Anticonvulsants and the Central Nervous System

• Cognition is the process of thought, embodying perception, attention, visuospatial cognition, language, learning, memory, and executive function with higher-order thinking skills.
• Central and peripheral nervous systems are the two major regions of the nervous system
• The central nervous system (CNS) is the brain and spinal cord.
• The peripheral nervous system (PNS) is everything else.
• Common CNS disorders include anxiety, depression, schizophrenia, ADHD, seizures, and Parkinson’s.

Anticonvulsants

• They stabilize cell membranes and suppress abnormal electric impulses in the cerebral cortex.
• Act as CNS depressants
• Used for the treatment and prevention of seizures, but do not cure
• Used to treat neuropathic pain
• An example neuropathic pain medication is Gabapentin
• Common Anticonvulsant medications include Phenytoin (Dilantin), Levetiracetam (Keppra), Gabapentin (Neurontin), and Valproic acid (valproate, divalproex)
• Pharmacological effects include increasing the threshold of activity in the motor cortex
• Pharmacological effects limit the spread of a seizure discharge and reduce the speed of nerve impulse conduction
• Adverse effects include behavioral and mood changes, fatigue, dizziness, somnolence, ataxia, GI upset/discomfort, and blurred vision.
• Dosage should be tapered; medications should not be stopped abruptly
• Monitor for worsening depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior
• Must take medications as directed
• Therapeutic effect can take weeks
• Avoid alcohol and other CNS depressants
• Could cause increased drowsiness and dizziness
• Monitor for suicidality

Phenytoin

• Improves seizure evidence, interferes with sodium channels in the brain, and decreases high-frequency neuronal discharges
• Used for tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures
• Used for prevention and treatment of seizures occurring during or following neurosurgery
• Adverse effects include nystagmus, ataxia, slurred speech, decreased coordination, somnolence, and mental confusion.
• Serious/fatal effects include dermatologic reactions, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), hematopoietic complications, and acute hepatoxicity
• Administer slowly via IV with cardiac monitoring and an in-line filter
• Use caution with clients who have renal or hepatic impairment, and elderly clients may require dosage adjustment
• It is contraindicated in pregnancy
• Requires IV administration and cardiac/serum drug monitoring
• Taper dose and discontinue at the first sign of rash due to potential drug interactions
• Can take weeks for therapeutic effect
• Abrupt discontinuation can cause status epilepticus
• Avoid alcohol and other CNS depressants
• Diabetic clients should monitor their blood glucose carefully
• Contraindications include pregnancy, heart block, and several drug interactions

Levetiracetam

• Exact mechanism of action is unknown
• May interfere with sodium, calcium, potassium, or GABA transmission
• Used for partial-onset seizures in clients with epilepsy
• Adverse effects include behavioral/mood changes, somnolence, fatigue, irritability, and coordination difficulties
• Serious/fatal effects include anaphylaxis or angioedema, dermatologic reactions, TEN, SJS, and hematopoietic complications
• Plasma levels can gradually decrease during pregnancy
• Monitor plasma levels closely during pregnancy
• Safety and effectiveness in pediatric clients 12 years and older have been established
• Can be used in clients as young as 1 month old via immediate release and solution
• Should not be stopped abruptly or withdrawal seizures may occur
• Use with caution in clients with renal impairment
• Monitor for safety, mobility, and falls risk
• Contraindications include clients who are suicidal or have altered hematology
• May cause increased dizziness and somnolence
• Monitor carefully for suicidality during medication therapy

Gabapentin

• Exact mechanism of action is unknown, but structurally similar to GABA
• Does not act on GAPA receptors or influence GABA
• Used for partial seizures and neuropathic pain
• Adverse effects include risk of suicidal thoughts or behavior, depression, mood changes, dizziness, CNS depression, DRESS, and multiorgan hypersensitivity
• Falls precautions should be considered for elderly patients
• Monitor elderly clients closely for suicidal ideation and DRESS syndrome
• The first dose should be taken at bedtime to decrease dizziness and drowsiness
• Exercise caution in use with children and elderly
• Do not take within 2 hours of antacid medications
• Taper dose and do not stop abruptly
• Monitor for worsening depression, along with suicidal thoughts or behavior/mood changes
• Pregnancy is a contradiction
• Take medications as directed, and do not take within 2 hours of antacids
• Risk of dizziness and drowsiness
• Monitor for suicidality

Antiparkinson Medications

• Increase levels of dopamine and/or antagonizing the effects of acetylcholine
• Slows progression of the disease, but does not cure it
• Common medications are Carbidopa/levodopa (Sinemet), Selegiline (Eldepryl, Emsam, Selgin), and Amantadine (Gocovri)
• Increases or replaces the levels of dopamine in the brain, thus improving the symptoms of Parkinson’s disease.
• Adverse effects are GI upset, insomnia, dizziness, somnolence (drowsiness), hallucinations, delirium, and psychosis
• Monitor for worsening depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
• Patients should be instructed to plan their mealtimes around medication times to improve the ability to use utensils
• Avoid diets high in protein due to decreased medication absorption
• Take medications as directed.
• Avoid taking OTC cold medicine
• Avoid alcohol and other CNS depressants
• May cause increased drowsiness and dizziness or insomnia
• Monitor for suicidality
• Avoid high-protein diets
• Can cause hallucinations

Carbidopa/Levodopa

• Levodopa is the metabolic precursor of dopamine that crosses the blood-brain barrier and converts to dopamine in the brain
• Carbidopa helps stop the breakdown of levodopa and reduces levodopa-induced nausea and vomiting
• Used for Parkinson’s disease, progressive supranuclear palsy (PSP), and restless leg syndrome
• Adverse effects are depression, suicidal ideation, hallucinations, fatigue, neuroleptic malignant syndrome (NMS) symptoms, dyskinesia (involuntary body movements), constipation, discolored body fluids, hypermobility with long-term use, and a higher risk for melanoma
• Observe carefully for depression and suicidal ideation
• Avoid high-protein diets
• Monitor hepatic, renal, and hematopoietic functions
• If gastric irritation occurs, eat food shortly after
• Use in clients >18 years
• Can take several weeks to see therapeutic effects
• Is contraindicated for use with monomine oxidase inhibitors (MAOIs)
• Use caution while driving or operating heavy machinery
• Monitor dosage reduction or discontinuation -NMS and plan meal times around medication times
• Take medications at regular intervals as directed, can cause increased drowsiness, dizziness, and orthostatic changes
• Instruct clients to assess skin to monitor for new lesions
• Parkinson’s disease is linked to increased alpha-synuclein protein, toxic to the cells of the substantia nigra nucleus in the midbrain

Selegiline

• Inhibits MAO-B, blocking the breakdown of dopamine
• Used as an adjunct in the management of Parkinsonian clients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy
• Side effects are dose-dependent, with larger doses posing a hypertensive crisis risk in conjunction with the consumption of food or beverages with tyramine
• Avoid foods with tyramine, such as aged cheeses, cured meats, smoked fish, and kimchi
• Large doses may inhibit MAO-A, promoting metabolism of tyramine in the GI tract, which can cause a hypertensive crisis
• Avoid foods high in tyramine, which may increase drowsiness, dizziness, hallucinations, sexual urges, and abnormal behaviors such as gambling
• Contraindicated for those with tyramine in their system

Amantadine

• Mechanism of action is unknown
• it is an antiviral drug that acts on dopamine receptors
• Used for Parkinson’s disease, medication-induced extrapyramidal symptoms, and influenza A
• Adverse effects include congestive heart failure, suicidal ideation, peripheral edema, intense gambling urges, sexual urges, intense urges to spend money, inability to control these urges, increased risk of melanoma, anticholinergic side effects, and hypersensitivity
• Contraindications include known hypersensitivity
• Monitor renal function, monitor mental state, and assess blood pressure
• Use cautiously with renal impairment
• This drug may cause suicidal ideation - do not stop abruptly
• NMS has been associated with dose reduction or withdrawal
• May cause drowsiness, dizziness, and orthostatic blood pressure changes
• Avoid using it with OTC cold medications or alcohol

CNS Depressants - Barbiturates

• Produces sedation and drowsiness by altering cerebellar function and depressing actions of the brain and sensory cortex
• Used primarily as an anticonvulsant, sedative, or pre-anesthetic agent
• Do not use for children less than 1 month of age
• Can harm fetus during pregnancy
• Avoid use in geriatric clients
• Adverse effects include CNS depression, suicidal thoughts or behaviors, GI disturbances, rashes, potentially fatal blood disorders, and habit formation
• Contraindicated for Clients with severe renal and hepatic disorders, severe respiratory depression, dyspnea or airway obstruction, and porphyria
• Do not abruptly stop taking medication to avoid seizure activity
• Do not take with alcohol or other CNS depressants
• Female clients using oral contraceptives should use non-hormonal contraceptives
• Symptoms of a toxic oral exposure to barbiturates may not occur until several hours following ingestion

Phenobarbital

• Alters cerebellar function and depresses actions of the brain and sensory cortex
• Usage - sedation, seizures
• Adverse effects - CNS depression, overdose & death, suicidal thoughts/behavior, respiratory depression, GI upset
• Contraindications - severe renal/hepatic disorders, severe respiratory depression, dyspnea/airway obstruction, porphyria, children under 1 month, pregnancy, geriatric clients
• Give orally, IM or IV and taper dose, do not stop abruptly
• Nursing considerations - take as directed, do not take with other CNS depressants/alcohol
• Client health teaching - take only as prescribed, do not abruptly stop, do not take with alcohol or other CNS medications

CNS Depressants - Benzodiazepines

• Binds to specific GABA receptors to potentiate the effects of GABA
• Uses include sedation, anti-anxiety and anticonvulsant
• May cause hallucinations, tremors, agitation, and may harm a fetus/ elderly
• Initial adult dosage should not exceed 2mg
• Infirm clients may be more susceptible to the sedative effects, including respiratory depression
• Adverse effects - Profound sedation, Respiratory depression, Coma, Death
• Contraindications - severe renal and hepatic disorders, severe respiratory depression, dyspnea or airway obstruction, and porphyria
• Take medication as prescribed
• Use caution while driving or operating machinery
• falls risk is a concern
• Do not consume alcohol for 24-48 hours after receiving Lorazepam

Lorazepam

• Binds to specific GABA receptors to potentiate the effects of GABA
• Reduces anxiety, reduce seizure activity, preanesthetic
• Adverse effects - oversedation & drowsiness, Respiratory depression, Coma and Death, Falls risk
• Severe hepatic impairment, respiratory depression, acute narrow angle glaucoma, pregnancy and lactation, and children under 12 are contradictions for Lorazepam usage
• Give SL, PO, IV, use cautiously in elderly, or use smaller doses for liver dysfunction patients Monitor for falls risk
• Take medication as prescribed, and do not abruptly stop if in long-term therapy.
• Avoid alcohol, avoid operating machinery or driving the client must adhere to this
• Client health teaching - Client must take only as prescribed, and do not abruptly stop Client must not take with alcohol, may be habit forming, falls risk

Antidepressants

• 4 classes of anti-depressant:
  • Tricyclic antidepressants (TCAs)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Monoamine oxidase inhibitors (MAOIs)

Antidepressants (TCAs)

• they tend to have sedative and anticholinergic effects, they act by inhibiting presynaptic a reuptake of NE and 5-HT into nerves
• the choice of TCA depends on individual response and tolerance to the drug used to treat with depression and to treat chronic neuropathic pain and insomnia
• Often administered at bedtime due to sedating effects and are contraindicated with MAOI
• geriatric clients are particularly sensitive to the anticholinergic side effects
• Elderly patients at higher risk for falls, should not be used in children
• use in those pregnant or lactating can be harmful
• Adverse/side effects - constipation, urinary retention, cardiac disturbances, hypotension, drowsiness, and sexual dysfunction
• myocardial infarction, concurrent use of MAOIs, pregnancy, lactation
• Take the prescribed medication
• Risk of suicidality and Risk of falls

Antidepressants (SSRIs)

• SSRIs inhibit the reuptake of serotonin
• Primarily used to treat depression.
• Used to treat disorders such as obsessive-compulsive disorder, bulimia, migraines, and anxiety disorders in addition to PTSD and PMS
• The antidepressant effect of fluoxetine develops slowly for up to 12 weeks
• Use caution in clients who are taking other CNS medications or who have liver dysfunction
• Contraindicated with MAOIs
• Adverse/side effects for all clients taking SSRIs is to monitor for increased suicide ideation
• Patients should avoid grapefruit juice

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• Inhibit the reuptake of serotonin and norepinephrine, with weak inhibition of dopamine reuptake
• Treatment of major depressive disorder
• MAOIs are contraindicated with SNRIs or within 14 days of stopping MAOI
• Dose adjustment may be needed for clients with renal/liver disease
• Elderly clients are at high risk for developing hyponatremia than normal adults
• Use with caution with other serotonin medications
• Adverse reactions include the usual including risk of suicide, worsening depression (mania), and the potential for increased blood pressure Also associated with serotonin syndrome, potentially lethal.
• More common adverse reactions are insomnia, anxiety, appetite loss/weight loss, elevated cholesterol and mani

Antidepressants (MAOIs)

• MAOIs have proven to be presumed with monoamine and are able to potentiate neurotransmitters in the central nervous system resulting from inhibition of the enzyme monoamine oxidase which deactivates norepinephrine, dopamine, epinephrine and serotonin
• By inhibiting MAO, the levels of these transmitters rise which then can create antidepressants
• Treatment of Major Depressive Disorder, treatment is useful for those not responding adequately to the normal antidepressants
• There are concerns such as Serious interactions and precautions with the many foods and beverages that contain tyramine
• Clients on the medication need to also be aware or all the medications that may show interactions such as tyramine and CNS depressants
• Client health teaching for antidepressant usage:
  • use medication as direction
  • dose is best tapered prior to discontinuation
  • Possible infections with increases in drowsiness or dizziness
  • Avoid consuming alcohol on the medication
  • adverse effect of potential suicidal ideation Adverse Effects that are not common with any other antidepressants.
• orthostatic hypotension
• hepatoxicity
• hypoglycemia in diabetic clients
• restlessnes
• Headaches
• Dizziness