Drugs Affecting the Neurological System Part 2

Definition of Epilepsy

• Group of disorders characterized by excessive excitability of neurons in the central nervous system

• Can produce a variety of symptoms that range from brief periods of unconsciousness to violent convulsions

• May also cause problems with learning, memory, and mood

Seizure: Generation

• Initiated by synchronous, high-frequency discharge from a group of hyperexcitable neurons called a focus

• Focus may result from the following:

  • Congenital defects

  • Hypoxia at birth

  • Head trauma

  • Brain infection

  • Stroke

  • Cancer

  • Genetic disorders

Partial (focal) seizures

• Simple partial

• Complex partial

• Secondarily generalized

Generalized seizures

• Tonic-clonic

• Absence (petit mal)

• Atonic

• Myoclonic

• Status epilepticus

• Febrile

Status epilepticus

• Life-threatening emergency

  • Hypotension, hypoxia and cardiac dysrhythmias

  • High risk of permanent brain damage and death – unless prompt appropriate treatment is instituted

Status epilepticus characteristics include

• Generalized tonic–clonic convulsions lasting for several minutes

• Generalized tonic–clonic convulsions occurring at close intervals during which consciousness is not regained

• Hypotension, hypoxia, and cardiac dysrhythmias

• High risk of permanent brain damage and death

  • Unless prompt, appropriate treatment is instituted

Status epilepticus causes

• Abruptly stopping meds in diagnosed seizure disorders

• Brain trauma or tumors

• Systemic or CNS infections

• Alcohol withdrawal, drug overdose

Antiseizure Medication Characteristics

• Usually control seizure activity

• Do not cure underlying disorder

Antiseizure Medication Characteristics Difficulties

• Trials of different drugs

• Monotherapy versus combination therapy

• Titrating dosage

• Lack of seizure control during drug selection and titration

• Social stigma

• Adverse medication effects

  • Often leading to poor compliance

• Undesirable drug interactions

Drugs to Treat Seizures (Anti-epileptics)

• Barbiturates – Phenobarbital

  • Pentobarbital (Nembutal), Primidone (Mysoline)

• Benzodiazepines (covered in chapter 54)

• GABA structural analogs – Gabapentin (Neurontin), Pregabalin (Lyrica)

• Hydantoins – Phenytoin (Dilantin), Fosphenytoin (Cerebyx)

• Iminostilbenes – Carbamazepine (Tegretol)

Barbiturates (Phenobarbital) Pharmacodynamics/Action

• Inhibits transmission in the nervous system and raises the seizure threshold.

• Depresses the sensory cortex, decreases motor activity, and alters cerebellar function.

Barbiturates (Phenobarbital) Uses/Indications

• Anticonvulsant activity, sedation.

• Parenteral form used to control acute seizures

Barbiturates (Phenobarbital) Contraindications

• Hypersensitivity

• comatose patients or those with pre-existing CNS depression;

• Severe respiratory disease with dyspnea or obstruction; uncontrolled severe pain.

• BBW - suicide

Barbiturates (Phenobarbital) adverse effects

CNS depression, cognitive impairment with sedation (hangover) Somnolence, agitation, confusion, vertigo, nightmares, delirium, depression, respiratory depression; angioedema.

Barbiturates (Phenobarbital) patient teaching

• Understand that this drug is administered long term for the treatment of seizure activity.

• Take the medication as prescribed, and do not stop the medication abruptly.

• Have regular tests to determine serum levels of the drug.

• Change positions slowly. This drug may cause drowsiness or syncope.

• Do not drive or operate machinery with central nervous system depression.

• If you are of childbearing age, use two forms of contraception.

• Notify your prescriber about the development of rashes or skin eruptions.

• Wear a medical alert bracelet or necklace stating that you have a seizure disorder and naming the medications you take

Barbiturates (Phenobarbital) Nursing considerations

• Nursing considerations: Monitor respiratory status, pulse, and BP and s/s of angioedema (swelling of the lips, face, throat, dyspnea) frequently in patient receiving IV.

• Education: Advise patient to notify HCP if s/s of angioedema, fever, sore throat, mouth sores, unusual bleeding or bruising, nosebleeds, or petechiae occur.

• Interactions: Additive CNS depression with other CNS depressants, including alcohol, antihistamines, opioid analgesics, and other sedative/hypnotics.

Benzodiazepines Pharmacodynamics/Action

• Exact mechanism unknown

• Depresses the CNS, probably by potentiating GABA, an inhibitory neurotransmitter

Benzodiazepines Uses/Indications

• Used as antidepressants, antiepileptics, or skeletal muscle relaxants

• Used for treatment of severe recurrent convulsive seizures and status epilepticus

Benzodiazepines Contraindications

• Known hypersensitivity

• Acute narrow-angle glaucoma, shock, coma, acute alcohol intoxication, and pregnancy

Benzodiazepines Adverse Effects

• Depression, disorientation, restlessness, confusion

• Paradoxical reaction

• Black Box- potential respiratory depression

Neurontin (Gabapentin) Pharmacodynamics/Action

• Structurally related to GABA

• Ability to inhibit postsynaptic responses and block post-tetanic potentiation

Neurontin (Gabapentin) Uses/Indications

• Used in treatment of partial seizures

• Used for neuropathic pain

Neurontin (Gabapentin) Contraindications

• Known hypersensitivity

• Impaired renal function

Neurontin (Gabapentin) Adverse Effects

• CNS depressions, dizziness, somnolence, insomnia, ataxia

• Pruritis, dry mouth, nausea, vomiting

• Suicidal ideation

• Patient teaching Box 53.6

  • Take the medication as prescribed and do not stop taking it abruptly.

  • Take the medication with food to decrease gastrointestinal discomfort.

  • Do not cut, crush, or chew extended-release capsules. If swallowing is difficult, sprinkle the contents of the capsule over soft food.

  • Notify your prescriber if seizure activity occurs.

  • You may experience nausea, vomiting, insomnia, fatigue, and confusion.

  • Do not drive or operate machinery with central nervous system depression.

  • Report severe nausea and vomiting, changes in stool or urine color, diarrhea, or changes in neurologic function to the prescriber.

Phenytoin (Dilantin) Pharmacodynamics/Action

• Stabilizes the neuronal membrane by delaying the influx of sodium ions into the neurons and preventing the excitability caused by excessive stimulation

• Slows the propagation and spread of abnormal discharges.

• Dilantin suppresses activity of seizure-generating neurons while leaving healthy neurons unaffected.

Phenytoin (Dilantin) Uses/Indication

• Control tonic–clonic seizures, psychomotor seizures, and nonepileptic seizures

• Prophylactic therapy of all types of seizures except absence seizures.

• Therapeutic Range: 5-20 mcg/dL

Phenytoin (Dilantin) Patient Teaching

• Take the drug as prescribed and do not stop taking it abruptly.

• Take the medication with food to prevent gastric upset.

• Have serum drug levels checked as ordered by your prescriber.

• Maintain good oral hygiene (regular brushing and flossing) to prevent gum disease.

• Have regular dental checkups.

• Use contraception if you are of childbearing age and are sexually active.

• Wear a medical alert bracelet or necklace stating that you have a seizure disorder and naming the medications you take.

Phenytoin (Dilantin) Drug Interactions

• Drugs That Increase the Effects of Phenytoin

  • Alcohol, amiodarone, chloramphenicol, omeprazole, and ticlopidine

  • Increase phenytoin levels

• Drugs That Decrease the Effects of Phenytoin

  • Enteral feedings

  • Decrease phenytoin absorption

• *Complex interactions and effects may occur when phenytoin and valproate are taken together. Phenytoin toxicity may result with apparently normal serum phenytoin levels.

Phenytoin (Dilantin) Contraindication

• Known hypersensitivity

• Seizures related to hypoglycemia, bradvcardia, heart block

Phenytoin (Dilantin) Adverse Effects

• lethargy, headache, drowsiness, and dizziness, which may occur even at therapeutic doses. High doses can cause nystagmus, confusion, ataxia, coma, and seizures.

• Bradycardia, V fib., hypotension, phlebitis, gingival hyperplasia, weight loss, and liver necrosis.

• Agranulocytosis, leukopenia, thrombocytopenia, and aplastic anemia, osteoporosis

• Can be a very toxic drug and patients must be monitored carefully during therapy.

• Abrupt discontinuation of phenytoin can induce status epilepticus.

Phenytoin (Dilantin) Nursing Responsibilities

• Urine may turn a harmless pinkish-red or reddish-brown color

• Take the same time every day with food or milk to prevent gastric upset yet needs to be low protein

• do not discontinue medication abruptly or without consulting physician

• Carry Medic-Alert identification stating medication use

• Use a soft-bristled toothbrush to prevent gum irritation and bleeding. Gingival hyperplasia (overgrowth of gums) is a side effect of this medication.

• Assess for seizure activity including type, location, duration, and character; provide seizure precautions

• Assess for mental status, mood, sensorium, affect, and memory (short and long term)

• Assess for respiratory depression, rate, depth, and character or respirations

• Assess for blood dyscrasias, fever, sore throat, bruising, rash, and jaundice

  • Sore throat, bruising, or nosebleeds should be reported to the HCP because this may indicate a blood dyscrasia

• Evaluate client for therapeutic responses such as decreases in severity of seizures and decreased ventricular dysrhythmias

• Serum glucose must be monitored more closely because Dilantin may inhibit insulin release, thus causing an increase in glucose level.

Iminostilbenes- (Carbamezapine) Pharmacodynamics/Action

• Not understood

• May be related to inhibition of post-synaptic responses

• Affect sodium channels within neurons

Iminostilbenes- (Carbamezapine) Uses/ Indications

• Partial seizures with complex symptoms

• Temporal lobe epilepsy

Iminostilbenes- (Carbamezapine) Contraindications

Hypersensitivity to carbamezapine or tricyclic antidepressant

Iminostilbenes- (Carbamezapine) Adverse effects

• Black Box warning- aplastic anemia and agranulocytosis

• Heart block, Steven-Johnson Syndrome

Other Antiepileptic Drugs (AEDs) - Table 53.1

• Carbonic Anhydrase Inhibitor – Acetazolamide (Diamox)

• Succimide – Ethosuximide (Zarontin)

• Histone deacetylase inhibitor – Valproate (Depakote)

• Mineral Electrolytes – Magnesium sulfate

• Phenyltriazine derivatives – Lamotrigene (Lamictal)

• Pyrrolidine derivatives - Levetiracetam (Keppra)

• Sulfamate-substituted monosaccharies – Topiramate (Topamax)

Valproic Acid (Depakote) Pharmacodynamics/Action

Increases concentrations of the inhibitory neurotransmitter GABA in the brain

Valproic Acid (Depakote) Uses/Indications

Seizure Disorders, Bipolar Disorder, Migraines

Valproic Acid (Depakote) Contraindications

Increase risk of bleeding with warfarin, blood levels and toxicity may be increased by aspirin, carbamazepine, erythromycin

Valproic Acid (Depakote) adverse effects

minimal sedation and cognitive impairment. GI effects are most common. Hepatotoxicity and pancreatitis are rare but serious

Valproic Acid (Depakote) Nursing considerations

• Seizures: Assess location, duration, and characteristics of seizure activity. Institute seizure precautions.

• Bipolar Disorder: Assess mood, ideation, and behavior frequently.

• Migraine Prophylaxis: Monitor frequency and intensity of migraine headaches.

Valproic Acid (Depakote) Education

• Advise pt & family to notify health care professional if thoughts about suicide or dying, depression, etc…

• Notify HCP if anorexia, abd pain, severe N&V, yellow skin & eyes, fever, sore throat, malaise, weakness, facial edema

Levetiracetam (Keppra) Pharmacodynamics/Action

Mechanism of action unknown

Levetiracetam (Keppra) Uses/Indications

Partial onset and tonic-clonic seizures

Levetiracetam (Keppra) Contraindications

• Known hypersensitivity

• Pregnancy and lactation

Levetiracetam (Keppra) Adverse Effects

• Drowsiness, dizziness, fatigue

• Decreases in WBC, double vision, amnesia, ataxia, emotional lability

Drug Therapy Failure Causes - Seizure

• Noncompliance, inadequate drug dosage

• Incorrect diagnosis or medication for seizure type

• Too frequent changes or premature withdrawal

• Drug overdoses, use of alcohol or recreational drugs

• Severe electrolyte imbalance

Drugs for Muscle Spasm and Spasticity

• Skeletal muscle relaxants are used to decrease muscle spasms or spasticity that occurs within neurologic and musculoskeletal disorders.

  • Muscle spasm: sudden, involuntary, painful muscle contraction

    • May be clonic or tonic

  • Spasticity: increased muscle tone or contraction and stiff, awkward movements

Muscle Spasm Causes

• Epilepsy

• Hypocalcemia

• Pain syndromes: Acute and chronic

• Trauma: Localized skeletal muscle injury

Therapy of Muscle Spasm - Physical measures

• Immobilization of affected muscle

• Cold compresses

• Whirlpool baths

• Physical therapy

Therapy of Muscle Spasm - drug therapy

Analgesic anti-inflammatory (aspirin)

General Characteristics of Skeletal Muscle Relaxants - Mechanism of action

General depression of the CNS

General Characteristics of Skeletal Muscle Relaxants - Indications for use

• Primarily as adjuncts to other treatments

  • Physical therapy

• Spastic disorders

General Characteristics of Skeletal Muscle Relaxants - Contraindications for use

• Impaired renal or hepatic function

• Respiratory depression

• Patients who must be alert for activities of daily living

General Characteristics of Skeletal Muscle Relaxants - Goal

relieve pain, muscle spasm, and muscle spasticity without impairing the ability to perform self-care activities

General Characteristics of Skeletal Muscle Relaxants - drug selection

Medication used depends mainly on the disorder being treated.

Drugs Used as Skeletal Muscle Relaxants – Treatment of Spasms & Spasticity

• Carbamate Derivatives – Carisoprodol (Soma)

• GABA Derivatives – Baclofen (Lioresal)

• Direct-Acting Skeletal Muscle Relaxants – Dantrolene sodium (Dantrium)

• Tricyclic Antidepressant Derivatives – Cyclobenzaprine (Flexeril)

• Centrally Acting - Chlorzoxazone (Parafon Forte)

• Imidazoline Derivatives – Tizanidine (Zanaflex)

Baclofen Pharmacodynamics/Action

Inhibits reflexes at the spinal level. Decreased muscle spasticity; bowel and bladder function may also be improved.

Baclofen Uses/Indications

Treatment of reversible spasticity due to multiple sclerosis or spinal cord lesions.

Baclofen Contraindications

• Hypersensitivity, OB, Lactation, Peds

• Use with caution: Increase CNS depression with other CNS depressants including alcohol, antihistamines, opioid analgesics and sedative/hypnotics

• Use with MAO inhibitors may lead to increased CNS depression or hypotension

Baclofen Adverse Effects

Seizures, dizziness, drowsiness, fatigue, weakness, nausea

Baclofen (Lioresal, Gablofen) Nursing considerations

• Assess muscle spasticity before and periodically during therapy

• Observe patient for drowsiness, dizziness, or ataxia. May be alleviated by a change in dose.

Baclofen (Lioresal, Gablofen) Education

• Instruct patient to take as directed. Take a missed dose within 1 hour; do not double doses.

• Caution patient to avoid abrupt withdrawal of this medication because it may precipitate an acute withdrawal reaction (hallucinations, increased spasticity, seizures, mental changes, restlessness). Discontinue gradually over 2 weeks or more.

Benzodiazepine (Diazepam) Pharmacodynamics/Action

Depresses the CNS, probably by potentiating GABA, an inhibitory neurotransmitter

Benzodiazepine (Diazepam) Uses/Indications

• Relief of anxiety, sedation, amnesia, skeletal muscle relaxation.

• Decreased seizure activity.

Benzodiazepine (Diazepam) Contraindications

• Hypersensitivity, comatose patients. OB, Peds, lactation.

• Interactions: Alcohol, antidepressants, antihistamines, and opioid analgesics

Benzodiazepine (Diazepam) Adverse Effects

dizziness, drowsiness, lethargy, respiratory depression

Benzodiazepine (Diazepam) Nursing considerations

Monitor BP, HR, and respiratory rate prior to and periodically throughout therapy and frequently during IV therapy. Prolonged high-dose therapy may lead to psychological or physical dependence.

Benzodiazepine (Diazepam) Education

Take as directed, do not take more than prescribed or increase dose if less effective after a few weeks without checking with HCP. Abrupt withdrawal of diazepam may cause insomnia, unusual irritability or nervousness and seizures.

Neuroleptic Malignant Syndrome

• Potentially fatal adverse reaction

• Symptoms include high fever, diaphoresis, muscle rigidity, tachycardia, BP fluctuations

• Without quick, aggressive treatment condition can deteriorate to stupor or coma

• Treatment includes antipyretics, electrolytes, muscle relaxants

Clinical Manifestations of ADHD

• Occur in various and multiple environments in the child’s life

• Symptoms worsen in situations that require sustained attention.

• Early diagnosis and treatment are essential.

• Evidence suggests that behavior management combined with pharmacotherapy yields the best outcomes.

Goals of ADHD Therapy

• Control symptoms

• Facilitate learning

• Promote social development

• Treatment based on individual signs and symptoms

Clinical Manifestations of Narcolepsy

• Disturbed nocturnal sleep

• Abnormal daytime sleep pattern

• Cataplexy - sudden loss of muscle tone or strength

• Hypnagogic hallucinations

• Sleep paralysis

Goal of Narcolepsy Therapy

• Based on individual symptoms and therapeutic response

• Prevention of sleep deprivation

• Regular sleep and waking times

• Avoiding shift work

• Short naps might be helpful

Stimulants

• Act by facilitating initiation and transmission of nerve impulses that excite other cells.

• ADHD, the drugs improve academic performance, behavior, and interpersonal relationships.

• narcolepsy, the drugs improve the performance of daily activities.

• Misuse and abuse can occur.

• Overdoses may occur.

Drugs to Treat ADHD & Narcolepsy

• Amphetamines – schedule II drugs, high potential for abuse and dependence, widely sold on the street

  • Dextroamphetamine (Dexedrine), combined with amphetamine (Adderal), Lisdexamfetamine (Vyvanse) – 57.2

• Amphetamine related CNS Stimulants –Methylphenidate (Ritalin) Modafinil, (Provigil) – 57.3

• Selective norepinephrine reuptake inhibitors – Atomoxetine (Strattera)

• Sympatholytics – Guanfacine (Intuniv, Tenex)

• CNS depressant – Sodium oxybate (Xyrem)

Amphetamines

• Schedule II drugs

• High potential for drug abuse and dependence

• Widely sold on the street

• Commonly abused

Amphetamine-Related Drugs

• Resemble amphetamines

• Schedule II drugs

• Risk of abuse and dependence

• Can be used for ADHD and narcolepsy

• May be useful for treatment of both acute and chronic conditions

Xanthines

• Caffeine is the prototype.

• Most frequently consumed CNS stimulant worldwide.

• Mostly from dietary sources.

• Low to moderate amounts can increase alertness, wakefulness, and capacity to work.

• Decreases fatigue and delays sleep.

Xanthines Adverse Effects

• Large amounts of caffeine can cause anxiety, agitation, diarrhea, hyperactivity, insomnia, irritability, nausea, nervousness, premature ventricular contractions, restlessness, tachycardia, tremors, and vomiting.

• Toxic amounts may cause delirium and seizures.

Substance Abuse

• Self-administration of a drug for prolonged periods or in excessive amounts to the point of producing

  • Physical or psychological dependence

  • Impairing functions of body organs

  • Reducing ability to function in usual ADLs

  • Decreasing ability and motivation to function as a productive member of society

Types of drugs typically abused

• CNS depressants

  • Alcohol

  • Antianxiety agents

  • Sedative–hypnotic agents

  • Opioids

• CNS stimulants

  • Cocaine, methamphetamine

  • Methylphenidate, nicotine

• Mind-altering drugs

  • Marijuana

  • “Ecstasy”

Effects of Substance Abuse

• Associated with feelings of

  • Pleasure

  • Positive reinforcement

  • Compulsive self-administration

• Repeated substance use produces tolerance.

  • Body adjusts to dosing, so dosing must be increased to achieve pleasure to avoid withdrawal symptoms

Characteristics of Drug Dependence

• Craving the drug

• Compulsive drug-seeking behavior

• Physical dependence

  • Withdrawal symptoms occurs if drug use is decreased or stopped.

• Psychological dependence

  • Unpleasant symptoms occur when the drug is stopped.

Theory of Drug Dependence

• Drugs stimulate or inhibit neurotransmitters.

  • Produce pleasure and euphoria

  • Decrease unpleasant feelings (e.g., anxiety)

• Neurotransmitter sites of action

  • Dopaminergic sites of action: alcohol, amphetamines, cocaine, nicotine, opiates

  • Noradrenergic sites of action: amphetamines, cocaine

Factors in Developing Drug Dependence

• Specific drug

• Amount, frequency, route of administration

• One’s psychological and physiological characteristics

  • Genetic factor (alcohol abuse)

• Environmental characteristics

• Circumstantial characteristics

  • Peer pressure

CNS Depressants

• Slow down or “depress” brain activity

  • Alcohol

  • Antianxiety agents

  • Sedative–hypnotic agents

  • Opiates

CNS Stimulants

• Produce stimulation and euphoria

  • Small amounts produce

    • Mental alertness, wakefulness

    • Increased energy

• Include amphetamines, methamphetamine, methylphenidate, cocaine, nicotine

Principles of Therapy Prevention of substance abuse

• Decrease availability

• Decrease demand

• Prescribing/administering drugs appropriately

• Home education, limiting availability within the home

Principles of Therapy Goals of therapy

• Detoxification

• Initiation of abstinence

• Prevention of relapse

• Treatments include

  • Inpatient, psychological rehabilitation, pharmacotherapy (limited)

Drugs to Treat Substance Use Disorders

• Anti-alcoholic drug – enzyme inhibitor – Disulfiram (Antabuse)

• Benzodiazepine – Chlordiazepoxide (Librium), Lorazepam (Ativan)

• GABA agonist/glutamate antagonist – Clonidine (Catapres)

• Benzodiazepine receptor antagonist – Flumazenil (Romazicon)

• Opioid antagonist – naloxone (Narcan) *

• Nicotine – varenicline (Chantix), buproprion (Wellbutrin)