Cholinergic Pharmacology of the ANS Flashcards
NAChR permeable to?
Na, K, Ca
M2 vs M3 Receptors
M2 is Gi and in heart/smooth muscle. M3 is Gq in glands/smooth muscle.
Synthesis of ACh
Choline taken up into terminal via cotransport with Na and Cl. Combined with acetyl-COA in ChAT and packaged.
How is ACh signal stopped?
Acetylcholinesterase hydrolyzes ACh.
Anticholinergic Drugs
Reduce transmission at cholinergic synapses.
Physostigmine
Anticholinesterase. Prevents AChE from hydrolyzing ACh. Indirect ACh agonist.
Effect of ACh on organs
Slows heart, decreases atrial contractile force, bronchoconstriction, increased secretions, increased GI motility, nearsightedness.
ACh effect on vasculature?
Dilation, because muscarinic receptors on it. This is paradoxical.
ACh effect on sweat glands?
Increased secretion, because sympathetic neurons that control sweating are cholinergic.
Physostigmine toxidrome
GI pain, N&V, sweating
Cholinesterase Poisoning (insecticides, nerve gases)
SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis. Killer B’s: Bradycardia, bronchospasm, bronchorrhea
nAChR subtypes
N - ganglionic
M- skeletal muscle
Drugs can be selective for one over the other
Nicotine
Direct agonist at both nAChRs. Stimulates both sympathetic and parasympathetic postganglionic neurons when given systemically.
Nicotine effect on organs
Pushes towards dominant tone of organ
Why do high levels of nicotine cause flaccid paralysis in skeletal muscle?
Due to depolarization blockade – Na+ channels remain inactivated, and can’t de-inactivate.
Hexamethonium
Selective antagonist at Nn receptors. Will block transmission at all ganglia (P and S). Target organs are functionally denervated, so the effect is the opposite of the dominant tone for that organ. Causes baroreceptor reflex inhibition
Effect of hexamethonium on baroreceptor reflex?
Severe problem with it. People frequently faint upon standing.
Tubocurarine
Selective Nm receptor antagonist. Induces flaccid paralysis of skeletal muscle.
Is acetylcholine used as a drug?
Yes, opthalmicly. When it’s administered IV, it activates muscarinic receptors, but is short acting because pseudocholinesterase in plasma and tissues degrades it quickly.
Parasympathomimetics
Muscarinic Agonists, produce similar effects to anticholinesterase drugs like physostigmine (broncoconstriction, bradycardia, diaphoresis).
One major difference between muscarinic agonists and physostigmine
Muscarinic agonists dilate vasculature and decrease diastolic BP because mAChRs exist on vasculature, they’re just not attached to anything.
How does exogenous ACh dilate BVs?
Mediated by NO. Muscarinic receptors expressed on tunica intima. When activated by ACh, they release NO, causing vascular smooth muscle to relax via GC and cGMP.
Atropine
Muscarinic antagonist. Causes dry mouth, trouble with near vision, tachycardia, heat, redness.
