NMNC 3230 Pharmacology - Neurological System

Nervous System Pharmacology

Baclofen (Lioresal)

Class: centrally acting muscle relaxant

Indication: relaxes the muscle

Mechanism of action: works in the brain, not on the muscles

ADVERSE EFFECTS:

• PO: nausea, weakness

• INFUSION PUMP: infection or spinal fluid leak, mechanical overdose,

Black box warning: stopping abruptly can cause confusion, hallucinations, difficulty breathing, seizures, and exacerbate 

can be injectable

Dantrolene (Dantrium, Ryanodex)

Class: muscle relaxant

Indications: muscle spasticity from a cerebrovascular accident or stroke spinal cord injury, multiple sclerosis, and cerebral palsy. malignant hyperthermia, neuroleptic malignant syndrome

Mechanism of Action: acts directly on muscle by inhibiting the release of calcium

ADR: muscle weakness, drowsiness, liver damage,

Safety: monitor for CNS depression

• muscle weakness can increase risk of falls

Contraindications: liver damage

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!

Drug Interactions, therapeutic monitoring

• 90-95% protein bound = drug-drug interactions likely

• Monitor blood concentrations (narrow therapeutic index)

Patient education

• Oral hygiene

• Avoid triggers

• Do NOT discontinue abruptly!

Black box warning: risk of severe hypotension or dysrhythmias if administered too fast.

• 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

ADR: dizziness, aplastic anemia & agranulocytosis, severe cutaneous reactions

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

• decreased plasma levels: phenytoin, barbiturates, theophylline

Safety:

• Black box warning

  • Severe dermatologic reactions: SJS/TEN

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

• Pregnancy category D

Nursing Interventions

• Give with food

• XL formulations - do not cut, crush, chew

• photosensitivity

• CBC monitoring

• Heart Failure

Beta 2 receptors

Lungs - cause bronchodilation

agonists

Medications that activate receptors to increase effects.

antagonist

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

Alpha 1 receptors

Blood vessels - cause vasoconstriction

Eyes - cause mydriasis (dilation of pupils)

Beta 1 receptors

Heart - cause increased HR + contractility

Seizure

brief episode of abnormal electrical activity 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

Status Epilepticus

Multiple seizures occur with NO RECOVERY period between them

RESULT: hypotension, hypoxia, brain damage

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 multiple sclerosis, cerebral palsy

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

Antiepileptic Therapy

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

• Epilepsy has no cure

• Serum drug concentrations must be measured

  • phenytoin, fosphenytoin, phenobarbital

Start with single-drug therapy, increase to multi-drug therapy if needed

• Use based on type of seizures and response to drug

General Anesthesia

Drugs that reduce/eliminate pain by depressing nerve function

Complete loss of consciousness and loss of body reflexes

Indication: used in surgery to produce:

• Unconsciousness

• Skeletal muscle relaxation

• Visceral smooth muscle relaxation

Dosage forms: gases for inhalation + injectables

Pharmacokinetics

• Rapid onset, quickly metabolized

Adverse effects

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

Local Anesthesia

“regional anesthetics”

Elimination of pain

Indication: make part of the body insensitive to pain

Mechanism of action: interferes with nerve impulse transmission to a specific area

TOPICAL

• applied directly to skin or mucous membranes

PARENTERAL

• Injected into or on to the CNS by spinal injection

Patient Teaching

• assure proper route of administration

• NPO until sensation returns

• protect treated area from burns, trauma

Balanced anesthesia

administration of a mixture of anesthetics that maximizes the advantages, but not the disadvantages of one anesthetic

Malignant Hyperthermia

Characterized by:

• sudden elevation in body temperature (> 104ºF)

• tachypnea

• tachycardia

• muscle rigidity

Life-threatening emergency, treat with:

• Cardiorespiratory supportive care

• dantrolene

Benzodiazepines

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

Treat: anxiety, agitation, sleep induction, skeletal muscle relaxation, seizures, treatment of alcohol withdrawal, and the induction of anesthesia

• LONG acting: Clonazepam, diazepam

• INTERMEDIATE acting: alprazola

• SHORT acting - midazolam

NURSING IMPLICATIONS

• Patient safety: fall risk

• can cause rebound insomnia after 3-4 weeks

• Can build a tolerance

• Dependence—wean off therapy to avoid withdrawal syndrome

• Avoid: Alcohol, opioids, muscle relaxants

flumazenil (Romazicon) = reversal agent

Diazepam (Valium)

Drug Class: Benzodiazepine

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

Mechanism of Action – potentiates GABA

ADVERSE EFFECTS

• CNS depression w/ alcohol or other CNS depressants

• Hypotension

• addiction

• Physical dependence → withdrawal syndrome

• Fall risk (especially elderly)

Toxicity/Overdose

• Somnolence, confusion, diminished reflexes, coma

• flumazenil (Romazicon) will stop overdose

Safety for 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, moderate sedation

Pharmacokinetics:

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

• ”milk of amnesia”

Adverse effects

• Injection site pain

• heart failure (10%)

• Propofol Infusion syndrome (mimics septic shock)

Safety

• cardiovascular + respiratory monitoring

• sterile technique

• Pregnancy category B

RN’s can’t give anesthetics

Types of Local Anesthesia

Spinal/Intraspinal: epidural

Infiltration: small local injections

Nerve block: deeper injections to block an area

Topical: creams + ointments applied to the skin

Lidocaine (Xylocaine)

Class: local anesthetic

• common suffix “-caine”

Indications: infiltration, nerve-block & topical anesthesia

Adverse effects:

• low incidence except if absorbed systemically in large doses

• local site irritation

Safety:

• prevent injury to the anesthetized area

• aspiration prevention after oral use

• pregnancy category B

Antiparkins 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 (decreases dopamine)

Pathophysiology: Dopamine and Acetylcholine imbalance.

4 Cardinal Signs:

• Tremor

• Rigidity

• Bradykinesia/Akinesia

• Postural Instability

Carbidopa-Levodopa (Sinemet)

Classification – Dopaminergic agonist

Indication: Parkinson’s Disease

Pharmacodynamics –

• Levodopa converted to dopamine in brain, replaces depletion

• Carbidopa - transports the levodopa to the brain (like a car)

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

ADR: dyskinesias, “On-off phenomenon”, “Wearing off phenomenon”

Drug-Drug Interactions: antipsychotics, vitamin B6, MAOI’s

Safety

• worsening or change in motor symptoms → toxicity

• Don’t give with high protein meal

Patient Teaching

• Increase fluid intake

• Don’t suddenly stop taking

Alzheimer’s disease

• degenerative neurological disease cause unknown

  • neurodegeneration

  • decreased acetylcholine levels

  • buildup of plaques and neurofibrillary tangles

  • neurons become unable to communicate with each other

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

Donepezil (Aricept)

Class: indirect-acting cholinergic agonist

Indication – mild/moderate Alzheimer’s disease for slightly improved memory

Mechanism of Action – cholinesterase inhibitor → increases levels of acetylcholine

Adverse Effects - GI upset, bradycardia, hypotension with reflex tachycardia,

NOT A CURE + does not work for late-stage Alzheimer’s

Mental Illness, Mood disorders

Pathophysiology: not well understood; imbalance in neurotransmitter concentration and activity in the brain.

Indication: Used in the treatment of emotional and mental disorders

• Anxiety

• Depression

• Bipolar disorder

• Psychosis/Schizophrenia

Anxiolytics

Anxiety – unpleasant state of mind characterized by a sense of fear and dread (nonspecific) Cause of disorder unknown

Classes of drugs used for anxiety:

• Benzodiazepines (diazepam, alprazolam, lorazepam)

• Buspirone (Buspar)

Buspirone (Buspar)

Class: miscellaneous anxiolytic

Indication - anxiety

Mechanism of Action – binds to serotonin receptors in the brain

Adverse Effects – paradoxical anxiety, blurred vision, nausea

Nursing Implications

• Do not give with MAOI’s

Highlight items:

• Takes 2-3 weeks of daily until it works

• Take everyday

• Does not cause dependence

• long-term treatment for depression

Mood Stabilizers

Treats bipolar disorder - Changes in mood that range from mania to depression and alternate back & forth over time

Classes of drugs used:

• Lithium

• Antidepressants

Pathophysiology: imbalance or inadequate concentrations of serotonin, norepinephrine, and dopamine in the brain

Lithium carbonate/citrate

Class: mood stabilizer

Indication – bipolar disorder, depression

Mechanism of Action – alters Na+ transport in nerve cells

Adverse Effects

• Cardiac dysrhythmias, hyponatremia, Drowsiness

Nursing Implications- Narrow Therapeutic Index

• monitor sodium levels

• Levels exceeding 1.5 to 2.5 mEq/L begin to produce toxicity,

  • GI discomfort Nausea/Vomiting, tremor, death.

• Keeping the sodium level in 135 to 145 mEq/L helps to maintain therapeutic lithium levels.

Highlight items

• Lots of drug-drug interactions: thiazide diuretics, ACE inhibitors, NSAIDS

• Contraindicated: dehydration, sodium imbalance, CVD, renal dysfunction

Depression

persistent feelings of worthlessness, loss of interest in activities, reduced energy and motivation, sleep disturbances, and recurrent thoughts of death or suicide

Classes of drugs used:

• MAOi’s

• TCA’s

• SSRI’s & SNRI’s

• Bupropion

Pathophysiology: caused by an imbalance in catecholamine concentrations

Amitriptyline (Elavil)

Class: Tricyclic Antidepressant (TCA)

Indication – depression, migraine prevention, trigeminal neuralgia

Mechanism of Action – blocks presynaptic uptake of serotonin and norepinephrine

Adverse Effects

• impotence, orthostatic hypotension, dysrhythmias

Contraindications: allergy, pregnancy, recent MI

Nursing Implications

• takes 2 – 3 weeks to achieve effect

• Black Box Warning: suicidal ideation

 Highlight Items: Toxicity/Overdose

• Lethal – 70-80% die before reaching the hospital

• Death results from seizure or cardiac dysrhythmia

• No Antidote

Antidepressants

• sedation

• affects weight

• takes a few weeks to work

• sexual dysfunction

• Black Box Warning: suicidal ideation

Anticholinergic affects

can’t see

can’t pee

can’t spit

can’t shit

Phenelzine (Nardil)

Class: Monoamine Oxidase inhibitor (MAOi)

Indication – depression, Parkinson’s disease

Mechanism of Action – inhibits the enzyme Monoamine Oxidase

Adverse Effects – dizziness, dyskinesias, when someone eats foods high in tyramine, it can cause a hypertensive crisis

Nursing Implications:

• Hypertensive crisis or urgency

• avoid foods high in tyramine

  • Amino acid found in food on a charcuterie board

  • MAO inactivates tyramine in the liver

Fluoxetine (Prozac)

Class: SSRI (selective serotonin reuptake inhibitor)/antidepressant

Indication – depression, bipolar disorder, obesity, eating disorders, PTSD, anxiety disorders, PMS

Mechanism of Action – selectively inhibits the reuptake of serotonin in the brain

Adverse Effects – insomnia, sexual dysfunction, serotonin syndrome

Nursing Implications

• Takes 1-4 weeks to take affect

• Patient Education: Do not discontinue abruptly→ discontinuation syndrome

• Black box: suicidal ideation

Venlafaxine (Effexor)

Class: SNRI (serotonin norepinephrine reuptake inhibitor)/antidepressant

Indication – depression, anxiety disorders (panic/social anxiety, etc.)

Mechanism of Action – inhibits the reuptake of serotonin and norepinephrine in the brain

Adverse Effects:

• GI distress

• abnormal bleeding

• Serotonin syndrome

Nursing Implications

• 4 – 6 weeks to antidepressant effect

• Patient education: avoid abrupt discontinuation – discontinuation syndrome

• Black box warning – suicidal ideation

Serotonin-related ADR

Discontinuation Syndrome

• occurs with abrupt discontinuation of SSRI or SNRI antidepressants

• taper slowly over 2 – 3 weeks

• BRAIN ZAPS, flu-like symptoms, sensory disturbances

Serotonin Syndrome

• serotonin toxicity

• delirium, tremors/spasms, renal failure, dysrhythmias

• Cause serotonin syndrome when combined with an SSRI or SNRI:

  • MAOI’s, TCA’s, methadone, “triptans” – migraine

  • buspirone – anxiety

  • amphetamines – ADHD MDMA/ecstasy

Bupropion (Wellbutrin*, Zyban**)

class: miscellaneous antidepressant

Indications – depression*, smoking cessation** (makes cigarette taste bad)

Mechanism of Action – inhibits reuptake of dopamine and norepinephrine in the brain

Adverse Effects – dizziness, tachycardia, dry mouth

Nursing Implications

• 1-4 weeks to achieve effect

• Black box: suicidal ideation

Seizure disorder – can lower seizure threshold

Psychosis

Severe emotional disorder that impairs mental function to the point that the individual cannot participate in activities of daily living, characterized by a loss of contact with reality

Classes of drugs used:

• 1st generation antipsychotics

• 2nd generation antipsychotics

  • better for both negative + positive schizophrenic symptoms

Pathophysiology: imbalance of dopamine activity in the brain

Antipsychotics - dopamine antagonists that help to normalize dopamine activity

Haloperidol (Haldol)

Class: 1st generation (typical) antipsychotic

Indication – Psychosis/Schizophrenia

Mechanism of Action – Block dopamine receptors in the brain

Adverse Effects - hematologic effects, dry mouth, extrapyramidal effects, neuroleptic malignant syndrome

Nursing Implications:

• evaluate cognitive function to determine efficacy

• ECG, CBC

• Black box warning: increased risk of death in elderly w/ dementia

Highlight items: two injectable dosage forms

• decanoate (IM only) + lactate (IV and IM)

Extrapyramidal effects (EPS)

Highlight: EPS - involuntary movements of hands, arms, legs, with a shuffling propulsive gait, a mask-like face, tremors, and drooling

• Akathisia (difficulty movement)

• Pseudoparkinsonism (tremors, shuffling gait, posture, etc.)

• Tardive dyskinesia (rapid blinking, grimacing, mouth movement, etc.)

Major adverse effect of antipsychotic drugs

Neuroleptic Malignant Syndrome

neuroleptic – “antipsychotic”

malignant – life-threatening if untreated

Life-threatening emergency characterized by:

• High fever

• Muscle rigidity

• Unstable vitals

• Treat with dantrolene

Risperidone (Risperdal)

Class: 2nd generation (atypical) antipsychotic

Indication: psychosis/schizophrenia, bipolar mania, autistic disorder

Mechanism of Action: Block dopamine receptors in the brain

Adverse Effects: QTc prolongation, seizures, dyskinesias,

Nursing Implications:

• Available PO, IM

• IM formulation lasts 2 weeks

Cholinergic reactions

“rest + digest”

GI tract - increased urination, defecation, emesis

Eyes - decreased IOP, small pupils (miosis)

CV - decreased HR

glandular - increased sweating + salvation

respiratory - bronchoconstriction, increased bronchial secretions

adrenergic/anticholinergic reactions

“fight or flight”

GI tract - urinary retention, CONSTIPATION

Eye - increased IOP, dilated pupils

CV - increased HR

glandular - decreased sweating, dry mouth

Respiratory - decreased bronchial secretions

“Wearing off” Phenomenon

• Medications lose their effectiveness occur

• May need a “drug holiday”

“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.