DEGENERATIVE DISEASES OF THE CENTRAL NERVOUS SYSTEM NCM 106: P

PARKINSON DISEASE

Characterized by tremors, rigidity, bradykinesia (slowness of movement), and difficulty with posture and gait

PARKINSONISM

A term for parkinson-like symptoms caused by drugs or brain injuries

Shuffling gait

drooling

slurred speech

mask-like expression

swallowing difficulties

PROGRESSION OF SYMPTOMS OF PARKINSON DISEASE:

PARKINSON DISEASE

does not affect cognitive abilities, so individuals may remain mentally sharp despite physical decline

Basal ganglia damage

Dopamine reduction

Motor system impact

Neurotransmitters

PATHOPHYSIOLOGY OF PD

Basal ganglia damage

neurons in the basal ganglia, particularly substantia nigra, degenerate

Dopamine reduction

decreased dopamine levels lead to a chemical imbalance

Motor system impact

impairment of muscle tone and coordination, affecting movement and posture

Neurotransmitters

imbalance between dopamine (inhibitory) and acetylcholine (excitatory) disrupts motor control

Motor symptoms

Speech and swallowing issues

Facial expression

Cognitive function

SYMPTOMS of PD:

Cognitive function

alertness remains intact, but physical decline occurs

Facial expression

mask like appearance due to cranial nerve

Speech and swallowing issue

drooling, slurred speech, difficulty swallowing

Motor symptoms

tremors, rigidity, bradykinesia, shuffling gait

No cure

Medications

Surgical procedures

TREATMENT OPTIONS of PD:

Surgical procedures

basal ganglia surgery has shown mixed results

Medications

aimed at restoring dopamine balance in the brain

Type 1 drugs

Type 2 drugs

Two types of Medications:

Type 2 drugs

block cholinergic effects (excitatory)

Type 1 drugs:

affect dopamine (inhibitory)

No cure

current treatment focus on symptom management

Exercise

Swallowing

Psychological support

Patient and family education

MANAGEMENT OF PD:

Exercise

encouraged to prevent skeletal deformities and improve mobility

Swallowing

speech therapy and thickening agents to aid swallowing

Psychological support

address emotional challenges like depression, as PD is a degenerative disease

Patient and family education

monitoring drug protocols and managing adverse effects

DOPAMINERGIC AGENTS

-Drugs that increase dopamine effects at receptors sites

-More effective than anticholinergics in treating parkinsonism

Amantadine

Apomorphine

Bromocriptine

Levodopa

Carbidopa-levodopa

pramipexole

Rasagiline

Ropinirole

Rotigotine

DOPAMINERGIC AGENTS (COMMON DRUGS INCLUDE:)

APOMORPHINE ADMINISTRATION

Administered subcutaneously, not orally

Often given with trimethobenzamide to prevent nausea

Important: ________ is used for quick relief of motor symptoms in advanced parkinson’s disease

Levodopa

precursor of dopamine, crosses the blood-brain barrier

Carbidopa

Inhibits peripheral metabolism of levodopa, allowing more levodopa to reach the brain

Combination (Sinemet)

Reduces levodopa dose needed, improving effectiveness and reducing side effects

Amantadine

Increases dopamine release, effective early in the disease

Apomorphine

Directly stimulates dopamine receptors

Bromocriptine, Pramipexole, Rotigotine

Direct dopamine agonists, act or dopamine receptors in the substantia nigra

Ropinirole

Newer agent, also used for restless leg syndrome

Rotigotine (Neupro)

Available in a transdermal patch, helpful when swallowing is difficult

Rasagiline

Inhibits MAO-B, increases dopamine levels, fewer peripheral side effects

MAOIs + Dopaminergics

Risk of hypertensive crisis; stop MAOls 14 days before starting dopaminergics

Levodopa + Vitamin B6 / Phenytoin

Decreased efficacy of levodopa

Dopamine antagonists

Can reduce the effectiveness of dopaminergics

Rasagiline

Avoid tyramine-rich foods, St. John's wort, and meperidine

ANTICHOLINERGIC AGENTS

oppose the effects of acetylcholine at receptor sites in the substantía nigra and corpus striatum

Help restore chemical balance in the brain

Benztropine (Cogentin)

Diphenhydramine (Benadryl)

Trihexyphenidyl (generic)

ANTICHOLINERGIC AGENTS (Common Drugs)

Blockage of Acetylcholine Receptors

These agents block acetylcholine receptors in the CNS, which helps balance the neurotransmitters

Adjunctive Therapy

Less effective than levodopa, but can help manage symptoms when levodopa alone is not sufficient indications

ANTICHOLINERGIC AGENTS

Variably absorbed from the Gl tract, peak levels in 1 to 4 hours

ANTICHOLINERGIC AGENTS

Allergy to the drug or its components

Narrow-angle glaucoma, Gl obstruction, GU obstruction, prostatic hypertrophy, and myasthenia gravis

Tricyclic antidepressants and phenothiazines

Increased risk of paralytic ileus and toxic psychoses

Antipsychotic drugs

May decrease the effectiveness of antipsychotic drugs due to central antagonism

Supportive Measures

Monitor closely and adjust doses if necessary

ADJUNCTIVE AGENTS

are used to improve the effectiveness of traditional Parkínson's disease therapies (such as carbidopa-levodopa)

Entacapone (Comtan)

Safinamide Xadago)

Selegiline (Eldepryl)

Tolcapono (Tasmar)

Examples of adjunctive agents:

Entacapone (Comtan)

● Inhibits COMT (catechol-O-methyltransferase) which breaks down dopamine

● Increases plasma concentration and duration of levodopa effects

Entacapone (Comtan)

● Max 8 doses per day

● Given with carbidopa-levodopa at a dose of 200 mg PO

Entacapone (Comtan)

● Available as Stalevo (fixed combination of levodopa, carbidopa, and entacapone

Tolcapone (Tasmer)

● Similar to entacapone, it inhibits COMT, prolonging levodopa effects

Tolcapone (Tasmer)

● 100-200 mg PO, up to 3 times a day, max dose: 600 mg/day

Safinamide (adago)

● MAO-B inhibitor. Blocks the breakdown of dopamine, enhancing its effects

● Used to treat "off* episodes in Parkinson's patients

Safinamide (adago)

● 50-100 mg once a day

● no need to adjust for tyramine intake

Selegiline (Eldepryl)

● Max dose: 10 mg/day

● Reduce levodopa dose when starting selegiline

Selegiline (Eldepryl)

● Used in combination with carbidopa-levodopa when response deteriorates

Selegiline (Eldepryl)

● Irreversibly inhibits MAO-B, which breaks down dopamine in the brain

● Enhances dopamine activity in the brain

Entacapone & Tolcapone

● Both inhibit COMT to increase levodopa effects

● Tolcapone has a higher risk of liver damage; use cautiously

MAO-B inhibitors

Block the breakdown of dopamine

Selegiline

Risk of hypertensive crisis with high tyramine intake

MUSCLE RELAXANTS

Muscle injuries, accidents, or CNS damage often lead to muscle spasm and Muscle relaxants help treat both muscle spasm and spasticity

Muscle spasm

Temporary muscle contraction due to injury

Muscle spasticity

Chronic, sustained muscle contraction due to CNS damage

Centrally Acting Relaxants

Direct-Acting Relaxants

Types of Muscle Relaxants:

Centrally Acting Relaxants

Work on the brain and spinal cord (e.g, baclofen, cyclobenzaprine)

Direct-Acting Relaxants

Act directly on muscle fibers (eg, botulinum toxin, dantrolene)

Spinal Motor Neurons

Muscle Contraction and Relaxation:

Spinal Motor Neurons

Cerebellum & Basal Ganglia

Brain Control

Regulate posture, balance, and movement

Cerebellum & Basal Ganglia

Coordinate muscle movements (both conscious and unconscious)

Brain Control

Cerebral cortex sends signals to control precise movements and muscle actions

Gamma Loop Reflex

Reflex Arc Pathway

Spinal Reflex Arcs:

Gamma Loop Reflex

Helps maintain muscle tone and body position

Reflex Arc Pathway

• Sensory neuron → Interneuron → Motor neuron → Muscle contraction

• Maintains posture, balance, and promotes venous return

Pyramidal Tract

Extrapyramidal Tract

Neuromuscular Junction

Motor Control Areas in the Brain:

Pyramidal Tract

Controls precise, voluntary movements

Extrapyramidal Tract

Coordinates unconscious muscle activities (balance, posture)

Neuromuscular Junction

Nerve impulses lead to muscle contraction via calcium release

Muscle Spasm

Muscle Spasticity

Neuromuscular Abnormalities Common Disorders:

Muscle Spasm

Caused by injury (muscle overstretch, joint wrenching)

Muscle Spasticity

out of NS damage leading to permanent contraction

Paralysis

Loss of movement control due to nerve damage

Muscle Spasm

● Involuntary contraction caused by injury

● Leads to pain, swelling, and inflammation

● Treated with centrally acting muscle relaxants

Muscle Spasticity

● Chronic condition due to CNS damage

● Results in sustained contractions and hypertonia (increased muscle tone)

● Treated with direct-acting relaxants (e.g., dantrolene)

Hypertonía

Increased muscle tone

Contractures

Permanent muscle shortening

Loss of Coordination

Disrupted muscle activity

Spasticity

● Excessive stimulation of muscles due to loss of inhibitory control

● Leads to sustained muscle contractions

● Can result in permanent muscle deformities and functional impairments

CENTRALLY ACTING MUSCLE RELAXANTS

are used to treat muscle Spasms

● These medications act on the central nervous system (CNS) to relieve discomfort associated with acute musculoskeletal conditions

Baclofen (Lioresal)

Carisoprodol (Soma)

Cyclobenzaprine (Amrix)

Tzanidline (Zanaflex)

Chlorzoxazone

Mctaxcalone

Methocarbamol

Orphenadrine

Diazepam (Valium)

CENTRALLY ACTING MUSCLE RELAXANTS EXAMPLES:

Spasmolytics

● Work on the CNS to interfere with reflexes causing muscle spasms

● Often referred to as

Tizanidine

A|pha-adrenergic agonist that increases inhibition of motor neurons

CENTRALLY ACTING MUSCLE RELAXANTS

● Relief of discomfort from acute musculoskeletal conditions

● Used as adjunctive therapy with rest. Physical therapy, and other measures

● Diazepam may be particularly useful when anxiety is contributing to muscle spasms

CENTRALLY ACTING MUSCLE RELAXANTS

● Rest of the affected muscle

● Ice for acute injuries to decrease inflammation

● Compression and elevation to reduce swelling

● Physical therapy to help restore normal muscle tone

● Heat applications to Improve blood flow and alleviate-pain causing chemicals

● NSAIDs for pain relief it the problem 's related to injury/inflammation

Baclofen

Available in oral and intrathecal forms; can be administered via delivery pump for central spasticity