Lecture 11: Cholinergics / ANS: Parasympathetic Flashcards
M1, M3, M5 act through which pathway
Gq - excitatory
M2, M4 acts through which pathway
Gi - inhibitory
inhibit AC and decrease cAMP
location of M1 R
ganglia
gastric, parietal, salivary glands
location of M2 R
heart
smooth muscle
autonomic nerve terminal (auto and heteroreceptors)
location of M3 R
smooth muscle
gastric and salivary glands
bladder, vascular smooth muscle
location of M4 R
auto and heteroreceptor
Location of M5 R
low level of expression - seen in cerebral artery VSM
pilocarpine
natural directly acting cholinergic drug (mimics ACh structure)
- used for glaucoma to decrease IOP
bethanechol
natural directly acting cholinergic drug (mimics ACh structure)
- used to make someone pee after surgery
- activates muscarinic receptors in detrusor muscle of bladder
reversible cholinesterase inhibitors (3)
physostigmine - crosses BBB, for glaucoma (decreases IOP)
neostigmine - quaternary ammonium compound, also doesn’t cross the BBB, taken po for myasthenia gravis
edrophonium - short-acting and given IV to diagnose myasthenia gravis
pralidoxime
2-PAM
- used to rescue irreversible inhibition of ACh-esterase at the early phosphorylation stage
echothiophate
irreversible acetylcholinesterase inhibitor
- organophosphate
- long action >100 hr
- used to treat glaucoma
- other side FX treated with atropine (musc. blocker) or 2-PAM
Anti-muscarinic agents for bronchodilation
LOW DOSE atropine - nonselective for musc Ach R Ant. Antagonizing M3 causes bronchodilation (M3 is Gq, blocking this = less calcium = less contraction), also decreases mucus
Selective M2 and M3 antagonists
- tiotropium
- ipratropium bromide (can be a rescue med)
less effective than beta2 agonists but used as adjunct in acute episodes or for beta 2 nonrespnders
pharmacological effects of atropine
non selective musc ach r blocker
- decreased secretions from gastric, bronchiole, salivary, sweat glands
- causes retention of urine
- dose-dependent changes in HR -> low dose causes bradycardia through CNS effects and high dose causes tachycardia through vagal block
- causes pupil dilation (mydriasis) (blocks musc. receptors on iris muscles)
- disorientation at high doses
red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, and full as a flask
Anticholinergic clinical presentation
refers to the symptoms of flushing, dry skin and mucous membranes, mydriasis (pupil dilation) with loss of accommodation, altered mental status (AMS), fever, and urinary retention
Plants that atropine can be found in
atropa belladonna
- deadly nightshade
datura stramonium
- jimsonweed
- jamestown
- stinkweed
- thorn-apple
- devil’s apple
therapeutic uses of atropine
- IV for acetylcholinesterase inhibitor poisoning (supportive)
- drops/ointment (CONTRAINDICATED in narrow angle glaucoma)
- low dose bronchodilation
duration of action is a couple hours, no tolerance in CV or eye. Long term use may cause urinary retention.
scopolamine
AKA hyoscine
- similar peripheral effects to atropine but also causes sedation so can be used for agitated patients
- used in surgery
- also used to prevent motion sickness (transdermal patch) to reduce GI motility
anti-muscarinics for urinary retention
darifenacin and tolterodine
both antagonize M3 in the detrusor muscle of the bladder - reduce contractility and urgency to urinate
three nicotinic Ach R agonists
- nicotine
- lobeline (less potent than nic)
- arecoline (has euphoric effects, similar to nicotine, toxic effects are CV, resp, GI, musc) - not used therapeutically
ganglionic blockers block what receptor?
nicotinic receptor (antagonize it) at the ganglion (between pre and postganglionic fibres of ANS)
- nicotine (an agonist) can also act as a blocker at high doses if it desensitizes
hexamethonium
gangalionic blocker - blocks nicotinic acetylcholine receptor at the ganglia
pharmacological effects of ganglionic blockers
depends on tone of the target tissue (PS vs S) and location of the receptor subtypes, but generally:
because of reduced Symp tone
- decreased blood pressure
because of reduced PS tone
- dilated pupils aka mydriasis
- less GI secretions and motility
- some bronchiole dilation, less secretions (but this is also under symp tone)
- dry and flushed skin
Trimethaphan camsylate
nAChR ganglia blocker
- IV infusion for rapid reduction in BP in hypertensive crisis
