnly a handful commonly used today due in part to the safety and efficacy of: BENZODIAZEPINES

Sedative-Hypnotics: BarbituratesFour categories:Ultrashortmephobexital, thiamylal, thiopentalShortpentobarbital, secobarbitalIntermediateaprobarbital, butabarbitalLongphenobarbital

Sedative-Hypnotics: BarbituratesBarbiturates have a very narrow therapeutic index. Therapeutic IndexDosage range within which the drug is effective but above which is rapidly toxic.

Sedative-Hypnotics: BarbituratesMechanism of ActionSite of action:Brain stem (reticular formation)Cerebral cortexBy inhibiting GABA, nerve impulses traveling in the cerebral cortex are also inhibited.

Sedative-Hypnotics: BarbituratesDrug EffectsLow doses:Sedative effects

High doses:Hypnotic effects (also lowers respiratory rate) Notorious enzyme inducers

Sedative-Hypnotics: BarbituratesTherapeutic UsesHypnoticsSedativesAnticonvulsantsSurgical procedures

Sedative-Hypnotics: BarbituratesSide EffectsBody SystemEffectsCNSDrowsiness, lethargy, vertigomental depression, coma RespiratoryRespiratory depression, apnea, bronchospasms, cough

Sedative-Hypnotics: BarbituratesSide EffectsBody SystemEffectsGINausea, vomiting, diarrhea OtherAgranulocytosis, vasodilation, hypotension, Stevens-Johnson syndrome

Sedative-Hypnotics: BarbituratesToxicologyOverdose frequently leads to respiratory depression, and subsequently, respiratory arrest.Can be therapeutic:Anesthesia inductionUncontrollable seizures: phenobarbital coma

Sedative-Hypnotics: BarbituratesDrug InteractionsAdditive effects:ETOH, antihistamines, benzodiazepines, narcotics, tranquilizersInhibited metabolism:MAOIs will prolong effects of barbituratesIncreased metabolism:Reduces anticoagulant response, leading to possible clot formation

CNS Depressants: BenzodiazepinesMost frequently prescribed sedative-hypnoticsMost commonly prescribed drug classesFavorable side effectsEfficacySafety

CNS Depressants: BenzodiazepinesClassified as either:Sedative-hypnotic or Anxiolytic (Medication that relieves anxiety)

CNS Depressants: BenzodiazepinesSedative-Hypnotic TypeLong-Acting:flurazepam (Dalmane), quazepam (Doral) Short-Acting:estazolam (Prosom), temazepam (Restoril),triazolam (Halcion)

CNS Depressants: BenzodiazepinesAnxiolytic Typealprazolam (Xanax)chloridiazepoxide (Librium)diazepam (Valium)lorazepam (Ativan)midazolam (Versed) zolpidem (Ambien) and zaleplon (Sonata)(nonbenzodiazepine hypnotic agents, share characteristics)

CNS Depressants: BenzodiazepinesMechanism of ActionDepress CNS activityAffect hypothalamic, thalamic, and limbic systems of the brainBenzodiazepine receptors

CNS Depressants: BenzodiazepinesDrug EffectsCalming effect on the CNSUseful in controlling agitation and anxiety

CNS Depressants: BenzodiazepinesTherapeutic UsesSedationSleep inductionSkeletal muscle relaxationAnxiety reliefTreatment of alcohol withdrawalAgitationDepressionEpilepsyBalanced anesthesia

CNS Depressants: BenzodiazepinesSide EffectsMild and infrequentHeadacheDrowsinessDizzinessVertigoLethargyParadoxical excitement (nervousness) Hangover effect

CNS Depressants: Nursing ImplicationsBefore beginning therapy, perform a thorough history regarding allergies, use of other medications,health history, and medical history.Obtain baseline vital signs and I & O, including supine and erect BPs.Assess for potential disorders or conditions that may be contraindications, and for potential drug interactions.

CNS Depressants: Nursing ImplicationsGive 15 to 30 minutes before bedtime for maximum effectiveness in inducing sleep.Most benzodiazepines (except flurazepam) cause REM rebound and a tired feeling the next day; use with caution in the elderly.Patients should be instructed to avoid alcohol and other CNS depressants.

CNS Depressants: Nursing ImplicationsCheck with physician before taking any other medications, including OTC medications.It may take 2 to 3 weeks to notice improved sleep when taking barbiturates.Abruptly stopping these medications, especially barbiturates, may cause rebound insomnia.

CNS Depressants: Nursing ImplicationsSafety is importantKeep side rails upDo not permit smokingAssist patient with ambulation (especially the elderly)Keep call light within reachMonitor for side effects

CNS Depressants: Nursing ImplicationsMonitor for therapeutic effectsIncreased ability to sleep at nightFewer awakeningsShorter sleep induction timeFew side effects, such as hangover effectsImproved sense of well-being because of improved sleep

Anticonvulsants and Drugs to Treat Other CNS Disorders

Chapter 8 TopicsEpilepsyParkinsons DiseaseMyasthenia GravisAttention-Deficit DisordersAmyotrophic Lateral Sclerosis (ALS)Multiple Sclerosis (MS)Alzheimers Disease

Learning ObjectivesDevelop an understanding of the physiologic processes that occur in epilepsy.Classify seizures and the goals of their therapy.Understand that specific drugs are used in different classes of seizures.

Learning ObjectivesBe familiar with Parkinsons disease and the drugs used in its treatment.Know the symptoms and treatments ofmyasthenia gravisattention-deficit disordersamyotrophic lateral sclerosismultiple sclerosisAlzheimers disease

EpilepsyCommon neurologic disorder with sudden and recurring seizuresCaused by abnormal electrical impulses in the brain

EpilepsyIn the U.S., 2.5 million people are affected.

Not all seizure disorders are epilepsy.

EpilepsySeizureAbnormal electrical discharges in the cerebral cortex caused by sudden, excessive firing of neuronsResult in a change in behavior of which the patient is not awareWhile conscious, the patient may or may not lose movement controlLoss of body control may affect one area or the entire body

EpilepsyCauses of Seizures Imbalance of excitatory and inhibitory neurotransmitters:Glutamate inhibitoryGABA excitatoryOther neurotransmitters can be involvedNeurotransmitter levels are controlled by enzymesDisruption in enzymes = disruption of neurotransmitters

EpilepsyCauses of SeizuresETOH withdrawalCardiovascular diseaseHigh feverHypocalcemiaHigh or low blood sugarHypoxia

Infection (meningitis)Metabolic abnormalitiesBrain tumorToxic substancesTrauma or injury to the head

EpilepsyClasses of SeizuresPartialGeneralized

EpilepsyClasses of SeizuresPartialSimple-partialComplex-partialGeneralized

EpilepsyClasses of SeizuresPartialSimple-partialComplex-partialGeneralizedTonic-clonic or grand malAbsence or petit malMyoclonicAtonic

EpilepsyPartial SeizuresLocalized in a specific area of the brainOccurs with 65% of epileptic patientsCan progress to generalized seizures

EpilepsyPartial SeizuresSimple-PartialComplex-Partial

EpilepsyPartial SeizuresSimple-PartialNo loss of consciousnessMay have muscle twitching or sensory hallucinationsComplex-Partial

EpilepsyPartial SeizuresSimple-PartialNo loss of consciousnessMay have muscle twitching or sensory hallucinationsComplex-PartialImpaired consciousnessWith confusion, blank stare, and postseizure amnesia

EpilepsyGeneralized SeizuresInvolves both hemispheres of the brain, not one specific locationTypesTonic-ClonicAbsenseMyoclonicAtonic

Generalized SeizuresTonic-Clonic SeizuresTonic body becomes rigid, lasts a minute or lessClonic initiated with muscle jerks, and may be accompanied by shallow breathing, loss of bladder control, and excess salivation

Generalized SeizuresAbsenceInterruption of activities by blank stare, rotating eyes, uncontrolled facial movements, rapid eye blinking, and/or jerking of an arm or legNo generalized convulsionsUsually lasts 30 seconds or lessMany times it progresses to tonic-clonic as the patient gets older

Generalized SeizuresMyoclonicOccurs with sudden, massive, brief muscle jerks or non-massive, quick jerksConsciousness is not lostCan occur during sleep

Generalized SeizuresAtonicBegins with sudden loss of muscle tone and consciousnessMuscles relax, limbs go limpLasts a few seconds to a minute, then patient can resume standing and walking

Generalized SeizuresStatus EpilepticusContinuous tonic-clonic seizures with or without return to consciousnessHigh fever and lack of oxygen severe enough to cause brain damage or death

DiscussionWhat percentage of status epilepticus patients die, regardless of treatment?

DiscussionWhat percentage of patients status epilepticus patients die, regardless of treatment?

Answer: 10%

Antiepileptic Drug TherapyGoals of TherapySeizure control or lessen the frequencyPrevent emotional and behavioral changes

DiscussionNote: 30% of patients are not compliant due to side effects (sedation and loss of cognitive processes).

What are some possible strategies health care providers can use to help improve drug therapy compliance?

Antiepileptic Drug TherapyNeuronal ActivityPolarized (resting)Depolarized (firing)Sodium and calcium enter the cellWhen sufficient amounts cross, neurotransmitters are releasedNeurotransmitter release leads to firing of the neuronRepolarization (return to resting)

Antiepileptic Drug TherapyAbnormal Neuronal ActivityDepolarizationIf excessive neurotransmitters are released it leads to uncontrollable firing of the neuron = seizureTreatmentBlock the firing of the neuron by raising the threshold of depolarization

Antiepileptic Drug TherapyStart with monotherapy at a low dose and titrate up slowlyMedication must be maintained at steady therapeutic levels (no missed doses)Polytherapy can be used if sufficient response is not seen with monotherapy

Antiepileptic Drug TherapyProblems with TherapyWrong medication is used for the seizure typeSide effects may cause problems with patient complianceIf doses are missed, there is an increased risk of seizure activity

Anticonvulsantscarbamazepine (Epitol, Tegretol)clonazepam (Klonopin)diazepam (Valium)divalproex (Depakote)ethosuximide (Zarontin)Fosphyenytoin (Cerebyx) gabapentin (Neurontin)Drug List

Anticonvulsantslamotrigine (Lamictal)levetiracetam (Keppra)lorazepam (Ativan)oxcarbazepine (Trileptal)phenobarbital (Luminal Sodium)phenytoin (Dilantin)Drug List

Anticonvulsantsprimidone (Mysoline)topiramate (Topamax)valproic acid (Depakene)zonisamide (Zonegran)Drug List

Therapeutic Regimens for Seizures

Therapeutic Regimens for Seizures

valproic acid (Depakene) and divalproex (Depakote)Increases the availability of GABA (inhibitory)Take with water, not a carbonated drinkDo not use aspirin

Dispensing IssuesDepakote and Depakene can easily be confused.Be careful with Depakote and Depakote ER.Depakote ER is only once a day.Warning!

phenytoin (Dilantin)May be used to prevent seizuresPromotes sodium outflow from cells stabilizes the neuronal membraneBe cautious of drug interactionsIntravenous phenytoin must be mixed carefully

Phenytoin Side EffectsDose RelatedAtaxiaDiplopiaDizzinessDrowsinessEncephalopathyInvoluntary movements

Phenytoin Side EffectsNon-Dose-RelatedGingival hyperplasiaPeripheral neuropathyVitamin deficiencies

Dispensing IssuesLook-Alike and Sound-Alike DrugsCerebyx (anticonvulsant)Celexa (antidepressant)Celebrex (for pain and arthritis)Warning!

carbamazepine (Epitol, Tegretol)Has effect on sodium channels which may alter synaptic transmission.Blood monitoring must be done regularly.Be cautious of interactions and side effects.

gabapentin (Neurontin)Used in conjunction with other medicationsNo significant drug interactionsUsed for many other disorders, particularly neuropathic pain

Dispensing IssuesNeurontin (anticonvulsant) and Noroxin (antibiotic) are sound-alike drugs, but they are easy to distinguish by strength.Warning!

clonazepam (Klonopin)Only indication is prophylaxis of seizuresDepresses nerve transmission in the motor cortexC-IV controlled substance (benzodiazepine)

Dispensing IssuesLook-Alike and Sound-Alike DrugsLamictal (anticonvulsant)Lamisil (antifungal)Lomotil (for diarrhea)Warning!

topiramate (Topamax)Is thought to alter sodium channels and thereby increases GABA activity and decreases glutamine activity Causes significant cognitive effectsDrink fluids to decrease risk of kidney stones

Dispensing IssuesLook-Alike and Sound-Alike DrugsKaletra (antiviral for HIV)Keflex (antibiotic)Keppra (anticonvulsant)Warning!

DiscussionWhich neurotransmitters play the greatest role in seizures?

DiscussionWhich neurotransmitters play the greatest role in seizures?

Answer Glutamate (excitatory) GABA (inhibitory)

Parkinsons DiseaseCharacteristic SignsResting tremorRigidityAkinesiaUsually affects people over 60

Parkinsons DiseasePhysiologyResult of pathologic alterations in the extrapyramidal system (part of the CNS that controls motor activities)Distinguishing feature: Lewy bodies (protein masses) found in the midbrain

Parkinsons DiseasePhysiologyNormal muscle movement requires balance of dopamine (inhibitor) and ACh (stimulator)In the substantia nigra, enough dopamine is released to counteract the effects of AChIn parkinsonism, enough dopamine is not released which leads to excessive motor nerve stimulation

Cutaway View of the Brain

Substantia Nigra

Parkinsons DiseaseDrug TherapyImproves the functional ability and clinical status of patientsAims at symptomatic relief, does not alter the disease processPatients may have temporary or prolonged remissionSide effects can be a problem

Anti-Parkinson Agentsamantadine (Symmetrel)benztropine (Cogentin)bromocriptine (Parlodel)entacapone (Comtan)levodopa (Dopar)levodopa-carbidopa (Sinemet)Drug List

Anti-Parkinson Agentslevodopa-carbidopa-entacapone (Stalevo)pergolide (Permax)pramipexole (Mirapex)ropinirole (ReQuip)selegiline (Eldepryl)tolcapone (Tasmar)Drug List

levodopa (Dopar)Metabolized to dopamine in the brain, but the brain does not receive a full doseDrug has very undesirable effectsAfter about 5 years of therapy, 2/3 of patients experience on-off phenomenon

levodopa-carbidopa (Sinemet)Probably the most common drug used for parkinsonismCarbidopa allows for lower doses of levodopa to be used which decreases side effects

Dispensing IssuesLook-Alike and Sound-Alike DrugsAmantadine (for Parkinsons)Ranitidine (for the stomach)Rimantadine (for the flu)Warning!

entacapone (Comtan)Indicated for patients who have a deteriorating response to levodopaLess toxic than tolcaponeTake without regard to food

DiscussionWhat are the two primary neurotransmitters involved in Parkinsons disease and what role do they play?

DiscussionWhat are the two primary neurotransmitters involved in Parkinsons disease and what role do they play?

Answer ACh (excitatory) Dopamine (inhibitory)

Myasthenia GravisAutoimmune disorder of the neuromuscular junctionACh receptors are destroyed at the motor end plateCharacterized by weakness and fatigability, especially of the skeletal muscles

Motor End Plate

Myasthenia GravisPresenting SignsPtosis (drooping eyelid)Diplopia (double vision)Dyarthria (speech)Dysphagia (swallowing)

Myasthenia GravisTreatmentBlocking the destruction of ACh causes improvement for the patient

Myasthenia Gravis Agentsazathioprine (Imuran)cyclophosphamide (Cytoxan)edrophonium (Enlon, Reversol)neostigmine (Prostigmin)pyridostigmine (Mestinon)Drug List

pyridostigmine (Mestinon)Blocks destruction of ACh Allows for ACh accumulation at the synaptic junction

cyclophosphamide (Cytoxan)Prevents cell division by targeting the auto-immune portion of the diseaseUse chemotherapeutic precautions

Attention-Deficit DisordersAttention-Deficit Hyperactivity Disorder (ADHD)Attention-Deficit Disorder (ADD)

Attention-Deficit DisordersAttention-Deficit Hyperactivity Disorder (ADHD)Characterized by purposeless, chronic, pervasive, driven behavior that affects a child in social, emotional, and academic settings.

Attention-Deficit DisordersAttention-Deficit Hyperactivity Disorder (ADHD)Characteristics for AssessmentHyperactivityImpulsivityDistractibility

Attention-Deficit DisordersAttention-Deficit Disorder (ADD)Has less hyperactivityChild is more lethargic and more easily distractedBoth disorders are more common in boys than girlsSome symptoms can persist into adulthood

Attention-Deficit Disorder Agentsatomoxetine (Strattera)clonidine (Catapres, Catapres-TTS)desipramine (Norpramin)dexmethylphenidate (Focalin), C-IIdextroamphetamine-amphetamine (Adderall), C-IIDrug List

Attention-Deficit Disorder Agentsimipramine (Tofranil)methylphenidate (Concerta, Metadate, Ritalin, Ritalin-SR), C-IInortriptyline (Aventyl, Pamelor)pemoline (Cylert), C-IVDrug List

methylphenidate (Concerta, Metadate, Ritalin, Ritalin-SR)C-II controlled substanceDrug of choice to treat ADD, ADHD, and narcolepsyIncreases levels of neurotransmitters in the brainConcerta is a QD dose outer shell dissolves to release medication immediately, then drug is slowly released through pores in the tablet

dextroamphetamine-amphetamine (Adderall)C-II controlled substanceEffects last about 6 hoursPrimary side effect is depression

Dispensing IssuesLook-Alike and Sound-Alike DrugsAdderall (ADD, ADHD)Inderal (anxiety, hypertension)Warning!

atomoxetine (Strattera)Nonstimulant inhibitor of norepinephrine reuptakeControls impulsivity and activityNot a controlled substance, so refills can be called inSide effects: weight loss and slowed growth

Dispensing IssuesLook-Alike and Sound-Alike DrugsClonidine (ADD, ADHD)Klonopin (seizures)Warning!

DiscussionCompare and contrast ADHD and ADD.

DiscussionCompare and contrast ADHD and ADD.

AnswerADHD hyperactivity, impulsivity, and distractabilityADD more lethargic and easily distracted

Amyotrophic Lateral Sclerosis (ALS)Known as Lou Gehrigs diseaseProgressive degenerative disease of the nervesLeads to muscle weakness, paralysis, and eventually deathCaused by excessive levels of glutamate

ALS Agentriluzole (Rilutek)Drug List

riluzole (Rilutek)First drug approved for ALSInhibits release of glutamateShown to improve survival rate by 3 months is some patients

Multiple Sclerosis (MS)Autoimmune disease in which myelin sheaths degeneratePatient loses use of muscles and often eyesight is affectedSome drugs can slow progression, but there is no cure

MS Agentsbaclofen (Lioresal)glatiramer acetate (Copaxone)interferon beta-1a (Avonex, Rebif)interferon beta-1b (Betaseron)mitoxantrone (Novantrone)tizanidine (Zanaflex)Drug List

interferon beta-1a (Avonex, Rebif)Used for ambulatory patientsReduces frequency of attacksDelays disabilityDrug should be taken at night with APAP to prevent flu-like side effects

baclofen (Lioresal)Skeletal muscle relaxantInhibits transmission of reflexes at the spinal cordOnset requires three to four days

Alzheimers DiseaseDegenerative disorder of the brain that leads to progressive dementia and changes in personality and behaviorProgressionMinor forgetfulnessInability to complete complex tasksComplete incapacitation, disorientation, and failure to thrive

Alzheimers DiseaseThere are no treatments that can reverse this disease

Depression should be treated according to symptoms

Alzheimers Agentsdonepezil (Aricept)galantamine (Reminyl)ginkgo memantine (Namenda)rivastigmine (Exelon)tacrine (Cognex)Drug List

donepezil (Aricept)Convenient with few side effectsImproves memory and alertnessGive once a day at bedtime

memantine (Namenda)May have fewer side effects than other drugsApproved for moderate to severe conditionsEvidence that the drug does slow disease

rivastigmine (Exelon)Has fewer interactions than AriceptMore difficult to dose and administer

DiscussionHow does Alzheimers disease affect patients families? Has the disease affected someone in your family?

DiscussionSeveral of the diseases presented in this chapter are degenerative and there is yet no known cure. How might this affect patients with a diagnosis of one of these conditions?