Pharmacokinetics
A.ch is inactive orally because it is poorly absorbed being a quaternary ammonium compound. I.V. it has very short duration of action because it is rapidly metabolized by choline esterase enzymes.
| True cholinesterase enzyme | Pseudocholinesterase enzyme | |
|---|---|---|
| Site | Cholinergic nerve - CNS – RBCs | Plasma – liver – intestine |
| Synthesis | 3 months | 2-3 weeks |
| Specificity | specific | Not specific |
Pharmacodynamics
Mechanism of Action: act via:
- Stimulation of the muscarinic receptors.
- Stimulation of the nicotinic receptors.
Cholinoceptors
- They are broadly subdivided into muscarinic and nicotinic receptors.
A. Muscarinic receptors (peripheral, M receptors) | â–şTypes:
-
M1 receptors: Are present in autonomic ganglia, CNS and parietal cells of the stomach
-
M2 receptors: Are present in heart. - also present presynaptically on the cholinergic fibers to inhibit acetylcholine release (feedback)
-
M3 receptors: are present in smooth muscle fibers and secretory glands.
-
M4 and M5 receptors: in the C.N.S.
B. Nicotinic receptors (central, N receptors) | â–şTypes:
- Nn (Neuronal nicotinic receptors): present in autonomic ganglia and suprarenal medulla.
- Nm (Muscle nicotinic receptors): present in the neuromuscular junction.
Pharmacological Effects
C.V.S
- Heart: Decreases all cardiac properties, except the conduction in the atria, which is increased.
- Blood vessels: generalized vasodilatation.
- Blood pressure: blood pressure is decreased.
G.I.T: A.ch increases gastric and intestinal peristalsis and relax the sphincters. It also stimulates salivary and gastric secretions.
Lung: bronchoconstriction and increased bronchial secretion.
Urinary tract: A.ch contracts the detrusor muscle and relaxes the sphincter of the urinary bladder.
Eye: A.ch produces meiosis.RR
Skeletal muscles: stimulate motor end plate.
Therapeutic Uses
It has limited use because of its short duration and non-selectivity.
Untoward Effects
All effects produced by A.ch are untoward effect.
INDIRECTLY ACTING PARASYMPATHOMIMETICS
(Cholinesterase Inhibitors)
Mechanism of action
By inhibiting cholinesterase, the indirect – acting agonists “amplify” the action of endogenous acetylcholine. Therefore, the indirect agents have muscarinic or nicotinic.