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Western Governors University
D116 Advanced Pharmacology for the Advanced Practice Nurse
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Cholinergic receptors are classified into muscarinic and nicotinic subtypes, each with distinct anatomical locations and physiological responses. These receptors mediate the actions of acetylcholine within the central and peripheral nervous systems. Understanding receptor distribution is critical for anticipating both therapeutic effects and adverse reactions of cholinergic and anticholinergic medications.
| Receptor Subtype | Primary Location | Physiological Response |
|---|---|---|
| Muscarinic (M1–M5) | CNS, heart, smooth muscle, glands | Regulation of heart rate, glandular secretion, smooth muscle contraction |
| Nicotinic (Nm) | Neuromuscular junction | Skeletal muscle contraction |
| Nicotinic (Nn) | Autonomic ganglia, adrenal medulla | Autonomic nervous system activation |
Pramipexole (Mirapex) belongs to the class of nonergot dopamine receptor agonists. It is primarily utilized in the management of Parkinson’s disease (PD) and restless legs syndrome (RLS).
Pramipexole selectively stimulates dopamine D2 and D3 receptors, with its therapeutic benefits largely attributed to D2 receptor activation. By directly mimicking dopamine in the basal ganglia, pramipexole compensates for dopamine deficiency characteristic of Parkinson’s disease.
In early-stage Parkinson’s disease, pramipexole may be used as monotherapy. In more advanced stages, it is commonly combined with levodopa to reduce motor fluctuations. Additionally, pramipexole is FDA-approved for moderate to severe restless legs syndrome.
Ergot-derived dopamine agonists, such as bromocriptine and cabergoline, were historically used in Parkinson’s disease management. However, their use has significantly declined.
Although these agents activate dopamine receptors, they also antagonize serotonergic and α-adrenergic receptors. This lack of selectivity increases the risk of adverse effects, including cardiac valvulopathy and fibrotic complications, leading to their avoidance in contemporary Parkinson’s disease treatment.
The first-line pharmacologic treatment for moderate to severe restless legs syndrome is pramipexole, due to its dopaminergic activity and favorable efficacy profile. Restless legs syndrome is characterized by uncomfortable lower-extremity sensations that provoke an urge to move, particularly during periods of rest.
Gabapentin is also commonly used, especially in patients with comorbid neuropathic pain or sleep disturbances, offering an alternative mechanism of symptom control.
Preventive therapy for cluster headaches focuses on reducing attack frequency and severity. Several medication classes are employed for prophylaxis:
| Drug Class | Examples | Clinical Rationale |
|---|---|---|
| Calcium channel blockers | Verapamil | First-line preventive agent |
| Glucocorticoids | Prednisone, dexamethasone | Short-term suppression of inflammation |
| Mood stabilizers | Lithium | Useful in chronic cluster headache |
Migraine pharmacotherapy is divided into abortive and preventive strategies, depending on treatment goals.
The objective of abortive therapy is to terminate an active migraine attack and alleviate associated symptoms such as nausea and vomiting. These agents are taken at the onset of symptoms.
Nonspecific agents: NSAIDs and opioid analgesics
Migraine-specific agents: Triptans (serotonin 5-HT1B/1D agonists) and ergot alkaloids
Preventive medications are used to decrease migraine frequency and severity over time.
| Drug Class | Examples |
|---|---|
| Beta blockers | Propranolol |
| Tricyclic antidepressants | Amitriptyline |
| CGRP receptor antagonists | Erenumab |
| Antiepileptics | Divalproex |
The primary objective of pharmacologic therapy in schizophrenia is relapse prevention and symptom stabilization. Maintenance treatment with antipsychotic medications significantly reduces the likelihood of acute psychotic episodes, although it may not fully prevent long-term cognitive or functional decline.
Ongoing assessment is essential when treating depression pharmacologically. Follow-up should focus on evaluating therapeutic response, side effects, and patient safety, including monitoring for suicidal ideation.
After initiating antidepressant therapy, the medication should be continued for 4 to 8 weeks to assess effectiveness. Dosages are typically started low and titrated upward to minimize adverse effects.
Increase the dosage
Switch to another medication within the same class
Switch to a different antidepressant class
Add an adjunctive agent, such as an atypical antidepressant
Lithium has a narrow therapeutic index, making laboratory monitoring essential.
| Serum Lithium Level | Clinical Effects |
|---|---|
| < 1.5 mEq/L | Therapeutic range; mild tremor, GI upset may occur |
| 1.5–2.5 mEq/L | Moderate toxicity; confusion, worsening tremor |
| > 2.5 mEq/L | Severe toxicity; seizures, coma, death |
Therapeutic serum levels generally range from 0.6 to 1.2 mEq/L, depending on the clinical indication.
Atypical antidepressants act through varied mechanisms, including dopamine and norepinephrine reuptake inhibition or serotonin receptor modulation.
Frequently reported side effects include agitation, headache, dry mouth, constipation, gastrointestinal upset, weight loss, dizziness, tremor, insomnia, blurred vision, and tachycardia. Individual drug profiles may vary.
Cholinesterase inhibitors enhance cholinergic transmission by preventing acetylcholine breakdown.
| Type | Duration of Action | Common Indications |
|---|---|---|
| Reversible inhibitors | Moderate | Myasthenia gravis, Alzheimer disease, glaucoma, Parkinson disease dementia |
| Irreversible inhibitors | Long-lasting | Limited therapeutic use; some used in glaucoma |
Reversible agents are preferred clinically due to their safer and more predictable effects.
Clonidine is a centrally acting α2-adrenergic agonist approved for hypertension, severe pain, and ADHD.
Patients should be instructed to:
Monitor and record blood pressure daily
Apply patches to clean, hairless, intact skin on the upper arm or torso
Replace the transdermal patch every 7 days
Avoid abrupt discontinuation to prevent rebound hypertension
American Psychiatric Association. (2022). Practice guideline for the treatment of patients with schizophrenia. APA Publishing.
Katzung, B. G., Vanderah, T. W., & Trevor, A. J. (2021). Basic & clinical pharmacology (15th ed.). McGraw-Hill Education.
Stahl, S. M. (2021). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (5th ed.). Cambridge University Press.
UpToDate. (2024). Pharmacologic management of Parkinson disease and migraine disorders. Wolters Kluwer.
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