Drugs Affecting the Central & Autonomic Nervous System

Overview of the Nervous System

• The Nervous System is divided into two primary divisions:   - Central Nervous System (CNS): Includes the Brain and the Spinal cord.   - Peripheral Nervous System: Divided into the Somatic nervous system (affecting skeletal muscle) and the Autonomic nervous system.
• The Autonomic Nervous System is categorized into two functional branches:   - Parasympathetic (Cholinergic): Mediated by the neurotransmitter Acetylcholine ($ACh$).   - Sympathetic (Adrenergic): Mediated by the neurotransmitter Norepinephrine ($NE$). Receptors include $Alpha$ ($1$, $2$) and $Beta$ ($1$, $2$).

Autonomic Nervous System (ANS) Responses

• Parasympathetic Nervous System ($PNS$): Known as the "Rest and Digest" Response.   - Eyes: Constricts pupils.   - Salivary Glands: Stimulates salivation.   - Heart: Slows heartbeat.   - Lungs: Constricts bronchi.   - Stomach: Stimulates digestion.   - Liver: Stimulates bile release.   - Intestines: Stimulates peristalsis and secretion.   - Bladder: Contracts bladder.   - Anatomical components involved: Medulla Oblongata, Vagus Nerve, Ganglion.
• Sympathetic Nervous System ($SNS$): Known as the "Fight or Flight" Response.   - Eyes: Dilates pupils.   - Salivary Glands: Inhibits salivation.   - Heart: Accelerates heartbeat.   - Lungs: Dilates bronchi.   - Stomach: Inhibits digestion.   - Liver: Stimulates glucose release.   - Kidneys: Stimulates epinephrine and norepinephrine release.   - Intestines: Inhibits peristalsis and secretion.   - Bladder: Relaxes bladder.   - Anatomical components involved: Solar Plexus, Chain of Sympathetic Ganglia.

Neurotransmission and Receptor Mechanisms

• Neurotransmitters: These are chemical substances that enable messages to be transmitted by crossing a synapse. A transmitter can either excite or inhibit a physiological response at a receptor site through:   - Receptor binding.   - Reuptake.   - Metabolism.
• Activation of the $SNS$ ($5/19/2026$):   - Direct: The drug itself attaches to the receptor and mimics the neurotransmitter.   - Indirect: Causes the release of the neurotransmitter from the pre-synaptic cleft, which then attaches to the receptor.   - Mixed: A combination of both direct and indirect mechanisms.

Sympathetic Nervous System (Adrenergic) Receptors

• Adrenergic Receptors receive catecholamines/neurotransmitters (norepinephrine and epinephrine) at specific body sites:   - $Alpha\,1$: Responsible for vasoconstriction, decreased Gastrointestinal ($GI$) and bladder motility, mydriasis (pupil dilation), decreased secretions, ejaculation, uterine contractions, and glycogenolysis.   - $Alpha\,2$: Located on the presynaptic nerve; functions to inhibit the $SNS$ response.   - $Beta\,1$: Primarily affects the heart, causing increased heart rate, contraction, and conduction.   - $Beta\,2$: Causes bronchodilation, uterine relaxation, glycogenolysis, and decreased $GI$ motility.
• Dopaminergic Receptors: Respond to the catecholamine dopamine.   - Increases blood flow to the brain, heart, kidneys, and viscera.   - At high doses, these receptors cause vasoconstriction.

Parasympathetic Nervous System (Cholinergic) Receptors

• Cholinergic Receptors receive the neurotransmitter acetylcholine ($ACh$):   - Muscarinic: Increases $GI$ and bladder motility, increases secretions, constricts pupils (miosis), causes bronchoconstriction, and decreases heart rate, contraction, and conduction.   - Nicotinic receptors.

Rationales for Receptor Selectivity and Drug Actions

• Receptor Selectivity: This allows drugs to alter biological activity at specific receptors without affecting others, resulting in fewer side effects and a more therapeutic outcome.
• Agonists: Drugs that activate receptors.
• Antagonists: Drugs that inhibit or block receptor activation.
• General Pharmacological Actions:   - Increase or decrease neurotransmitter synthesis.   - Promote or inhibit the release of neurotransmitters.   - Activate receptors by binding (agonists).   - Block activation of receptors (antagonists).   - Block or promote neurotransmitter reuptake.   - Inactivate or promote enzymes that metabolize neurotransmitters.

Adrenergic Agonists (Sympathomimetics)

• Mechanism of Action: These drugs mimic the actions of norepinephrine ($NE$), epinephrine ($Epi$), and dopamine on $Alpha\,1$, $Alpha\,2$, $Beta\,1$, $Beta\,2$, and dopaminergic receptors.
• Physiological "Fight or Flight" Effects: Increased visual acuity, alertness, and muscle strength.
• Pharmacokinetics: Characterized by a rapid onset and a shorter half-life.
• Clinical Indications:   - Respiratory: Asthma and bronchitis (via $Beta\,2$ bronchodilation); Example: Albuterol (Ventolin).   - Nasal Congestion: Vasoconstriction of nasal arterioles (via $Alpha\,1$); Example: Phenylephrine (Neo-Synephrine).   - Ophthalmic: Conjunctival congestion, glaucoma, and mydriasis for eye exams (via $Alpha\,1$ or $Beta\,2$); Example: Epinephrine (Adrenalin).   - Cardiovascular: Heart failure, shock, and surgery (vasoactive/cardioselective effects via $Alpha\,1$, $Beta\,1$, $Beta\,2$, and dopaminergic receptors).     - Dobutamine (Dobutrex).     - Dopamine (Intropin).     - Norepinephrine (Levophed).     - Midodrine (ProAmatine): Specifically treats hypotension.     - Epinephrine (Adrenalin): Emergency use for anaphylactic shock.

Adrenergic Agonist Side Effects and Considerations

• Side Effects:   - $CNS$ Stimulation: Headache ($HA$), restlessness, insomnia, etc.   - Cardiovascular: Chest pain, vasoconstriction, Hypertension ($HTN$), tachycardia, palpitations, and dysrhythmias.   - Other: Sweating, nausea/vomiting, muscle cramps, and decreased urinary output.
• Warning: Monitor for IV infiltration to minimize tissue necrosis from leakage.
• Geriatric Considerations ($5/19/2026$):   - Decreased efficiency of the heart; stress, heat, and $Beta$ agonists can lead to $HTN$.   - Decreased baroreceptor sensitivity can lead to orthostatic hypotension.

Nursing Management for Adrenergic Agonists

• Nursing Activities:   - Collect a thorough health history and physical assessment.   - Monitor Blood Pressure ($BP$), Heart Rate ($HR$), breath sounds, peripheral pulses, skin color, capillary refill, and mental status.   - Assess for sensitivity to light, nausea, constipation, and urinary output.   - Always use an IV pump and assess the IV site frequently.
• Patient Education:   - Wear Medic-Alert bracelets.   - Instruction on equipment use and prevention measures for respiratory patients.

Adrenergic Antagonists (Sympatholytics)

• Mechanism of Action: These drugs "lyse" or inhibit $SNS$ stimulation by blocking adrenergic receptors.   - Alpha-blockers: Inhibit $Alpha\,1$ receptors.   - Beta-blockers: Inhibit $Beta\,1$ and/or $Beta\,2$ receptors.
• Alpha 1 Blockers:   - Action: Blocks the typical $SNS$ vasoconstriction response, leading to vasodilation.   - Indications:     - $HTN$: Doxazosin (Cardura) causes arterial and venous dilation.     - Benign Prostatic Hyperplasia ($BPH$) and Urinary Obstruction: Tamsulosin (Flomax) decreases resistance to urinary outflow in males.     - Tissue Necrosis: Phentolamine (Regitine), a potent vasodilator, is used for extravasation of IV alpha adrenergics.   - Side Effects: Severe hypotension (leading to falls or passing out) and orthostatic hypotension.   - Nursing Activities: Assess $BP$ while sitting and standing; assess apical $HR$ for $1\,minute$.   - Education: Stand slowly; avoid excessive heat, exercise, and alcohol.

Beta-Adrenergic Blockers

• Functional Specificity:   - $Beta\,1$ Blockers: Affect the heart; slow $HR$, conduction, and contractility.   - $Beta\,2$ Blockers: Affect the lungs; block bronchodilation, narrowing airways and increasing shortness of breath.
• Indications: Angina, Myocardial Infarction ($MI$), dysrhythmias, $HTN$, Heart Failure ($HF$), and migraine headaches.   - Carvedilol (Coreg).   - Metoprolol (Lopressor).   - Propranolol (Inderal): Noted for lipophilicity, allowing it to enter the $CNS$ easily.
• Contraindications:   - Drug allergies, Heart block, slow $HR$, low $BP$, pregnancy, pulmonary disease, and caution in diabetics.
• Side Effects:   - Bradycardia, decreased cardiac output/hypotension, bronchoconstriction, and hypoglycemia.

Nursing Management for Beta Blockers

• Nursing Activities:   - Monitor $BP$ and apical $HR$ for $1\,minute$.   - Assess breath sounds.
• Education Provided to Clients:   - Do not abruptly discontinue taking medications.   - Monitor daily weights.   - Prevent constipation by increasing fiber and fluids.   - Be aware the drug may cause depression and possible sexual dysfunction.   - Avoid excessive heat, exercise, and alcohol.   - Consider wearing a Medic-Alert bracelet.

Cholinergic Agonist Drugs (Parasympathomimetics)

• Mechanism of Action: Mimic the neurotransmitter acetylcholine ($ACh$) at muscarinic and nicotinic receptors.
• "Rest and Digest" Response ($5/19/2026$):   - Increased $GI$ motility and contraction of the bladder.   - Constriction of the pupil (miosis).   - Decreased heart rate and dilation of blood vessels.   - Constriction of the bronchioles.
• Direct-Acting Cholinergics:   - Indications: Glaucoma, eye surgery, xerostomia (dry mouth), urinary retention, and $GI$/bladder atony.   - Bethanechol (Urecholine).
• Indirect-Acting Cholinergics (Acetylcholinesterase inhibitors):   - Indications: Myasthenia gravis (rapid weakness of voluntary muscles) and Alzheimer’s (decreased $ACh$ levels).   - Pyridostigmine (Mestinon) for Myasthenia gravis.   - Donepezil (Aricept) and Memantine (Namenda) for Alzheimer’s.
• Contraindications:   - Drug allergy, $GI$ or $GU$ obstruction, gastric ulcers, bradycardia, hypotension, and pulmonary disorders.

Side Effects and Nursing Management for Cholinergic Agonists

• Side Effects: Hypotension, bradycardia, syncope, diarrhea, blurred vision, difficulty breathing, and urinary frequency.
• Toxicity (Cholinergic Crisis): Identified by the acronym SLUDGE:   - Salivation.   - Lacrimation.   - Urinary incontinence.   - Diarrhea.   - $GI$ cramps.   - Emesis.
• Nursing Activities:   - Post-surgery: Walk the patient, provide high fiber foods and hydration.   - Monitor for urinary output, bowel movements ($BM$), increased muscle strength, and improved memory.   - Assess lung sounds and vital signs.   - Administer drugs with meals to reduce $GI$ upset.   - Assist with walking, dressing, and toileting.
• Patient Education:   - Avoid abrupt withdrawal of meds.   - Change positions slowly.   - Connect with community resources (Alzheimer’s support, Meals on Wheels, prescription assistance).

Anticholinergic Drugs (Antagonists)

• Action: Parasympatholytic; inhibits the rest and digest response. Competitively blocks $ACh$ at muscarinic receptors.
• Physiological Responses (Dose Dependent):   - Heart: Blocks slowing; increases $HR$, conduction, and contraction.   - Lungs: Blocks bronchoconstriction; results in bronchodilation.   - $GI$ Tract: Blocks increased motility; results in decreased motility.   - Bladder: Blocks bladder emptying; results in bladder retention.   - Eye: Blocks pupil constriction; results in dilation.   - Glands: Blocks secretions; results in decreased secretions.   - $CNS$: Low dose results in decreased muscle rigidity/tremors; high dose results in drowsiness, disorientation, and hallucinations.
• Indications:   - Parkinson's and Extrapyramidal symptoms from antipsychotic drugs.   - Eye exams.   - Irritable bowel and diarrhea: Dicyclomine (Bentyl).   - Incontinence and neurogenic bladder: Oxybutynin (Ditropan).   - Bradycardia and heart blocks: Atropine (AtroPen).   - Asthma, bronchitis, and emphysema.   - Reducing secretions (mouth, nose, bronchi) for common colds or surgery: Glycopyrrolate (Robinul).
• Side Effects: Dry mouth, blurred vision, urinary retention, constipation, and tachycardia.

Nursing Management for Anticholinergic Drugs

• Nursing Activities ($5/19/2026$):   - Monitor patterns of bowel movements and urinary output.   - Monitor heart rate.   - Prevent constipation.   - Oral Care: Provide oral care; suggest chewing gum or sucking on hard candy; ensure fluids are available.   - Dermal Patch: Apply to dry, non-hairy, non-irritated area; rotate sites.   - Eye Drops: Apply light pressure to the inner canthus for $30-60\,seconds$; advise wearing sunglasses in light.
• Patient Education:   - Avoid extreme heat and exercise.   - Drugs may cause drowsiness.