Chapter 10

DRUGS FOR CENTRAL NERVOUS SYSTEM PROBLEMS

INTRODUCTION TO CLINICAL PHARMACOLOGY

  • Clinical pharmacology focuses on the study of drugs used in the treatment of diseases and their effects on biological systems.

NERVOUS SYSTEM OVERVIEW

  • The Nervous System is categorized into:
      - Central Nervous System (CNS)
      - Peripheral Nervous System (PNS)

  • Two types of neurotransmitters are identified:
      - Excitatory Neurotransmitters
      - Inhibitory Neurotransmitters

DOPAMINE AGONISTS

  • Common names for dopamine agonists include:
      - Pramipexole (Mirapex)
      - Ropinirole (Requip)

  • Purpose: Helps patients with Parkinson's disease to improve mobility and movement.

ACTION AND USES

  • Dopamine agonists are effective in reducing muscle tremors and rigidity.

  • They also improve:
      - Mobility
      - Muscular coordination
      - Performance

EXPECTED SIDE EFFECTS

  • Potential side effects include:
      - Postural hypotension
      - General hypotension
      - Headache
      - Gastrointestinal disturbances
      - Insomnia
      - Dream abnormalities
      - Impulse control issues
      - Confusion

ADVERSE REACTIONS

  • Severe side effects can include dyskinesia.

DRUG INTERACTIONS

  • Severe hypotension may occur when combined with other dopamine agonists.

  • Mixing with older, non-selective MAO inhibitors can precipitate a hypertensive crisis.

NURSING IMPLICATIONS AND PATIENT TEACHING

  • Ensure proper assessment of:
      - Postural hypotension
      - Melanoma or closed-angle glaucoma

  • Monitor blood test results.

  • Stress proper self-administration.

  • Evaluate for adverse effects such as akinesia, tardive dyskinesia, and dystonia.

  • Educate patient and family regarding the use and effects of dopamine agonists.

CATECHOL-O-METHYLTRANSFERASE (COMT) INHIBITORS

  • Medications: Include Entacapone, Tolcapone, and Opicapone.

  • Function: These are prescription medications that are used alongside levodopa/carbidopa to treat Parkinson’s disease.

  • They enhance levodopa's effectiveness by preventing its premature breakdown, effectively reducing "wearing-off" symptoms.

COMMON SIDE EFFECTS

  • Include:
      - Dyskinesia
      - Diarrhea
      - Changes in urine color.

ACTION AND USES

  • COMT inhibitors work by inhibiting an enzyme that breaks down catecholamine-based neurotransmitters, which include dopamine.

EXPECTED SIDE EFFECTS/ADVERSE REACTIONS

  • Possible side effects include dyskinesia and hypotension.

DRUG INTERACTIONS

  • COMT inhibitors should not be taken with other MAO inhibitors.

NURSING IMPLICATIONS AND PATIENT TEACHING

  • Key assessments include monitoring for orthostatic hypotension and liver function tests.

  • Evaluate for akinesia, dystonia, and tardive dyskinesia.

MONOAMINE OXIDASE TYPE B (MAO-B) INHIBITORS

  • Function: They break down dopamine and serotonin.

EXPECTED SIDE EFFECTS

  • Possible side effects include:
      - Dry mouth
      - Nausea
      - Constipation
      - Lightheadedness.

ADVERSE REACTIONS

  • Hypertension may occur but is typically only present at high doses.

DRUG INTERACTIONS

  • Significant drug interactions include:
      - Opiate drugs
      - Tricyclic antidepressants
      - Amphetamines
      - Phenylephrine
      - Dextromethorphan

NURSING IMPLICATIONS AND PATIENT TEACHING

  • Vital signs need to be monitored.

  • Observe for behavior changes.

CHOLINESTERASE INHIBITORS

  • Commonly used medications:
      - Donepezil (Aricept)
      - Rivastigmine (Exelon)
      - Galantamine (Razadyne)
      - Pyridostigmine (Mestinon)
      - Neostigmine/Physostigmine (for neuromuscular blockade reversal).

ACTION

  • All cholinesterase inhibitors bind to acetylcholinesterase and slow its action, increasing acetylcholine levels in the brain.

EXPECTED SIDE EFFECTS

  • Common effects include:
      - Mild diarrhea
      - Headache
      - Loss of appetite
      - Gastrointestinal discomfort.

ADVERSE REACTIONS

  • Can include hallucinations, dysrhythmias, gastrointestinal bleeding, and difficulty with urination.

DRUG INTERACTIONS

  • Should not be combined with other drugs that can prolong the QT interval on ECG.

NURSING IMPLICATIONS AND PATIENT TEACHING

  • Assessment should include baseline weight and monitoring for gastrointestinal bleeding.

  • Patients with asthma require close monitoring for worsening symptoms during treatment.

  • Evaluate improvements using Alzheimer's disease assessment scales.

NMDA (N-METHYL-D-ASPARTATE) BLOCKERS

  • Common NMDA receptor medications:
      - Memantine (Namenda): Used for moderate to severe Alzheimer's disease.
      - Esketamine (Spravato): Fast-acting nasal spray for treatment-resistant depression.
      - Amantadine (Gocovri): For Parkinson's disease and some neuro-pain conditions.

ACTION AND USES

  • NMDA blockers reduce neuronal damage associated with Alzheimer's disease by blocking calcium entry into neurons.

EXPECTED SIDE EFFECTS

  • Possible side effects include:
      - Headaches
      - Dizziness
      - Constipation.

ADVERSE REACTIONS

  • May lead to hallucinations, worsening confusion, depression, and weight loss.

DRUG INTERACTIONS

  • Attention to other drugs affecting renal excretion of memantine is crucial to prevent side effects.

NURSING IMPLICATIONS AND PATIENT TEACHING

  • Comprehensive assessments of patient condition must be done, which include monitoring for side effects and efficacy of treatment.

DRUGS FOR EPILEPSY

  • Definition: Seizures are characterized by sudden, unregulated muscle contractions occurring without conscious control.

  • Common Causes: These can result from diseases, disorders, head injuries, or can be idiopathic.

  • Major Drug Classes: Include:
      - Phenytoin
      - Carbamazepine
      - Ethosuximide
      - Phenobarbital
      - Valproic Acid

ACTIONS AND USES

  • Phenytoin: Binds to sodium channels on nerve membranes, reducing their activity.

  • Carbamazepine: Alters sodium channel activity to limit neuronal excitation spread.

  • Ethosuximide: Raises seizure threshold through calcium channel modulation.

  • Phenobarbital: Enhances GABA activity leading to CNS depression.

  • Valproic Acid: Increases GABA activity, though other mechanisms remain unclear.

EXPECTED SIDE EFFECTS

  • Each drug class has specific side effects, such as:
      - Phenytoin: Gum hyperplasia
      - Carbamazepine: Abdominal discomfort, increased risk of sunburn
      - Ethosuximide: Nausea, dizziness
      - Phenobarbital: Drowsiness
      - Valproic Acid: Menstrual irregularities

ADVERSE REACTIONS

  • Include serious adverse effects such as birth defects, anemia, and gastrointestinal bleeding associated with phenytoin and carbamazepine.

DRUG INTERACTIONS

  • Combinations of various drugs may lead to complex interaction effects, warranting careful monitoring.

NEWER ANTIEPILEPTIC DRUGS

  • Common Medications Include:
      - Oxcarbazepine:
        - Action: Blocks sodium channels
        - Side Effects: Drowsiness, dizziness.
      - Lamotrigine:
        - Action: Used for partial seizures and bipolar disorder
        - Risks: Life-threatening rashes.
      - Lacosamide:
        - Action: Stabilizes neuronal membranes
        - Risks: Can cause euphoria, psychological dependence.
      - Topiramate:
        - Action: Reduces seizure spread without raising the threshold
        - Risks: Memory impairment.
      - Levetiracetam:
        - Action: Modulates neurotransmitter release
        - Risks: Agitation, depression.

NURSING IMPLICATIONS AND PATIENT TEACHING

  • There are extensive drug interactions across newer medications, requiring attention to patient education and monitoring for side effects.

SPECIFIC DRUGS FOR MULTIPLE SCLEROSIS

  • Biological Response Modifiers:
      - Modify immune response against harmful triggers.

  • Monoclonal Antibodies:
      - Attack lymphocytes to preserve myelin integrity.

  • Neurologic Drugs:
      - Tecfidera: Reduces CNS inflammation.
      - Ampyra: Maintains action in unmyelinated nerves.

DRUGS FOR AMYOTROPHIC LATERAL SCLEROSIS (ALS)

  • Glutamine Antagonists:
      - Riluzole: Inhibits glutamate actions, providing neuroprotection.
      - Side effects may include gastrointestinal disturbances and neutropenia.
      - Require careful monitoring of liver function and neurological symptoms during treatment.

DRUGS FOR MYASTHENIA GRAVIS

  • Acetylcholinesterase Inhibitors:
      - Inhibit the breakdown of acetylcholine.

  • Expected Side Effects:
      - Include nausea, vomiting, and increased salivation.
      - Adverse effects necessitate close monitoring of respiratory function and vital signs, especially in patients with respiratory conditions.