Pharmacology Week 5 CNS Drugs

 

Parkinson’s Disease - Pathophysiology

Chronic progressive neurological disorder

Caused by loss of dopaminergic receptors & reduced concentration of dopamine and excess Acetylcholine.

Symptoms:

◦dyskinesia - abnormal involuntary movements

◦akinesia: muscle rigidity

◦Postural instability

◦bradykinesia: slowness of motion

◦Tremor at rest: early sign, progressive

Arch

Involved in thought learning and memory, activates muscle action in the body and associates with attention and waking

Adrenaline

Produced in stressful situations, increases hr, leading to physical boost and heightened awareness

GABA

Calms firing nerves in the CNS with high levels improve focus, low levels cause anxiety. Contributes to motor control and vision

Noradrenaline

Affects attention and responding actions in the brain. Contracts blood vessels

Dopamine

Feelings of pleasure, addiction, movement and motivation. People repeat behaviors that lead to dopamine release

Glutamate

Most common. Learning and memory. Regulates development and creation of nerve contacts

Serotonin

Well-being and happiness helps sleep cycle and digestive system regulation. Affected by exercise and light exposure

Endorphins

Released during exercise, sex. Producing well-being and euphoria reducing pain

Dopaminergic agents

Promote activation of dopamine receptors

Anticholinergic agents

Prevent activation of cholinergic receptors

Dopaminergic agents

These drugs increase dopamine levels or stimulate dopamine receptors.

Levodopa/Carbidopa (Sinemet):

•Levodopa is converted to dopamine in the brain.

•Carbidopa prevents peripheral breakdown of levodopa, allowing more to reach the brain.

Dopamine Agonists:

•Stimulate dopamine receptors directly.

•Examples: Pramipexole, Ropinirole, Bromocriptine.

MAO-B Inhibitors:

•Inhibit monoamine oxidase B, an enzyme that breaks down dopamine in the brain.

•Examples: Selegiline, Rasagiline.

COMT Inhibitors:

•Inhibit catechol-O-methyltransferase, which breaks down levodopa in the periphery.

•Examples: Entacapone, Tolcapone.

Amantadine:

•Increases dopamine release and blocks its reuptake; also has anticholinergic and NMDA antagonist properties.

Carbidopa/levodopa (sinemet)

Mechanism of action: Levodopa(precursor to dopamine) converts to dopamine in the brain

Carbidopa prevents breakdown of levodopa in the periphery

◦combination reduces dose of levodopa by 75%

◦decreased stimulation of medullary emetic center = less N/V

◦increase stability of symptom control

◦greater clinical improvement 

•Side effects: Long-term use may cause motor fluctuations

•(e.g., "wearing off" phenomena) and dyskinesias (involuntary movements).

Amino acids compete in intestine for absorption

◦Encourage a low protein diet

◦Initially effective in 75% of patients with a 50% reduction in symptoms – full effect may take several months

◦First two years promising, less after 5 years

◦Patients have “off” and “on” periods when drug is working or not. May help to change dosing schedule.

Adverse Drug Reactions:

◦N/V – chemoreceptor zone in medulla is triggered by drug.

◦Give low dose or with food: caution that food decreases absorption

◦Involuntary movements! Despite being treatment against this, 80% of people develop.

◦Postural Hypotension – reason unknown

Psychiatric effects - confusion, paranoia, hallucinations

Darkens sweat and urine

HTN with mao-I inhibitors

Drugs for Parkinson’s Disease: Dopamine Agonists:

Drugs that stimulate / activate the dopaminergic receptors:

 

◦pramipexole (Mirapex)

 

◦ropinerole (Requip)*

 

◦apomorphine (Apokyn)

 

◦bromocriptine (Parlodel)

 

●First line for mild/moderate symptoms, especially if younger patient

●Used alone or with levodopa/carbodopa

Dopamine agonists

Advantages:

◦Does not compete with dietary protein

◦No need for enzymatic conversion

◦Lower incidence of Dyskinesias

◦Fewer response failures

 

◦Disadvantages:

◦Hallucinations, “sleep attacks”, postural hypotension if used with levodopa

◦Pramipexole: impulse control disorders

Drugs for Parkinson’s Disease - COMT

◦Catechol-O-methyltransferase  COMT inhibitors

●used in combination with levodopa to treat the motor symptoms of Parkinson's disease.

●Block degradation of levodopa in periphery, prolongs levodopa availability to the brain

●Similar to carbidopa

◦entacapone (Comtan)*

◦tolcapone (Tasmar)

Side effects: Diarrhea, liver toxicity (with Tolcapone), and may exacerbate dyskinesias.

Monoamine Oxidase B Inhibitors (MAO-B inhibitors):

◦selegiline (Carbex, Eldepryl) Rasagiline (Azilect): : inhibits MAO, the enzyme that breaks down dopamine

◦Side effects: insomnia and hypertension at high doses.

●More dopamine from levodopa available to brain

●May decrease progression of disease, if used early

●Effects may be brief (1-2 years)

Nursing Considerations:

◦Avoid combining with SSRIs or TCAs

◦Monitor BP

Anticholinergic Agents- block the action of acetylcholine

benztropine (Cogentin)*

◦biperiden (Akineton)

◦Trihexyphenidyl

●Reduce acetylcholine activity → improves tremors

●Used in the early stages of Parkinson’s disease

●Used in younger patients

Side Effects:

◦Dry mouth

◦Blurred vision

◦Urinary retention

◦Confusion

Nursing Considerations:

◦Avoid in older adults

Increases fall and confusion risk

Alzheimer’s Dementia (AD) - Pathophysiology

Decreased acetylcholine

◦Neuronal degeneration in the brain

◦Progressive cognitive decline

◦Acetylcholine in CNS important for:

◦memory, learning, judgement, sustained arousal, consciousness, judgement

Risk Factors

◦Increasing age (onset at 40-65 year)

◦Family history

◦Sedentary lifestyle

◦female

Signs & Symptoms

◦Personality changes

◦Difficulty with self-care, ADL’s

◦Behavioral problems, “sun downing”

◦Difficult communication

Alzheimer’s Drug Therapy

Cholinesterase inhibitors: Prevent breakdown of acetylcholine

Examples: donepezil(Aricept)*galantamine (Razadyne) rivastigmine (Exelon)

Side Effects:

◦Nausea

◦Vomiting

◦Diarrhea

◦Bradycardia

◦Weight loss

Nursing Considerations:

◦Administer with food if GI upset occurs

◦Monitor heart rate

◦Assess weight regularly

◦May increase fall risk

NMDA receptor antagonist

(N-methyl D aspartate receptor antagonists)

 

◦Example: memantine (Namenda)*

◦targets, reduces glutamate at NMDA

◦Overstimulation of NMDA receptors by glutamate can lead to neuronal damage, and memantine helps to prevent this.

Multiple Sclerosis (MS):

Chronic autoimmune demyelinating disease of the CNS relapsing and non-relapsing forms

Signs & symptoms: numbness, paresthesia*, decreased motor control, vision changes*, spasm, decline in mental health

◦Treat disease progression & treat symptoms, no cure

Acute Relapse (Exacerbation) Treatment

◦High-Dose Corticosteroids

◦Methylprednisolone (IV)

◦Prednisone (oral taper)

Mechanism of Action:

◦Suppress inflammation

◦Decrease immune response

◦Reduce edema around demyelinated areas

Nursing Considerations:

◦Monitor blood glucose

Disease Modifying Drugs for MS:
Immunomodulators

◦Used to reduce relapse rate and slow progression

Interferon Beta (lowers immune system)

◦Examples:

◦Interferon beta-1a (Avonex, Rebif)

◦Interferon beta-1b (Betaseron)

Mechanism:

◦Modulates immune response

◦Reduces inflammatory activity

Side Effects: Flu-like symptoms, Injection site reactions, Depression

Nursing Considerations:

◦Administer at bedtime to reduce flu-like symptoms

◦Monitor liver enzymes

◦Monitor mood for depression

Other drugs for MS - monoclonal antibodies

Lab produced antibodies, designed to bind to antigens

◦Targets antibody - antigen responsible for destruction in multitude of diseases (cancer, anemia, arthritis, lupus, autoimmune disorders including, IBD, MS…)

Example Drug: Ocrevus (ocrelizumab)

◦Side Effects:

◦Serious infections

◦Nursing Considerations:

◦Monitor neurologic status

◦Screen for infections

Epilepsy

neurological disorder characterized by recurrent seizures due to abnormal electrical activity in the brain
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

Anti epileptic drugs

Goals of treatment:

◦Prevent seizures

◦Minimize side effects

◦Maintain quality of life

Antiepileptic drugs (AEDs) are long-term therapy

Antiepileptic drugs work through various mechanisms to stabilize neuronal activity and prevent seizures, including:

Special Considerations

◦Pregnancy: many AEDs are teratogenic

◦Drug interactions common

◦Abrupt withdrawal → seizure risk

◦Consistent dosing is critical

Patient Education

◦Take medication exactly as prescribed

◦Wear medical alert ID

◦Avoid seizure triggers

◦Do not skip doses

◦Avoid alcohol unless approved

 

 

Major Classes of Antiepileptic Drugs

1. Sodium Channel Blockers

Used for: Focal and generalized tonic-clonic seizures

Examples

◦Phenytoin

◦Carbamazepine

◦Lamotrigine

◦Mechanism of Action

◦Block sodium channels → stabilize neuronal membranes → reduce repetitive firing

Antiepileptic Drugs

Phenytoin (Dilantin):

Monitor for toxicity: Monitor therapeutic drug levels

◦narrow therapeutic range (10 to 20 mcg/mL) (nystagmus, ataxia - staggering, lethargy, sedation, hepatotoxicity

◦Administration: IV, IM, oral(with food); extended release available

 

•Side effects: Gingival hyperplasia((Maintain good oral hygiene, floss, gum massage)

•hirsutism, nystagmus, ataxia, rash, osteomalacia, and teratogenicity(fetal hydantoin syndrome), Cardiovascular effects(cardiac arrhythmia & hypotension with rapid IV infusion)

•Increases levels and effects of alcohol, diazepam and other CNS depressants : Avoid

Antiepileptic Drugs
       

Carbamazepine (Tegretol)*

Adverse effects:

◦CNS symptoms—dizziness, drowsiness, N/V; minimal compared to phenytoin (Dilantin)

◦Leukopenia, anemia, and thrombocytopenia (teach pt to report flu like symptoms & fatigue (signs of low Hgb/ Hct levels), monitor CBCs

◦Rash and photosensitivity reactions

◦Birth defects: Preg Cat D / fetal harm

◦Interactions: grapefruit juice (↓ metabolism)

Antiepileptic Drugs

2. GABA-Enhancing Medications

◦Used for: Various seizure types, status epilepticus

Examples

◦Valproic acid

◦Benzodiazepines (lorazepam, diazepam)

◦Phenobarbital

Mechanism of Action

◦Increase inhibitory effects of GABA

Antiepileptic Drugs

Divalproex

(Depakene, Depakote)

Uses: Seizure disorder ALL TYPES!

◦Also: Bipolar disorder, migraine prevention

 

Adverse effects:

◦GI effects: *N/V, take with food, try coated formulas

◦Hepatotoxicity: metabolized in liver; rare but avoid in liver failure; increases bleeding time, thrombocytopenia

◦Monitor liver function tests

◦Avoid alcohol

◦Pancreatitis (acute): rare, but potentially life threatening

◦Teratogenic effects: Preg Cat D

Antiepileptic Drugs

Barbiturates (phenobarbital)

Use: generalized & partial seizures, status epilepticus sedation, insomnia

◦promotes sleep and sedation

 

Adverse effects: neurotoxicity, drowsiness, depression, inattention, confusion, hypnotic effects; respiratory depression with IV dose

Monitor respiratory status

 

◦Monitor serum levels (therapeutic: 10-30 mcg/mL)

Antiepileptic Drugs

3. Calcium Channel Blockers

Example: Ethosuximide- Used for: Absence seizures

Mechanism of Action

◦Suppresses neurons in motor cortex by decreasing calcium influx

Side Effects

◦GI upset

◦Fatigue

◦Headache

Nursing Considerations

◦Drug of choice for absence seizures in children

◦Take with food to reduce GI upset

◦Monitor CBC

Antiepileptic Drugs

4. Glutamate Inhibitors / Broad-Spectrum AEDs

Used for: Multiple seizure types

◦Examples

◦Topiramate

◦Levetiracetam

Mechanism of Action

◦Reduce excitatory neurotransmission (glutamate)

Side Effects

◦Cognitive slowing

◦Mood changes (levetiracetam)

◦Weight loss (topiramate)

Nursing Considerations

◦Monitor mood and behavior

◦Encourage hydration (topiramate)

◦Assess for depression or irritability

Antiepileptic Drugs

5. Emergency Management: Status Epilepticus

Continuous seizures lasting >5 minutes or repeated seizures without recovery

First-Line Treatment

◦IV benzodiazepines (lorazepam)

Second-Line Treatment

◦Phenytoin

Nursing Priorities

◦Maintain airway

◦Administer oxygen

◦Monitor cardiac rhythm

◦Prepare for intubation if needed

Antiepileptic Drugs

 

Benzodiazepines

Action: GABA agonist- enhance the effects of GABA(inhibitory neurotransmitter)

 

◦Example Drugs:

◦diazepam (Valium)

◦clonazepam (Klonopin)

◦midazolam (Versed)

◦clorazepate (Tranxene)

◦Adverse effects: weakness, respiratory depression, hypotension, jaundice (hepatic metabolism)

◦Uses:

◦status epilepticus (IV diazepam); absence seizures; simple or partial seizures

◦ETOH withdrawal, anxiety, muscle spasm- muscle relaxant

Newer Anti – Epileptics-
better tolerated*

gabapentin (Neurontin)

◦pregabalin (Lyrica)

◦lamotrigine (Lamictal)

◦oxcarbazepine (Trileptal)*

◦tiagabine (Gabitril)

◦topiramate (Topamax)

◦zonisamide (Zonegran)

◦rufinamide (Banzol)

◦lacosamide (Vimpat)

 

Oxcarbazepine (Trileptal)

Action: blocks neuronal Na+ channels

 

◦Use: seizure (partial), trigeminal neuralgia, bipolar disorder

◦More $$, better tolerated, as effective

 

Adverse effects: dizziness, drowsiness, double vision (caution: driving)

 

◦Preg Cat C: teach use birth control

◦Interaction: ↓ oral contraceptives effect

◦Can increase phenytoin’s levels

Gabapentin (Neurontin)

Action: Thought to enhance GABA release

 

◦Uses: absence seizures and other seizures, also post-herpetic neuralgia, neuropathy

 

◦off label use: restless leg syndrome, insomnia

 

Adverse effects: well tolerated dizziness, fatigue, confusion, depression, drowsiness

Skeletal Muscle Relaxants

Two groups of drugs that cause skeletal muscle relaxation

◦One group for localized muscle spasm

◦One group for spasticity

Muscle spasm: involuntary contraction of skeletal muscle, or muscle groups)

◦Causes: muscle overuse (fatigue), dehydration acute and chronic pain syndromes, localized skeletal muscle injury(trauma)

◦Spasms can lead to pain and decreased functioning, although usually short - lived

◦Treatment of spasm(physical measures): PT, stretching, immobilization of affected muscle, cold compresses, whirlpool baths

◦Drug Therapy: anti-inflammatory agents(ASA)

For spasm (non-CNS origin) Spasmolytics (Muscle Relaxants for Acute Muscle Spasms)

○carisoprodol (Soma)

○cyclobenzaprine (Amrix, Flexeril)

○methocarbamol (Robaxin)

○metaxalone (Skelaxin)

For spasticity (CNS origin) Antispastic Agent

○baclofen (Lioresal)

○dantrolene (Dantrium)

Centrally acting Muscle Relaxants

Used to control skeletal muscle spasticity

●Spasticity: disorder of CNS origin, imbalance of impulses

●Prolonged, hyperactive reflexes

◦Causes: upper motor neuro disorders, multiple sclerosis, cerebral palsy, cerebral vascular accidents, Lou Gehrig's disease (ALS), spinal cord injuries: spasticity of muscle

oInterferes with rehab, causes pain, contractures

Muscle Relaxants

◦Can decrease local pain and tenderness

◦Can increase range of motion

◦Sedation

Spasmolytics (Muscle Relaxants for Acute Muscle Spasms)

Cyclobenzaprine (Flexeril)

•Mechanism of action: Cyclobenzaprine works in the CNS (central nervous system) to inhibit motor activity, acting as a sedative and reducing muscle tone.

•Use: Used for short-term relief of muscle spasms associated with acute musculoskeletal conditions.

•Side effects: Drowsiness, dry mouth, blurred vision, constipation, and urinary retention. Not recommended for long-term use due to sedative effects and potential for abuse.

Methocarbamol (Robaxin)

•Mechanism of action: Methocarbamol acts centrally to reduce the frequency and severity of muscle spasms by inhibiting the reflex pathways in the CNS.

•Use: Used for muscle spasms due to injury, inflammation, or other musculoskeletal conditions.

•Side effects: Drowsiness, dizziness, nausea, and vomiting. It is generally considered safer for short-term use.

Centrally Acting Skeletal Muscle Relaxants

Baclofen

◦Uses: Spasticity related to MS or spinal cord injury

Mechanism of Action:

◦Activates GABA-B receptors

◦Inhibits spinal reflexes

Side Effects:

◦Drowsiness

◦Dizziness

◦Weakness

◦Hypotension

Nursing Considerations:

◦Do NOT stop abruptly (risk of seizures)

Peripherally Acting Muscle Relaxants

Dantrolene (Dantrium)-Direct Acting Muscle Relaxant  - Acts directly on skeletal muscle(not in CNS)
Action: suppress  Ca+ release within skeletal muscle, thus decreasing contraction

◦Uses: Spasticity associated with multiple sclerosis, cerebral palsy, and spinal cord injury and treatment / prevention of malignant hyperthermia (hereditary)

◦adverse drug reactions: muscle weakness, and drowsiness monitor for incontinence, difficulty breathing

◦Dose related liver damage: monitor LFTs regularly

Antispastic Agents (Muscle Relaxants for Spasticity)

Diazepam (Valium)
Benzodiazepine class: mimics (GABA)

 

◦Used for spasticity or spasm

◦Also used for: anxiety, seizure, muscle spasm, alcohol withdraw

◦adverse drug reaction: CNS depression (sedation), additive sedation with alcohol & opioids

 

◦Pregnancy class D or X

 

◦No analgesic effect

Central Nervous System Stimulants

Sympathomimetics (adrenergic agonist), act on dopamineand norepinephrine

Increase the activity of central nervous system (CNS) neurons

Used for ADHD:

◦Amphetamine mixtures (Adderall XR)

◦dexmethylphenidate (Focalin, Foxalin XR)

◦dextroamphetamine (Dexedrine)

◦lisdexamphetamine (Vyvanse) (long-acting)– ADHD and binge eating disorder

◦High potential for misuse and dependence

__________________________________________

◦methylxanthines (Caffeine)

◦methylphenidate (Ritalin*, Concerta*) – ADHD

◦modafinil (Provigil) – approved for narcolepsy

Methylphenidate (Ritalin, Concerta, Daytrana)

Mechanism of action: Increases the release of dopamine and norepinephrine in the brain by inhibiting their reuptake.

•Uses: Primarily used to treat ADHD and narcolepsy.

◦Concerta ER: do not crush, chew, dissolve

◦Daytrana – transdermal patch

Amphetamine/Dextroamphetamine (Adderall, Adderall XR)

Mechanism of action: Promotes the release of dopamine and norepinephrine while inhibiting their reuptake.

•Uses: Treatment for ADHD and narcolepsy.

Dexmethylphenidate (Focalin)

Mechanism of action: works similar to methylphenidate on dopamine and norepinephrine reuptake inhibition.

•Uses: Used for ADHD treatment.

Lisdexamfetamine (Vyvanse)

Mechanism of action: A prodrug of dextroamphetamine that is converted to active form in the body, increasing dopamine and norepinephrine.

•Uses: Used to treat ADHD and binge eating disorder.

Side Effects and Adverse Reactions of stimulants

Cardiovascular effects: Increased heart rate, elevated blood pressure, and tachycardia. Patients with preexisting heart conditions should be carefully monitored.

•Central nervous system effects: Insomnia, anxiety, restlessness, nervousness, tremors, and agitation.

•Appetite suppression: Common with stimulants like amphetamine and methylphenidate, leading to weight loss.

•Gastrointestinal effects: Dry mouth, nausea, abdominal pain, and constipation.

•Psychiatric effects: Mood swings, irritability, psychosis, and in rare cases, hallucinations or manic episodes.

•Risk of abuse and dependence: Amphetamines and related drugs have a high potential for abuse, leading to dependence and addiction, especially when used recreationally.

Nursing Implications for Stimulants

Monitor BP, HR, and weight

◦Monitor growth in children

◦Administer early in the day-Give last dose before 6 pm (sleep disruption)

◦Assess for substance misuse

◦Contraindicated in uncontrolled hypertension

◦Avoid caffeine-containing beverages

◦Drug holidays (maybe weekends)

◦Monitor behavior

◦Be cautious with extended-release formulations, which are designed to be taken once daily. These should not be crushed or chewed.

 

Non-Stimulants for ADHD

ADHD (especially when stimulants are not tolerated)

Examples

◦Atomoxetine

◦Guanfacine

◦Clonidine

Mechanism of Action

◦Atomoxetine: selective norepinephrine reuptake inhibitor

◦Guanfacine & clonidine: alpha-2 adrenergic agonists

Side Effects

◦Sedation (alpha-2 agonists)

◦Hypotension

◦Dry mouth