ANS Part 1: cholinergic Flashcards
homeostasis is regulated by ____ nervous system
autonomic
what makes up the central nervous system
- brainstem
- hypothalamus
what parts of the spinal cord are for sympathetic NS
thoracic and lumbar
what parts of the spinal cord are for parasympathetic NS
cranial (lower brainstem and medulla) and sacral
in the parasympathetic NS, the ganglia and post-ganglial fibers are ____ (close/far) to the organs innervated
close or within
sympathetic pre-ganglion and post-ganglion length
- pre: short
- post: long
parasymp pre-ganglion and post-ganglion length
- pre: long
- post: short
salivary composition for symp and parasymp
- symp: high mucin
- parasymp: high water and electrolytes
all pre- and post- ganglia have Ach except for ___
sympathetic post-ganglion: uses NE
the NE released from symp post bind to ___ receptors
NE binds to adrenergic receptors
the Ach released from parasymp post bind to ___ receptors
Ach binds to muscarinic receptors
which NS innervates the adrenal medulla
sympathetic NS
what receptors are found on adrenal medulla
nicotinic
what does the adrenal medulla release
epinephrine
adrenergic agonists are called
sympathomimetics
cholinergic agonists are called
parasympathomimetics
adrenergic antagonists are called
sympatholytics
cholinergic antagonists are called
parasympatholytics
what is the target for direct-acting agonists/antagonists
receptors (either pre or post synaptic)
pre-synaptic receptors are excitatory or inhibitory or both
inhibitory only
4 things that indirect acting Ag and Antag target
- uptake or re-uptake mechanisms
- enzyme
- storage
- exocytosis
2 examples of indirect acting agents and their mechanism
- amphetamine (stim release of NE - exocytosis - indirect Ag)
- cocaine (prevent re-uptake of A/NA - indirect Ag)
what enzyme synthesizes Ach
CAT
what enzyme degrades Ach
acetylcholinesterase (AChE)
what is the rate-limiting step of Ach synthesis
availability of choline
choline transporter inhibition
hemicholinium
vesicular transport inhibition
vesamicol
2 examples of inhibitors for Ach exocytosis
- botulinum toxin A
- tetanus toxin
example of stimulators for Ach exocytosis
black widow spider venom (alpha-latrotoxin)
reversible inhibitors for AchE
- physostigmine
- neostigmine
- tacrine
- edrophonium
- rivastigmine
- donepezil
irreversible inhibitors for AchE
- organophosphates (eg. sarin and parathion)
- echothiophate
structure of nicotinic Ach receptor
ionotropic, pentameric
4 agonists for nicotinic Ach receptor
- nicotine
- lobeline
- Ach
- carbachol
antagonist for nicotinic Ach receptor
alpha-bungarotoxin
2 types of nicotinic Ach receptors
- neuronal (Nn)
- muscular (Nm)
agonist for Neuronal nicotinic receptor (Nn)
dimethylphenyl piperazinium (DMPP)
3 antagonist for Neuronal nicotinic receptor (Nn)
- hexamethonium
- trimethaphan
- mecamylamine
agonist for muscular nicotinic receptor (Nm)
phenyltrimethylammonium (PMA)
antagonist for muscular nicotinic receptor (Nm)
curare (d-tubocurarine)
decamethonium
what subunits are sites in muscular nicotinic receptors
alpha-1 and beta-1 only!
4 changes that result from nicotine stimulation at ganglion
- increase heart rate
- increase blood pressure
- increase GI activity
- increase salivation
4 changes that result from hexamethonium stimulation at ganglion
- decrease heart rate
- decrease blood pressure
- decrease GI activity
- decrease salivation
drug that blocks nicotonic receptor on ganglion
trimethaphan camsylate (Arfonad)
which subtypes of muscarinic Ach receptors are excitatory and inhibitory
M 1,3,5 - excitatory
M 2,4 - inhibitory
what type of receptors are muscarinic Ach receptors
GPCR
Agonist for non-selective muscarinic receptor
- muscarine
- carbachol
Antag for non-selective muscarinic receptor
ATROPINE! (causes mydriasis)
which G protein is associated with M 1,3,5
Gq (increases IP3 and DAG)
Ag M1 drugs and effect
- muscarine and oxotremorine
- increase secretory glands
Antag M1 drugs and effects
- atropine and pirenxipine
- decrease gastric secretion
Ag M3 drugs and effects
muscarine
-miosis (pupil constriction) and constriction of ciliary muscle, and increase secretory glands
Antag M3 drugs and effects
atropine (mydriasis) and 4-DAMP
Ag M5 drugs and effects
muscarine (endothelial cells => increase NO => vasodilation)
Antag M5 drugs and effects
atropine
2 selective antagonists on muscarinic receptors
pirenzipine and 4-DAMP
muscarine and carbachol is used to treat ___
urinary retention and glaucoma
which G proteins are involved in M2,4
G i/o, decreases adenylyl catalase and cAMP
M2 antagonist
gallamine (selective antagonist)
what does gallamine do
inhibits myocardium and smooth m
M4 is found in
myenteric plexus
what does atropine do (5 things)
- increase cardiac inotropy and chronotropy
- decrease GI motility
- blurred vision
- pupillary dilation (mydriasis)
- hot and dry skin
what is the endogenous ligand for direct-acting cholinergic Ag
acetylcholine
pilocarpine has a higher affinity for which receptor
muscarinic
what does pilocarpine do
increase salivation, flushing, blurred vision
what is pilocarpine used to treat
- xerostomia
- glaucoma
what does carbachol do
miosis and decreases IOP
what is carbachol used to treat
- xerostomia
- pilocarpine-resistant glaucoma
what class of drugs is used to treat xerostomia
sialagogues
what are sialagogues
drugs that promote the secretion of saliva
name 2 drugs used to treat xerostomia (2 sialagogues)
- pilocarpine (salagen)
- cevimeline (evoxac)
cevimeline (evoxac) has a high affinity for which receptor
muscarinic receptor
what does cevimeline do
increase salivation
hexamethonium is a nicotinic Antag at the ganglion. name 6 things that it does
- lower BP
- blood pools in extremities
- mydriasis
- lower GI mobility; constipation
- moderate bronchodilation
- hot and dry skin
what can hexamethonium be used to treat
hypertension (rarely used)
atropine is an anticholinergic drug. what are the side effects of atropine? (saying)
- dry as a bone (dry skin)
- hot as a hare (hot skin)
- red as a beet (peripheral vasodilation)
- blind as a bat (mydriasis and blurred vision)
- mad as a hatter (disorientation, delirium)
which has a longer half-life: hyoscine or atropine?
hyoscine
what is hyoscine used to treat
- antispasmodic GI and urinary smooth m
- prevent motion sickness
name 3 synthetic muscarinic antag
- ipratropium bromide
- benzotropine
- darifenacine
ipratropium bromide tx
COPD and asthma
benzotropine tx
parkinson’s
darifenacine tx
incontinence and overactive bladder
homatropine hydrobromide: classification and tx
- muscarinic antag
- tx: ophthalmic admin for eye exam
homatropine butylbromide: classification and tx
- muscarinic antag
- Tx: gi motility disorders
which of the homatropine drugs can cross the BBB
homatropine hydrobromide
indirect-acting drugs that inhibit AchE are considered Ag or Antag
AchE inhibitors are considered indirect-acting Ag
what are the clinical signs of overdose/toxicity of AchE inhibitors
Salivation Lacrimation Urination Defecation Gi upset Emesis (vomiting) -miosis -resp/CV distress
specific cholinesterase or neuronal cholinesterase
AchE
non-specific or pseudo-cholinesterase
BchE
short-acting carbamate derivative that reversibly inhibits AchE
edrophonium
what two drugs are used to treat myasthenia gravis
edrophonium and neostigmine
3 medium-acting carbamate derivative (AchE inhibitor)
- physostigmine
- neostigmine
- rivastigmine
medium-acting PIPERIDINE derivative (AchE inhibitor)
donepezil
physostigmine Tx
glaucoma
neostigmine tx
myasthenia gravis
rivastigmine tx
alzheimer’s
donepezil tx
alzheimer’s
2 examples of organophosphates
- sarin (nerve gas)
- parathion (insecticide)
what is the antidote for organophosphate poisoning
pralidoxime (2-PAM)
what are the two amino acid residues at the site on AchE
serine and histidine
what is echothiophate (AchE irreversible inhibitor) used to treat
glaucoma
how does the 2-PAM antidote work
reverses binding to enzyme and then binds to P on organophosphate which prevents binding to AchE
what is the irreversible stage when organophosphates bind to AchE
aged phosphorylation
