Autonomic Pharmacology of the Gastrointestinal Tract Flashcards
Which autonomic system predominates tone of the following systems?
- arterioles
- veins
- sweat glands
- heart, S-A Nodes
- Iris
- Ciliary muscle
- GI Tract
- Urinary bladder
- Salivary gland
- arterioles
- SNS
- veins
- SNS
- sweat glands
- SNS
- heart, S-A Nodes
- PNS
- Iris
- PNS
- Ciliary muscle
- PNS
- GI Tract
- PNS
- Urinary bladder
- PNS
- Salivary gland
- PNS
Identify the neurotransmitters and receptors on the sympathetic and parasympathetic systems of the digestive tract
What is the major regulators of GI activity?
Describe this general process
- enteric nervous system: responsible for the largely autonomous nature of most GI activity
- responds to local environment
- also responds to ANS-CNS stimulation
- local sensory receptors relayed to motor neurons via interneurons; motor neurons then respond by stimulating the release of appropriate excitatory or inhibitory neurotransmitters
What are the two types of coupling that occur during excitation of smooth muscle?
- Electro-mechanical coupling
- ionotropic receptors can mediate changes in membrane potential, which in turn activate voltage-dependent Ca2+ channels to trigger an influx of Ca2+
- pharmaco-mechanical coupling
- metatropic receptors activate various signal transduction pathways to release Ca+ from intracellular stores
Inhibitory receptors on smooth muscles act through which enzymes?
What occurs at the cellular level?
provide an example
cAMP and cGMP dependent protein kinases (PKA and PKG)
- hyperpolarizaiton
- decreased intracellular Ca2+
- reduced myosin and actin interactions
Example
- NO relaxation of smooth muscle may occur throught he cGMP pathway and opening of K+ channels
What are the most common neurotransmitter in the GI tract & they general functions
- Acetylcholine (Ach)
- primary neurotransmitter of excitatory neurotransmitters
- tachykinins, co-released, may also be involved
- Nitric Oxide (NO)
- primary inhibitory neurotransmitter
- ATP, casoactive intestinal peptide, adn pituitary adenylyl cyclase-activating peptide (PACAP), corelease, also play a role
- Serotonin (5-HT)
- modulatin of motility, secretion, and emesis released by enterochromaffin cells in response to mucosal sensory activity
- exhibits activity on teh enteric neurons
- excessive release may lead to comiting b/c stimulatin of vagal nerve endings in prodimal small intestine
- this system is an important therapeutic target
- modulatin of motility, secretion, and emesis released by enterochromaffin cells in response to mucosal sensory activity
What are the two types of cholinergic receptors?
Where are each located and what stimuli do they receive?
Both respond to Ach
- Muscarinic
- nerve
- heart and smooth muscle
- glands and endothelium
- Nicotinic
- neuromuscular end plate
- skeletal muscle
- autonomic ganglion cells
What are the direct acting agents for cholinergic receptors?
- direct-acting
- alkaloids
- pilocarpine (major)
- muscarine
- arecoline
- choline esters (all charged)
- acetylcholine (endogenous)
- methacholine
- carbachol
- bethanechol
- alkaloids
Describe the process of the cholinergic synapse
- Acetyl CoA + Choline combine to form acetylcholine
- by choline acetyl transferase
- taken into the vesicle & stored with other transmitters
- upon stimulation there is a release of ACh into the synaptic cleft
- ACh will effect some postsynaptic receptor (either nicotinic or muscarinic)
- ACh is rapidly hydrolyzed broken down into choline and acetate
- by acetylcholine esterase
- choline taken back into the nerve cell & used for synthesis of ACh
- ALSO - presynaptic muscarinic receptors involved in regulation of release of ACh
What are the indirect acting agents on cholinergic receptors?
- indirect-acting (increase ACh by inhibiting acetylcholine estersase)
- reversible
- mono and bis-quarternary ammonium alcohols
- edrophonium, 4x amine
- DOA- minutes
- carbamates
- neostigmine, 4x; physostigmine, 3x; pyridostigmine, 4x; donepezil and tacrine, 3x)
- DOA- hours
- mono and bis-quarternary ammonium alcohols
- irreversibleorganophosphorus inhibitors
- echothiophate, parathion, malathion, sarin (nerve gas)
- DOA- 100s of hours
- reversible
Absorption and distribution of cholinergic drugs is primarily based on what factor?
What is the common metabolism and excretion of cholinergic drugs?
- absorption adn distribution
- tertiary vs. quarternary
- metabolism adn excretion
- most are metabolized to inactive products with usually renal excretion
- some are prodrugs
Adverse effects of cholinergic drugs
- follows physiology and anatomy
- dual innervation
- predominant tone
- overstimulatin of receptors by direct acting cholinermimics or excess accumulation of ACh to indirect acting cholinomimetics
- bradycardia
- increased salivation
- respirator distress
- excessive blockade of cholinergic receptors
- dry mout, visual disturbances, urinary retention
- depends upon drug reachign site of action in effective concentration
What are the antimuscarinic agents?
- atropine
- scopolamine
- pirenzipine
- diphenhydramine (antihistamine)
- thioridazine (neuroleptic)
- amitriptiline (antidepressant)
General characteristics of atropine blockade
- atropine - prototype
- competitive, reversible
- specific for muscarinic receptors
- dose related
- not usualy selective for subtypes
- some selectivity indicated at very selective doses (low doses)
- distributed based on structure
- quarternary analogs of atropine
What are the adrenergic agonists?
What are the adrenergic antagonists?
- agonists
- norepinephrine
- epinephrine
- dopamine
- antagonists
- prazosin
- phentolamine
- propanolol
- metoprolol
Describe the adrenergic junction & steps specific to adrenergic transmission
- tyrosine is the initial agent used to produce
- dopamine, epinephrine, and norepinephrine
- dopamine is included in a vesicle
- if beta hydroxylase is present in the vesicle, dopamine is converted to norepinephrine
- you then get exocytosis of the neurotransmitter and other molecules that are present within the vesicle into the junctional cleft
- neurotransmitter will effect post-synaptic receptor (ie. alpha 1)
- termination
- reuptake into the nerve terminal by uptake 1 or neurotransmitter neurotransporter involved in the presynaptic membrane
- metabolism by momamine oxidase via production of deaminated metabolites
- uptake into post-synaptic cell by similar transporter
- metabolism by catacholomethyltransferase which produces O-methylated metabolites which are transported to the kidney and excreted
- reuptake into the nerve terminal by uptake 1 or neurotransmitter neurotransporter involved in the presynaptic membrane
Identify the inidicated receptors
