Pharmacology of Choline Esters

Study Notes

Ach is not used clinically due to its short duration of action, widespread effects, and ineffectiveness when taken orally.
Bethanechol is the only clinically used choline ester, and it lacks cardiovascular adverse effects, making it useful for:
- Treating atony of the gastrointestinal tract (gastric atony, paralytic ileus, and congenital megacolon).
- Treating postoperative and postpartum urinary retention, as well as neurogenic bladder.
- Increasing salivary secretion in cases of xerostomia.

Nausea, vomiting, and diarrhea.
Spasm of accommodation.
Salivation, sweating, lacrimation, and cutaneous vasodilation (flushing).
Hypotension, bradycardia, syncope, and cardiac arrest.
Bronchospasm and pulmonary edema in severe cases due to increased secretions.
Treatment of toxicity involves atropine and supportive and symptomatic treatments.

Pilocarpine is a naturally occurring alkaloid derived from the pilacarpus leaflet.
It acts by directly stimulating muscarinic receptors.
Pharmacokinetics:
- Absorbed orally.
- Distributed throughout the body and crosses the blood-brain barrier.
- Not metabolized by cholinesterase enzyme, but partially metabolized by the liver.
- Excreted by the kidney unchanged.
Mechanism of action:
- Increases secretion in exocrine glands, especially sweat glands.
- Affects smooth muscles, including:
  - Eye (miosis and accommodation for near vision, decreases IOP).
  - Intestine (increases motility).
  - Bronchial (bronchospasm).
- Initial stimulation followed by depression in the CNS.

These agents bind covalently to the enzyme and are extremely toxic.
They are mainly used as:
- Insecticides (e.g., parathion, malathion).
- War gases (e.g., sarin, soman, tabun).
The only clinically used organophosphorous compounds include:
- Di-isopropyl-fluro-phosphate (DFP) or isoflurophate, used as an eye ointment in treating glaucoma.
- Echothiophate (phospholine), used as eye drops in managing glaucoma.

Generalized cholinergic stimulation.
Paralysis of motor function, causing breathing difficulties, and convulsions.
Intense miosis.
Symptoms:
- Muscarinic effects: lacrimation, miosis, salivation, bradycardia, hypotension, bronchospasm, excessive secretion, colic, and diarrhea.
- Nicotinic effects: initial skeletal muscle twitches followed by paralysis.
- CNS: convulsions followed by coma and death.
Cause of death: respiratory failure due to peripheral and central mechanisms.
Treatment:
- Respiratory support: care of respiration via endotracheal intubation, artificial respiration.
- Atropine in high doses can reverse many of the muscarinic and central effects.