Autonomic Pharmacology: Nervous System Drugs

• Autonomic pharmacology studies drugs affecting the autonomic nervous system (ANS).
• The ANS regulates involuntary functions, including heart rate, blood pressure, digestion, and body temperature.
• The ANS has two main divisions: the sympathetic (SNS) and parasympathetic (PNS) nervous systems.
• The SNS is responsible for the "fight or flight" response.
• The PNS is responsible for "rest and digest" functions.

Neurotransmission in the ANS

• Neurotransmission involves neurotransmitter release that binds to target tissue receptors.
• Acetylcholine (ACh) is the primary neurotransmitter in the PNS and at preganglionic synapses of both the SNS and PNS.
• Norepinephrine (NE) is the primary neurotransmitter in the SNS at postganglionic synapses.
• Adrenergic receptors bind NE and epinephrine (Epi), while cholinergic receptors bind ACh.

Cholinergic Pharmacology

• Cholinergic drugs affect the PNS by mimicking or blocking ACh effects.
• Cholinergic agonists (parasympathomimetics) stimulate cholinergic receptors.
• Cholinergic antagonists (parasympatholytics) block cholinergic receptors.
• Cholinergic receptors include nicotinic and muscarinic receptors.
• Nicotinic receptors are ligand-gated ion channels at neuromuscular junctions and autonomic ganglia.
• Muscarinic receptors are G protein-coupled receptors in the heart, smooth muscle, and glands.

Cholinergic Agonists

• Direct-acting agonists bind directly to cholinergic receptors such as acetylcholine, bethanechol, carbachol, and pilocarpine.
• Indirect-acting agonists inhibit acetylcholinesterase (AChE), which breaks down ACh, and include physostigmine, neostigmine, pyridostigmine, and edrophonium.
• Clinical uses for cholinergic agonists include:
  • Glaucoma (pilocarpine)
  • Urinary retention (bethanechol)
  • Myasthenia gravis (pyridostigmine, neostigmine)
  • Alzheimer's disease (donepezil, rivastigmine, galantamine, which increase ACh levels in the brain by inhibiting AChE)
• Adverse effects of cholinergic agonists include:
  • Increased salivation, sweating, and lacrimation
  • Bradycardia and hypotension
  • Bronchoconstriction
  • Increased gastrointestinal motility

Cholinergic Antagonists

• These drugs block acetylcholine action at cholinergic receptors.
• Antimuscarinic drugs block muscarinic receptors, for example, atropine, scopolamine, ipratropium, and oxybutynin.
• Ganglionic blockers block nicotinic receptors at autonomic ganglia; mecamylamine is an example.
• Neuromuscular blockers block nicotinic receptors at the neuromuscular junction; examples include tubocurarine, succinylcholine, and vecuronium.
• Clinical uses of cholinergic antagonists include:
  • Treatment of bradycardia (atropine)
  • Reduction of respiratory secretions (atropine, scopolamine, glycopyrrolate)
  • Treatment of motion sickness (scopolamine)
  • Treatment of overactive bladder (oxybutynin, tolterodine)
  • Bronchodilation in COPD and asthma (ipratropium, tiotropium)
  • Preanesthetic medication to reduce secretions (atropine, glycopyrrolate)
  • Muscle relaxation during surgery (tubocurarine, succinylcholine, vecuronium)
  • Reversal of neuromuscular blockade (neostigmine, edrophonium)
• Adverse effects of cholinergic antagonists include:
  • Dry mouth
  • Blurred vision
  • Urinary retention
  • Constipation
  • Tachycardia
  • Confusion and hallucinations, especially in the elderly

Adrenergic Pharmacology

• Adrenergic drugs affect the SNS by mimicking or blocking NE and Epi effects.
• Adrenergic agonists (sympathomimetics) stimulate adrenergic receptors.
• Adrenergic antagonists (sympatholytics) block adrenergic receptors.

Adrenergic Receptors

• Adrenergic receptors are divided into alpha (α) and beta (β) receptors.
• Alpha-1 (α1) receptors are in smooth muscle and cause vasoconstriction, increased blood pressure, and mydriasis (pupil dilation).
• Alpha-2 (α2) receptors are in presynaptic nerve terminals and inhibit NE release.
• Beta-1 (β1) receptors are in the heart and increase heart rate and contractility.
• Beta-2 (β2) receptors are in smooth muscle and cause bronchodilation, vasodilation, and uterine relaxation.
• Beta-3 (β3) receptors are in adipose tissue and promote lipolysis.

Adrenergic Agonists

• Direct-acting agonists bind directly to adrenergic receptors.
  • Examples include epinephrine, norepinephrine, isoproterenol, dopamine, dobutamine, phenylephrine, albuterol, and clonidine.
• Indirect-acting agonists increase NE release or decrease reuptake; amphetamine and cocaine are examples.
• Clinical uses of adrenergic agonists include:
  • Anaphylaxis (epinephrine)
  • Asthma and COPD (albuterol, salmeterol)
  • Hypotension and shock (norepinephrine, dopamine)
  • Nasal congestion (phenylephrine, pseudoephedrine)
  • ADHD and narcolepsy (amphetamine, methylphenidate)
  • Glaucoma (brimonidine, apraclonidine)
  • Cardiac arrest (epinephrine)
• Adverse effects of adrenergic agonists include:
  • Increased blood pressure and heart rate
  • Arrhythmias
  • Anxiety and restlessness
  • Insomnia
  • Tremors

Adrenergic Antagonists

• These drugs block NE and Epi action at adrenergic receptors.
• Alpha-blockers block alpha receptors.
  • Examples include prazosin, terazosin, doxazosin (selective α1-blockers), phentolamine, phenoxybenzamine (non-selective α-blockers).
• Beta-blockers block beta receptors.
  • Examples include propranolol and nadolol (non-selective β-blockers), metoprolol, atenolol, and bisoprolol (selective β1-blockers).
• Clinical uses of adrenergic antagonists include:
  • Hypertension (prazosin, metoprolol, propranolol)
  • Benign prostatic hyperplasia (prazosin, terazosin, tamsulosin)
  • Angina (metoprolol, propranolol, atenolol)
  • Heart failure (carvedilol, bisoprolol, metoprolol succinate)
  • Glaucoma (timolol)
  • Hyperthyroidism (propranolol)
  • Migraine prophylaxis (propranolol)
  • Pheochromocytoma (phenoxybenzamine, phentolamine)
  • Anxiety (propranolol)
• Adverse effects of adrenergic antagonists include:
  • Hypotension
  • Bradycardia
  • Bronchospasm (especially with non-selective beta-blockers)
  • Fatigue
  • Dizziness
  • Erectile dysfunction
  • Depression
  • Masking of hypoglycemia symptoms, especially with non-selective beta-blockers

Specific Drug Examples and Their Uses

• Atropine: an antimuscarinic agent used to treat bradycardia and reduce respiratory secretions.
• Scopolamine: an antimuscarinic agent used to treat motion sickness.
• Ipratropium: an antimuscarinic agent used as a bronchodilator in COPD and asthma.
• Oxybutynin: an antimuscarinic agent used to treat overactive bladder.
• Pilocarpine: a direct-acting cholinergic agonist used to treat glaucoma.
• Bethanechol: a direct-acting cholinergic agonist used to treat urinary retention.
• Pyridostigmine: an indirect-acting cholinergic agonist used to treat myasthenia gravis.
• Epinephrine: a non-selective adrenergic agonist used to treat anaphylaxis and cardiac arrest.
• Albuterol: a selective β2-adrenergic agonist used to treat asthma and COPD.
• Phenylephrine: a selective α1-adrenergic agonist used as a nasal decongestant.
• Clonidine: a selective α2-adrenergic agonist used to treat hypertension.
• Prazosin: a selective α1-adrenergic antagonist used to treat hypertension and BPH.
• Metoprolol: a selective β1-adrenergic antagonist used to treat hypertension, angina, and heart failure.
• Propranolol: a non-selective β-adrenergic antagonist used to treat hypertension, angina, migraine, and anxiety.
• Carvedilol: a non-selective β-adrenergic and α1-adrenergic antagonist used to treat heart failure and hypertension.

Clinical Considerations

• Drug interactions can occur between autonomic drugs and other medications.
• Certain medical conditions can affect the response to autonomic drugs.
• Individual variability in drug metabolism and receptor sensitivity can influence drug effects.
• Age-related changes in the ANS can affect drug responses in elderly patients.

Explore drugs affecting the autonomic nervous system (ANS), regulating involuntary functions like heart rate and digestion. Understand neurotransmission involving acetylcholine (ACh) and norepinephrine (NE). Learn about cholinergic and adrenergic receptors and their roles.