Drugs for Degenerative Diseases of the Nervous System

Alzheimer’s Multiple sclerosis Parkinson’s disease

Most common degenerative disease of CNS Progressive loss of brain function Memory loss, confusion, dementia

Structural Damage in Brain  Consists of Amyloid plaques Neurofibrillary tangles  Changes found during autopsies  Structural changes cause loss of neuron number and function  Symptoms result from progressive damage to neurons in hippocampus Requires acetylcholine as neurotransmitter

Goals of Pharmacotherapy for Alzheimer’s Disease  Slow memory loss  Slow dementia symptoms  Improve activities of daily living  Improve behavior  Improve cognition

Acetylcholinesterase (AchE) Inhibitors  Prevent breakdown of acetylcholine Enhances transmission in cholinergic neurons  Only slows progression  Examples Donepezil hydrochloride (Aricept) Galantamine (Razadyne, Reminyl) Rivastigmine tartrate (Exelon) Tacrine (Cognex)

Acetylcholinesterase (AChE) Inhibitors  Prototype drug: donepezil hydrochloride (Aricept)  Mechanism of action: to prevent breakdown of acetylcholine; enhance transmission in neurons  Primary use: slow progression of the disease  Adverse effects: nausea/vomiting, dizziness and headache, bronchoconstriction, liver injury (tacrine(Cognex))

Nursing Considerations with AChE Inhibitors  Assess baseline vitals  Monitor for hypotension  Monitor for change in mental status or mood  Monitor for dizziness, insomnia, anorexia  Clients with narrow-angle glaucoma should not take revastigmine (Exelon)

AChE Inhibitors Client Teaching  Take with food or milk to avoid GI upset  Take as prescribed  Teach signs and symptoms of overdose Severe nausea/vomiting, sweating, salivation, hypotension Bradycardia, convulsions, increased muscle weaknesses (including respiratory muscles)

Adjunct AD Medicines  Antipsychotic agents  Anxiolytics  Mood stabilizers

Demyelination of neurons in CNS Progressive weakness, visual disturbances Mood alterations, cognitive deficits

Multiple Sclerosis  Etiology unknown  Possible causes Genetic or microbial factors  Climate Microscopic pathogens

Multiple Sclerosis (continued)  Demyelination of neurons in CNS  Destruction of axons impairs ability of nerves to conduct electrical impulses  Inflammation; plaque (scleroses)

Signs and Symptoms of MS  Fatigue  Heat sensitivity  Neuropathic pain; spasticity  Impaired cognitive ability  Disruption of balance and coordination  Visual disturbances; slurred speech  Bowel and bladder symptoms  Dizziness; vertigo

Efficacy of Drug Therapy  No cure  Moderate efficacy  All drugs have equal efficacy  Ineffective in late stages  New drugs under investigation Namenda Aricept

Immunomodulators  Disease modifying drugs used for treatment of relapse-remitting MS and secondary-progressive MS  Two categories Interferon beta (Avonex, Rebif, Bataseron) Glatiramer acetate (Copaxone)  Synthetic protein that simulates myelin basic protein  Reduce symptoms and decrease lesions

Immunomodulators  Drugs Interferon beta (Avonex, Rebif, Betaseron) glatiramer acetate (Copaxone)  Primary Use: Reduce severity of symptoms; decrease lesions  Adverse Effects: flushing, chest pain, weakness, infection, pain, nausea, joint pain, anxiety, muscle stiffness

Immunosuppressants  Used for progressive-relapsing MS patients  Mitoxantrone (Novantrone)  Primarily a chemotherapeutic drug; toxicity is concern

Immunosuppressants  Drug: Mitoxantrone (Novantrone)  Primary Use: for MS patients who have not responded to immune- modulating therapy  Adverse Effects: toxicity; hair loss; GI discomfort; allergic symptoms; blue-green tint to urine

Second most common CNS disease Progressive loss of dopamine Tremor, muscle rigidity Abnormal movement and posture

Symptoms of Parkinson’s Disease  Symptoms known as parkinsonism Tremors Muscle rigidity Bradykinesia Postural instability Affective flattening

Health Problems in Parkinsons’ Patients  Primarily affects muscle movement  Patients often experience other health issues Anxiety, depression Sleep disturbances Dementia Autonomic nervous system disturbances

Neurotransmitters  Dopamine and acetylcholine in corpus striatum Affect balance, posture Affect muscle tone, involuntary movement  Absence of dopamine Allows acetylcholine stimulation

Antiparkinsonism Agents  Restore balance of dopamine and acetylcholine in brain Dopaminergic drugs  Dopaminergic adjunct agents Anticholinergics (cholinergic blockers)

Drug Therapy for Parkinsonism  Restores dopamine function  Blocks acetylcholine  Clients exhibit extrapyramidal side effects (EPS) due to lack of dopamine Recall when we give psychotic patients dopamine inhibitors, they also get EPS

Dopaminergics  Restore balance of dopamine and acetylcholine  Dopaminergic examples Levodopa (Larodopa), Levodopa and carbidopa (Sinemet)

Dopaminergic Agents  Prototype drug: levodopa (Larodopa) Mechanism of action: Increases biosynthesis of dopamine within nerve terminals  Primary use: to restore dopamine function or stimulate dopamine receptors within the brain

Dopaminergic Agents (continued)  Adverse effects: dizziness, light- headedness, sleep dysfunction, fatigue, nausea, vomiting, constipation, orthostatic hypertension, dystonia, dyskinesia, wearing off effect  Need liver function studies can cause hepatoxicity

Role of the Nurse: Dopaminergic Drug Therapy  Contraindicated in narrow-angle glaucoma  Monitor for hypotension and tachycardia  Look for symptoms of drug toxicity

Dopaminergics Client Teaching  *Increase fiber and fluids  Avoid food and drugs high in pyridoxine (B6) i.e., protein  May take several months for full effect  Abruptly stopping the drug may cause Parkinsonism crisis  Take on an empty stomach

Dopaminergic Adjunct Agents  Inhibit enzymes Example: Tolcapone (Tasmar)  Activate dopamine receptors (dopamine agonists) Example: Ropinirole (Requip)  Cause dopamine release from nerve terminals Example: Amantadine (Symmetrel)

Anticholinergic Agents  Centrally acting  Block acetylcholine Inhibits overactivity in brain  Used in early stages  Examples Benztropine mesylate (Cogentin) Triexyphenidyl hydrochloride (Artane)

Anticholinergic Agents  Prototype drug: benztropine mesylate (Cogentin)  Mechanism of action: block acetylcholine; inhibit overactivity in brain  Primary use: in early stages of disease  Adverse effects: dry mouth, blurred vision, photophobia, urinary retention, constipation, tachycardia, glaucoma

Anticholinergics Client Teaching  Relieve dry mouth with frequent drinks or sugarless hard candy  Take with food or milk to prevent GI upset  Avoid alcohol  Wear dark glasses; avoid bright sunlight  Do not stop taking abruptly

Catechol-O-Methyl Transferase (COMT) Inhibitors  Reduce requirement for L-dopa  Increase concentration of existing dopamine; improve motor fluctuations  Examples: entacapone (Comtan) tolcapone (Tasmar)

Drugs for Neuromuscular Disorders

Muscle Movement Dependent on Body Systems  Nervous  Muscular  Endocrine  Skeletal

Muscle Spasms  Involuntary contractions of muscles Tonic spasm Clonic spasm  Diminished level of functioning

Causes of Muscle Spasms and Spasticity  Excessive use or local injury to skeletal muscle  Overmedication with antipsychotics  Epilepsy  Hypocalcemia pain  Neurologic disorders

Nonpharmacologic Treatment of Muscle Spasms  Immobilization  Application of heat or cold  Hydrotherapy  Ultrasound  Supervised exercise  Massage  Manipulation  PT, surgery

Pharmacologic Treatment  Combination of Analgesics Anti-inflammatory agents Centrally acting skeletal muscle relaxants

Centrally Acting Skeletal Muscle Relaxants  Inhibit motor neurons within brain and/or spinal cord Depress CNS effects; alter spinal reflexes  Reduce pain; increase range of motion  Potential to cause sedation

Centrally Acting Muscle Relaxants  Prototype drug: cyclobenzaprine (Flexeril)  Mechanism of action: inhibits upper-motor- neuron activity Causes CNS depression, alters simple spinal reflexes  Primary use: to treat localized spasms  Adverse effects: CNS depression, hepatic toxicity, physical dependence, anticholinergic effects

Direct-Acting Antispasmodics  Act at neuromuscular junction and skeletal muscle  Suppress hyperactive reflexes  Are used for spasms associated with CNS disorders

Direct-Acting Antispasmodics  Prototype drug: dantrolene (Dantrium)  Mechanism of action: interferes with release of calcium ions in skeletal muscle  Primary use: to relieve dystonias and leg cramps, also used for *malignant hyperthermia  Adverse effects: hepatic toxicity, muscle weakness, drowsiness, diarrhea