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Central Nervous System Drug TherapyDrug Therapy for Myasthenia GravisNeuromuscular disorder that fluctuates between muscle weakness and rapid fatigueCommon symptoms: ptosis, difficulty swallowing, weakness of muscles including respiratory (BULBAR SYMPTOMS)Reversible Cholinesterase InhibitorsPrototype: Pyridostigmine (Mestinon)MOA: prevents the breakdown of acetylcholineAdverse effects: excessive muscarinic stimulation (increased salivation, sweating, GI motility, urination, bradycardia, miosis), paralysis of respiratory muscles in toxic dosesCONTRAINDICATIONS: clients with obstruction of GI or urinary tractLIFETIME TREATMENTCAUTION: clients with peptic ulcer disease, asthma, coronary insufficiency, or hyperthyroidism Drug Interactions: muscarinic antagonists, nondepolarizing & depolarizing neuromuscular blockers (anesthesia) Dosage: 60-1500 mg/day Q 3-4 hoursStart with small doses increasing to optimal dosage…improvements of bulbar symptoms. Patient modification is accepted.Myasthenic CrisisInadequate medicationExtreme muscle weaknessTreat with cholinesterase inhibitorNEOSTIGMINE** is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor.Cholinergic CrisisOverdose of a cholinesterase inhibitorExtreme muscle weakness or frank paralysisTreatment includes respiratory support, withhold cholinesterase, & atropine administrationMyasthenic Crisis Vs Cholinergic CrisisMedication history Challenge dose of Edrophonium (tensilon)If the symptoms get better it is a myasthenic crisisIf the symptoms worsen it is a cholinergic crisis (NOT GOOD )Emergency equipment (atropine and respiratory support)Nursing InterventionsClient Education>Assess client for s/s of MG.>Teach client meds are life long>Assess for adverse effects of meds.>Teach importance of adhering to med schedule>Assess respirations & swallowing.>Teach to take meds 30-60 mins prior to meals>Administer meds exactly as scheduled.>Encourage to carry med card at all times.>Encourage to wear MedAlert braclet/necklaceDrug Therapy for Parkinson’s DiseaseNeurodegenerative disorderCharacterized by 4 involuntary movements:TremorRigidityBradykinesiaPostural instabilityDopamine and actecholine**Therapeutic GoalsNo CureImprove ability to carry out ADL’sDrug selection & dosages determined by the extent PD interferes with client’s lifeWorkBathingDressingEatingDrug TherapyDopaminergic agentsMost commonly used for PDPromote activation of dopamine receptorsAnticholinergic agentsPrevent activation of cholinergic receptorsLess effective than levodopa, better toleratedMost appropriate for younger clients with mild symptomsDopaminergic AgentsLevodopa (cross BBB and converts into dopamine)Dopamine agonistsCOMT inhibitorsDopamine ReleaserMAO-B InhibitorDopamine cannot be used as replacement therapy, it does not cross blood brain barrierDopamine ReplacementsPrototype: Levodopa/carbidopa (Sinemet, Sinemet CR) – reduction in symptoms will happen in a short period of time in pt’s with true Parkinson’s MOA: Levodopa is converted to dopamine in the CNS. Carbidopa (not therapeutic effect on its own- use with levodopa) prevents peripheral destruction of Levodopa.Adverse Effects: N/V* (administer in sm doses at the start of treatment et w/food) dyskinesias**(abnormal movement – often happens because of over medication) (decrease dosage of med, but the decrease may result in resumption of PD symptoms)postural hypotension* (monitor BP, instruct about hypotension – dizziness/lightheadedness)dysrhythmias**(monitor VS, ECG, notify PCP, use cautiously in clients w/cardiovascular disorders)psychosis**(administer antipsychotic med such as clozapine)darkened sweat & urine (harmless side effect)akinetic spells (immobilized for periods of time – on/off periods)Loss of effect (wearing off – at the end of the dose intervals – minimized by shortening dose interval or giving a drug that prolongs Levodopa’s half-life (comtan or mirapax or sinemet CR)Acute loss of effect can occur at anytime during treatment, can also be referred to as on/off phenomenon – can last from min to hrs – as a patients disease process worsens these will also worsen(*=early AE **=late AE (2-3 yrs of treatment)Food retards the absorption, not best teaching – may be done early on, but teach pt AE will subsideContraindications: history of melanoma, narrow-angle glaucoma(dopamine drugs increase pressure), vitamin B6, MAO inhibitors & antipsychotic drugsDosage: 10/100, 25/100, 25/250, 25/100mg CR, 50/200mg CR Nursing InterventionsAssess client’s s/s of PDMonitor for adverse effectsAssess for psychiatric behaviorAssess client’s skin & teach skin assessmentDivide protein intake into several times throughout the day – dopamine binds to proteinClient EducationAvoid driving or operating heavy machinery until drug is workingTeach about Vitamin B6 - contraindication (Pyridoxine)Darkened sweat and urine (harmless)Teach about orthostatic hypotensionInstruct client to NEVER abruptly discontinue medications and always take at the same timeInform clients that effects usually increase over a couple of monthsUsually works best within the 1st 2 years of treatment, it is not uncommon to revert after 5 yr – because of disease progressionAnticholinergic AgentsPrototype: trihexyphenidyl (Artane) – not as affect but better toleratedMOA: blocks muscarinic receptors in the striatumReduces tremor and some rigidityAdverse Effects: dry mouth, urinary retention, tachycardia, blurred vision, constipation, photophobia, confusion, & hallucinationsMuch better for young pt, not good for older pts because of CNS symptoms Contraindications: narrow-angle glaucoma & prostatic hypertrophy or urinary retentionDosage: 1-2mg 3 times/day Nursing InterventionsAssess client’s s/s of PD.Monitor urinary output.Assess for psychiatric behavior.Watch for signs of orthostatic hypotension.Client EducationEncourage the use of chewing gum or mouthwash for dry mouth.Avoid overheating or hot places.Eat high fiber and 8 8 oz servings of H20.Teach client to never discontinue meds T InhibitorsPrototype: entacapone (Comtan) – added to sinemet**MOA: inhibit breakdown of levodopa in the peripheryWith levodopa it causes blood levels to be smoother and more sustained Adverse Effects: dyskinesias, orthostatic hypotension, nausea, hallucinations, & sleep disturbancesContraindications: don’t use in combination with methyldopa, dobutamine, or isoproterenol,Dosage: 200 mg to be taken with each dose of Sinemet, up to 1600mg per day**DO NOT TAKE ALONEClient EducationInstruct client to take with levodopa/carbidopa (sinemet).Avoid driving or activities that require alertness until response to drug is rm client that drug may change urine to a brownish orange color.Caution client to change positions slowly.Dopamine AgonistsPrototype: pramipexole (Mirapex) – used with sinemet (for wearing off)MOA: stimulates dopamine receptors in the striatum of the brainAdverse Effects: SLEEP ATTACKS (suddenly w/out warning) when used alone (call doc immediately) Nausea (take with food), constipation Dizziness , weakness daytime somnolence, insomnia hallucinations (administer antipsychotic med)Elderly do not tolerate well because of AE’s When used as monotherapy: orthostatic hypotension & dyskinesiasWhen used with Levodopa it has beneficial and harmful interactions. Use with Levodopa can decrease motor control fluctuations and allow for lower dosage of Levodopa. Concurrent use can also increase the risk of orthostatic hypotension and dyskinesiasContraindications: Cimetidine – TagametDosage: 0.125mg – 1.5mg TID gradually increased over 2 monthsCan be taken alone – often used for restless leg syndromeNursing InterventionsClient Education>Assess for S/S of PD before & throughout therapy.>Take with meals>Assess for hallucinations & confusion.>Avoid driving/other activities that require alertness>Assess for drowsiness & sleep attacks. until drug response is known>Change positions slowlyMAO-B InhibitorPrototype: selegeline (Eldepryl)MOA: inhibits breakdown of dopamineMay delay progression of PD (use 1st in pt that is newly diagnosed with PD)Adverse Effects: insomnia, dry mouthContraindications: can increase the effects of levodopa, don’t use in combination with meperidine or fluoxetineDosage: 5mg with breakfast & lunch Nursing InterventionsAssess for S/S of PD prior to and during therapy.Assess BP periodically during therapy.Administer with breakfast and lunch only.Client EducationTake with breakfast & lunch. Taking it late in the day can cause insomnia.Do not double dose. Increased doses can cause a hypertensive crisis.**Teach S/S of hypertensive crisis.Increase fluids or chew gum to avoid dry mouth.Drug Therapy for Alzheimer’s DiseaseAlzheimer’s DiseaseIrreversible disease characterized by progressive memory loss, impaired thinking, neuropsychiatric symptoms, & inability to perform ADL’sCholinesterase InhibitorsPrototype: donepezil (Aricept)MOA: prevent the breakdown of ACh by acetycholinesterase & thereby increase the availability of ACh at cholinergic synapses.Adverse Effects: GI effects, dizziness, H/A, bronchconstriction, caution in clients with asthma & COPDDrug Interactions: (blocks) antihistamines, tricyclic antidepressants, conventional antipsychoticsDosage: QHSThey slow down the progression (by a few month), they do not cure.MemantinePrototype: memantine (Namenda) newest on the marketMOA: modulates the effects of glutamate at NMDA (n-methal d-aspartate) receptors: believed to play critical role in learning and memoryAdverse effects: dizziness, H/A, confusion, constipation (very minimal) – much more tolerated than Aricept Drug Interactions: NMDA antagonist, sodium bicarbonate (Be CAREFUL w/ Renal Patients)Dosage: 5mg/day – 20mg/day (twice/day) – tritated up over a months time Alternative & Questionable TherapiesVitamin ESelegilineEstrogen – delays dementiaGinkgo Biloba – improves symptom, but has anticoagulant effectNSAIDS – long term useNursing ResponsibilitiesEnsure client has no history of asthma or COPD.Monitor for GI symptoms.Obtain current medication list.Client & Family EducationFollow titration schedule as directed.Notify physician if side effects are intolerable.Do not abruptly stop treatment.Notify physician if any changes or addition of medication is made.Drug Therapy for Multiple SclerosisMultiple SclerosisA chronic, inflammatory, autoimmune disorder that damages the myelin sheath of neurons in the CNS, causing a wide variety of sensory and motor deficits.Disease-Modifying Drugs I: Immunomodulators – Interferon BetaPrototype: Interferon beta-1a (Avonex- IM Qweek), (Rebif-subq 3xweek), Interferon beta-1b (Betaseron subq every other day)MOA: suppresses autoimmune destruction of myelinAdverse Effects: Flu-like symptoms(go away over time – take Tylenol), hepatotoxicity (usually rare but serious – test baseline, then Q3months – if elevated – decrease/stop dose), myelosuppression (supress bone marrow – monitor CBC – baseline 3,6 mos and 1year), injection-site reactions, depressionDrug Interactions: other drugs that can cause bone marrow suppression or liver injuryRecommended for relapsing-remitting and secondary-progressive still experiencing acute exacerbationGlatiramer AcetatePrototype: Copaxone (for relapsing-remitting – subQ daily) better tolerated than all other betaMOA: protects myelin by inhibiting the immune response to myelin basic proteinAdverse Effects: injection-site reactions &, self-limited post injection reaction(10% of pt get – last for about 15 min – flushing, palpitations, chest pains, anxiety) Nursing & Client Education>Obtain and monitor LFT’s and CBC>Minimize side effects-analgesics/antipyretics>Identify high-risk clients-oral Benadryl, topical hydrocortisone>Instruct on IM and SQ injections-apply ice to injection siteDisease-Modifying Drugs II: ImmunosuppressantsPrototype: Mitoxantrone (Novantrone) – for MS pts with lots of neuromuscular complications (worsening relapsing-remitting) severe casesMOA: suppress production of immune system cells & decreases autoimmune destruction of myelinAdverse Effects: myelosuppression, cardiotoxicity, fetal harm, hair loss, GI distress, menstrual irregularities, & blue-green tint to urine, skin, & scleraDosage: IV every 3 months Nursing InterventionsMonitor CBC’s at baseline, before each dose, & 10-14 days after each dose.Monitor LFT’s at baseline and before each dose.Perform a pregnancy test before each dose.Perform echocardiogram before each dose & whenever heart failure develops.Client EducationAvoid contact with people who have infections & report s/s of infections immediately.Avoid becoming pregnant.Discuss all other potential side effect with client & family.Drug Therapy for Muscle Spasm and SpasticityMuscle spasm – involuntary contraction of muscle or muscle groupCausesEpilepsyHypocalcemia Acute & chronic pain syndromesTraumaCentrally Acting Muscle RelaxantsMechanism of ActionThrough enhancing presynaptic inhibition of motor neurons in the CNSTherapeutic UseRelieve localized spasm resulting from muscle injuryDecrease local pain & tendernessIncrease range of motionTherapeutic use is almost always associated with sedationDrugs for Muscle Spasms>Diazepam (Valium)>Methocarbamol (Robaxin)>Carisoprodol (Soma)>Orphenadrine (Norflex)>Chlorzoxazone (Paraflex)>Tizanidine (Zanaflex)>Cyclobenzaprine (Flexeril)>Metaxalone (Skelaxin)Adverse Effects>CNS depression >Hepatic toxicity (Zanaflex, Skelaxin &Paraflex)>Physical Dependence>Dry mouth, blurred vision, photophobia, urinary retention, constipation (Flexeril & Norflex)>Interesting……brown, black, or green urine (Zanaflex) Also, ↓bp, hallucinations, & psychotic symptomsDrugs for SpasticitySpasticity - Movement disorder of CNS origin characterized by heightened muscle tone, spasm, and loss of dexterityCausesMultiple sclerosisCerebral palsyBaclofen (Lioresal)Acts in the CNSDecreases spasticityAllows increased performance Helpful only for spinal cord injury, MS, & CPWill also seen it used in CVA patientsUsually titrated up over timeAdverse Effects of Baclofen CNS effectsGI symptoms (nausea, constipation)(Advise client to increase intake of high fiber foods)Urinary retention (Monitor client I&O’s)No antidote for overdose** (can cause coma, respiratory distress/failure)Withdrawal – does not cause dependence, but if abruptly stopped it can cause high fever, spasticity, muscle breakdown, hallucinations, seizures, etc.Avoid alcoholDiazepam (Valium)Only benzodiazepine labeled for treating spasticityActs in CNSMimicks the actions of GABA at the receptors in spinal cord and brainDoes not affect skeletal muscle directlyAdverse Effect of DiazepamSedationDantrolene (Dantrium)Acts directly on skeletal muscleSuppresses the release of calcium from the sarcoplasmic reticulumThe only peripherally acting muscle relaxantUsesSpasticity associated with MS, CP, & spinal cord injuryMalignant hyperthermia**Adverse Effects Hepatic toxicityMuscle weaknessDrowsinessAnorexia, N/V, DiarrheaAcne-like rashNursing InterventionsAssess for s/s of muscle spasms and spasticity.Assess for adverse med effects.Monitor liver enzymes.Not the best med for patients with active life due to the muscle weakness it causesClient EducationCaution client to avoid CNS depressants.Teach client to take med as prescribed.Warn client against abruptly stopping rm of CNS effects & advise to avoid driving & other hazardous activities if impairment occurs.Drug Therapy for HeadachesOverview of Migraine TherapyAbortive TherapyNon-specific analgesicsMigraine-specificPreventative TherapyBeta blockersTricyclic antidepressantsAntiepilepticsAbortive TherapyGoalEliminate h/a painSuppress n/v – metoclopramide (Reglan)Drug selection (only take 1-2/wk)Depends on intensity of attackMild to moderate – aspirin-like drugModerate to severe – migraine-specific drugFailed therapy - opioids AnalgesicsAspirin + Reglan can be quite effective with fewer side effectsDo not use acetaminophen aloneExcedrin Migraine = acetaminophen + aspirin + caffeineMidrin = acetaminophen + isometheptene + dichloralphenazoneOpioids - meperidine (demerol) - buthorphanol nasal spray (Stadol NS)Ergot AlkaloidsPrototype: Ergotamine (Cafergot) used for migraines and cluster headaches: should not be used on a daily basis, can cause dependency MOA: promotes vasoconstriction & reduces the amplitude of pulsationsAdverse Effects: N/V, leg weakness, myalgia, parasthesias to fingers & toes, angina-like pain, tachycardia & bradycardiaOverdose: Ergotism- ischemia secondary to constriction of peripheral arteries: causing cold extremities, paleness, numbness, gangrene Contraindications: Triptans, clients with hepatic or renal impairment, sepsis, CAD, PVD, & pregnancyDosage: SL, oral, intranasal, & rectalWithdrawl symptoms: headache, N/V, ….continuous cycleNursing ResponsibilitiesAssess frequency, location, duration, & characteristics of h/a. Assess pain before & after med administration.Monitor BP & peripheral pulses periodically during therapy.Assess for s/s of ergotism.Assess for n/v & administer anti-nausea meds if ordered.Client EducationInstruct client to take at first sign of an impending h/a.Do not exceed the maximum dose.Encourage to rest in a quiet, dark room after taking ergotamine.Review s/s of toxicity & instruct to report these immediately.Caution client against smoking & exposure to cold.Caution client to avoid driving until response to drug is known.Serotonin1B/1D-Receptor Agonists (Triptans)Prototype: Sumatriptan (Imitrex)MOA: actions of vasoconstriction & suppression of inflammationAdverse Effects: vertigo, tingling sensations, chest symptoms, coronary vasospasms (50% complain of Chest pressure and heavy arms: this is not related to CAD, this med causes pulmonary vasoconstriction)Dosage: PO, SubQ, nasal sprayContraindications: Ergot alkaloids, other triptans, MAOI’s, hx of CAD, MI, or HTN, smoking, obesity, DMDosage: SQ, NS, & PODo not give to patients with parathesias with migraine because of the increased vasoconstrictionNursing ResponsibilitiesReview client’s health history.Assess pain location, intensity, duration, and associated symptoms during migraine attack prior to & after med administration.Monitor for s/s of coronary vasospasm.Client EducationInform client that sumatriptan is only to be used for relief of migraine attack & not to prevent attacks.Instruct client to take sumatriptan as soon as symptoms of migraine appear.Advise client to lie down in a quiet, dark room after taking medication.Caution client to avoid during pregnancy or if planning to become pregnant.Advise client to notify physician if pain or tightness in chest occurs during use.Advise client to avoid driving until response to medication is known.Preventative Therapy (two or more attacks a month and do not respond adequately to abortive therapy)Beta Blockers – preferred drug propanolol (Inderal)Tricyclic antidepressants amitryptyline (Elavil)benefits equal to propanolol anticholinergic effects (dryness) Antiepileptics Drugsdivalproex (Depakote) only extended release approvedS/E – nausea, wt. gain, tremor, hair losstopiramate (Topamax) approved in 2004titrate slowly (benefits takes several weeks)S/E – parasthesias, fatigue, weight loss, cognitive dysfunctionEstrogens – used to prevent menstrual migraines (onset is 2 days before cycle begins)topical estrogensbirth control pillsfrovatriptan (Frova)Other Drugs for ProphylaxisCalcium Channel Blockers (varapamil)Angiotensin II Receptor Blocker (ARB)SupplementsRibloflavin Coenzyme Q-10FeverfewButterbur ................
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