NMNC 3230 Pharmacology - Neurological System

Nervous System Pharmacology

Baclofen (Lioresal)

Class: muscle relaxant

Indication: relief of chronic muscle spasticity (from cerebral palsy, MS, stroke, spinal cord injury)

• PO form also used as acute skeletal muscle relaxant

• Injectable: implanted automatic pump for continuous infusion

Mechanism of action: centrally acting muscle relaxant

ADVERSE EFFECTS:

• PO: confusion, nausea, weakness, tiredness

• INFUSION PUMP: unwanted movement of catheter/pump, infection or spinal fluid leak, mechanical overdose, mechanical failure (underdose that will precipitate withdrawal)

Black box warning: abrupt discontinuation may cause confusion, hallucinations, difficulty breathing, seizures, and exacerbate 

Dantrolene (Dantrium, Ryanodex)

Class: muscle relaxant

Indications: muscle spasticity that occurs as a result of cerebrovascular accident or stroke spinal cord injury, multiple sclerosis, and cerebral palsy. malignant hyperthermia, neuroleptic malignant syndrome

Mechanism of Action: acts directly on skeletal muscle tissue by inhibiting the release of calcium, which is necessary for normal muscle contraction.

ADR: muscle weakness, drowsiness, dizziness, diarrhea, liver damage (at higher doses & long-term therapy)

Safety: monitor for CNS depression

• paired with muscle weakness-increases risk of falls

Contraindications: liver damage (esp. age > 35); report jaundice or abdominal pain to provider

Phenytoin (Dilantin)

Drug Class: Hydantoin/Antiepileptic

Indications: prevention of seizures, status epilepticus

Mechanism of action: affects ion movement within neurons, stabilizing the seizure threshold

Adverse Effects:

• Rash/Steven-Johnsons Syndrome

• Gingival Hyperplasia

• CNS disturbances (lethargy, confusion)

• IV site necrosis – use fosphenytoin!

• ADR with long-term use: Acne, hirsutism, osteoporosis

Drug Interactions, therapeutic monitoring

• Pharmacokinetics: 90-95% protein bound, induces P450 enzymes = drug-drug interactions likely

• Monitor blood concentrations (narrow therapeutic index)

Patient education

• Oral hygiene

• Avoid triggers (stress, trauma, sleep loss, overexertion, recreational. drugs, ethanol)

• Take around-the-clock

• Do NOT discontinue abruptly!

 Safety

• Black box warning: severe hypotension &/or dysrhythmias if given too fast (do not exceed 50 mg/min)

• Pregnancy category D

  • Pregnant mother needs to be seizure free during pregnancy

  • Neonates at risk for bleeding

Nursing Considerations

• Assess skin for rash

• Inspect the oral mucosa

Carbamazepine

Class: Antiepileptic drug

Indications: partial and tonic-clonic seizures, mood stabilizer, trigeminal neuralgia

Mechanism of Action: inhibits the influx of Na+ through Na+ channels, decreasing high-frequency repetitive firing of neurons

ADR: dizziness, blurred vision/diplopia, ataxia, GI upset, weight gain, SIADH, aplastic anemia & agranulocytosis, severe cutaneous reactions

Metabolized by hepatic CYP450

• interactions: increased plasma levels & toxicity: grapefruit juice, P450 inhibitors: antifungals, erythromycin, verapamil

• decreased plasma levels: phenytoin, barbiturates, theophylline

Safety:

• Black box warning

  • Severe dermatologic reactions: SJS/TEN

  • Genetics & Pharmacy: people of Asian descent with HLA-B*1502 antigen are more at risk

  • aplastic anemia & agranulocytosis: complete baseline hematology studies before treatment initiation

• Pregnancy category D

Nursing Interventions

• Give with food

• XL formulations - do not cut, crush, chew

• photosensitivity

• CBC monitoring

• HF: edema, decreased urine output, shortness of breath

Valproic Acid

Beta 2

Lungs - cause bronchodilation

parasympathetic nervous system (PNS)

neurotransmitters - acetylcholine

receptor - cholinergic

recebptor subtype - nictotinic + muscarinic

Antagonist - parasympatholytics + anticholiergics

agonists

Medications that activate receptors to increase effects.

antagonist

Medications that block or reduce receptor activation, decreasing normal effects.

Central Nervous System

Brain + spinal cord

SNS

Neurotransmitter - epinephrine + norepinephrine

Receptor - adrenergic

Receptor types - alpha 1&2, beta 1,2,3

Antagonists - sympatholytics

CNS

cholinergic activation - headache, insomnia, giddiness, confusion, + drowsiness

Anticholinergic - AGITATION, confusion disorientation

GI tract

cholinergic - increased urination, defecation, emesis

Anticholinergic - urinary retention, CONSTIPATION

Eye

cholinergic - decreased IOP, small pupils (miosis)

anticholinergic - increased IOP, dilated pupils

CV

cholinergic - decreased HR

anticholinergic - increased HR

Glandular

cholinergic - increased sweating + salvation

anticholinergic - decreased sweating, dry mouth

respiratory

cholinergic - bronchoconstriction, increased bronchial secretions

anticholinergic - decreased bronchial secretions

Neurotransmitter

chemicals within the body that transmit signals from 1 neuron to the next

Neuron

cells that conduct nerve impulses in the CNS

Alpha 1

Blood vessels - cause vasoconstriction

Eyes - cause mydriasis (dilation of pupils)

Beta 1

Heart - cause increased HR + contractility

Seizure

brief episode of abnormal electrical activity in nerve cells of the brain

Convulsion

involuntary spasmodic contractions of any/all voluntary muscles throughout the body

Epilepsy

a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, associated with abnormal electrical activity in the brain.

can be treated with antiepileptic drugs (AED’s)

Status Epilepticus

Multiple seizures occur with NO RECOVERY period between them

RESULT: hypotension, hypoxia, brain damage, death

TRUE MEDICAL EMERGENCY

Treatment: benzodiazepines, phenobarbital, fosphenytoin are treatments of choice

• BENZODIAZEPINES are 1st line for status epilepticus

Muscle relaxants

Acute muscle spasms – associated with trauma, inflammation, anxiety and pain

Management of muscle spasticity - associated with severe chronic disorders like multiple sclerosis (MS), cerebral palsy

Most work within the CNS (centrally acting) and have sedative effects

Effects are similar to the muscle relaxant/sedative effects of diazepam.

Antiepileptic Therapy

 GOAL – to control or prevent seizures while maintaining a reasonable quality of life

• Epilepsy has no cure: therapy is lifelong (some people can get off but

• Serum drug concentrations must be measured

  • phenytoin, fosphenytoin, phenobarbital

Many drugs available; start with single-drug therapy, increase to multi-drug therapy if

needed

• Use based on type of seizures and response to drug

• Other AED’s: Carbamazepine, lamotrigine, valproic acid, levetiracetam, topiramate, ethosuximide, zonisamide, clobazam, gabapentin, pregabalin, tiagabine, perampanel, vigabatrin

General Anesthesia

drugs that reduce or eliminate pain by depressing nerve function in the central nervous system (CNS) and peripheral nervous system.

complete loss of consciousness and loss of body reflexes including paralysis of respiratory muscles

Indication: used during surgical procedures to produce the following

• Unconsciousness

• Skeletal muscle relaxation

• Visceral smooth muscle relaxation

Dosage forms: volatile gases for inhalation, injectables

Pharmacokinetics

• Rapid onset, quickly metabolized

Adverse effects consist of management of toxicity and overdose

• in large doses, anesthetics are potentially life-threatening

• cardiac and respiratory arrest are ultimate causes of death in an overdose

• administered in a controlled, monitored environment

Local Anesthesia

“regional anesthetics”

elimination of pain sensation in the tissues innervated by anesthetized nerves, no paralysis of respiratory function

Indication: used to render a specific portion of the body insensitive to pain without causing LOC

Mechanism of action: interferes with nerve impulse transmission to specific areas of the body

TOPICAL

• applied directly to skin or mucous membranescreams, ointments,solutions, gels, ophthalmic drops, powders, suppositories

PARENTERAL

• Injected into or on to the CNS by various spinal injection techniques

Balanced anesthesia

administration of a mixture of small amounts of several neuronal depressants (opioids and inhaled anesthetics) that maximizes the advantages, but not the disadvantages of, the individual components of the mixture

Malignant Hyperthermia

occurs during or after volatile inhaled general anesthesia

Characterized by:

• sudden elevation in body temperature (> 104ºF)

• tachypnea

• tachycardia

• muscle rigidity

Life-threatening emergency, treat with:

• Cardiorespiratory supportive care

• dantrolene (a skeletal muscle relaxant)

Benzodiazepines

End in -lam or -pam + have a z in their name

Class of drugs used to treat a variety of disorders such as anxiety, agitation, sleep induction, skeletal muscle relaxation, seizures, treatment of alcohol withdrawal, and the induction of anesthesia

CATEGORIZED based on their duration of action

• LONG acting: Clonazepam, diazepam

• INTERMEDIATE acting: alprazola

• SHORT acting - midazolam

NURSING IMPLICATIONS

• Patient safety: fall risk

• REM interference: can cause rebound insomnia after 3-4 weeks

• Tolerance – doses may need to be increased with continuous use

• Dependence—wean off therapy to avoid withdrawal syndrome

• Interaction with alcohol/ethanol: avoid taking benzo’s with ethanol or other CNS depressants

  • Alcohol, opioids, muscle relaxants

• Schedule IV controlled substances

flumazenil (Romazicon) = reversal agent

Diazepam (Valium)

Drug Class: Benzodiazepine

Indications – sedation, sleep induction (insomnia), skeletal muscle relaxation to reduce anxiety before surgical procedures, anxiety-related depression, acute seizure disorders, alcohol withdrawal, agitation relief, balanced anesthesia, moderate/conscious sedation

Mechanism of Action – potentiates GABA

• Gamma-Amino-Butyric acid (GABA): inhibitory neurotransmitter

• Binds @ benzodiazepine receptors to potentiate GABA

ADVERSE EFFECTS

• CNS depression – especially with alcohol or other CNS depressants

• Hypotension

• Psychological dependence (addiction)

• Physical dependence leads to withdrawal syndrome

• Fall risk (especially elderly)

Toxicity/Overdose

• Somnolence, confusion, diminished reflexes, coma

• Benzodiazepine ANTAGONIST flumazenil (Romazicon) will stop overdose

CNS depressants

Safety FOR ALL CNS DEPRESSANTS

• Risk for sedation

• Fall risk

• Do not mix with alcohol

• Use caution when using more than one CNS depressant

Propofol (Diprivan)

Class: parenteral general anesthetic

indications: anesthetic, hypnotic, sedation during mechanical ventilation in ICU settings, moderate sedation

Pharmacokinetics:

• very lipid soluble, onset of action 30 seconds (FAST!)

• ”milk of amnesia”

Adverse effects

• Injection site pain (28%)

• involuntary muscle movement (17%)

• heart failure (10%)

• apnea

• other cardiopulmonary effects

• sepsis

• Propofol Infusion syndrome (mimics septic shock)

Safety

• cardiovascular monitoring

• respiratory monitoring

• use careful sterile technique

Developmental Concerns

• Pregnancy category B

Legal & Ethical Issues

• RN’s can’t give anesthetics

Types of Local Anesthesia

Spinal/Intraspinal

• intrathecal, epidural

Infiltration

• small local injections

Nerve block

• deeper injections to block an area

Topical

• creams, oinments applied to the skin

Lidocaine (Xylocaine)

common suffix “-caine”

• benzocaine, lidocaine, bupivacaine, procaine, cocaine, tetracaine

Class: local anesthetic

Indications: infiltration, nerve-block & topical anesthesia

Adverse effects:

• low incidence except if absorbed systemically in large doses

• local site irritation

Safety:

• prevent injury to anesthetized area

• aspiration prevention after oral use

• pregnancy category B

• pediatrics: careful topical use

Nursing Process for local anesthesia

Assessment

• skin intact for topical use

Implementation

• Administration

  • don’t dilute

  • intradermal or subQ – aspirate before injection

• Patient Teaching

  • assure proper route of administration

  • NPO until sensation returns

  • protect treated area from burns, trauma

Evaluation

• return of sensation

Antiparkins on Drugs

does not slow disease progression

therapy is aimed at slowing symptom progression

Parkinson’s Disease

Chronic, progressive, degenerative disorder

Affects dopamine-producing neurons in the brain

Caused by an imbalance of two neurotransmitters

Pathophysiology

• Dopamine (inhibitory) and Acetylcholine (excitatory) imbalance. Dopamine is decreased.

4 Cardinal Signs:

• Tremor

• Rigidity

• Bradykinesia/Akinesia

• Postural Instability

Carbidopa-Levodopa (Sinemet)

Classification – Dopaminergic agonist

Pharmacodynamics –

• Levodopa converted to dopamine in brain, replaces depletion

• Carbidopa inhibits initial breakdown of levodopa in the periphery, and allows for much lower doses of levodopa to be used

may take up to 6 mo. to achieve full therapeutic response

ADR:

• nausea, vomiting, orthostatic hypotension, palpitations, urinary retention

• dyskinesias

Safety

• Orthostatic hypotension precautions

Administration

• take with food, but avoid high-protein foods

Drug-Drug Interactions: antipsychotics, vitamin B6 (pyridoxine), MAOI’s

“On–off phenomenon”

Rapid swings in response to levodopa occur

Parkinson's Disease worsens when too little dopamine is present.

Dyskinesia occurs when too much dopamine is present.

“Wearing-off phenomenon”

Medications lose their effectiveness occur

May need a “drug holiday”

Nursing Process for levodopa

Assessment

• Symptoms – worsening or change in motor symptoms may indicate toxicity

Implementation

• Don’t give with high protein meal

• Patient Teaching

  • Increase fluid intake

  • Don’t suddenly stop taking

  • Dosing needs may/will change over time

Evaluation

• Symptoms

• Kidney and liver function labs

Alzheimer’s disease

• degenerative neurological disease, cause unknown

  • neurodegeneration

  • decreased acetylcholine levels

  • buildup of amyloid plaques and neurofibrillary tangles

  • neurons become unable to communicate with each other

• symptoms: cognitive impairments, memory loss, dementia over a period of years

  • range from no impairment – severe functional decline/death

Donepezil (Aricept)

 class: indirect-acting cholinergic agonist

Indication – mild/moderate Alzheimer’s disease

Mechanism of Action – cholinesterase inhibitor that increases levels of acetylcholine in the brain

Adverse Effects -- usually mild; GI upset, drowsiness, dizziness, insomnia, muscle cramps; cardiovascular adverse effects: bradycardia, syncope, hypotension with reflex tachycardia, hypertension