Exam 3 Flashcards
(35 cards)
Parasympathetic NS postsynaptic nerves release what neurotransmitter?
Acetylcholine (ACh)
What are the parasympathetic receptors called?
muscarinic receptors (M)
General idea of parasympathetic NS?
Rest and digest
Relaxed
Safe
Parasympathetic effects on organs
heart: slows below normal HR
pupils: constrict Lens: focused close
Lungs: constricted, mucus thicker, not watery secretions
Digestion: constriction of muscle
Glands: secretion of fluids in lungs, stomach, general sweating, mouth, lacrimation (tears)
Bladder: contraction of muscle
Relax of sphincter
Cholinergic Agonist Effects Acronym
SLUDS Salivation Lacrimation Urination Defecation Sweating
Two types of Cholinergic Receptors
Nicotinic Receptors-Ion channels
and
Muscarinic Receptors-GPCR, M1 (m1, m3, m5) and M2 (m2, m4)
M1 Receptors
couple to G(alpha)q
Increase Ip3, DAG, intracellular Ca2+, PKC activation
contract smooth muscle!
increase secretion!
M2 Receptors
couple to G(alpha)I
located in the Heart
activation of K channels and inhibit adenyl cyclase, decrease in cAMP, inhibition of Ca2+ channels results in decreased heart rate and contractility
Blood Vessels
lack parasympathetic nerves but contain muscarinic receptors on vascular endothelium
increase of cytosolic calcium causes release of NO that diffuses into the smooth muscle causing relaxation
Heteroceptors locations
presynaptic sympathetic neurons that cause inhibition of NT release
lungs
GI and bladder sphincters
vascular smooth muscles
Serious problems with muscarinic receptor agonists
bradycardia, the heart may even stop
bronchoconstriction, caution in asthma/COPD patients. excess lung secretion
Pilocarpine
topical product used for glaucoma that constricts pupil to allow for better flow of aqueous humor
AE: watery, blurry, poor night vision
cevimeline
M1 selective, results in loss of M1 receptors
less dangerous than non-selective muscarinic drugs because don’t lose M2 receptors
only treats the symptoms
Blood pressure effects of muscarinic agonists
Don’t see any.
muscarinic antagonists
must be an agonist present (ACh) to see effect of antagonists, and there normally is
effects of muscarinic antagonist
opposite of agonists except for one:
NO EFFECT on BLOOD VESSEL TONE, NO VASOCONSTRICTION
tropicamide
used for eye exams, blocks normal constriction of pupil
Atropine
start a stopped/slow heart, tachycardia
muscarinic antagonists
can’t pee (urinary retention)
can’t see (dry eyes, photophobia)
can’t spit (xerostomia)
can’t shit (constipation)
glycopyrrolate
control drooling, decrease salivation, less cardiac effects
muscarinic antagonists for COPD
decreased effect on respiratory secretions
Muscarinic agonist SAR
- Nitrogen that can have positive charge, preferably quaternary ammonium
- No larger than methyls on N
- Oxygen (Ester or ether) that can H bond
- 2 carbons between N and O
Muscarinic Antagonist SAR
- R1 and R2 rings limited to phenyl size (at least one is aromatic)
- R3 can be H OH CH2OH
- X can be Ester (or amide or ether or N/a)
- Nitrogen is either quaternary ammonium or tertiary amine with methyl ethyl propyl or isopropyl sub
- Distance between X and N is 2-4 carbons
Features to treat Parkinsons
Antagonist
Teritary amine
Lipophilic (nonpolar)
