💊Intro to Pharmacology Unit 4 – Autonomic Nervous System Drug Therapies

Key Concepts and Terminology

• Autonomic nervous system (ANS) division of the peripheral nervous system that regulates involuntary functions (heart rate, digestion, respiration)
• Sympathetic nervous system (SNS) branch of the ANS responsible for "fight or flight" responses, increases heart rate and blood pressure, dilates pupils
• Parasympathetic nervous system (PNS) branch of the ANS responsible for "rest and digest" functions, slows heart rate, increases digestion, constricts pupils
• Neurotransmitters chemical messengers that transmit signals between neurons (acetylcholine, norepinephrine)
• Receptors proteins on cell surfaces that bind to specific neurotransmitters or drugs, causing a cellular response
  • Agonists drugs that activate receptors, mimicking the action of neurotransmitters
  • Antagonists drugs that block receptors, preventing neurotransmitter binding and cellular response
• Adrenergic receptors receptors that respond to norepinephrine and epinephrine, found in the SNS (α1, α2, β1, β2)
• Cholinergic receptors receptors that respond to acetylcholine, found in the PNS (nicotinic, muscarinic)

Anatomy and Physiology Review

• ANS consists of the SNS and PNS, which work together to maintain homeostasis
• SNS originates from the thoracic and lumbar regions of the spinal cord, while the PNS originates from the brainstem and sacral region
• Preganglionic neurons neurons that originate in the central nervous system and synapse with postganglionic neurons in autonomic ganglia
• Postganglionic neurons neurons that originate in autonomic ganglia and innervate target organs
• Adrenal medulla endocrine gland that releases epinephrine and norepinephrine directly into the bloodstream when stimulated by the SNS
• Cholinergic neurons release acetylcholine as their primary neurotransmitter (preganglionic neurons in both SNS and PNS, postganglionic neurons in PNS)
• Adrenergic neurons release norepinephrine as their primary neurotransmitter (most postganglionic neurons in SNS)
  • Exceptions include sweat glands and some blood vessels, which are innervated by cholinergic postganglionic neurons in the SNS

Neurotransmitters and Receptors

• Acetylcholine (ACh) primary neurotransmitter in the PNS, binds to nicotinic and muscarinic receptors
  • Nicotinic receptors ligand-gated ion channels found in neuromuscular junctions and autonomic ganglia
  • Muscarinic receptors G protein-coupled receptors found in target organs (heart, smooth muscle, glands)
• Norepinephrine (NE) primary neurotransmitter in the SNS, binds to adrenergic receptors (α1, α2, β1, β2)
  • α1 receptors cause vasoconstriction, smooth muscle contraction, and pupil dilation
  • α2 receptors inhibit neurotransmitter release and cause vasodilation in some blood vessels
  • β1 receptors increase heart rate and contractility
  • β2 receptors cause bronchodilation and vasodilation in skeletal muscle
• Epinephrine (EPI) released from the adrenal medulla, binds to adrenergic receptors with similar effects to NE
• Dopamine (DA) neurotransmitter in the central nervous system, plays a role in reward pathways and motor control
  • Also acts as a precursor for NE and EPI synthesis
• Serotonin (5-HT) neurotransmitter involved in mood regulation, sleep, and appetite

Sympathetic vs. Parasympathetic Systems

• SNS and PNS have opposing effects on target organs to maintain homeostasis
• SNS activation prepares the body for "fight or flight" responses
  • Increases heart rate and contractility, dilates pupils, bronchodilation
  • Decreases digestion and urination, constricts blood vessels in the skin and gastrointestinal tract
  • Releases glucose from the liver and fatty acids from adipose tissue for energy
• PNS activation promotes "rest and digest" functions
  • Decreases heart rate, constricts pupils, increases digestion and urination
  • Dilates blood vessels in the skin and gastrointestinal tract
  • Promotes storage of glucose and fatty acids
• Dual innervation some organs receive both sympathetic and parasympathetic innervation (heart, eyes, lungs, digestive tract)
• Single innervation some organs receive only sympathetic (blood vessels, sweat glands, adrenal medulla) or parasympathetic (salivary glands, lacrimal glands) innervation

Drug Classes and Mechanisms

• Cholinergic agonists drugs that activate cholinergic receptors, mimicking the effects of ACh (bethanechol, pilocarpine)
• Cholinergic antagonists drugs that block cholinergic receptors, preventing the effects of ACh (atropine, scopolamine)
  • Muscarinic antagonists specifically block muscarinic receptors (ipratropium, tiotropium)
  • Nicotinic antagonists specifically block nicotinic receptors (tubocurarine, pancuronium)
• Adrenergic agonists drugs that activate adrenergic receptors, mimicking the effects of NE and EPI (ephedrine, phenylephrine)
  • α1 agonists specifically activate α1 receptors (midodrine)
  • β2 agonists specifically activate β2 receptors (albuterol, salmeterol)
• Adrenergic antagonists drugs that block adrenergic receptors, preventing the effects of NE and EPI (propranolol, phentolamine)
  • α1 antagonists specifically block α1 receptors (prazosin, tamsulosin)
  • β1 antagonists specifically block β1 receptors (metoprolol, atenolol)
• Indirect-acting sympathomimetics drugs that increase the release or prevent the reuptake of NE (amphetamine, cocaine)
• Cholinesterase inhibitors drugs that prevent the breakdown of ACh, increasing its availability (donepezil, rivastigmine)

Common Medications and Their Uses

• Atropine muscarinic antagonist used to treat bradycardia, cycloplegia, and as an antidote for organophosphate poisoning
• Ipratropium muscarinic antagonist used to treat chronic obstructive pulmonary disease (COPD) and asthma
• Pilocarpine muscarinic agonist used to treat glaucoma and xerostomia (dry mouth)
• Albuterol β2 agonist used to treat asthma and COPD
• Epinephrine non-selective adrenergic agonist used to treat anaphylaxis, cardiac arrest, and as a local vasoconstrictor
• Phenylephrine α1 agonist used as a decongestant and to treat hypotension
• Propranolol non-selective β antagonist used to treat hypertension, angina, and migraine prophylaxis
• Metoprolol selective β1 antagonist used to treat hypertension, heart failure, and tachyarrhythmias
• Prazosin α1 antagonist used to treat hypertension and benign prostatic hyperplasia (BPH)
• Tamsulosin selective α1A antagonist used to treat BPH

Side Effects and Contraindications

• Cholinergic agonists may cause bradycardia, hypotension, increased secretions, and gastrointestinal distress
  • Contraindicated in patients with asthma, cardiovascular disease, and gastrointestinal obstruction
• Cholinergic antagonists may cause tachycardia, dry mouth, constipation, and urinary retention
  • Contraindicated in patients with narrow-angle glaucoma and urinary retention
• Adrenergic agonists may cause tachycardia, hypertension, anxiety, and insomnia
  • Contraindicated in patients with cardiovascular disease, hyperthyroidism, and closed-angle glaucoma
• Adrenergic antagonists may cause bradycardia, hypotension, fatigue, and erectile dysfunction
  • Contraindicated in patients with asthma, heart block, and peripheral vascular disease
• Drug interactions cholinergic and adrenergic drugs may interact with other medications, such as monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and digoxin
  • Careful monitoring and dose adjustments may be necessary when combining these medications

Clinical Applications and Case Studies

• Case 1 A 65-year-old male presents with difficulty urinating and a weak urine stream. He is diagnosed with BPH and prescribed tamsulosin, an α1A antagonist. The medication improves his symptoms by relaxing the smooth muscle in the prostate and bladder neck.
• Case 2 A 28-year-old female with a history of asthma presents with shortness of breath and wheezing. She is given albuterol, a β2 agonist, via inhaler. The medication causes bronchodilation, relieving her symptoms and improving her lung function.
• Case 3 A 50-year-old male with a history of hypertension and angina is prescribed metoprolol, a selective β1 antagonist. The medication reduces his heart rate and contractility, lowering his blood pressure and reducing the workload on his heart.
• Case 4 A 72-year-old female with Alzheimer's disease is prescribed donepezil, a cholinesterase inhibitor. The medication increases the availability of acetylcholine in the brain, leading to improved cognitive function and memory.
• Case 5 A 35-year-old male presents with severe allergic reaction after being stung by a bee. He is given an intramuscular injection of epinephrine, a non-selective adrenergic agonist. The medication causes vasoconstriction, bronchodilation, and increases his heart rate, effectively treating his anaphylaxis.
• Case 6 A 60-year-old female with COPD is prescribed ipratropium, a muscarinic antagonist, via inhaler. The medication blocks the effects of acetylcholine on the airways, reducing bronchoconstriction and mucus secretion, and improving her breathing.