Autonomic Nervous System Drugs: Parasympathomimetics

Study Notes

Autonomic Nervous System drugs produce effects similar to acetylcholine (ACh).
Cholinergic drugs, also known as cholinomimetics or parasympathomimetics, either mimic or enhance ACh effects.

Types of Cholinergic Drugs:
- Directly-acting: Bind and activate muscarinic and nicotinic receptors.
- Indirectly-acting: Inhibit cholinesterase, increasing local ACh concentration.

Acetylcholine: Stimulates both muscarinic (M) and nicotinic (N) receptors, resulting in diffuse action; associated with higher adverse effects.
Choline Esters: Rapidly hydrolyzed by AChE; e.g., Bethanechol (selectively stimulates muscarinic receptors).
Alkaloids: e.g., Pilocarpine; strong muscarinic effects, used therapeutically for glaucoma and dry mouth conditions.

Physostigmine, Neostigmine, Pyridostigmine: Reversible anticholinesterases, primarily used for myasthenia gravis and skeletal muscle stimulation.
Edrophonium: Short-acting anticholinesterase used for diagnostic purposes in myasthenia gravis.
Echothiophate: Irreversible anticholinesterase; linked to organophosphate poisoning.

Muscarinic Receptors (M): G-protein coupled receptors; involved in various physiological functions including miosis, increased GI motility, and secretion.
Nicotinic Receptors (N): Ion-channel linked receptors; associated with skeletal muscle contraction and autonomic ganglia activation.

Eyes:
- Miosis (contraction of iris circular muscle).
- Enables accommodation for near vision; reduces intraocular pressure, crucial for glaucoma management.
Smooth Muscle:
- Increases GI motility and secretions.
- Promotes bronchospasm and mucus secretion in the respiratory tract (via M3 receptors).
Urinary Bladder:
- Contraction of detrusor muscle facilitates urination; relaxation of sphincter muscles encourages micturition.
Cardiovascular System:
- Decreases heart rate (HR) and force of contraction, leading to lower blood pressure (BP).
- Vasodilation effects via blood vessels (M3 receptors).
Glands:
- Enhances secretions from salivary and lacrimal glands; salivation and tearing are typical effects.

Cholinergic drugs used in treating various conditions such as glaucoma, myasthenia gravis, and dry mouth syndrome.
Potential adverse effects include sweating, nausea, and decreased heart rate and blood pressure due to excessive stimulation of cholinergic pathways.### Adverse Effects of Cholinergic Drugs
Bronchospasm, flushing, abdominal pain, and diarrhea are common adverse effects.
Cholinergic drugs can inhibit acetylcholine breakdown, leading to toxic responses if misused as pesticides.

Excessive stimulation occurs at both muscarinic and nicotinic receptors.
Muscarinic effects include DUMBBELSS: diarrhea, urination, miosis (pinpoint pupils), bradycardia, bronchoconstriction, CNS/muscle excitation, lacrimation, salivation, and sweating.

Organophosphorus poisoning leads to a depolarizing neuromuscular blockade resulting in excitation followed by paralysis.
Symptoms include CNS stimulation, convulsions, and coma, necessitating respiratory support.

Atropine serves as an antidote, blocking all muscarinic effects.
Pralidoxime (PAM) can reactivate inactive AChE if administered before aging begins.

An autoimmune disorder where antibodies attack nerve-muscle communication, causing skeletal muscle weakness.
Primarily affects voluntary muscles controlling the eyes, mouth, throat, and limbs.
Most common in young women (ages 20-30) and men older than 50.

Drooping eyelids (ptosis), double vision (diplopia), altered speech, and difficulty swallowing.
Limited facial expressions and fatigue after physical activities like climbing stairs and brushing teeth.

Acetylcholinesterase inhibitors (e.g., pyridostigmine) enhance nerve-to-muscle communication.
Immunosuppressants (e.g., azathioprine) may reduce antibody production.
Thymectomy, a surgical procedure to remove the thymus gland, is indicated in certain cases.