Cholinergic Agents

Cholinergic Agents
Chapter 19

I Cholinergic Agents: drugs that stimulate the PSNS (parasympathetic nervous system). The opposing system to the SNS. (seemed to be used in biological warfare)
A. Rest or digest.
B. only one we need to know is ACh.
C. AKA as cholinergic agonists or parasympathomimetics.
D. Mimic the effects of the PSNS neurotransmitter acetylcholine (ACh)
E. 2 types determined by location and action once stimulated
1. Nicotinic receptors
a. Located in the ganglia of both the PSNS and SNS
b. Named “nicotinic” bc can be stimulated by the alkaloid nicotine
2. Muscarinic receptors
a. Located postsynaptically
1. smooth muscle
2. cardiac muscle
3. glands of parasympathetic fibers
4. effector organs of cholinergic sympathetic fibers
b. Can be stimulated by the alkaloid muscarine
II Mechanism of Action
A. Direct acting cholinergic agonists
1. bind to cholinergic receptors, activating them
B. Indirect acting (cholinesterase inhibitors)
1. inhibit the enzyme cholinesterase which breaks down ACh
2. result: more ACh is available at the receptors
3. can be:
a. reversible: bind to cholinesterase for a period of minutes or hours
b. irreversible: bind to cholinesterase and form a permanent covalent bond. The body must make new cholinesterase as in nerve gas damage.
III Drug Effects
A. Effects seen when the PSNS is stimulated
B. The PSNS is the “rest and digest” system
C. SLUDGE (some kind of excretion)
Salivation
Lacrimation (tears)
Urinary incontinence
Diarrhea
Gastrointestinal cramps
Emesis
D. Stimulate intestine and bladder
1. increased gastric secretions
2. increased GI motility
3. increased urinary frequency
E. stimulate pupil
1. contriction (miosis)
2. reduced intraocular pressure (used for glaucoma)
F. increased salivation and sweating
G. Cardiovascular effects
1. decreased heart rate
2. vasoldilation
H. respiratory effects
1. bronchial constriction
2. narrowed airways
I At recommended doses, the cholinergics primarily affect the muscarinic receptors.
1. desired effect are from the stimulation of muscarinic
J. At high doses they stimulate the nicotinic receptors.
1. many undesirable effects are due to stimulation of nicotinic receptors.
***focus on drug effects for muscarinic...sludgeIV Indications
A. direct acting
1. reduce intraocular pressure
2. useful for glaucoma and intraocular surgery
a. acetylcholine, carbachol, pilocarpine
3. topical application due to poor oral absorption
4. bethanechol
a. increases tone and motility of bladder and GI tract
b.