PNS drugs Flashcards
2 main types of cholinergic receptors and mechanism of receptor action
- muscarinic - GPCR
2. nicotinic - ligand gated ion channels
locations of 3 types of M receptors
M1- CNS, autonomic ganglia, glands, enteric nerves
M2- CNS, heart, smooth muscle, autonomic terminals
M3- CNS, smooth muscle (iris, glands, GI) heart
functions of 3 types of M receptors
M1- stim juices
M2- SA node slowing, AV node slowing, myocardium slow contraction
M3- smooth muscle contraction
location of N receptors (2)
Nm - at neuromuscular junction - skeletal muscle contraction
Nn - autonomic ganglia (firing of post-synaptic neuron), adrenal medulla (secretion of catecholamines)
M1,3,5 mechanism of action
Gq > activation of PLC > hydrolysis of PIP has 2 actions
- IP3 > release of stored calcium > contraction of smooth muscle
- DAG > activated PKC > phosphorylation of substrate proteins
M2,4 mechanism of action
Gi/o > inhibs adenosine cyclase > lower cAMP has 2 actions
- activation of inward K channels >membrane hyperpolarization> less activity
- inhibition of neuronal channels
3 N receptor actions
- autonomic - stims postganlionic SNS and PNS neurons
- adrenal medulla - release catecholamines
- muscle - contract skeletal muscle
what are drugs that turn on PNS
- parasympathicomimetics
- cholinergics
- muscarinic agonists
- nicotinic agonsists
- acetylcholinesterase inhibitors
what are drugs that turn off PNS
- parasympatholytics
2. cholinergic, muscarinic, nicotinic antagoinists
M receptor agonists
- Ach
- muscarine
- pilocarpine
- methacholine
- carbachol
issues with Ach
- endogenous
2. not well absorbed, need large IV doses, doesn’t cross BBB
what is methacholine used for and why
diagnosis of bronchial activity - ashtma
- greater duration and no N receptor activity
-
what is carbachol
- M and N actions
- resitiance to cholinesterase
- used for glaucoma by causing pupil consrition and draining
what is pilocarpine
- mainly M
- increase salivation and sweating
- mostly for glaucoma
what is bethanechol
- M actions
- resitiance to cholinesterase
- used for GI and GU motility
what is indirect Ach drug
acetylocholinesterase
why use
more selective that agonists because selects for sites that actively release Ach
** watch for block and neuromuscular JCT - fatal crisis
3 reversible Achase inhibs
- physostigmine - glaucoma
- neostigmine - myasthenia gravis treatment
- edrophonium - short acting
what are irreversible Achase inhibs
nerve gasses and pesticides
4 nicotine agonists
- nicotine - multiple effects
- lobeline - used of nicotine withdrawal
- arecoline - from betel nut
- succinylcholin - used of paralysis during surgery because causes depolarizing blockade
5 actions of nicotine
- stim sym ganglia> then stim para ganglia> the parasymp blockade at high doses
- stim sym fibers to release NE within vacular walls and heart
- stim adrenal to release Epi
- stim ADH release
- tremor and nausea due to crossing BBB
4 M receptor antagonists
- atropine
- scopolamine
- glycopyrate
- ipratropium and tiotropium
what does atropine do
belladonna
- decrease secretion
- dilates pupils
- increase HR
- antidote for cholinergic poisoning
what does scopolamine do
tertiary amine with CNS effects
- treatment of motion sickness, antiemetic
what does glycopyrrolate do
quaternary amine
- less oral secretions
for peptic ulcer disease
what does ipratropium and tiotropium
used for COPD and asthma for resp effects
what does antimuscarinics do for bladder
calm it down so can use for overactive bladder - esp. M3 antagonist
when do we use N receptor antagonists
produce non-depolarizing neuromuscular blockade
- can be used to reverse autonomic blockade associated with ACHase inhibs
4 features of neuromuscular blockers
- non-depolarizing and polarizing types
- structural analogues of ACH
- very polar so must be given paraenterally
- act by blocking cholinergic tranmission between nerve and the muscle receptor
what are 2 actions of non-depolarizing blockers
- low doses act as an antagonist by blocking
2. high doses can enter the pore and and make it even harder to overcome
what is mech of depolarizing blockers
bind and depolarize, but then tire it out so no more
