2. SYMPATHETIC
Increase BP & HR, glucose
Perfusion to skeletal muscles
Mydriasis, bronchodilatation
PARASYMPATHETIC
Miosis, decreased HR, BP, bronchia secretion,
Insulin release, Digestion, excretion

3. Cholinergic Agonists

4. Sites of Cholinergic Transmission
ACh is major neurohumoral transmitter at autonomic, somatic and central nervous system:
All preganglionic sites (Both Parasympathetic and sympathetic)
All Postganglionic Parasympathetic sites and sympathetic to sweat gland and some blood vessels
Skeletal Muscles
CNS: Cortex, Basal ganglia, spinal chord and others
Parasympathetic Stimulation –(Ach) synthhesis, storage, release, binding of Ach to Rs, degradation and recycling.

7. Cholinoceptors Muscarinc Receptors
Two families of cholinoceptors: M and N receptors, can be distinguished on the basis of their different affinities
Muscarinc Receptors
G protein–coupled receptors (metabotropic receptors)
recognize muscarine, an alkaloid /in certain poisonous mushrooms
weak affinity for nicotine
M1, M2, and M3 receptors have been functionally characterized.
ganglia of the peripheral nervous system and on the autonomic effector organs, such as the heart, smooth muscle, brain, and exocrine glands

8. There are five subclasses of muscarinic receptors: M1, M2, M3, M4, and M5.
Only M1, M2 and M3, receptors have been functionally characterized.
M1 receptors /on gastric parietal cells
M2 receptors on cardiac cells and smooth muscle
M3 receptors on the bladder, exocrine glands, and smooth muscle

12. Nicotinic Receptors
Nicotinic receptors are located in the CNS, adrenal medulla, autonomic ganglia, and the NMJ.
Those at the neuromuscular junction are sometimes designated NM and the others NN.
Nicotinic receptors of autonomic ganglia differ from those of the NMJ. E.g. ganglionic receptors selectively blocked by Hexamethonium, whereas NMJ Rs specifically blocked by Tubocurarine.

13. Signal transduction (cont.)
N Rs / composed of five subunits (a ligand-gated ion channel)
Binding of two Ach molecules elicits a conformational change that allows the entry of sodium ions, resulting in the depolarization of the effector cell.
Schematic illustration of ACh receptors

15. Direct-Acting Cholinomimetics
Direct-Acting Cholinergic Agonists (N & M)
Cholinergic agonists (parasympathomimetics) mimic the effects of ACh on cholinoceptors.
These agents broadly classified into:
Endogenous choline esters, Ach
Synthetic esters of choline, carbachol and bethanechol.
Naturally occurring alkaloids, nicotine, pilocarpine
  All of the direct-acting cholinergic drugs have longer durations of action than acetylcholine
As a group, the direct-acting agonists show little specificity in their actions, which limits their clinical usefulness

16. Acetylcholine (Ach) Quaternary ammonium compound --------
Site of action
Both muscarinic and nicotinic activity
Therapeutic uses -----
HR & CO (vagal stimulation).
Effect of IV Ach on:
Heart: due to

17. II. Blood Pressure Injection of Ach
vasodilation and lowering BP ( indirect mechanism of action)
activates M3 receptors on endothelial cells lining SM of BVs
production of nitric oxide from arginine
NO diffuses to vascular SM stimulates PK G production
hyperpolarization (SM relaxation through PDE-3 inhibition)

18. III. Other Actions of ACh
 GIT: increases salivary secretion & intestinal secretions and motility.
Bronchiolar secretions are also enhanced.
Genitourinary tract: the tone of the detrusor urinae muscle is increased, causing expulsion of urine.
Eye: stimulating ciliary muscle contraction for near vision
Constriction of the pupillae sphincter muscle, causing miosis
ACh (1% solution) is instilled into the anterior chamber of the eye to produce miosis during ophthalmic surgery.

19. The Eye
The Eye

20. Adverse Effects of Cholinomimetics