What NT do both the Somatic and Parasymp. NS share?
(both pre and post synaptic)
What class of receptor do both the Somatic and ANS share?
N1 = skeletal muscle (somatic) (Nm)
N2 = Parasym (Nn)
Where are cholinergic cell bodies located in the CNS and what role do cholinergic neurons play in the brain?
nucleus basalis of Meynert
Higher functions (attention, cognition, memory)
How/where is Ach synthesized?
Location: nerve terminal
choline + acetyl CoA > choline acetylase transferase = Ach
↑ Ca2+ causes the binding of which 2 proteins needed for exocytosis?
SNARE & syntaxin
What enzyme breaks ↓ Ach?
AchE > choline + acetate
What happens to choline?
reuptake and reused
Are nicotinic receptors ionotropic or metabotropic?
Are muscarinic receptors ionotropic or metabotropic?
Decscribe the three types of muscarinic receptors, location and 2nd messangers?
Which drug is used to treat Alzheimer's and what is the mechanism?
anti-AchE = ↑ Ach in brain synapses
What happens to skeletal muscle when nicotinic receptors are activated?
-Ach binds >conformational change
-Na+ enters and depolarizes muscle cell
-Ach dissociates and receptor resets
What happens with continued Ach exposure to nicotinic receptors?
-conformational change in receptor to "locked"
-Ach has HIGH affinity and stays bound (can't be opened)
What are general uses for cholinergic and anti-cholinergic drugs?
What drug inhibits the RELEASE of Ach via blocking fusion of synaptic vesicles?
reduce wrinkles or treat spasmodic torticollis
What are anticholinesterases?
inhibit Ach degradation
What is a Reversible anticholinesterase & how does it work?
-reversibly binds to cholinesterase enzyme
-synthetic drug > DOESNT cross BBB
-very short half-life (30min)
Uses for Anti-cholinesterases
1. Improve transmission at NMJ in Myasthenia Gravis
2. ↑ parasym. tone
3. ↑ cholinergic CNS activity
What is the "Tensilon Test" and which drug is used?
-injected into muscle of patient
-if injection improves muscle fatigue, patient has MG
How do AntiChE treat Glaucoma?
causes miosis (pupil constriction)
aids in aqueous humor drainage
covalently bind to active sites
Example of an Organophosphate and why they are dangerous?
What is used to treat irreversible AntiAchE (especially in warfare)?
What is a Nicotinic agonist & how does it work?
strongly binds to N1 (skeletal muscle)
How is succinylcholine used clinically?
muscle paralysis (surgery)
What is a muscarinic agonist & how is it used?
synthetic Ach (effects similar to parasmpathetics)
-similar treatments as antiChE (glaucoma)
Nicotinic ANTAGONIST (Nm)
-skeletal muscle paralysis (surgery)
-competitive antagonist (prevents Ach binding)
Tubocurarine vs Succinylcholine
both cause muscle parlysis
Tubocurarine > competitive antagonist
Succinylcholine > nicotinic agonist (depolarizing blockade)
Which of those two drugs can be overcome by ↑ Ach & by which drug?
blocks Ach enzyme > increasing Ach
-used in surgery to overcome Tubocurarine
mydriasis (dilated pupil), tachycardia, reduced sweating
Clinical uses of atropine
alkaloid from "belladonna" berry
competitive muscarinic antagonist
Treatment: AntiChE (raises Ach levels)
Effects of Atropine Poisoning
hot > no sweating
blind > dilated pupils
dry > no sailvation
mad > CNS
red > flushing